text
stringlengths 297
230k
| title
stringlengths 4
145
| cui
stringlengths 4
10
| idx
int64 0
30.7k
| source
stringclasses 6
values | source_url
stringlengths 33
155
| retrieved_date
timestamp[s] | classification_map
stringlengths 2
1.45k
|
|---|---|---|---|---|---|---|---|
For a general phenotypic description and a discussion of genetic heterogeneity of open angle glaucoma (POAG), see 137760.
Mapping
Wiggs et al. (2004) identified 25 pedigrees with typical juvenile-onset OAG (JOAG), demonstrating autosomal dominant inheritance. They sequenced the myocilin gene (MYOC; 601652) in probands from each family and found mutations in 8%. To identify novel genes responsible for JOAG, they used families that did not have myocilin mutations for a genomewide screen. Multipoint linkage analysis of chromosome 20 markers achieved a peak hlod score of 4 between markers D20S189 and D20S104 on chromosome 20p12. Critical recombinants identified a 19-cM region between markers D20S894 and D20S878.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
|
GLAUCOMA 1, OPEN ANGLE, K
|
c2981140
| 27,500 |
omim
|
https://www.omim.org/entry/608696
| 2019-09-22T16:07:21 |
{"doid": ["1067"], "omim": ["608696"], "orphanet": ["98977"], "synonyms": ["Alternative titles", "GLAUCOMA, PRIMARY OPEN ANGLE, JUVENILE-ONSET, 3"]}
|
A number sign (#) is used with this entry because of evidence that hypopigmentation, organomegaly, and delayed myelination and development (HOD) is caused by de novo heterozygous mutation in the CLCN7 gene (602727) on chromosome 16p13.
Description
Hypopigmentation, organomegaly, and delayed myelination and development (HOD) is characterized by hypopigmented skin and hair with normally pigmented irides; organomegaly including enlargement of liver, kidney, and spleen; and delayed myelination on brain MRI accompanied by developmental delay in both gross and fine motor skills. Biopsy findings from skin and other organs are consistent with a lysosomal storage disorder (Nicoli et al., 2019).
Clinical Features
Nicoli et al. (2019) reported 2 unrelated children, a 22-month-old Caucasian girl (patient 1) and a 14-month-old Ghanaian boy (patient 2), who had hypopigmented hair and skin but normally pigmented irides. Growth and development were delayed, and brain MRIs in both probands showed delayed myelination, thin posterior corpus callosum, hyperintensity of the subthalamic nuclei, and cerebellar atrophy. The probands also exhibited organomegaly involving the liver, kidneys, and spleen; biopsies were suggestive of a lysosomal storage disorder, with amorphous floccular storage material observed in hepatic macrophages and duodenal histiocytes from patient 1, as well as abnormal cytoplasmic inclusions in the skin. Transmission electron micrography of renal tissue from patient 2 showed numerous interstitial macrophages containing abundant cytoplasmic inclusions. Neither patient exhibited dysostosis multiplex or osteopetrosis.
Molecular Genetics
In 2 unrelated children with hypopigmentation, organomegaly, and delayed myelination and development, Nicoli et al. (2019) performed exome sequencing and identified heterozygosity for the same missense mutation in the CLCN7 gene (Y715C; 602727.0007) in both probands. The mutation arose de novo in both cases, and was not found in public variant databases.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Other \- Intrauterine growth retardation \- Postnatal delayed growth HEAD & NECK Ears \- Profound hearing loss, unilateral (patient 1) Eyes \- Normally pigmented irides \- Reduced visual acuity (patient 1) \- Rod-cone dystrophy seen on electroretinography (patient 1) ABDOMEN Liver \- Hepatomegaly \- Abnormal cytoplasmic inclusion bodies in hepatic macrophages Spleen \- Splenomegaly Gastrointestinal \- Abnormal cytoplasmic inclusion bodies in duodenal histiocytes GENITOURINARY Kidneys \- Enlarged kidneys \- Poor corticomedullary differentiation \- Abnormal cytoplasmic inclusion bodies in renal interstitial macrophages SKELETAL Limbs \- Short long bones \- Diffuse hypermobility of upper extremities (patient 1) SKIN, NAILS, & HAIR Skin \- Hypopigmentation Electron Microscopy \- Abnormal cytoplasmic inclusion bodies in interstitial macrophages \- Immature melanosomes \- Disorganized melanosomes Hair \- Hypopigmentation MUSCLE, SOFT TISSUES \- Decreased muscle mass in lower extremities (patient 1) NEUROLOGIC Central Nervous System \- Delayed gross motor development \- Delayed fine motor development \- Generalized hypotonia (patient 1) \- Sustained clonus of lower extremities (patient 2) \- Myoclonic jerks of lower extremities (patient 2) \- Delayed myelination seen on brain MRI \- Hyperintensity of subthalamic nuclei \- Thin posterior corpus callosum \- Cerebellar atrophy PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios Delivery \- Premature birth LABORATORY ABNORMALITIES \- Enlarged lysosomal storage vacuoles in liver, spleen, and kidney MISCELLANEOUS \- Based on report of 2 unrelated children, ages 22 months and 14 months (last curated August 2019) MOLECULAR BASIS \- Caused by mutation in the chloride channel-7 gene (CLCN7, 602727.0007 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
|
HYPOPIGMENTATION, ORGANOMEGALY, AND DELAYED MYELINATION AND DEVELOPMENT
|
None
| 27,501 |
omim
|
https://www.omim.org/entry/618541
| 2019-09-22T15:41:32 |
{"omim": ["618541"]}
|
Primary sclerosing cholangitis (PSC) is characterized by inflammation in the bile ducts (cholangitis) that leads to scarring (sclerosis), narrowing of the ducts, and a buildup of bile in the liver. Early signs and symptoms include extreme tiredness, abdominal pain, and itchiness. As the condition worsens it may cause jaundice, an enlarged spleen, and eventually liver cirrhosis and failure. Other complications may include weight loss, vitamin deficiency, and osteoporosis. Many people with PSC develop other autoimmune conditions such as inflammatory bowel disease, type 1 diabetes, celiac disease, or thyroid disease. PSC is also a risk factor for cancer of the bile ducts (cholangiocarcinoma).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
|
Primary sclerosing cholangitis
|
c0566602
| 27,502 |
gard
|
https://rarediseases.info.nih.gov/diseases/1280/primary-sclerosing-cholangitis
| 2021-01-18T17:58:10 |
{"mesh": ["D015209"], "orphanet": ["171"], "synonyms": ["Cholangitis, primary sclerosing", "Sclerosing cholangitis"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of primary open angle glaucoma (POAG), see 137760.
Clinical Features
Suriyapperuma et al. (2007) reported 7 families with adult-onset primary open angle glaucoma that was not linked to previously identified POAG loci. Age at diagnosis ranged from 32 to 78 years. The maximum intraocular pressure values varied from moderate (24 mm Hg) to high (60 mm Hg). Those affected had optic nerve damage varying from early to late stages, with cup-disc ratios of up to 0.9 and significant glaucomatous visual field loss.
Mapping
Suriyapperuma et al. (2007) performed an initial genome scan and subsequent saturation mapping in 322 subjects with adult-onset POAG from 91 unrelated families unlinked to previously identified POAG loci and found consistent linkage to chromosome 2p16-p15 in 7 families. Analysis in 1 large family with 12 affected members revealed a common haplotype extending from D2S123 to D2S2165, a region of approximately 11 Mb. All affected members of the other 6 families shared similar haplotypes that overlapped with that of the large family, but with no founder effect. Combined analysis of the 7 families produced the highest lod score of 9.30 with marker D2S2320.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
|
GLAUCOMA 1, OPEN ANGLE, H
|
c1969811
| 27,503 |
omim
|
https://www.omim.org/entry/611276
| 2019-09-22T16:03:24 |
{"mesh": ["C566976"], "omim": ["611276"]}
|
This article may require cleanup to meet Wikipedia's quality standards. The specific problem is: This article does not meet the requirements of the guidelines “Citing non-English sources.” Please substitute the corresponding sources in English for those in Russian and in Polish Please help improve this article if you can. (January 2013) (Learn how and when to remove this template message)
Masked depression (MD) was a proposed form of atypical depression[1] in which somatic symptoms or behavioural disturbances dominate the clinical picture and disguise the underlying affective disorder.[2] The concept is not currently supported by the mental health profession.[3]
## Contents
* 1 Clinical manifestations
* 2 Dispute about the concept
* 3 Epidemiology
* 4 Official diagnostic status
* 5 Diagnostic criteria
* 6 See also
* 7 References
* 8 External links
## Clinical manifestations[edit]
Somatic manifestations of MD are distinguished by an extreme diversity[4]:110 and include headaches, back pain, abdominal pain etc. Pathological behaviour masking depression may take the form of compulsive gambling, compulsive work, changes in arousal or orgasmic function, decreased libido or, on the contrary, impulsive sexual behaviour, alcoholism, or drug addiction.
## Dispute about the concept[edit]
MD has been variously described as "depression sine (without) depression" (K. Schneider, 1925), "latent" depression (Lange J., 1928), "vegetative depression" (R. Lemke, 1949[5]) "hidden" or "masked" depression (Lopez Ibor J.J. [es], 1972;[6] Kielholz J.J., 1983; Pichot P.; Hasson J., 1973), "larvate" or "somatisation depression" (Gayral L., 1972), "depressive equivalents" etc.[7] Most investigators, especially those in the German-speaking countries, assumed masked depression (German: die larvierte Depression[8]) to be endogenous depression.[9] The term was largely used in the 1970s and 1980s, but at the end of the 20th century there was a decline in interest in the study of masked depression. Today this diagnosis does not play a significant clinical or scientific role.[10]
## Epidemiology[edit]
MD is supposed to be a common clinical phenomenon.[11] According to some authors, masked depression is as frequent as overt depression.[12] Although masked depression can be found at any age, it has been observed more commonly after mid-life.[12]
Making the diagnosis and the management of MD in clinical practice are complicated by the fact that he who has got MD is unaware of his mental illness. Patients with MD are reluctant to associate their physical symptoms with an affective disorder[13] and refuse mental health care. As a rule, these patients attribute their disturbances to physical illness, seek medical care for them, and report only somatic complaints to their physicians,[14] with the consequence that many of such depressions are not recognized or are misdiagnosed and mistreated[11] Estimates of depressed patients who are correctly identified and treated range from 5% to 60%.[15] Recent data show that about 10% of people who consult a physician for any reason originally suffer from affective disorders disguised by physical symptoms.[12][16]
## Official diagnostic status[edit]
Current classifications: ICD-10 and DSM-IV do not contain the term "masked depression".[1] Some Ukrainian psychiatrists claim that MD is to be qualified as "depression with somatic symptoms" (F 3x.01), according to ICD-10.[17]
## Diagnostic criteria[edit]
This section needs expansion. You can help by adding to it. (January 2013)
Affective disorders in patients with MD can only be detected by means of a clinician-administered diagnostic interview.[4]:408[18]:576[19] Organic exclusion rules[19] and other criteria are used in making the diagnosis of MD.[20]:185–188
## See also[edit]
* Psychiatry portal
* Somatisation
* Somatoform disorder
## References[edit]
1. ^ a b Anna Miodek; Paweł Szemraj, Józef Kocur, Anna Ryś (2007). "Depresja maskowana – historia i współczesność" [Masked Depression – History and Present Days] (PDF). Pol. Merk. Lek. (in Polish). MEDPRESS. XXIII (133): 78–80. ISSN 1426-9686. Retrieved 2013-01-04 The paper is accompanied with an abstract in EnglishCS1 maint: multiple names: authors list (link)
2. ^ Verster, G. C.; Gagiano, C. A. (August 1995). "Gemaskerde depressie" [Masked depression] (PDF). South African Medical Journal (in Afrikaans). Health and Medical Publishing Group. 85 (8): 759–762. ISSN 0256-9574 Revue : Anglais
3. ^ Treating Child and Adolescent Depression. Lippincott Williams & Wilkins. 2012. p. 5. ISBN 1451153031.
4. ^ a b (in Russian) Коркина М. В., Лакосина Н. Д., Личко А. Е. Психиатрия: Учебник. — М.: Медицина, 1995. — 608 с.; ил. — [Учеб. лит. для студентов мед. вузов] ISBN 5-225-00856-9
5. ^ Thormann, J.; Himmerich, H.; Steinberg, H. (December 2011). "The concept of "vegetative depression" (1949) by Rudolf Lemke". Pharmacopsychiatry. 21 (06): A110. doi:10.1055/s-0031-1292551.
6. ^ López Ibor J.J. (March 1972). "Masked Depressions". Br. J. Psychiatry. 120 (556): 245–258. doi:10.1192/bjp.120.556.245.
7. ^ For more detail, see: Katon, W.; Kleinman, A.; Rosen, G. (Jan 1982). "Depression and somatization: a review. Part I.". Am. J. Med. 72 (1): 127–35. doi:10.1016/0002-9343(82)90599-x.
8. ^ Steffen Walter’s entry at ProZ.com.
9. ^ (in Russian) Вертоградова О.П. К проблеме депрессий в общесоматической практике // Сб. Депрессии в амбулаторной и общесоматической практике (вопросы диагностики и терапии). М., 1984, с. 12–17.
10. ^ Encyclopedia of Clinical Neuropsychology > Masked Depression
11. ^ a b Fisch R. Z. (1987). "Masked depression: its interrelations with somatization, hypochondriasis and conversion". Int J Psychiatry Med. 17 (4): 367–79. doi:10.2190/cr7j-wu5n-hc5x-2jq5. PMID 3326856.
12. ^ a b c Alexopoulos, George S. (1990). "Clinical and Biological Findings in Late-Onset Depression". In Tasman, Allan; Goldfinger, Stephen M.; Kaufmann, Charles A. (eds.). American Psychiatric Press Review of Psychiatry. 9. American Psychiatric Press. p. 250.
13. ^ "Physical Symptoms in Depression: Interview with Thomas W. Koenig, MD" (PDF). Advanced Studies in Medicine.
14. ^ Brody, D.S.; Thompson T.L. etc. (March 1995). "Recognizing and managing depression in primary care". Gen Hosp Psychiatry. 17 (2): 93–107. doi:10.1016/0163-8343(94)00093-s. PMID 7789790.
15. ^ Patricia A. Carney etc. (December 1999). "Recognizing and Managing Depression in Primary Care A Standardized Patient Study". The Journal of Family Practice. 48 (12).
16. ^ Schneider, Frank; Sandra Kratz etc. (February 26, 2004). "Insufficient depression treatment in outpatient settings". Ger Med Sci. 2: Doc01. PMC 2703210. PMID 19675684.
17. ^ (in Russian) Подкорытов В. С., Чайка Ю. Ю. Депрессии. Современная терапия Archived 2017-12-29 at the Wayback Machine. — Харьков: Торнадо, 2003. — С. 54. — ISBN 966-635-495-0
18. ^ (in Russian) Психиатрия: Учебник. / Коркина М. В., Лакосина Н. Д., Личко А. Е., Сергеев И. И. — 2-е изд., доп., перераб. — М.: МЕДпресс-информ, 2002. ISBN 5-901712-12-9
19. ^ a b (in Russian) Жариков Н. М., Тюльпин Ю. Г. Психиатрия: Учебник. — М.: Медицина, 2000. — С. 193. ISBN 5-225-04189-2
20. ^ (in Russian) Психиатрия. Национальное руководство / Под ред. Т.Б. Дмитриевой, В.Н. Краснова, Н.Г. Незнанова, В.Я. Семке, А.С. Тиганова. — М.: ГЭОТАР-Медиа, 2011. — 1000 с. — (Национальные руководства). — 3000 экз. — ISBN 978-5-9704-2030-0
## External links[edit]
* Masked depression // The Free Dictionary
* v
* t
* e
Mental and behavioral disorders
Adult personality and behavior
Gender dysphoria
* Ego-dystonic sexual orientation
* Paraphilia
* Fetishism
* Voyeurism
* Sexual maturation disorder
* Sexual relationship disorder
Other
* Factitious disorder
* Munchausen syndrome
* Intermittent explosive disorder
* Dermatillomania
* Kleptomania
* Pyromania
* Trichotillomania
* Personality disorder
Childhood and learning
Emotional and behavioral
* ADHD
* Conduct disorder
* ODD
* Emotional and behavioral disorders
* Separation anxiety disorder
* Movement disorders
* Stereotypic
* Social functioning
* DAD
* RAD
* Selective mutism
* Speech
* Stuttering
* Cluttering
* Tic disorder
* Tourette syndrome
Intellectual disability
* X-linked intellectual disability
* Lujan–Fryns syndrome
Psychological development
(developmental disabilities)
* Pervasive
* Specific
Mood (affective)
* Bipolar
* Bipolar I
* Bipolar II
* Bipolar NOS
* Cyclothymia
* Depression
* Atypical depression
* Dysthymia
* Major depressive disorder
* Melancholic depression
* Seasonal affective disorder
* Mania
Neurological and symptomatic
Autism spectrum
* Autism
* Asperger syndrome
* High-functioning autism
* PDD-NOS
* Savant syndrome
Dementia
* AIDS dementia complex
* Alzheimer's disease
* Creutzfeldt–Jakob disease
* Frontotemporal dementia
* Huntington's disease
* Mild cognitive impairment
* Parkinson's disease
* Pick's disease
* Sundowning
* Vascular dementia
* Wandering
Other
* Delirium
* Organic brain syndrome
* Post-concussion syndrome
Neurotic, stress-related and somatoform
Adjustment
* Adjustment disorder with depressed mood
Anxiety
Phobia
* Agoraphobia
* Social anxiety
* Social phobia
* Anthropophobia
* Specific social phobia
* Specific phobia
* Claustrophobia
Other
* Generalized anxiety disorder
* OCD
* Panic attack
* Panic disorder
* Stress
* Acute stress reaction
* PTSD
Dissociative
* Depersonalization disorder
* Dissociative identity disorder
* Fugue state
* Psychogenic amnesia
Somatic symptom
* Body dysmorphic disorder
* Conversion disorder
* Ganser syndrome
* Globus pharyngis
* Psychogenic non-epileptic seizures
* False pregnancy
* Hypochondriasis
* Mass psychogenic illness
* Nosophobia
* Psychogenic pain
* Somatization disorder
Physiological and physical behavior
Eating
* Anorexia nervosa
* Bulimia nervosa
* Rumination syndrome
* Other specified feeding or eating disorder
Nonorganic sleep
* Hypersomnia
* Insomnia
* Parasomnia
* Night terror
* Nightmare
* REM sleep behavior disorder
Postnatal
* Postpartum depression
* Postpartum psychosis
Sexual dysfunction
Arousal
* Erectile dysfunction
* Female sexual arousal disorder
Desire
* Hypersexuality
* Hypoactive sexual desire disorder
Orgasm
* Anorgasmia
* Delayed ejaculation
* Premature ejaculation
* Sexual anhedonia
Pain
* Nonorganic dyspareunia
* Nonorganic vaginismus
Psychoactive substances, substance abuse and substance-related
* Drug overdose
* Intoxication
* Physical dependence
* Rebound effect
* Stimulant psychosis
* Substance dependence
* Withdrawal
Schizophrenia, schizotypal and delusional
Delusional
* Delusional disorder
* Folie à deux
Psychosis and
schizophrenia-like
* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
* v
* t
* e
Antidepressants (N06A)
Specific reuptake inhibitors and/or receptor modulators
SSRIs
* Citalopram
* Escitalopram
* Fluoxetine#
* Fluvoxamine
* Indalpine‡
* Paroxetine
* Sertraline
* Zimelidine‡
SNRIs
* Desvenlafaxine
* Duloxetine
* Levomilnacipran
* Milnacipran
* Tofenacin
* Venlafaxine
NRIs
* Atomoxetine
* Reboxetine
* Viloxazine
NDRIs
* Amineptine‡
* Bupropion
* Nomifensine‡
NaSSAs
* Mianserin
* Mirtazapine
* Setiptiline
SARIs
* Etoperidone
* Nefazodone
* Trazodone
SMS
* Vilazodone
* Vortioxetine
Others
* Agomelatine
* Amisulpride
* Esketamine†
* Etryptamine‡
* Indeloxazine
* flupentixol
* Ketamine†
* Medifoxamine‡
* Metryptamine‡
* Oxaflozane‡
* Pivagabine‡
* Tandospirone
* Teniloxazine
* Tianeptine
Tricyclic and tetracyclic antidepressants
TCAs
* Amineptine‡
* Amitriptyline#
* Amitriptylinoxide
* Butriptyline‡
* Clomipramine#
* Demexiptiline‡
* Desipramine
* Dibenzepin
* Dimetacrine‡
* Dosulepin
* Doxepin
* Imipramine
* Imipraminoxide‡
* Iprindole‡
* Lofepramine
* Melitracen
* Metapramine‡
* Nitroxazepine
* Nortriptyline
* Noxiptiline
* Opipramol
* Pipofezine
* Propizepine‡
* Protriptyline
* Quinupramine‡
* Tianeptine
* Trimipramine
TeCAs
* Amoxapine
* Maprotiline
* Mianserin
* Mirtazapine
* Setiptiline
Others
* Tiazesim
Monoamine oxidase inhibitors
Non-selective
* Irreversible: Benmoxin‡
* Iproclozide‡
* Iproniazid‡
* Isocarboxazid
* Isoniazid#
* Linezolid#
* Mebanazine‡
* Nialamide‡
* Octamoxin‡
* Phenelzine
* Pheniprazine‡
* Phenoxypropazine‡
* Pivhydrazine‡
* Safrazine‡
* Tedizolid
* Tranylcypromine
* Reversible: Caroxazone‡
* Mixed: Bifemelane
MAOA-selective
* Reversible: Eprobemide
* Metralindole
* Minaprine‡
* Moclobemide
* Pirlindole
* Tetrindole
* Toloxatone
MAOB-selective
* Irreversible: Selegiline
Adjunctive therapies
* Atypical antipsychotics (aripiprazole, brexpiprazole, lurasidone, olanzapine, quetiapine, risperidone)
* Buspirone
* Lithium (lithium carbonate, lithium citrate)
* Thyroid hormones (triiodothyronine (T3), levothyroxine (T4))
Miscellaneous
* Ademetionine (SAMe)
* Hypericum perforatum (St. John's Wort)
* Oxitriptan (5-HTP)
* Rubidium chloride (RbCl)
* Tryptophan
* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Masked depression
|
c0338897
| 27,504 |
wikipedia
|
https://en.wikipedia.org/wiki/Masked_depression
| 2021-01-18T19:09:48 |
{"wikidata": ["Q2580627"]}
|
## Summary
### Clinical characteristics.
Isolated methylmalonic acidemia/aciduria, the topic of this GeneReview, is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Onset of the manifestations of isolated methylmalonic acidemia/aciduria ranges from the neonatal period to adulthood. All phenotypes are characterized by periods of relative health and intermittent metabolic decompensation, usually associated with intercurrent infections and stress.
* In the neonatal period the disease can present with lethargy, vomiting, hypotonia, hypothermia, respiratory distress, severe ketoacidosis, hyperammonemia, neutropenia, and thrombocytopenia and can result in death within the first four weeks of life.
* In the infantile/non-B12-responsive phenotype, infants are normal at birth, but develop lethargy, vomiting, dehydration, failure to thrive, hepatomegaly, hypotonia, and encephalopathy within a few weeks to months of age.
* An intermediate B12-responsive phenotype can occasionally be observed in neonates, but is usually observed in the first months or years of life; affected children exhibit anorexia, failure to thrive, hypotonia, and developmental delay, and sometimes have protein aversion and/or vomiting and lethargy after protein intake.
* Atypical and "benign"/adult methylmalonic acidemia phenotypes are associated with increased, albeit mild, urinary excretion of methylmalonate.
Major secondary complications of methylmalonic acidemia include: intellectual impairment (variable); tubulointerstitial nephritis with progressive renal failure; "metabolic stroke" (acute and chronic basal ganglia injury) causing a disabling movement disorder with choreoathetosis, dystonia, and para/quadriparesis; pancreatitis; growth failure; functional immune impairment; and optic nerve atrophy.
### Diagnosis/testing.
Diagnosis of isolated methylmalonic acidemia relies on analysis of organic acids in plasma and/or urine by gas-liquid chromatography and mass spectrometry. Establishing the specific subtype of methylmalonic acidemia requires cellular biochemical studies (including 14C propionate incorporation and B12 responsiveness, complementation analysis, and cobalamin distribution assays) and molecular genetic testing. The finding of biallelic pathogenic variants in one of the five genes (MMUT, MMAA, MMAB, MCEE, and MMADHC) associated with isolated methylmalonic acidemia – with confirmation of carrier status in the parents – can establish the diagnosis.
### Management.
Treatment of manifestations: Critically ill individuals are stabilized by restoring volume status and acid-base balance; reducing or eliminating protein intake; providing increased calories via high glucose-containing fluids and insulin to arrest catabolism; and monitoring serum electrolytes and ammonia, venous or arterial blood gases, and urine output. Management includes a high-calorie diet low in propiogenic amino acid precursors; hydroxocobalamin intramuscular injections; carnitine supplementation; antibiotics such as neomycin or metronidazole to reduce propionate production from gut flora; gastrostomy tube placement as needed; and aggressive treatment of infections. Other therapies used in a limited number of patients include N-carbamylglutamate for the treatment of acute hyperammonemic episodes; liver, kidney, or combined liver and kidney transplantation; and antioxidants for the treatment of optic nerve atrophy.
Prevention of primary manifestations: In some cases, newborn screening allows for presymptomatic detection of affected newborns and early treatment.
Agents/circumstances to avoid: Fasting and increased dietary protein.
Other: Medic Alert® bracelets and up-to-date, easily accessed, detailed emergency treatment protocols facilitate care.
### Genetic counseling.
Isolated methylmalonic acidemia is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible using molecular genetic techniques if the pathogenic variants in the family are known. In some circumstances, prenatal diagnosis for pregnancies at increased risk is possible by enzyme analysis and metabolite measurements on cultured fetal cells (obtained by chorionic villus sampling or amniocentesis).
## Diagnosis
For this review, the term "isolated methylmalonic acidemia" refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood and urine that result from the failure to convert methylmalonyl-CoA into succinyl-CoA during propionyl-CoA metabolism in the mitochondrial matrix, without hyperhomocysteinemia or homocystinuria, hypomethioninemia, or variations in other metabolites, such as malonic acid (Figure 1).
#### Figure 1.
Major pathway of the conversion of propionyl-CoA into succinyl-CoA. The biotin-dependent enzyme propionyl-CoA carboxylase converts propionyl-CoA into D-methylmalonyl-CoA, which is then racemized into L-methylmalonyl-CoA and isomerized into succinyl-CoA, (more...)
Isolated methylmalonic acidemia results from any ONE of the following:
* Complete (mut0 enzymatic subtype) deficiency or partial (mut– enzymatic subtype) deficiency of the enzyme methylmalonyl-CoA mutase encoded by MMUT
* Diminished synthesis of its cofactor 5'-deoxyadenosylcobalamin, associated with cblA, cblB, or cblD-MMA complementation groups caused by biallelic pathogenic variants in MMAA, MMAB, or MMADHC, respectively
* Deficient activity of methylmalonyl-CoA epimerase encoded by MCEE
Note that the following disorders are NOT included in the scope of this GeneReview (see Differential Diagnosis):
* Methylmalonic acidemia associated with succinyl-CoA ligase deficiency, caused by mutation of SUCLA2 or SUCLG1, is discussed in SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria and SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria, respectively.
* Methylmalonic acidemia associated with hyperhomocysteinemia or homocystinuria caused by defects in other steps of intracellular cobalamin metabolism is discussed in Disorders of Intracellular Cobalamin Metabolism.
* Rare defects, such as combined malonic and methylmalonic acidemia, methylmalonate semialdehyde dehydrogenase deficiency, transcobalamin receptor deficiency, and combined methylmalonic acidemia and homocysteinemia, cblX type, are discussed briefly under Differential Diagnosis.
### Suggestive Findings
Because the presenting signs and symptoms of isolated methylmalonic acidemia are nonspecific, suggestive findings can include the following:
* In neonates: lethargy, vomiting, hypotonia, hypothermia, respiratory distress, severe ketoacidosis, hyperammonemia, neutropenia, and thrombocytopenia
Note: In states with an expanded newborn screening program, isolated methylmalonic acidemia can be diagnosed in well-appearing newborns prior to an episode of acute decompensation.
* In older infants and children: failure to thrive, renal syndromes and hypotonia, intellectual disability or other acute (basal ganglia stroke) and chronic neurologic symptoms
In patients with partial mut enzymatic deficiency, cblA, or cblB, suggestive findings at various ages can include the following:
* An attenuated MMA phenotype [Lerner-Ellis et al 2004, Lerner-Ellis et al 2006, Hörster et al 2007]
* Isolated renal tubular acidosis or chronic renal failure [Dudley et al 1998, Coman et al 2006]
* Metabolic stroke of the basal ganglia [Korf et al 1986, Heidenreich et al 1988]
* Catastrophic/lethal ketoacidosis following an intercurrent illness [Ciani et al 2000]
### Establishing the Diagnosis
An overview of the process of intracellular propionate and cobalamin metabolism is depicted in Figure 1. A flowchart for the work up of a person with elevated methylmalonic acid in urine and/or plasma is provided in Figure 2, a modified algorithm that includes the consideration of methylmalonyl-CoA epimerase deficiency, succinyl-CoA ligase deficiency, and other rare defects in the pathway, as well as the use of in vivo vitamin B12 responsiveness in the work up of an individual who is found to have methylmalonic acidemia at any age.
#### Figure 2.
An algorithm of conditions to be considered in the differential diagnosis of elevated serum or urine methylmalonic acid detected either during the follow up of an increased propionylcarnitine (C3) on newborn screening or a positive urine organic acid (more...)
Step 1. In a proband with suspicious clinical findings and a positive urine organic acid screen for MMA, laboratory testing that can help to establish the diagnosis includes: glucose, electrolytes, ammonia, blood gas, lactate, CBC, and urine ketones, plasma MMA, tHcy, and B12 levels, plasma amino acids, and acylcarnitine profile. Relevant findings:
* High plasma and urine MMA with normal B12, tHcy, and methionine levels
* Elevated propionylcarnitine (C3)
* High anion gap metabolic acidosis in arterial or venous blood gas testing and huge quantities of ketone bodies and lactate in the urine
* Hyperammonemia
* Hyperglycinemia
* Lactic acidosis
* CBC showing neutropenia, thrombocytopenia, anemia
Step 2. In newborns found to have elevation of propionylcarnitine (C3) by expanded newborn screening and in individuals at high genetic risk for the disorder (e.g., sibs of a proband), the first priority is to establish the presence of significantly elevated methylmalonic acid, which is best done by urine organic acid analysis (by GC/MS) and plasma acylcarnitine profile (by TMS). Note: At the same time, obtaining levels of plasma MMA, amino acids, plasma homocysteine, and serum vitamin B12 (in both the newborn and the mother) helps further differentiate the cause of methylmalonic acidemia should that be confirmed (see Step 3).
In addition to elevated methylmalonic acid, the following biochemical findings may also be seen:
* Presence of 3-hydroxypropionate, 2-methylcitrate, and tiglylglycine detected on GC/MS analysis of urine
* Elevated plasma concentration of glycine on plasma amino acid analysis
* Elevated plasma concentration of propionylcarnitine (C3) and variable elevations in C4-dicarboxylic or methylmalonic/succinylcarnitine (C4DC) measured by TMS
Step 3. Once elevation of methylmalonic acidemia and aciduria have been established, a normal plasma homocysteine and vitamin B12 level can help differentiate isolated MMA from other disorders (see Figure 2, left two columns). Note: Although plasma and/or urine methylmalonic acid concentration can be precisely quantitated (Table 1), this is generally not needed immediately for diagnostic purposes.
### Table 1.
Methylmalonic Acid Concentration in Phenotypes and Enzymatic Subtypes of Methylmalonic Acidemia
View in own window
Methylmalonic Acidemia Phenotype/Enzymatic Subtype 1Methylmalonic Acid Concentration
Urine 2Blood
Infantile/non-B12-responsive 3
mut0, mut–, cblB1,000-10,000 mmol/mol Cr100-1,000 µmol/L
B12-responsive 3 cblA, cblD-MMA
cblB, mut– (rare)Tens - hundreds mmol/mol Cr5-100 µmol/L
"Benign"/adult methylmalonic acidemia 410-100 mmol/mol Cr100 µmol/L
MCEE deficiency 550-1,500 mmol/mol Cr7 µmol/L
Normal 6<4 mmol/mol Cr 7<0.27 µmol/L 7
MCEE = methylmalonyl-CoA epimerase; ND = not determined
1\.
Biochemical parameters and clinical phenotype are not always concordant, partly because renal function can influence plasma MMA concentration [Kruszka et al 2013, Manoli et al 2013]. Patients in kidney failure show massive elevations in plasma MMA that can exceed 5,000 µmol/L.
2\.
In some centers, analysis of urine by 1H-NMR spectroscopy can also be used to demonstrate increased methylmalonate concentration [Iles et al 1986].
3\.
Approximate numbers, representing the author's experience with >80 individuals with the B12-responsive and non-B12-responsive types
4\.
From Giorgio et al [1976] and converted into µmol/L for plasma concentration
5\.
Bikker et al [2006], Dobson et al [2006], Nagarajan et al [2005], Gradinger et al [2007]
6\.
From Gradinger et al [2007]
7\.
Normal values have not been exclusively derived from children or neonates. Some laboratories report urine MMA concentrations in mg/g/Cr (normal: <3 mg/g/Cr) and serum concentrations in nmol/L (normal: <271 nmol/L). The molecular weight of MMA is 118 g/mol.
Step 4. In vivo responsiveness to vitamin B12 should be determined in all affected individuals. No standard regimen has been documented. When stable, affected individuals can be given 1.0 mg of hydroxocobalamin (OH-Cbl) (see Note) intramuscularly or intravenously every day for one to two weeks followed by assessment of production of MMA and related metabolites (3-OH-propionic, 2-methylcitrate) by serial urine organic acid analyses and/or measurement of plasma concentrations of MMA, propionylcarnitine, and homocysteine. A significant (>50%) reduction in metabolite production and plasma concentration(s) is considered to indicate responsiveness [Fowler et al 2008, Kruszka et al 2013]. In vivo response was reported in all individuals with cblA and only rare individuals with cblB [Hörster et al 2007].
Note: Hydroxocobalamin (not cyanocobalamin) is the preferred preparation for treatment of methylmalonic acidemia; thus, if the in vivo response to intramuscular hydroxocobalamin is questionable or borderline, vitamin B12 administration should be continued and a skin biopsy should be obtained to isolate fibroblasts to assess B12 responsiveness by 14C propionate incorporation in vitro.
Step 5. Molecular genetic testing (Table 2) can be used to establish the diagnosis of isolated MMA by identifying biallelic pathogenic variants in one of the five genes (MMUT, MMAA, MMAB, MCEE, and MMADHC) and confirming carrier status in the parents. In addition, the enzymatic subtype of isolated methylmalonic acidemia is mostly determined by molecular genetic testing due to the limited access to, cost of, and invasive nature of cellular biochemical testing.
Molecular testing approaches can include the following:
* Tiered single-gene testing. Because the phenotype of isolated methylmalonic acidemia can be identical regardless of the mutated gene, molecular genetic testing can be performed in the following order:
1.
UT and MMAB in vitamin B12-non-responsive individuals
2.
MMAA in vitamin B12-responsive individuals
3.
MCEE and MMADHC testing if results of testing of the first three genes (MMUT, MMAB, and MMAA) are unrevealing
Note: For all genes, sequence analysis is performed first, followed by deletion/duplication analysis if only one pathogenic variant has been detected.
* Use of a multigene panel that includes these five genes and other genes in the metabolic pathway (see Differential Diagnosis). Note: The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
### Table 2.
Molecular Genetic Testing Used in Isolated Methylmalonic Acidemia
View in own window
Gene 1Proportion of Isolated MMA Attributed to Mutation of This Gene 2Proportion of Variants Detected by This Method
Sequence analysis 3Deletion/duplication analysis 4
MMUT60%
(78% mut0 enzymatic subtype, 22% mut– enzymatic subtype)96% 5, 6Unknown, none reported
MMAA25%97% 7Unknown, none reported
MMAB12%98% 8Unknown, none reported
MCEEUnknown4 probands/families 9Unknown, none reported
MMADHCUnknown6 probands/families 10Unknown, none reported
1\.
See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.
2\.
Based on Worgan et al [2006] and Hörster et al [2007]
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.
5\.
Worgan et al [2006]
6\.
For individuals of Hispanic descent, targeted exon 2 analysis for the MMUT c.322C>T pathogenic variant may be considered.
7\.
Lerner-Ellis et al [2004]
8\.
Lerner-Ellis et al [2006]
9\.
Gradinger et al [2007]
10\.
Stucki et al [2012]
Step 6. Cellular biochemical testing on skin fibroblasts is the gold standard for determining the MMA subtype and B12 responsiveness in vitro and is useful when the above testing methods fail to provide a firm diagnosis to guide management. For details of biochemical testing, click here (pdf).
#### Newborn Screening
In the past decade, the implementation of tandem mass spectrometry (MS/MS) in newborn screening (NBS) by many states in the US and countries worldwide has identified newborns with methylmalonic acidemia through detection of elevated concentration of blood propionylcarnitine (C3), a metabolite increased in the blood of individuals with methylmalonic acidemia and the related disorder, propionic acidemia [Chace et al 2001, Therrell et al 2014].
Note: Since propionylcarnitine is one of the analytes most frequently responsible for false positive results, ratios including C3/C2, C3/C0, C3/C16, and new biomarkers such as C16:1OH are recommended in combination with high blood concentration of C3 as decision criteria for "positive" testing in newborn screening acylcarnitine analysis by MS/MS for methylmalonic acidemia and propionic acidemia [Lindner et al 2008].
Second-tier testing of 3-hydroxypropionic, methylmalonic, and/or 2-methylcitric acids could be used to reduce the costs and anxiety associated with false positive results [Matern et al 2007, la Marca et al 2008].
* If C3 and C5OH are increased, the diagnosis of holocarboxylase deficiency and/or biotinidase deficiency needs to be considered.
* Elevated C4-dicarboxylic acylcarnitine (C4DC) is a marker for both methylmalonylcarnitine and succinylcarnitine, and can indicate methylmalonic aciduria associated with succinyl-CoA ligase deficiency [Fowler et al 2008, Morava et al 2009].
Recommended action (ACT) sheet and confirmatory algorithm describing the basic necessary steps involved in follow up of an infant who has screened positive are available; see American College of Medical Genetics (ACMG) Newborn Screening ACT Sheet and National Academy of Clinical Biochemistry Guidelines (pdf) [Dietzen et al 2009].
## Clinical Characteristics
### Clinical Description
The phenotypes of isolated methylmalonic acidemia described below that are associated with the mut0 enzymatic subtype, mut– enzymatic subtype, cblA, cblB, and cblD-MMA share clinical presentations and a natural history characterized by periods of relative health and intermittent metabolic decompensation, usually associated with intercurrent infections and stress [Zwickler et al 2012]. Each such decompensation can be life-threatening. Of note, the natural history of isolated methylmalonic acidemia requires further study, particularly with respect to medical complications including renal disease, the effect of solid organ transplantation, and molecular pathology.
Infantile/non-B12-responsive phenotype (mut0 enzymatic subtype, cblB). The most common phenotype of isolated methylmalonic acidemia presents during infancy. Infants are normal at birth but rapidly develop lethargy, vomiting, and dehydration on initiation of protein-containing feeds. At presentation, they exhibit hepatomegaly, hypotonia, and in many, hyperammonemic encephalopathy. Laboratory findings typically show a severe, high anion-gap metabolic acidosis, ketosis and ketonuria (highly abnormal in neonates and strongly suggestive of an organic aciduria), hyperammonemia, and hyperglycinemia [Matsui et al 1983, Kölker et al 2015a]. Dialysis may be needed especially if hyperammonemia is significant and persistent.
Thrombocytopenia and neutropenia, suggestive of neonatal sepsis, can be seen.
The catastrophic neonatal presentation of isolated methylmalonic acidemia can result in death, despite aggressive intervention. Infants with the B12-responsive mut– enzymatic subtype or cblA can also present with an acute neonatal crisis.
Partially deficient or B12-responsive phenotypes (mut– enzymatic subtype, cblA, cblB [rare], cblD-MMA). This intermediate phenotype of isolated methylmalonic acidemia can occur in the first few months or years of life. Affected infants can exhibit feeding problems (typically anorexia and vomiting), failure to thrive, hypotonia, and developmental delay. Some have protein aversion and/or clinical symptoms of vomiting and lethargy after protein intake.
Until the diagnosis is established and treatment initiated these infants are at risk for a catastrophic decompensation (like that in neonates) [Shapira et al 1991, Lerner-Ellis et al 2004, Lerner-Ellis et al 2006, Hörster et al 2007].
During such an episode of metabolic decompensation, the child may die despite intensive intervention if prompt treatment specific for MMA is not instituted and the symptoms are misdiagnosed as, for example, diabetic ketoacidosis [Ciani et al 2000].
Before the onset of newborn screening, infants with the subtypes cblA or mut– would present with a devastating injury in the basal ganglia (more specifically lacunar infarcts in the globus pallidus) resulting in a debilitating movement disorder [Korf et al 1986, Heidenreich et al 1988].
Patients with partial mut enzymatic deficiency, cblA, or cblB can also present with isolated renal tubular acidosis or chronic renal failure [Dudley et al 1998, Coman et al 2006].
Methylmalonyl-CoA epimerase deficiency. Pathogenic variants in MCEE are a very rare cause of persistent moderate methylmalonic aciduria. Findings in infants/children with mutation of MCEE have ranged from complete absence of symptoms to severe metabolic acidosis with increased MMA and 2-methylcitrate and ketones in the urine at initial presentation [Dobson et al 2006, Gradinger et al 2007]. Symptoms include ataxia, dysarthria, hypotonia, mild spastic paraparesis, and seizures; however, many affected persons were from consanguineous unions — including the first identified individual, who also had a DOPA-responsive dystonia resulting from homozygous pathogenic variants of SPR, the gene encoding sepiapterin reductase [Bikker et al 2006].
Secondary complications. Despite increased knowledge about isolated methylmalonic acidemia and possibly earlier symptomatic diagnosis, isolated methylmalonic acidemia continues to be associated with substantial morbidity and mortality [de Baulny et al 2005, Dionisi-Vici et al 2006, Kölker et al 2015b] that correlates with the underlying defect [Hörster et al 2007]. Individuals with the mut0 enzymatic subtype and the cblB subtype have a higher rate of mortality and neurologic complications than those with the mut– enzymatic subtype and cblA.
The major secondary complications include:
* Intellectual disability. Intellectual disability may or may not be present even in those with severe disease. In a retrospective, survey-based review, about 50% of individuals with the mut0 enzymatic subtype and 25% of those with the cblA/cblB enzymatic subtype had an IQ below 80 and significant neurologic impairment [Baumgarter & Viardot 1995].
In another study about 50% of individuals with mut0, 85% with mut–, 48% with cblA, and 70% with cblB had an IQ above 90 [Hörster et al 2007].
In a recent natural history study, the mean FSIQ of all individuals with isolated methylmalonic acidemia (n = 37) was 85.0 ± 20.68, which is in the low average range (80 ≤ IQ ≤89). Individuals with cblA (n = 7), cblB (n = 6), and mut diagnosed prenatally or by newborn screening (n = 3) had mean FSIQs in the average range (90 ≤ IQ ≤109). The age of disease onset, the presence of severe hyperammonemia at diagnosis, and a history of seizures were associated with more severe impairments [O'Shea et al 2012].
* Tubulointerstitial nephritis with progressive impairment of renal function. All individuals with isolated methylmalonic acidemia, even those who are mildly affected or who have received a liver allograft [Nyhan et al 2002], are at risk of developing renal insufficiency [Walter et al 1989, Kruszka et al 2013]. End-stage renal disease (ESRD) was common in individuals with the mut0 enzymatic subtype (61%) and the cblB (66%) enzymatic subtype, and occurred less frequently in those with the cblA (21%) enzymatic subtype [Hörster et al 2007].
Secondary mitochondrial dysfunction rather than direct nephrotoxicity of methylmalonic acid is hypothesized. Cell-specific mitochondrial pathology primarily in the proximal tubules, associated with cytochrome c oxidase deficiency and increased markers of oxidative stress in the urine and plasma, have been shown in human and mouse studies [Atkuri et al 2009, Mc Guire et al 2009, Manoli et al 2013, Zsengellér et al 2014].
An acute renal syndrome, seen in the setting of metabolic decompensation, may also exist [Stokke et al 1967] and requires further clinical delineation. Moreover, renal tubular dysfunction presenting as a decrease in urine concentrating ability and acidification, hyporeninemic hypoaldosteronism, tubular acidosis type 4, and hyperkalemia have been reported in a number of affected individuals, and are supported by murine studies [Walter et al 1989, D'Angio et al 1991, Pela et al 2006, Manoli et al 2013].
* Neurologic findings. Some individuals develop a "metabolic stroke" or infarction of the basal ganglia (characteristically the globus pallidus externa) during acute metabolic decompensation, which can produce an incapacitating movement disorder [Korf et al 1986, Heidenreich et al 1988]. The reported incidence in different cohorts is 17%-30% [Baumgarter & Viardot 1995, Hörster et al 2007]. Distinct segments of the globus pallidus (and sometimes the substrantia nigra in the cerebral peduncles) are affected, suggesting a non-uniform, cell-specific sensitivity to the mechanism of infarct [Baker et al 2015].
Delayed myelination, incomplete opercularization, subcortical white matter changes, and brain stem and cerebellar changes have been described [Harting et al 2008, Radmanesh et al 2008].
Of note, individuals who have undergone liver and/or kidney transplantation can develop acute lesions without overt metabolic decompensation, suggesting that the enzyme deficiency in the brain remains unchanged and trapping of toxic metabolites in the CNS compartment can lead to injury despite other systemic benefits of the transplantation [Chakrapani et al 2002, Kaplan et al 2006, Vernon et al 2014].
* Pancreatitis. The incidence of pancreatitis in isolated methylmalonic acidemia is unknown, but it is a well-recognized complication [Kahler et al 1994]. It can occur acutely or chronically. Pancreatitis may be under-recognized because it can manifest nonspecifically with vomiting and abdominal pain.
* Growth failure. Growth failure is frequent and multifactorial. It is the result of severe chronic illness and perhaps relative protein malnutrition that is complicated further by chronic renal failure. Many infants are less than three standard deviations below normal for both length and weight.
Some children have documented growth hormone (GH) deficiency, but response to GH therapy may vary (see Management).
* Functional immune impairment. This results in an increased susceptibility to severe infections, particularly by fungal and gram-negative organisms [Oberholzer et al 1967, Wong et al 1992].
* Bone marrow failure. During episodes of metabolic decompensation patients can exhibit pancytopenia, with bone marrow hypoplasia and/or dysplasia that most frequently revert to normal with supportive care.
* Optic nerve atrophy. Late-onset optic atrophy associated with acute visual loss, resembling the presentation of the mitochondrial disorder Leber hereditary optic neuropathy (LHON), has been reported in isolated methylmalonic acidemia [Wasserstein et al 1999, Williams et al 2009, Pinar-Sueiro et al 2010, Traber et al 2011], as well as in propionic acidemia [Williams et al 2009, Martinez Alvarez et al 2016].
* Hepatoblastoma. Isolated instances of hepatoblastoma have been reported in the native or donor liver in individuals with mut MMA; however, the overall incidence of cancer in these patients is unknown [Cosson et al 2008, Chan et al 2015]
Survival in isolated methylmalonic acidemia has improved over time [Matsui et al 1983, van der Meer et al 1994, Baumgarter & Viardot 1995, Nicolaides et al 1998, Kölker et al 2015a].
In those with the mut0 enzymatic subtype, survival at age one year has improved from 65% in the 1970s to more than 90% in the 1990s; five-year survival has improved from 33% in the 1970s to more than 80% in the 1990s.
In one series, the median age of death of those with the mut0 enzymatic subtype was compared over time: 100% died at a median age of 1.6 years in the 1970s, 50% died at a median age of 7.6 years in the 1980s, and 20% died at a median age of 2.2 years in the 1990s. Overall mortality was about 50% for those with the mut0 enzymatic subtype (median age of death 2 years) as compared to 50% for the cblB enzymatic subtype (median age of death 2.9 years), 40% for the mut– enzymatic subtype (median age of death 4.5 years), and about 5% for the cblA enzymatic subtype (1 death at 14 days) [Hörster et al 2007].
The effect of early organ transplantation on overall survival has not been systematically studied.
Effect of newborn screening. The limited number of infants detected by newborn screening (NBS) and the short duration of their follow up do not allow conclusions regarding the effect of NBS on the long-term outcome of methylmalonic acidemia [Leonard et al 2003, Dionisi-Vici et al 2006]. Moreover, it must be emphasized that a significant number of infants with the mut0 enzymatic subtype may present clinically before the NBS results become available. Limited observations in sibs with the cblA enzymatic subtype suggest that the IQs of the individuals treated from the newborn period were significantly better than those of their older affected sibs who were diagnosed after the onset of symptoms [Hörster et al 2007].
Of note, before the availability of newborn screening individuals with cblA and some with cblB often manifested in early childhood with encephalopathy and globus pallidus injury, which in theory could have been avoided if they had been detected by NBS and treated before symptoms appeared.
### Genotype-Phenotype Correlations
Precise genotype-phenotype correlations are difficult to determine since most affected individuals are compound heterozygotes.
Homozygosity for the p.Asn219Tyr MMUT pathogenic variant is frequently associated with severe mutase deficiency (i.e., the mut0 enzymatic subtype) [Acquaviva et al 2001]. p.Arg108Cys, which is also associated with a mut0 enzymatic subtype, is more common in individuals of Hispanic descent [Worgan et al 2006].
Homozygosity for the p.Gly717Val MMUT pathogenic variant, which is associated with the mut– enzymatic subtype [Worgan et al 2006], is more common in individuals of African descent.
The clinical phenotype depends on a number of factors that cannot be accurately predicted by the genotype, including whole-body enzyme activity, in vivo responsiveness to cobalamin, environmental factors, and perhaps the efficiency and activation of alternative propionyl-CoA disposal pathways. It is possible that better understanding of clinical correlations in isolated methylmalonic acidemia could be achieved by estimating the amount of whole-body residual metabolic capacity based on stable isotope studies [Leonard 1997].
### Prevalence
Several studies have estimated the birth prevalence of isolated methylmalonic acidemia [Sniderman et al 1999]. Urine screening for isolated methylmalonic acidemia in Quebec identified "symptomatic methylmalonic aciduria" in approximately 1:80,000 newborns screened [Sniderman et al 1999], which approximates the observation of Chace et al [2001] of ten cases of isolated methylmalonic acidemia identified in a sample of 908,543 newborns screened by mass spectrometry in the US.
In Japan, the birth prevalence may be as high as 1:50,000 [Shigematsu et al 2002].
It appears that the prevalence of isolated methylmalonic acidemia may therefore fall between 1:50,000 and 1:100,000; confirmation, however, would require larger studies.
## Differential Diagnosis
Atypical methylmalonic acidemia is associated with increased, usually mild urinary excretion of methylmalonate. Rare defects, such as succinate-CoA ligase deficiency, combined malonic and methylmalonic aciduria, cblX deficiency, transcobalamin receptor defect, and methylmalonate semialdehyde dehydrogenase deficiency can cause methylmalonic acidemia/aciduria, although most patients will have additional biochemical findings.
The only known X-linked disorder related to the intracellular cobalamin metabolic pathway is cblX deficiency, caused by mutation of HCFC1 and associated with combined methylmalonic acidemia and hyperhomocysteinemia, severe intellectual disability, complex seizures, and other neurologic findings. cblX deficiency is a recently described disorder with unknown spectrum, but likely to include X-linked developmental delay either without biochemical abnormalities or with isolated elevations of methylmalonic acid.
"Benign" methylmalonic acidemia. Newborn screening in the province of Quebec identified infants with mild-to-moderate urinary methylmalonic acid excretion. Follow up revealed resolution in more than 50% of children, as well as an apparently benign, persistent, low-moderate methylmalonic acidemia in some [Ledley et al 1984, Sniderman et al 1999]. Additional individuals with a relatively benign type of methylmalonic acidemia have been reported [Coulombe et al 1981, Martens et al 2002]. Caution is necessary in follow up of these individuals as some can belong to a mild mut– enzymatic subtype and carry a significant risk for acute metabolic crisis [Shapira et al 1991].
The long-term outcome and clinical phenotype of these individuals awaits further description. Of note, a subgroup had a combined biochemical phenotype of malonic and methylmalonic acidemia and therefore likely represents combined malonic and methylmalonic (CMAMMA) caused by ACSF3 deficiency.
Combined malonic and methylmalonic aciduria (CMAMMA) caused by ACSF3 deficiency. Patients with CMAMMA show high malonic acid (MA) and methylmalonic acid (MMA) levels in their urine or plasma, with MMA excretion typically being higher than MA excretion (MMA/MA >5). Because C3 (propionylcarnitine) is not elevated, infants with CMAMMA are not detected by newborn screening based on a dried blood spot acylcarnitine analysis.
The phenotypic spectrum is broad, ranging from completely asymptomatic individuals to adults with neurologic syndromes (seizures, memory problems, psychiatric disease, and/or cognitive decline) or children with a wide range of manifestations, such as coma, ketoacidosis, hypoglycemia, failure to thrive, elevated transaminases, microcephaly, dystonia, axial hypotonia, and/or developmental delay. The full natural history of this disorder remains to be elucidated.
Mutation of ACSF3 (encoding a methylmalonyl- and malonyl-CoA synthetase that produces the first substrate, malonyl-CoA, for intra-mitochondrial fatty acid synthesis) is causative [Alfares et al 2011, Sloan et al 2011].
Methylmalonate semialdehyde dehydrogenase deficiency (MMSDH). In the last enzymatic steps in the valine degradation pathway, 3-hydroxyisobutyrate dehydrogenase converts 3-hydroxyisobutyrate to (S)-methylmalonic semialdehyde (MMSA), and methylmalonate semialdehyde dehydrogenase (MMSDH) converts (S)-methylmalonic semialdehyde to propionyl-CoA). Of note, the same enzyme catalyzes the oxidative decarboxylation of the (R)-methylmalonic semialdehyde enantiomer generated from thymine metabolism to propionyl-CoA.
A small number of patients with pathogenic variants in ALDH6A1, which encodes the MMSDH enzyme, have had extremely variable biochemical phenotypes: some have displayed 3-hydroxyisobutyric aciduria [Chambliss et al 2000, Sass et al 2012], while others have also displayed transient methylmalonic acidemia/aciduria [Marcadier et al 2013]. They have also had extremely variable clinical phenotypes, including severe intellectual impairment associated with significant brain myelination defects.
Transcobalamin receptor defect (TCblR/CD320). The index case and four additional affected individuals were asymptomatic newborns identified on NBS with an elevated C3 and elevated C3/C2 ratio. They also had increased plasma and urine MMA and normal serum vitamin B12 levels; two of the four were stated to have elevated homocysteine.
In the index case, biochemical abnormalities normalized with a single hydroxocobalamin injection and remained normal for nine months [Quadros et al 2010]. Fibroblasts showed decreased uptake of transcobalamin.
A CD320 pathogenic variant was also identified in a boy age seven weeks with retinal artery occlusions born to consanguineous parents [Karth et al 2012]. All reported affected individuals are homozygous for NM_016579.3:c.262_264del (p.Glu88del). Polymorphisms in the TCblR have been associated with increased risk for neural tube defects in an Irish cohort [Pangilinan et al 2010].
Combined methylmalonic acidemia and hyperhomocysteinemia/homocystinuria. Disorders that interfere with the intracellular metabolism of cobalamin can cause a perturbation in the synthesis of adenosylcobalamin and/or methylcobalamin. However, these conditions are usually accompanied by clinically significant hyperhomocysteinemia. The following are included in this group of disorders:
* Cobalamin C deficiency (cblC) is perhaps the most common inborn error of intracellular cobalamin metabolism. Individuals with this disorder almost always have increased plasma concentrations of homocysteine and methylmalonic acid, with low levels of methionine, and historically a highly variable age of onset. Affected individuals frequently have developmental delay and develop a pigmentary retinopathy and a "bull's eye" maculopathy. cblC is caused by biallelic pathogenic variants in MMACHC which encodes a protein involved in the processing and trafficking of intracellular cobalamin. The pathogenic variant c.271dupA;p.Arg91LysfsTer14 accounts for approximately 40% of alleles [Lerner-Ellis et al 2006].
* Deficiencies of complementation groups cblD, cblF, and cblJ are extremely rare autosomal recessive disorders.
* cblD deficiency is biochemically heterogeneous [Suormala et al 2004]. Coelho et al [2008] determined that mutation of MMADHC (previously known as C2ORF25) is responsible for cblD and identified genotype/phenotype correlations. MMADHC has multiple translation initiation codons (ATG), and encodes distant polypeptides. The location and nature of the pathogenic variant therefore determines whether a patient will display methylmalonic aciduria, homocystinuria, or both metabolic abnormalities:
* The cblD-methylmalonic aciduria subtype (cblD-MMA) (previously known as cblD-variant 2) is caused by pathogenic nonsense and frame-shifting variants in exons 3 and 4;
* The cblD-homocystinuria subtype (previously known as cblD variant 1) is caused by pathogenic missense variants in exons 6-8;
* A cblD-combined subtype (cblD) that features elevations of both MMA and homocysteine is caused by frame-shifting pathogenic variants in exon 5, exon 8, and intron 7.
Note: Individuals with complementation cblD-homocystinuria [Coelho et al 2008], cblE (methionine synthase reductase), and cblG (methionine synthase) abnormalities do not have methylmalonic acidemia, but rather isolated homocystinuria/hyperhomocysteinemia caused by impaired methyl-cobalamin synthesis.
* cblF deficiency is caused by mutation of LMBRD1, which encodes a putative lysosomal cobalamin exporter [Rutsch et al 2009], affecting the synthesis of the cofactors for the enzyme methylmalonyl-CoA mutase (encoded by MMUT) and the enzyme methyltetrahydrofolate: homocysteine methyltransferase, also known as methionine synthase (MS) (encoded by MTR).
* cblJ deficiency caused by mutation of ABCD4, an ATP-binding cassette (ABC) transporter that affects the lysosomal release of Cbl into the cytoplasm similar to cblF and presents with hypotonia, lethargy, poor feeding, bone marrow suppression, macrocytic anemia, and congenital heart disease in some patients [Coelho et al 2012].
It is important to note that several individuals with cblF or cblJ can have decreased serum vitamin B12 levels, suggesting a role for the lysosome in intestinal uptake of ingested cobalamin.
* cblX deficiency is caused by mutation of the X-linked gene HCFC1, a transcriptional co-regulator affecting the expression of MMACHC. All described affected males to date had MMAemia and MMAuria, and most, when studied, displayed combined hyperhomocystinuria and methylmalonic acidemia. The clinical phenotype features intractable epilepsy and profound neurocognitive impairment without the specific bull's-eye maculopathy of cblC deficiency [Yu et al 2013]; however, the phenotype needs further characterization.
Vitamin B12 deficiency. Individuals with vitamin B12 deficiency can have methylmalonic acidemia and homocystinuria.
Maternal B12 deficiency can produce a methylmalonic acidemia syndrome in an infant that ranges from severe encephalopathy to elevated serum concentration of propionylcarnitine (C3) detected by newborn screening [Chace et al 2001]. This metabolic abnormality can occur in a breastfed infant of a vegan mother, in an infant born to a mother with subclinical pernicious anemia [Marble et al 2008], and in infants born to mothers who have had gastric surgery [Grange & Finlay 1994, Celiker & Chawla 2009]. The mother does not necessarily have a very low serum concentration of vitamin B12. Intramuscular vitamin B12 replacement therapy to normalize vitamin B12 serum concentration reverses the metabolic abnormality.
Mitochondrial encephalomyopathy with elevated methylmalonic acid. Mild methylmalonic aciduria has been described in succinate-ligase alpha subunit (caused by biallelic SUCLG1 pathogenic variants) and succinate-ligase ADP-forming beta subunit (caused by biallelic SUCLA2 pathogenic variants) associated with mitochondrial DNA depletion presenting with severe lactic acidosis and encephalomyopathy.
Succinyl-CoA ligase (SUCL) catalyzes the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, and comprises an α subunit encoded by SUCLG1 and a β subunit encoded by either SUCLA2 or SUCLG2.
Biallelic pathogenic variants in SUCLG1 result in a severe phenotype, associated with lactic acidosis and early death in the first week of life. (See SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria.)
Biallelic SUCLA2 pathogenic variants are associated with hypotonia, muscle atrophy presenting around ages three to six months (with mtDNA depletion, complex I, III, and IV deficiency in the muscle), hyperkinesia, seizures, severe hearing impairment, and growth failure. Patients develop a Leigh syndrome-like disorder, cortical and basal ganglia atrophy, and dystonia. Some affected individuals die in infancy; others have survived into their 20s. (See SUCLA2-Related mtDNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria.)
Methylmalonic aciduria ranges from 10 to 200 mmol/mol creatinine in these individuals and is accompanied by raised plasma concentrations of lactate, methylcitrate, 3-hydroxyproprionic and 3-hydroxyisovaleric acid, proprionylcarnitine, and C4-dicarboxylic carnitine (C4DC) [Elpeleg et al 2005, Carrozzo et al 2007, Ostergaard et al 2007, Morava et al 2009].
Reye-like syndrome. A Reye-like syndrome of hepatomegaly and obtundation in the face of a mild intercurrent infection can be seen as an unrecognized presentation of a number of inborn errors of metabolism, including isolated methylmalonic acidemia [Chang et al 2000].
Other entities that can display methylmalonic acidemia despite normal methylmalonyl-CoA mutase enzyme activity include the following:
* "Atypical" methylmalonic acidemia with progressive neurodegenerative disease, microcephaly, and cataracts (2 sibs) [Strømme et al 1995] or with a mitochondrial depletion syndrome/complex IV deficiency and combined propionic and methylmalonic acidemia (1 person) [Yano et al 2003]. These cases have similarities with the phenotype caused by mutation of SUCLA2.
* Benign methylmalonic acidemia with distal renal tubular acidosis (one sibship) [Dudley et al 1998]
* Malonyl-CoA decarboxylase deficiency, usually associated with combined methylmalonic and malonic aciduria, with significantly higher malonic versus methylmalonic acid levels [Brown et al 1984]
* Isolated methylmalonic aciduria and normal plasma concentrations of methylmalonic acidemia (2 families) [Sewell et al 1996, Martens et al 2002]
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with isolated methylmalonic acidemia, the following evaluations are recommended:
* A serum chemistry panel (Na+, K+, CI–, glucose, urea, creatinine, bicarbonate, AST, ALT, alkaline phosphatase, bilirubin [T/U], triglycerides, and cholesterol); complete blood count with differential; arterial or venous blood gas; plasma ammonium and lactic acid concentration; formal urinalysis and ketone measurement; quantitative plasma amino acids; and urine organic acid analysis by gas chromatography and mass spectrometry (GC-MS)
* If possible, measurement of plasma concentrations of methylmalonic acid, methylcitrate, free and total carnitine, and an acylcarnitine profile to document propionylcarnitine (C3 species) concentration
* Measurement of serum vitamin B12 concentration to determine if a nutritional deficiency is present in the patient and possibly the mother (in newborns)
* Biochemical genetics consultation
### Treatment of Manifestations
No consensus exists among various metabolic centers regarding treatment of acute and chronic complications of methylmalonic acidemia. Recent guidelines developed by professionals across 12 European countries and the US based on rigorous literature evaluation and expert group meetings outline the current management recommendations and areas for further research [Baumgartner et al 2014].
Stabilization of critically ill individuals
* Volume replacement with isotonic solutions
* All IV solutions should contain glucose, preferably D10 or D12.5. If hyperglycemia develops, an insulin infusion may be needed.
* The total base deficit should be followed serially with repeat electrolyte and venous or arterial blood gas measurements and corrected by hydration and bicarbonate replacement, as needed [Baumgartner et al 2014]. Adequate kcals must be delivered. Central or peripheral total parenteral nutrition (TPN), which typically contains glucose and amino acids, and in some instances, lipids, may be required. Total protein administration is usually completely withdrawn for no more than 24-48 hours and reinstated gradually depending on the patient's acid-base balance and remaining test values, including ammonia, lactic acid, and plasma amino acids among others.
* Lipid infusions must be used with caution for the risk of pancreatitis.
* Carnitine may be administered intravenously at 50-100 mg/kg/d bid-qid.
* Urine output and serum sodium and potassium concentration need to be monitored.
* Dietary protein should be reintroduced enterally as soon as is feasible given the clinical scenario and may need to be further augmented with TPN. Nasograstric or orogastric feeding should be strongly considered so that enteral feedings can be reintroduced without delay.
* N-carbamylglutamate (NCG, Carbaglu®) may be considered in the event of hyperammonemia. NCG allosterically activates CPS1 (carbamyl phosphate synthetase 1), the first step of the urea cycle. It has been effective in normalizing the blood ammonia concentration in patients with a deficiency of NAGS (N-acetylglutamate synthase) and can also benefit some patients with propionic and possibly methylmalonic acidemia [Tuchman et al 2008, Ah Mew et al 2010].
* Hemodialysis or hemofiltration may be required in the event of treatment failure (uncontrollable acidosis and/or hyperammonemia).
A letter given to the family to present to emergency department physicians that specifies the recommended acute management protocol should be standard of care.
Medic Alert® bracelets and emergency treatment protocols outlining fluid and electrolyte therapy should be available for all affected individuals.
Other
Aside from episodes of critical illness, patients with intercurrent illness such as viral infection or those undergoing surgery for various reasons should have aggressive fluid, metabolic, and nutritional management.
Specialists in physiatry, physical therapy, and occupational therapy can help address the complex challenges faced by patients and families, maximize functionality, and improve quality of life [Ktena et al 2015b].
Special considerations regarding choices of anesthetic agents in this patient population may apply [Ktena et al 2015a, Ruzkova et al 2015].
Most individuals require "sick day" management regimens, which typically consist of reducing or eliminating protein intake and increasing fluids and glucose to ensure delivery of adequate calories and to arrest lipolysis. Immediate hospitalization is usually required if signs suggest intercurrent infection.
Although all of the treatments discussed above may be needed in fragile individuals, they still may not prevent death, the severe sequelae of metabolic decompensation (e.g., metabolic stroke of the basal ganglia), or renal disease. The correlation and identification of treatment patterns and outcomes is needed to develop more effective management protocols for individuals with isolated methylmalonic acidemia.
Many affected individuals require gastrostomy/gastrojejunostomy tube feeding because of anorexia and vomiting to ensure caloric and fluid intake and improve growth.
Bone marrow failure during episodes of metabolic decompensation on rare occasion requires granulocyte-colony stimulating factor (GCSF).
Anemia is an expected complication of chronic renal failure and is treated with erythropoietin and eventually renal transplantation [Inoue et al 1981, Guerra-Moreno et al 2003, MacFarland & Hartung 2015].
Some children have had documented growth hormone (GH) deficiency; however, because response to GH therapy may vary, diet and GH replacement dose need to be carefully adjusted [Bain et al 1995, Al-Owain et al 2004]. The indications for GH replacement therapy and the response to GH replacement in treated individuals require further investigation.
### Prevention of Primary Manifestations
#### Dietary Management
Nutrition. After stabilization, nutritional management is critical. This typically includes instituting a low-protein, high-calorie diet. When available, accurate assessment of resting energy expenditure can guide dietary and caloric prescriptions and eliminate overfeeding [Hauser et al 2011].
Natural protein needs to be carefully titrated to allow for normal growth, while avoiding an excessive propiogenic amino acid load (isoleucine, valine, methionine, and threonine) into the pathway. Adjustment of dietary whole (complete)-protein intake, based on clinical and laboratory findings, is needed throughout life for these patients.
The FAO/WHO/UNU report [2007] recommended that safe levels per age group should be the aim for natural protein intake [Baumgartner et al 2014]; however, the individual protein amount prescribed will depend on growth parameters, metabolic stability, stage of renal failure, and other factors. A propiogenic amino acid-deficient formula (e.g., Propimex®-1/2,, XMTVI-1/2, OA-1/2) and protein-free formula (e.g., Pro-Phree®, Duocal®) are given to some individuals to provide extra fluid and calories. As the infant grows, the total protein load is slowly reduced, based on growth, plasma amino acid concentrations, and plasma and urine methylmalonic acid concentrations.
Of note, in patients with low protein tolerance, severe restriction of propiogenic amino acid precursors (isoleucine, valine, methionine, and threonine) can produce a nutritional deficiency state. Furthermore, an iatrogenic essential amino acid deficiency can be induced by the relatively high leucine intake through the MMA formulas that can negatively affect long-term growth and possibly other outcomes [Manoli et al 2016b]. Medical foods should be used in moderation with the relative intake of natural protein to propiogenic amino-acid deficient formula not exceeding a ratio of 1:1. Isolated valine or isoleucine supplementation should be avoided.
These dietary guidelines do not apply for patients with CblC deficiency, a separate disorder in the pathway [Manoli et al 2016a].
Hydroxocobalamin injections. 1.0-mg injections every day to every other day are usually required in individuals who are vitamin B12 responsive. The regimen of B12 injections needs to be individually adjusted according to the patient's age and, possibly, weight.
Carnitine can be given at a dose of 50-100 mg/kg/day, up to approximately 300 mg/kg/day. As a dietary supplement, carnitine may replace the free carnitine pool and enhance the conjugation and excretion of propionylcarnitine. The contribution of propionylcarnitine excretion to the total propionate load is, however, small. The relief of intracellular CoA accretion may be the mechanism by which carnitine supplementation benefits some individuals.
Antibiotics. A variety of antibiotic regimens to reduce the production of propionate from gut flora can be used:
* Oral neomycin, 250 mg by mouth 4x/day, was the original regimen reported by Snyderman et al [1972].
* Metronidazole at 10-15 mg/kg/day has also been reported.
The intervals at which affected individuals are treated may vary, but a typical course is one week to ten days of treatment per one to three months.
Although oral antibiotics reduce the propionate load that derives from gut flora in affected individuals, chronic antibiotic therapy is not innocuous; it introduces the risk of repopulation of the individual with resistant flora. This could pose a serious infectious threat and could be especially dangerous to individuals with isolated methylmalonic acidemia, since most deaths are related to metabolic decompensation, often precipitated by infection.
Response to antibiotic administration should be determined in treated persons by demonstrating either a decrease in whole body output of methylmalonic acid on antibiotic therapy by a timed urine collection or a decrease in the plasma methylmalonic acid concentration compared to the baseline value for that individual.
Rotating antibiotic regimens may be considered in some persons.
Antioxidants. One individual with isolated methylmalonic acidemia who was documented to be glutathione deficient after a severe metabolic crisis responded to ascorbate therapy [Treacy et al 1996]. Several recent studies document increased oxidative stress, glutathione depletion, and specific respiratory chain complex deficiencies in persons with the mut0 enzymatic subtype with methylmalonic acidemia [Schwab et al 2006, Atkuri et al 2009, Chandler et al 2009, de Keyzer et al 2009, Manoli et al 2013], suggesting a potential benefit of treatment with antioxidants or other mitochondria-targeted therapies in these patients.
A regimen of coenzyme Q10 and vitamin E has been shown to prevent progression of acute optic nerve involvement in a patient with MMA [Pinar-Sueiro et al 2010] and was shown to attenuate the progression of kidney disease in a mouse model of MMA [Manoli et al 2013].
#### Organ Transplantation
The number of individuals who have undergone liver and/or kidney transplantation, the detailed effects on the underlying metabolic disorder, and the overall outcome in those undergoing this procedure have yet to be determined [Sloan et al 2015]. Inclusion of enzymatic and genotype information in case series of transplanted patients will allow better comparisons of the outcomes and genotype-phenotype associations that could inform decisions about the indication and timing of transplantation in individual cases.
Liver transplantation. Because most of the metabolic conversion of propionate occurs in the liver, replacing the liver could contribute enough enzyme activity to avert metabolic decompensation. Liver transplantation has been shown to largely protect against metabolic instability but is not curative, and individuals with isolated MMA remain at risk for long-term complications of MMA including renal disease, basal ganglia injury, and neurologic complications [Chakrapani et al 2002, Nyhan et al 2002, Kaplan et al 2006, Vernon et al 2014]. To date, more than 35 individuals with isolated methylmalonic acidemia have undergone living donor or cadaveric, orthotopic, or partial liver transplantation or combined liver-kidney transplantation (>20 patients) [van't Hoff et al 1998, van't Hoff, McKiernan et al 1999, Kayler et al 2002, Nyhan et al 2002, Hsui et al 2003, Kasahara et al 2006, Morioka et al 2007, McGuire et al 2011, Niemi et al 2015].
* The underlying biochemical parameters and the frequency of metabolic decompensation improved significantly in individuals undergoing liver transplantation despite persistent metabolic abnormalities [Nyhan et al 2002, Kaplan et al 2006, Niemi et al 2015], probably as a result of increased extrahepatorenal methylmalonic acid production primarily from the skeletal muscle [Chandler et al 2007].
* Following liver transplantation, some individuals continued to have progressive renal failure as well as high CSF concentrations of methylmalonic acid [Nyhan et al 2002, Kaplan et al 2006].
* Neurologic complications post-transplant, including globus pallidus injuries [Chakrapani et al 2002, Cosson et al 2008, McGuire et al 2011] suggest that adequate protein restriction and supportive care should be continued after the transplantation.
Earlier transplantation particularly for individuals with mut0 (who are very fragile) is gaining support as surgery techniques and outcomes improve [Niemi et al 2015, Spada et al 2015]. The choice of the kind and timing of the indicated transplant procedure remains challenging for families and treating physicians [Sloan et al 2015]. In the long term, the details regarding development of renal disease, optic nerve atrophy, and neurologic complications will be most important.
Kidney transplantation. Some individuals have received only renal allografts [Van Calcar et al 1998, Lubrano et al 2001, Coman et al 2006, Cosson et al 2008, Clothier et al 2011].
One of the first reports on isolated renal transplantation in mut0 methylmalonic acidemia was claimed to provide enough enzyme activity to normalize methylmalonic acid excretion and allow for increased dietary protein tolerance; however, it was later determined that that patient had cblA deficiency and responded to vitamin B12. Thus, this individual, who has a much milder case, is not representative of the outcomes of isolated renal transplantation in individuals with severe MMA subtypes (mut0 or cblB) [Lubrano et al 2001, Lubrano et al 2007, Lubrano et al 2013].
Elective kidney transplantation, even before the onset of renal disease, has been advocated as a form of "cell therapy" to help stabilize individuals with mut0 MMA [Brassier et al 2013]. However, one patient died after developing hepatoblastoma, neurologic deterioration accompanied by CSF lactic acidosis, and multiorgan failure; a second patient developed progressive neurologic symptoms; and two others developed metabolic decompensations post transplant. Long-term follow up is necessary to determine if this is a safe alternative to liver transplantation or liver-kidney transplantation, especially in persons with severe mut0 MMA.
### Prevention of Secondary Complications
Frequent monitoring of plasma amino acids is necessary to avoid deficiencies of essential amino acids (particularly isoleucine, valine, and methionine) as a result of excessive protein restriction and the development of acrodermatitis-enteropathica-like cutaneous lesions in methylmalonic aciduria, as in other organic acidurias (glutaric aciduria-I) and amino acid disorders (maple syrup urine disease) [De Raeve et al 1994].
Low plasma amino acids can reflect low natural protein intake, imbalanced intake of branched chain amino acid from use of metabolic formulas, or effects of chronic acidosis on branched chain amino acid metabolism [Manoli et al 2016b].
### Surveillance
During the first year of life, infants may need to be evaluated as frequently as every week. No guidelines regarding the recommended type or frequency of laboratory testing have been published.
The following should be monitored on a regular six-month to one-year basis or more frequently if the patient is unstable and requires frequent changes in management:
* Plasma amino acids
* Plasma and urine MMA levels
* Serum acylcarnitines and free and total carnitine levels
* Chemistry: Na+, K+, CI–, glucose, urea, creatinine, bicarbonate, AST, ALT, alkaline phosphatase, bilirubin (T/U), triglycerides, and cholesterol
* Liver, kidney, and bone health
* Bone marrow indices
Monitoring of kidney function periodically with creatinine, cystatin-C, and, if available, studies of glomerular filtration rate (GFR) (e.g., iohexol plasma decay), in addition to imaging of the kidneys, will allow for early referral to nephrology and appropriate timing of renal transplantation when needed [van't Hoff et al 1999, Kruszka et al 2013]. Combined equations based on creatinine and cystatin-C are expected to reflect more accurately the kidney function in this patient population [Schwartz et al 2009].
Regular ophthalmology and audiology evaluations to screen for optic nerve thinning/pallor and hearing loss [Authors, unpublished observations] are recommended.
### Agents/Circumstances to Avoid
The following should be avoided:
* Fasting. During acute illness, intake of adequate calories is necessary to arrest/prevent decompensation.
* Stress
* Increased dietary protein
* Supplementation with the individual propiogenic amino acids valine and isoleucine, as they directly increase the toxic metabolite load in patients with disordered propionate oxidation [Nyhan et al 1973, Hauser et al 2011, Manoli et al 2016b]
### Evaluation of Relatives at Risk
Depending on the genotype and phenotype of the proband, evaluation of sibs at risk should be performed using biochemical testing with treatment instituted as soon as possible if a sib is affected. Molecular genetic testing (if the pathogenic variants in the family are known) or cellular enzymology typically can further confirm the results of biochemical studies. Prenatal diagnosis of at-risk sibs may allow for prompt treatment of affected newborns at the time of delivery.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Oral and intramuscular vitamin B12 has been administered to women pregnant with a fetus with vitamin B12-responsive MMA, resulting in decreased maternal MMA urine output [Ampola et al 1975, van der Meer et al 1990]. Despite these observations, maternal vitamin B12 supplementation for isolated MMA needs further study.
Despite high maternal MMA levels, fetal growth and development were normal for all reported pregnancies of women with MMA [Wasserstein et al 1999, Deodato et al 2002].
Complications observed in pregnancies of women with MMA can include acute decompensation or hyperammonemia, deterioration of renal function, and obstetric complications including preeclampsia, preterm delivery, and cesarean section [Raval et al 2015].
### Therapies Under Investigation
Carefully designed clinical studies are required to evaluate the efficacy of antioxidant regimens in patients with MMA.
Gene therapy. Preliminary studies in human-derived hepatocytes and animal models of methylmalonic acidemia suggest a potential benefit of gene therapy [Chandler & Venditti 2008, Carrillo-Carrasco et al 2010, Chandler & Venditti 2010, Chandler & Venditti 2012, Sénac et al 2012]. The effect of that therapeutic approach in patients and especially on the long-term complications of methylmalonic acidemia remains to be elucidated in appropriate clinical studies.
Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Isolated Methylmalonic Acidemia
|
c0268583
| 27,505 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1231/
| 2021-01-18T21:17:05 |
{"mesh": ["C537358"], "synonyms": ["Isolated Methylmalonic Aciduria"]}
|
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Ammonia poisoning" – news · newspapers · books · scholar · JSTOR (April 2014) (Learn how and when to remove this template message)
Schematic representation of the flow of Nitrogen through a common aquarium.
Ammonia poisoning is a common fish disease in new aquariums, especially when immediately stocked to full capacity. Ideally, the level of ammonia (NH3) and ammonium compounds (i.e. those containing NH4+) should be zero. Although trace amounts are generally harmless, they can still lead to problems over time. Understanding the nitrogen cycle is essential for the keeping of any aquatic life. The amount of ammonia present is usually accompanied by a rise in pH. As ammonia is a base, it is stabilized by acidic water. It can cause damage to the gills at a level as small as 0.25 mg/L.
## Contents
* 1 Diagnosis
* 2 Prevention
* 3 Prevention (Tank Cycling)
* 4 See also
* 5 References
## Diagnosis[edit]
A history of the tank: filter changes, power outages, excessive feeding, or the addition of microbicidal or antibiotic agents to aquarium can aid in diagnosis. An ammonia test is the most sure way of diagnosing ammonia poisoning.
Symptoms include:
1. Purple, red or bleeding gills
2. Fish may clamp, may appear darker in color
3. Red streaking on the fins or body
4. Fish may gasp for air at the surface of the tank water
5. Torn & jagged fins
6. Fish may appear weak and lay at the bottom of the tank
## Prevention[edit]
The nitrogen cycle in an aquarium.
Ammonia poisoning is currently impossible to cure however it can be prevented easily by first cycling the tank (see below). Treatments include immediately reducing the ammonia level through many small water changes. Alternatively an ammonia detoxifier can be used (try not to do this unless absolutely necessary), though such chemicals are best used in emergencies only, and do not provide a substitute for adequate tank cycling. Once the ammonia is removed, the fish may recover if the damage is not too extensive. Increasing aeration may be desirable, as the fishes' gills are often damaged by the ammonia. This can increase the probability of survival slightly. Also, all other sources of stress should be removed, and the cause of the ammonia should be addressed.
## Prevention (Tank Cycling)[edit]
Tank cycling is a process during which ammonia reducing bacteria are built up sufficiently to handle the tank load. This process can take two to four weeks.
## See also[edit]
* Ammonotelic
## References[edit]
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Ammonia poisoning
|
c0597829
| 27,506 |
wikipedia
|
https://en.wikipedia.org/wiki/Ammonia_poisoning
| 2021-01-18T19:06:31 |
{"wikidata": ["Q4747283"]}
|
## Description
The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart.
One peculiar form of thyroid tumors is characterized by the presence of cell oxyphilia. Oxophil cells are found in a minority of thyroid tumors, either benign or malignant. These cells show a large volume of granular eosinophilic cytoplasm and are very rich in mitochondria. The familial occurrence of thyroid tumors with cell oxyphilia was reported by Katoh et al. (1998). Canzian et al. (1998) reported such a family with affected members in 3 generations and by linkage analysis mapped the gene to 19p13.
For general phenotypic information and a discussion of genetic heterogeneity of NMTC, see 188550.
Clinical Features
The family in which Canzian et al. (1998) demonstrated linkage to 19p13.2 had been reported by Kraimps et al. (1997) to be affected with familial papillary thyroid carcinoma (PTC). This 3-generation family originated from a nonendemic goiter area of western France and included 3 individuals with multinodular goiter plus 3 individuals with nonmedullary thyroid carcinoma. The age at operation in the affected individuals ranged from 10 to 63 years. None of the patients had a history of any other type of cancer-prone syndrome or radiation exposure. There was no history of autoimmune disease in the family. In this family both the benign and the malignant thyroid tumors exhibited some extent of cell oxyphilia. The findings suggested that relatives of patients with sporadic nonmedullary thyroid carcinoma with cell oxyphilia should be investigated carefully.
In an attempt to elucidate further the features of familial thyroid neoplasia of follicular cell origin, Harach et al. (1999) investigated the pathologic findings from the affected members of the family in which Canzian et al. (1998) had demonstrated linkage to 19p13.2. All the affected members of the family (7 males and 2 females; mean age 23 years) were clinically euthyroid and presented with nodular goiter. Tumor recurrence after thyroidectomy was observed in 4. In 4 of the 5 patients studied, the tumors were multifocal, bilateral well demarcated or encapsulated, and composed of follicles, papillae, trabeculae/solid areas (often resembling hyalinizing trabecular adenoma of the thyroid) or an admixture, formed by cells with pale to intense cytoplasmic eosinophilia. All tumors were of follicular cell origin as shown by immunocytochemistry. Less than one-third of the benign tumors and all 3 carcinomas showed a variable number of neoplastic cells diffusely immunostained for mitochondria. Harach et al. (1999) suggested that histologic findings of a 'multiple adenomatous goiter,' nonendemic 'multinodular goiter,' or multiple neoplasms of follicular cell origin with the morphology of those they described, particularly in young patients, should alert the pathologist and physician to the possibility of an inherited trait, with its implications for family screening. The tumors are usually benign and well demarcated but because of multicentricity and consequently increased risk of recurrence and/or progression to carcinoma, total thyroidectomy should be advocated.
Mapping
To evaluate the roles of MNG1 (138800), TCO1, PTCPRN (605642), PTEN (601728), TSHR (603372), and TRKA (191315) in familial nonmedullary thyroid cancer, Bevan et al. (2001) carried out a comprehensive mutation and linkage analysis of these loci in 22 families. One family was linked to chromosome 19q13.2, confirming that TCO1 underlies a subset of familial nonmedullary thyroid cancer. In contrast to the family previously linked to TCO1 by Canzian et al. (1998), the thyroid cancers in this family were papillary rather than Hurthle cell. None of the families was linked to MNG1 or PTCPRN, and there was no evidence to support the roles of PTEN, TSHR, or TRKA. The authors concluded that familial nonmedullary thyroid cancer is genetically heterogeneous and that none of these genes accounts for the majority of families.
In 10 families with nonmedullary thyroid cancer, 9 of which presented with cell oxyphilia, McKay et al. (2004) found evidence for linkage at both TCO1 and NMTC3 (606240), with lod scores of 1.56 and 2.85, respectively. Two-locus linkage analysis, using a multiplicative risk model for the development of nonmedullary thyroid cancer, achieved a maximum lod score of 3.92, with a lod score of 4.51 when assuming 70% of the families were linked, indicating that the segregation in these families is consistent with an interaction model. A large Tyrolean family alone achieved a 2-locus lod score of 3.21.
Molecular Genetics
### Exclusion Studies
Maximo et al. (2005) excluded mutations in the GRIM19 gene (NDUFA13; 609435) in affected members of the family reported by Canzian et al. (1998).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
THYROID CARCINOMA, NONMEDULLARY, WITH OR WITHOUT CELL OXYPHILIA
|
c1863925
| 27,507 |
omim
|
https://www.omim.org/entry/603386
| 2019-09-22T16:13:06 |
{"mesh": ["C537842"], "omim": ["603386"], "orphanet": ["319487"], "synonyms": ["Familial pure nonmedullary thyroid carcinoma", "FNMTC", "Alternative titles", "TCO1", "TCO"]}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-70 (DFNB70) is caused by homozygous mutation in the PNPT1 gene (610316) on chromosome 2p16. One such family has been reported.
Clinical Features
Von Ameln et al. (2012) reported a consanguineous Moroccan family in which 3 sibs had nonsyndromic severe hearing impairment with onset in early childhood.
Inheritance
The transmission pattern of DFNB70 in the family reported by von Ameln et al. (2012) was consistent with autosomal recessive inheritance.
Mapping
By homozygosity mapping of a consanguineous Moroccan family with early-onset deafness, von Ameln et al. (2012) found linkage to a 13.2-Mb region on chromosome 2p16.1 between markers D2S119 and D2S378 (maximum multipoint lod score of 2.7). The locus was designated DFNB70.
Molecular Genetics
By homozygosity mapping followed by candidate gene analysis of a Moroccan family with DFNB70, von Ameln et al. (2012) identified a homozygous mutation in the PNPT1 gene (E475G; 610316.0002). The mutant protein was expressed, stable, and showed normal mitochondrial localization in HEK293T cells, but in vitro studies in bacteria, yeast, and mammalian cells showed that the mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. The findings indicated that PNPT1 plays a role in auditory function.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, bilateral MISCELLANEOUS \- Prelingual onset \- One family has been reported (last curated November 2012) MOLECULAR BASIS \- Caused by mutation in the polyribonucleotide nucleotidyltransferase 1 gene (PNPT1, 610316.0002 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
DEAFNESS, AUTOSOMAL RECESSIVE 70
|
c1824925
| 27,508 |
omim
|
https://www.omim.org/entry/614934
| 2019-09-22T15:53:43 |
{"doid": ["0110521"], "omim": ["614934"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
|
A rare, autoimmune, bullous skin disease characterized clinically by multiple flaccid blisters, typically occurring on the face, scalp, trunk and extremities, which rapidly evolve into scaly, crusted, pruritic skin erosions. Histopathologically, superficial acantolytic blisters, as well as intercellular deposits of IgG autoantibodies directed against desmoglein 1 (and occasionally against desmoglein 3) in the upper epidermis, are observed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Superficial pemphigus
|
None
| 27,509 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=46485
| 2021-01-23T16:55:25 |
{"icd-10": ["L10.2", "L10.3", "L10.4"]}
|
Waardenburg syndrome (WS) is a disorder characterized by varying degrees of deafness and minor defects in structures arising from neural crest, including pigmentation anomalies of eyes, hair, and skin. WS is classified into four clinical and genetic phenotypes.
## Epidemiology
The worldwide incidence is estimated at around 1/40,000. Waardenburg syndrome type 1 (WS1) and type 2 (WS2) are the most common types of Waardenburg syndrome. Waardenburg syndrome type3 (WS3) and type 4 (WS4; see these terms) are rarer, with only a few cases of WS3 described worldwide so far. WS accounts for about 3% of all institutionalized cases of congenital hearing loss.
## Clinical description
Clinical manifestations vary within and between families. Frequent clinical manifestations include congenital sensorineural deafness, heterochromic or hypoplastic blue irides, white forelock or early graying of the scalp hair before the age of 30 years. All these manifestations, along with a suggestive family history are major criteria, as is dystopia canthorum in WS1 and WS3. Minor criteria include congenital leukoderma, synophrys/medial eyebrow flare, broad/high nasal root with prominent columella and hypoplastic alae nasi. WS is defined by the association of at least 2 major, or 1 major and at least 2 minor clinical criteria (early graying of the hair is considered either a major or minor criteria depending of the WS type). WS1 combines these criteria with dystopia canthorum. The absence of dystopia canthorum clinically differentiates WS2 from WS1, whereas WS3 is similar to WS1, but additionally includes upper limb abnormalities. WS4 is characterized as WS2 with added characteristics of Hirschsprung disease.
## Etiology
WS is genetically heterogeneous. To date, mutations in 6 different genes have been identified: PAX3 (2q36.1), MITF (3p14-p13), SNAI2 (8q11.21), SOX10 (22q13.1), EDNRB (13q22.3), and EDN3 (20q13.32). Mutations in PAX3 gene are associated with WS1 and WS3, while MITF gene is mutated in cases of WS2. Dysgenic inheritance of MITF mutation in combination with a TYR mutation (and/or the TYRR402Q hypomorphic allele) has been reported in two families with WS2 and ocular albinism (see this term). Homozygous SNAI2 deletions have been described in two WS2 patients. SOX10 mutations are found in WS4 and WS2 affected patients. Mutations in EDNRB and EDN3 genes have also been reported in WS4.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Waardenburg syndrome
|
c3266898
| 27,510 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3440
| 2021-01-23T19:12:33 |
{"gard": ["5525"], "mesh": ["D014849"], "omim": ["148820", "193500", "193510", "600193", "606662", "608890", "611584"], "umls": ["C0043008", "C3266898"], "icd-10": ["E70.3"]}
|
## Clinical Features
Hall and Riggs (1975) reported a family in which 6 of 15 offspring of first-cousin unaffected parents had a characteristic syndrome consisting of severe mental retardation, microcephaly, depressed nasal bridge with anteverted nostrils, large lips, and progressive abnormalities of the bony skeleton. They had unexplained episodes of vomiting in infancy. None of the 6 developed speech even as adults. Scoliosis, flat femoral heads and short femoral necks, relatively short proximal segments of the arms, retarded growth, and flat epiphyses in the fingers and at the ankle were skeletal features. Cataracts, corneal clouding, visceromegaly, joint contractures, and lumbar gibbus were notable for their absence.
Silengo and Rigardetto (2000) reported a second family with Hall-Riggs syndrome. The male and female sibs presented with short stature, microcephaly, hypertelorism, a flat nasal bridge, large nose with a large tip and anteverted nostrils, a wide mouth with thick lips, and severe mental retardation. Radiographs showed mild spondylometaphyseal dysplasia with some epiphyseal involvement. Both children also had cysts in the septum pellucidum and a cavum vergae on MRI scan, and abnormal EEGs.
INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Failure to thrive HEAD & NECK Head \- Microcephaly Eyes \- Hypertelorism \- Epicanthal folds Nose \- Flat nasal bridge \- Large nose with large nasal tip \- Anteverted nostrils Mouth \- Wide, carp-shaped mouth \- Thick lips Teeth \- Small deciduous teeth \- Enamel hypoplasia ABDOMEN Gastrointestinal \- Feeding problems SKELETAL \- Osteoporosis \- Delayed bone age Spine \- Scoliosis \- Kyphosis \- Irregular end plates \- Platyspondyly Limbs \- Mild metaphyseal dysplasia \- Epiphyseal hypoplasia Hands \- Mild brachydactyly NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures \- Septum pellucidum cyst \- Large cavum vergae \- Absent speech VOICE \- Absent speech ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
HALL-RIGGS MENTAL RETARDATION SYNDROME
|
c1856198
| 27,511 |
omim
|
https://www.omim.org/entry/234250
| 2019-09-22T16:27:14 |
{"mesh": ["C535623"], "omim": ["234250"], "orphanet": ["2107"]}
|
## Summary
### Clinical characteristics.
Shwachman-Diamond syndrome (SDS) is characterized by: exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multilineage cytopenias and susceptibility to myelodysplasia syndrome (MDS) and acute myelogeneous leukemia (AML); and bone abnormalities. In almost all affected children, persistent or intermittent neutropenia is a common presenting finding, often before the diagnosis of SDS is made. Short stature and recurrent infections are common.
### Diagnosis/testing.
The diagnosis of SDS is established in a proband with the classic clinical findings of exocrine pancreatic dysfunction and bone marrow dysfunction and/or by identification of biallelic pathogenic variants in DNAJC21, EFL1, or SBDS, or a heterozygous pathogenic variant in SRP54.
### Management.
Treatment of manifestations: Care by a multidisciplinary team is recommended. Exocrine pancreatic insufficiency is treated with oral pancreatic enzymes and fat-soluble vitamin supplementation. Blood and/or platelet transfusions may be considered for anemia and/or thrombocytopenia associated with bi- or trilineage cytopenia. If recurrent infections are severe and absolute neutrophil counts are persistently ≤500/mm3, treatment with granulocyte-colony stimulation factor (G-CSF) can be considered. Hematopoietic stem cell transplantation (HSCT) should be considered for treatment of severe pancytopenia, MDS, or AML.
Prevention of secondary complications: Aggressive dental hygiene should be pursued to promote oral health. Consider prophylactic antibiotics and G-CSF to reduce risk of infection during complex dental procedures or orthopedic surgery.
Surveillance: Complete blood counts at least every three to six months; assessment of development, growth, and nutritional status every six months. Following baseline examination, repeat bone marrow examination every one to three years or more frequently if bone marrow changes are observed. Monitor for orthopedic complications with x-rays of hips and knees during the most rapid growth stages. Perform bone densitometry before puberty, during puberty, and thereafter based on individual findings. Perform neuropsychological screening in children age 6-8 years, 11-13 years, and 15-17 years.
Agents/circumstances to avoid: Prolonged use of cytokine and hematopoietic growth factors (e.g., G-CSF) should be considered with caution. Some drugs used in standard HSCT preparative regimens (e.g., cyclophosphamide and busulfan) may not be suitable because of possible cardiac toxicity.
### Genetic counseling.
SDS is inherited in an autosomal recessive (most commonly) or an autosomal dominant manner.
* Autosomal recessive SDS. SDS caused by pathogenic variants in DNAJC21, EFL1, or SBDS is inherited in an autosomal recessive manner. Most parents of children with autosomal recessive SDS are heterozygotes (carriers of one pathogenic variant); however, de novo pathogenic variants have been reported. When both parents are known to be carriers, the sibs of a proband have a 25% chance of being affected, a 50% chance of being an unaffected carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for relatives at risk is possible if both pathogenic variants in a family are known.
* Autosomal dominant SDS. SDS caused by pathogenic variants in SRP54 is inherited in an autosomal dominant manner; most such affected individuals reported to date have resulted from a de novo SRP54 pathogenic variant.
If the pathogenic variant(s) in a family are known, prenatal and preimplantation genetic testing are possible.
## Diagnosis
### Suggestive Findings
Shwachman-Diamond syndrome (SDS) should be suspected in individuals with some or all of the following clinical findings.
Exocrine pancreatic dysfunction, documented with any one of the following:
* Low serum concentrations of the digestive enzymes pancreatic isoamylase and cationic trypsinogen, adjusted to age *
* Low levels of fecal elastase
* Supportive features including:
* An abnormal fecal fat balance study of a 72-hour stool collection (with exclusion of intestinal mucosal disease or cholestatic liver disease)
* Evidence of pancreatic lipomatosis on imaging
* Reduced levels of fat-soluble vitamins (A, D, E, K)
* Note: Exocrine pancreatic dysfunction may be difficult to detect because the production of individual pancreatic enzymes varies during childhood and because severe perturbations of enzyme levels are required to meet diagnostic criteria [Schibli et al 2006]. Additionally:
* Serum pancreatic isoamylase concentration is not reliable in children younger than age three years [Ip et al 2002].
* Serum cationic trypsinogen concentration increases to pancreatic-sufficient levels during early childhood in approximately 50% of children with SDS [Durie & Rommens 2004].
Hematologic abnormalities caused by bone marrow dysfunction and involving one or more of the following:
* Hypoproductive cytopenias. Persistent or intermittent depression of at least one lineage (for ≥2 measurements taken over a period of ≥3 months):
* Neutropenia (absolute neutrophil count <1,500 neutrophils/mm3)
* Thrombocytopenia (platelet count <150,000 platelets/mm3)
* Anemia or macrocytosis (with hemoglobin concentration below normal range for age)
* Pancytopenia. Trilineage cytopenia with persistent neutropenia, thrombocytopenia, and anemia
* Abnormal findings on bone marrow examination:
* Varying degrees of hypocellularity and fatty infiltration of the marrow compartments for age, indicating marrow failure and disordered hematopoiesis
* Aplastic anemia and/or myelodysplasia with or without abnormal cytogenetic findings (which can include deletion of 20q11, monosomy 7, isochromosome 7, or other chromosomal changes seen in bone marrow failure syndromes).
* Leukemia. In particular acute myleogenous leukemia
Other primary features [Myers et al 2014]:
* Short stature
* Skeletal abnormalities, most commonly chondrodysplasia or congenital thoracic dystrophy
* Congenital anomalies including cardiac defects, ear malformations / hearing loss, or skin rashes
* Hepatomegaly with or without elevation of serum aminotransferase levels
* Family history consistent with autosomal recessive inheritance
### Establishing the Diagnosis
The diagnosis of SDS is established in a proband with the classic clinical findings of exocrine pancreatic dysfunction and bone marrow failure and/or identification of biallelic pathogenic variants in DNAJC21, EFL1, or SBDS, or a heterozygous pathogenic variant in SRP54 by molecular genetic testing (see Table 1).
Note: Although the diagnosis of SDS has classically relied on evidence of exocrine pancreatic dysfunction and bone marrow failure with single- or multilineage cytopenia [Rothbaum et al 2002, Dror et al 2011, Myers et al 2013a], a publication based on the North American SDS Registry reported that almost half of the 37 individuals with genetically confirmed SDS did not have this classic combination of manifestations [Myers et al 2014], indicating that the phenotypic spectrum of SDS is broader than previously thought, leading to underdiagnosis when the diagnosis is based on clinical findings alone. Myers et al [2014] found that the features supporting the diagnosis of SDS in individuals with neutropenia included bone marrow abnormalities (hypocellularity, dysplasias, and clonality for deletion 20q11), as well as the presence of congenital anomalies and a family history consistent with autosomal recessive inheritance of SDS.
Molecular genetic testing approaches can include a combination of gene-targeted testing (concurrent or serial single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of SDS is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of SDS has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of SDS, molecular genetic testing approaches can include concurrent or serial single-gene testing or use of a multigene panel.
Concurrent or serial single-gene testing. If available, concurrent testing of all the genes known to be associated with SDS (see Table 1) is recommended. Sequence analysis detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.
Perform sequence analysis first. If only one or no pathogenic variant is found perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
Alternatively, serial single-gene testing can be done starting with SBDS, the gene most commonly associated with SDS. If testing of SBDS is not diagnostic, the other three genes can be tested in any order.
View in own window
Note: Analysis of SBDS is complicated by the presence of a highly homologous pseudogene, SBDSP. Common pathogenic variants in the active SBDS arise from recombination and gene conversion with the pseudogene (see Molecular Genetics).
Targeted analysis for the three common SBDS pathogenic variants in exon 2, which are derived from SBDS, can be performed first:
* c.183_184delinsCT
* c.258+2T>C
* c.[183_184delinsCT; 258+2T>C] (a complex allele resulting from gene conversion with SBDSP)
Targeted testing of SBDS detects at least one pathogenic variant in 90% of affected individuals and both pathogenic variants in approximately 62% of affected individuals who have SDS associated with SBDS [Boocock et al 2003].
Note: Because the complex c.[183_184delinsCT; 258+2T>C] allele occurs through a gene conversion event, parental testing is needed to distinguish:
* In cis configuration (i.e., c.[183_184delinsCT; 258+2T>C] on the same allele)
FROM
* In trans configuration (i.e., c.183_184delinsCT on one allele and c.258+2T>C on the other allele)
A multigene panel that includes DNAJC21, EFL1, SBDS, SRP54, and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).
View in own window
Note: Analysis of SBDS is complicated by the presence of a highly homologous pseudogene, SBDSP. Common pathogenic variants in the active SBDS arise from recombination and gene conversion with the pseudogene (see Molecular Genetics). A multigene panel not specifically designed for SDS or exome analysis may not detect common SDBS pathogenic variants, although pathogenic variants in one of the other genes could be detected.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the diagnosis of SDS is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which genes are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
View in own window
Note: Analysis of SBDS is complicated by the presence of a highly homologous pseudogene, SBDSP. Common pathogenic variants in the active SBDS arise from recombination and gene conversion with the pseudogene (see Molecular Genetics). Exome analysis may not detect common SDBS pathogenic variants although pathogenic variants in one of the other genes could be detected.
Exome array (when clinically available) may be considered if exome sequencing is not diagnostic.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Shwachman-Diamond Syndrome
View in own window
Gene 1, 2Proportion of SDS Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
EFL1<1%6/6 6Unknown 7
DNAJC21<1%3/4 81/4 8
SBDS~92%>90% 9<2% 10
SRP54<1%3/3 11Unknown 7
Unknown 12<10%NA
1\.
Genes are listed in alphabetic order.
2\.
See Table A. Genes and Databases for chromosome locus and protein.
3\.
See Molecular Genetics for information on allelic variants detected in this gene.
4\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, and multiplex ligation-dependent probe amplification (MLPA) and a gene-targeted microarray designed to detect single-exon deletions or duplications. Assay design is complicated by the presence of SBDSP.
6\.
Stepensky et al [2017]
7\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
8\.
Dhanraj et al [2017]
9\.
Rare pathogenic variants, such as c.297_300delAAGA, are also likely the consequence of gene conversion with SBDSP [Carvalho et al 2014; J Rommens, personal communication].
10\.
Rare whole-exon deletions [Costa et al 2007], extended conversions of exon 2 and flanking introns, or gene rearrangements involving exon 2 have been observed.
11\.
Carapito et al [2017]
12\.
A limited number (<10%) of persons with clear clinical indications of SDS do not appear to have pathogenic variants in any of the known genes, suggesting that pathogenic variants in another gene(s) may also be causative.
## Clinical Characteristics
### Clinical Description
The clinical spectrum of Shwachman-Diamond syndrome (SDS) is broad and varies among affected individuals, including sibs [Ginzberg et al 1999]. Earlier studies suggested that gastrointestinal and hematologic findings were observed in all affected individuals [Cipolli et al 1999, Ginzberg et al 1999]; with wider use of molecular genetic testing, however, this belief has been challenged (see Diagnosis) [Myers et al 2014].
Presentation. Neonates generally do not show manifestations of SDS; however, early presentations have included acute life-threatening infections, severe bone marrow failure, aplastic anemia [Kuijpers et al 2005], asphyxiating thoracic dystrophy caused by rib cage restriction, and severe spondylometaphyseal dysplasia [Nishimura et al 2007].
More commonly, SDS presents in infancy with failure to thrive and poor growth secondary to exocrine pancreatic dysfunction.
It should be noted, however, that the presentation of SDS varies greatly, with nearly half of individuals in the North American SDS Registry presenting without classical neutropenia and steatorrhea [Myers et al 2014].
Exocrine pancreatic dysfunction resulting from severe depletion of pancreatic acinar cells is a classic feature of SDS, with the majority of dysfunction identified within the first year of life, often in the first six months. Manifestations vary widely from asymptomatic to severe dysfunction with significant malabsorption of nutrients, steatorrhea, and failure to thrive.
For unclear reasons, in many individuals manifestations resolve with age, with as many as 50% being able to discontinue pancreatic enzyme supplementation with normal fat absorption by age four years even when enzyme secretion remains deficient [Mack et al 1996].
A general acinar defect has also been identified, with increased parotid acinar dysfunction in persons with SDS compared to controls [Stormon et al 2010]. In a study of histologic changes in gastrointestinal mucosal biopsies of symptomatic individuals with SDS, Shah et al [2010] identified duodenal inflammation in more than 50%, suggesting a possible enteropathic component to their disease. This enteropathy may contribute to vitamin deficiencies observed in some individuals with SDS despite nutritional supplementation and enzymatic replacement [Pichler et al 2015].
Pancreatic histopathology reveals few acinar cells and extensive fatty infiltration. Pancreatic imaging studies with ultrasonography or CT may reveal small size for age. In a series of individuals with SDS in whom SBDS pathogenic variants had been identified, MRI revealed fatty infiltration with retained ductal and islet components [Toiviainen-Salo et al 2008b]. Normal imaging studies do not rule out the diagnosis of SDS as these abnormal findings may emerge over time [Myers et al 2014].
Hematologic abnormalities. Neutropenia and impaired neutrophil chemotaxis are likely the most critical contributors to recurrent infections seen in young children [Dror & Freedman 2002, Stepanovic et al 2004, Kuijpers et al 2005]. Despite impaired neutrophil chemotaxis, individuals with SDS maintain the ability to form empyema and abscess, in contrast to other disorders of neutrophil chemotaxis [Aggett et al 1979, Rothbaum et al 1982]. Acute and deep-tissue infections can be life threatening, particularly in young children [Cipolli 2001, Grinspan & Pikora 2005]. Persistent or intermittent neutropenia is recognized first in almost all (88%-100%) affected children, often before the diagnosis of SDS is made [Ginzberg et al 1999].
Although anemia and thrombocytopenia are also seen in the majority of individuals with SDS, these findings may be intermittent or clinically asymptomatic. Severe aplastic anemia with pancytopenia occurs in a subset of individuals. The French Severe Chronic Neutropenia Registry found that 41 (40%) of 102 individuals with SDS demonstrated significant hematologic manifestations, including those with intermittent severe cytopenias and 21 with persistent severe cytopenias (9 classified as malignant, 9 as nonmalignant, and 3 progressing from nonmalignant to malignant) [Donadieu et al 2012].
The risk for myelodysplasia (MDS) or progression to leukemia – typically acute myelogeneous leukemia (AML) – is significant in individuals with SDS; however, data remain limited with specific reports varying by definition of MDS and cohort age.
* One 25-year survey revealed that seven of 21 individuals with SDS developed myelodysplastic syndrome; five of these seven developed AML [Smith et al 1996].
* In 55 individuals with SDS in the French registry, rates of transformation to MDS/AML were 18.8% and 36.1% at 20 years and 30 years, respectively [Donadieu et al 2012].
* The Severe Congenital Neutropenia International Registry (SCNIR) reported an overall incidence of 8.1% of MDS/AML in 37 individuals with SDS over a ten-year period, representing a 1% per year rate of progression to MDS or AML [Dale et al 2006, Rosenberg et al 2006].
* A cumulative transformation rate of 18% was reported in 34 individuals with SDS by the Canadian Inherited Bone Marrow Failure Study (CIBMFS) [Hashmi et al 2011].
Of note, the above findings contrast with other reports from the Israeli (3 individuals) [Tamary et al 2010] and NIH (17 individuals) [Alter et al 2010] registries in which no one developed MDS/AML. Conclusions remain difficult given the small sample sizes; however, these differences may be attributable to cohort age [Myers et al 2013a].
The risk for malignant transformation involving dysplasia or AML is considered to be lifelong, with AML generally associated with poor outcome [Donadieu et al 2005]. To date, reported malignancies other than AML have been rare; they include isolated case reports of bilateral breast cancer [Singh et al 2012], dermatofibrosarcoma [Sack et al 2011], pancreatic adenocarcinoma, and CNS lymphoma [Sharma et al 2014].
It is well recognized that individuals with SDS may develop certain characteristic cytogenetic clonal changes, such as del(20)(q11) and i(7)(q10), in the absence of overt MDS or AML. It has been suggested that these changes may persist and fluctuate over time without high risk of progression to MDS/AML [Cunningham et al 2002, Crescenzi et al 2009, Maserati et al 2009]. Novel cytogenetic abnormalities in the presence or absence of classic del(20)(q11) and i(7)(q10) have been reported in a cohort of 91 Italian individuals with SDS, including unbalanced structural anomalies of chromosome 7, complex rearrangements of the del(20)(q), and unbalanced translocation with partial trisomy 3q and partial monosomy 6q [Valli et al 2017].
Studies in which patient and non-patient marrow cells are co-cultured indicate problems with both the stem cell compartments and stromal microenvironment [Dror & Freedman 1999]. These findings, together with the wide range of abnormalities seen in the bone marrow, are consistent with SDS being a bone marrow failure syndrome.
Growth. Children with adequate nutrition and pancreatic enzyme supplementation have normal growth velocity and appropriate weight for height; however, approximately 50% of children with SDS are below the third percentile for height and weight [Durie & Rommens 2004].
Characteristic skeletal changes appear to be present in all individuals with a molecularly confirmed diagnosis [Mäkitie et al 2004]; however, skeletal manifestations vary among individuals and over time. In some individuals the skeletal findings may be subclinical.
Cross-sectional and longitudinal data from the study of Mäkitie et al [2004] revealed the following:
* Delayed appearance of secondary ossification centers, causing bone age to appear to be delayed
* Variable widening and irregularity of the metaphyses in early childhood (i.e., metaphyseal chondrodysplasia), followed by progressive thickening and irregularity of the growth plates
* Generalized osteopenia
Of note, the epiphyseal maturation defects tended to normalize with age and the metaphyseal changes tended to progress (worsen) with age [Mäkitie et al 2004].
Further skeletal findings can include rib and joint abnormalities, the latter of which can result from asymmetric growth and can be sufficiently severe to warrant surgical intervention.
Additionally, low-turnover osteoporosis has been reported as a feature of SDS. Toiviainen-Salo et al [2007] reported bone abnormalities in ten of 11 individuals with genetically confirmed SDS including reduced bone mineral density by Z-scores. Vertebral compression fractures were reported in three. Vitamin D and K deficiencies, both detrimental to bone health, were each identified in six individuals. It is important to ensure accurate measurement of bone mineral density, as adults with SDS have short stature and may have an incorrectly reported low bone mineral density due to low height Z-score [Shankar et al 2017].
Hepatomegaly and liver dysfunction with elevated serum aminotransferase concentration can be observed in young children but tend to resolve by age five years [Toiviainen-Salo et al 2007]. Elevated bile acids were reported in one Finnish study in seven of 12 individuals with SDS, three of whom had persistent or intermittent elevation over time, raising concern for ongoing cholestasis [Toiviainen-Salo et al 2009]. Mild histologic changes may also be evident in liver biopsies, and although they do not appear to be progressive, it has been noted that liver complications have occurred in older individuals following bone marrow transplantation [Ritchie et al 2002].
Cognitive/psychological. Individuals with SDS have also been recognized to have cognitive and/or behavioral impairment as well as structural brain changes [Kent et al 1990, Cipolli et al 1999, Ginzberg et al 1999, Toiviainen-Salo et al 2008a, Perobelli et al 2012, Booij et al 2013].
Kerr et al [2010] compared the neuropsychological function of 32 children with SDS with age- and gender-matched children with cystic fibrosis and sib controls. On a number of measures, those with SDS displayed a far wider range of abilities than controls, from severely impaired to superior. Approximately 20% of children with SDS demonstrated intellectual disability in at least one area, with perceptual reasoning being most affected. They were also far more likely than the general population to have the diagnosis of pervasive developmental disorder (6% vs 0.6%). Attention deficits were also more common in children with SDS and in their unaffected sibs than in children with cystic fibrosis.
Other possible findings
* Ichthyosis and eczematous lesions
* Oral disease including delayed dental development, increased dental caries in both primary and permanent teeth, and recurrent oral ulcerations [Ho et al 2007]
* Endocrine dysfunction including congenital hypopituitarism [Jivani et al 2016], diabetes, and growth hormone deficiency [Myers et al 2013b]
* Immune dysfunction [Dror et al 2001]
* Congenital anomalies including: cardiac, gastrointestinal, neurologic, urinary tract/kidney, or eye and ear anomalies [Myers et al 2014]
### Genotype-Phenotype Correlations
No genotype-phenotype correlations have been observed for any of the genes associated with SDS.
### Nomenclature
Previously used terms for SDS:
* Shwachman's syndrome
* Congenital lipomatosis of the pancreas
* Shwachman-Bodian syndrome
### Prevalence
It has been estimated that SDS occurs in one of 77,000 births based on the observation that it is approximately 1/20th as frequent as cystic fibrosis in North America [Goobie et al 2001].
SDS occurs in diverse populations including those with European, Indian, aboriginal (North America), Chinese, Japanese, and African ancestry.
## Differential Diagnosis
Features of Shwachman-Diamond syndrome (SDS) (e.g., poor growth and transient neutropenia) may have multiple causes in young children (see Table 2).
### Table 2.
Disorders to Consider in the Differential Diagnosis of Shwachman-Diamond Syndrome (SDS)
View in own window
Disorder /
Clinical
CircumstanceGene(s)MOI 1Clinical Features of the Disorder / Comments
Overlapping w/SDSDistinguishing from SDS
Cystic fibrosis (CF)CFTRARCF often presents w/both upper-respiratory infections & exocrine pancreatic dysfunction.In CF:
* ↑ sweat chloride values
* No primary bone marrow failure
Johanson-Blizzard syndrome (JBS)
(OMIM 243800)UBR1ARExocrine pancreatic dysfunctionIn JBS:
* Anomalies & severe DDs
* No hematologic abnormalities
Severe malnutritionNANAFailure to thriveIn severe malnutrition:
* Clinical picture consistent w/inadequate caloric/protein intake
* No underlying syndromic diagnosis
* No exocrine pancreatic dysfunction
Pearson marrow-pancreas syndrome (PMPS)
(OMIM 557000)See footnote 2.mtExocrine pancreatic dysfunction & bone marrow dysfunctionIn PMPS:
* Normal cellularity in bone marrow, w/distinct cytoplasmic vacuolization in myeloid precursors
* mtDNA contiguous-gene deletions/duplications
SPINK1-related severe infantile isolated exocrine pancreatic insufficiency 3SPINK1ARExocrine pancreatic dysfunctionNo bone marrow failure or neutropenia
Diamond-Blackfan anemia (DBA)18 genesAD
XLBone marrow failureIn DBA:
* Progressive macrocytic anemia w/reticulocytopenia
* Normal cellularity bone marrow w/markedly ↓ or absent erythroid precursors
* No primary exocrine pancreatic dysfunction
Fanconi anemia (FA)21 genesAR
AD
XLBone marrow failureIn FA:
* Progressive pancytopenia w/positive chromosome breakage studies
* Variable cellularity of bone marrow w/↓ precursors
* No primary exocrine pancreatic dysfunction
Dyskeratosis congenita (DC)11 genesXL
AD
ARBone marrow failureIn DC:
* Abnormally shortened telomere length
* Variable cellularity of bone marrow w/↓ precursors
* No primary exocrine pancreatic dysfunction
Medications or infectionsNANANeutropeniaNeutropenia caused by medications or infections is transient.
Kostmann congenital neutropenia
(OMIM 610738)HAX1ARNeutropeniaIn Kostmann congenital neutropenia:
* Severe neutropenia
* On hematologic testing: early myeloid arrest at promyelocyte/ myelocyte stage, w/atypical nuclei & cytoplasmic vacuolization
ELANE-related neutropenia 4ELANEADNeutropeniaIn ELANE-related neutropenia:
* Severe neutropenia w/mutation of ELANE
* On hematologic testing: isolated neutropenia
Cartilage-hair hypoplasia (CHH)RMRPARSkeletal dysplasiaIn CHH:
* Short at birth, w/abnormal long-bone growth. ↑ incidence of scoliosis, abnormal pubertal growth spurt, & global dysfunction of skeletal growth (axial & appendicular)
* Gastrointestinal features are secondary to complications of infection (rather than to exocrine pancreatic insufficiency as in SDS).
AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; MOI = mode of inheritance; mt = mitochondrial; NA = not applicable; XL = X-linked
1\.
Ordered by relative frequency if multiple modes of inheritance
2\.
Pearson marrow-pancreas syndrome is caused by mtDNA contiguous gene deletions/duplications (OMIM 557000).
3\.
Venet et al [2017]
4\.
ELANE-related neutropenia includes cyclic neutropenia and severe congenital neutropenia.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs of an individual following the initial diagnosis of Shwachman-Diamond syndrome (SDS), current consensus practice typically recommends the following evaluations to assess the status of the pancreas, liver, bone marrow, and skeleton [Dror et al 2011].
* Assessment of growth: height, weight in relation to age
* Assessment of nutritional status to determine if supplementation with pancreatic enzymes is necessary and/or effective:
* Measurement of fat-soluble vitamins (vitamin A, 25-OH-vitamin D, and vitamin E) or their related metabolites
* Measurement of prothrombin time (to detect vitamin K deficiency)
* Assessment of serum concentration of the digestive enzyme cationic trypsinogen and, if sufficiency is observed, subsequent confirmation with a 72-hour fecal fat balance study (with discontinuation of enzyme supplementation for at least a 24-hour period)
* Pancreatic imaging by ultrasound
* Complete blood count with white cell differential and platelet count
* Measurement of iron, folate, and B12
* Bone marrow examination with biopsy and cytogenetic studies at initial assessment
* Immunoglobulins and lymphocyte subpopulations
* Skeletal survey with radiographs of at least the hips and lower limbs
* Bone densitometry as clinically indicated
* Assessment of serum aminotransferase levels
* Assessment of developmental milestones (including pubertal development) with neuropsychological evaluation
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
A multidisciplinary team including specialists from the following fields is recommended: hematology, gastroenterology, clinical genetics, orthopedics, endocrinology, immunology, dentistry, child development, psychology, and social work as needed [Dror & Freedman 2002, Rothbaum et al 2002, Durie & Rommens 2004, Dror et al 2011, Myers et al 2013a].
Exocrine pancreatic insufficiency can be treated with the same oral pancreatic enzymes commonly used in treatment of cystic fibrosis; dose should be based on results of routine assessment of pancreatic function and nutritional status. Steatorrhea often resolves in early childhood, but pancreatic enzyme levels can remain low; routine monitoring (see Surveillance) is recommended.
Supplementation with fat-soluble vitamins (A, D, E, and K) is recommended.
Hematologic abnormalities. Blood and/or platelet transfusions may be considered for anemia and bi- or trilineage cytopenia.
If recurrent infections are severe and absolute neutrophil counts are persistently ≤500/mm3, treatment with prophylactic antibiotics and granulocyte-colony stimulation factor (G-CSF) can be considered with caution (see Agents/Circumstances to Avoid).
Hematopoietic stem cell transplantation (HSCT) should be considered for treatment of severe pancytopenia, bone marrow transformation to myelodysplastic syndrome, or acute myelogeneous leukemia (AML). Chemotherapy can be utilized as a bridge to HSCT in individuals with SDS and AML; however, sustained complete remission is problematic and prompt continuation to HSCT remains imperative. Although earlier reports indicate that survival is fair, cautious myeloablation and newer reduced-intensity regimens have demonstrated improved outcomes in small cohorts [Cesaro et al 2005, Vibhakar et al 2005, Sauer et al 2007, Bhatla et al 2008].
Note: Bone marrow abnormalities are not treated unless severe aplasia, myelodysplastic changes, or leukemic transformation are present.
Skeletal abnormalities. Skeletal manifestations of SDS may range from clinically asymptomatic to severe, and can evolve or progress over time. Severe manifestations such as asphyxiating thoracic dystrophy due to rib cage restriction will require subspecialty care including pediatric pulmonary and orthopedic specialists. Other rib and joint abnormalities may require surgical intervention if severe, and consultation with an orthopedic surgeon familiar with SDS may be beneficial for those with skeletal dysplasia.
Evaluate for treatment for low bone density if indicated by bone densitometry*.
Growth. Children with poor growth and delayed puberty benefit from ongoing consultation with an endocrinologist, who may also consult with orthopedists regarding possible surgical management of asymmetric growth and joint deformities.
Other. Cognitive, learning, and behavioral complications can be features of SDS, and remedial interventions are considered beneficial.
### Prevention of Secondary Complications
Frequent dental visits to monitor tooth development and oral health are recommended to reduce the incidence of mouth ulcers and gingivitis. Home care should include aggressive dental hygiene with topical fluoride treatments to help prevent dental decay.
Prophylactic antibiotics and G-CSF may be especially helpful when interventions such as complex dental procedures or orthopedic surgery are being considered (see Agents/Circumstances to Avoid).
### Surveillance
The following are recommended given the intermittent nature of some features of SDS and the evolution of the phenotype over time [Rothbaum et al 2002, Dror et al 2011, Myers et al 2013a]:
* Complete blood counts with white blood cell differential and platelet counts at least every three to six months, or more frequently if peripheral blood counts are changing or infections are recurrent and debilitating
* Bone marrow examinations every one to three years following the baseline examination, and more frequently if changes in bone marrow function or cellularity are observed
* Assessment of nutritional status every six months and measurement of serum concentration of vitamins to evaluate effectiveness of or need for pancreatic enzyme therapy
* Monitoring for orthopedic complications with x-rays of hips and knees during the most rapid growth stages
* Bone densitometry before puberty, during puberty, and thereafter based on individual findings. Results must be interpreted in the context of stature and pubertal status.
* Developmental assessment every six months from birth to age six years and growth every six months
* Neuropsychological screening in children age 6-8 years, 11-13 years, and 15-17 years
### Agents/Circumstances to Avoid
Prolonged use of cytokine and hematopoietic growth factors such as G-CSF is cautioned against in view of their potential contribution to leukemic transformation [Rosenberg et al 2006].
Some drugs (e.g., cyclophosphamide and busulfan) used in standard HSCT preparative regimens may not be suitable because of possible cardiac toxicity [Mitsui et al 2004, Cesaro et al 2005, Vibhakar et al 2005, Sauer et al 2007].
### Evaluation of Relatives at Risk
It is appropriate to evaluate as early as possible the older and younger sibs of a proband in order to identify those who will benefit from treatment and preventive measures. This can also potentially prevent asymptomatic affected sibs from being used as bone marrow transplant donors. Evaluations can include:
* Molecular genetic testing if the pathogenic variants in the family are known;
* Testing for exocrine pancreatic dysfunction and evidence of bone marrow failure with single- or multilineage cytopenia if the pathogenic variants in the family are not known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
For pregnancies in women with SDS, high-risk pregnancy care including consultation with a hematologist is recommended [Alter et al 1999]. Women with SDS are at increased risk for recurrent miscarriages, but the rates of elective abortion, live birth, and spontaneous miscarriage are comparable to the general population [Giri et al 2018].
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Shwachman-Diamond Syndrome
|
c0272170
| 27,512 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1756/
| 2021-01-18T20:57:02 |
{"mesh": ["C537330"], "synonyms": ["Shwachman-Bodian-Diamond Syndrome"]}
|
A rare skin disease characterized by transient wrinkling of the skin, edema, formation of whitish papules, pruritus, burning sensation, or pain, on the palms and/or soles in response to contact with water. Duration of exposure and water temperature affect the rate of development and intensity of the lesions. The condition is more common in females than in males and frequently occurs in patients with cystic fibrosis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Aquagenic palmoplantar keratoderma
|
None
| 27,513 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=498359
| 2021-01-23T17:25:03 |
{"synonyms": ["Aquagenic keratoderma", "Aquagenic syringeal acrokeratoderma", "Aquagenic wrinkling of the palms", "Transient reactive papulotranslucent acrokeratoderma"]}
|
Bonnet–Dechaume–Blanc syndrome
Other namesArteriovenous aneurysm of mid-brain and retina, facial nevi and mental changes, Cerebrofacial arteriovenous metameric syndrome type 2
CT scan showing intracranial hemorrhage
SpecialtyMedical genetics
Bonnet–Dechaume–Blanc syndrome, also known as Wyburn-Mason syndrome, is a rare congenital disorder characterized by arteriovenous malformations of the brain, retina or facial nevi.[1] The syndrome has a number of possible symptoms and can, more rarely, affect the skin, bones, kidneys, muscles, and gastrointestinal tract.[2] When the syndrome affects the brain, people can experience severe headaches, seizures, acute stroke, meningism, and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.[2][3]
In the retina, the syndrome causes retinocephalic vascular malformations that tend to be present with intracranial hemorrhage and lead to decreased visual acuity, proptosis, pupillary defects, optic atrophy, congestion of bulbar conjunctiva, and visual field defects.[4][5] Retinal lesions can be unilateral and tortuous, and symptoms begin to appear in the second and third decades of life.[4]
The syndrome can present with cutaneous lesions, or skin with different texture, thickness, and color, usually on the face.[5] The facial features caused by the syndrome vary from slight discoloration to extensive nevi and angiomas of the skin.[3] In some cases, the frontal and maxillary sinus may also be affected.[5]
There have only been 52 reported cases of patients with Bonnet–Dechaume–Blanc syndrome as of 2012.[2] Symptoms are rarely noticed in children and the syndrome is often diagnosed in late childhood or early adulthood when visual impairment is noticed.[3] Fluorescein angiography is commonly used to diagnose the syndrome.[6]
There have been several methods in treating patients with Bonnet–Dechaume–Blanc syndrome. However, the optimal treatment is uncertain. Patients with intracranial lesions have been treated with surgical intervention and in some cases, this procedure has been successful. Other treatments include embolization, radiation therapy, and continued observation.[5]
With limited research on Bonnet–Dechaume–Blanc syndrome, researchers have focused on the clinical and radiological findings rather than how to manage this rare and non-heritable syndrome.[3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 References
* 7 External links
## Signs and symptoms[edit]
Left eye showing proptosis.
Typically not diagnosed until late childhood or later, Bonnet–Dechaume–Blanc syndrome usually presents itself with a combination of central nervous system features (midbrain), ophthalmic features (retina), and facial features.[7] The degree of expression of the syndrome's components varies both clinically and structurally. Common symptoms that lead to diagnosis are headaches, retro-orbital pain, and hemianopia.[5]
Visual field of homonymous hemianopia
The ophthalmic features of Bonnet–Dechaume–Blanc syndrome occur as retinal arteriovenous malformation (AVMs). There are three categories of AVMs based on their severity. The first category consists of the patient having small lesions that usually are asymptomatic. The second category, more severe than the first, is when the patient's malformation is missing a connecting capillary between an artery and a vein; without it, edema, hemorrhage, and visual impairment can result. Category three refers to malformations so severe that their dilated vessels no longer distinguish between artery and vein, and the patient has a significantly increased risk of vision loss.[3] Since the retinal lesions categorized vary from large vascular malformations that affect a majority of the retina to malformations that are barely visible, the lesions can cause a wide range of symptoms, including decrease in visual sharpness, proptosis, pupillary defects, optic nerve degeneration, and visual field defects.[5] The most common type of visual field impairment due to AVMs is homonymous hemianopia,[2] which is usually unilateral.[7]
Central nervous system (CNS) symptoms of Bonnet–Dechaume–Blanc syndrome are highly dependent on the locations and sizes of cerebral AVMs.[2][5][7] The most common CNS feature is an intracranial hemangioma in the midbrain.[3] Cerebral malformations can result in severe headaches, cerebral hemorrhages, vomiting, meningism, seizures, acute strokes, and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.[3]
The facial features of Bonnet–Dechaume–Blanc syndrome vary from case to case. A person showing signs of the syndrome may display faint skin discoloration, nevi, or angiomas of the skin.[3] Some patients with this disorder also present with high-flow AVMs in the maxillofacial or mandibular (jaw) regions.[8] Another facial indicator of this disease is malformations affecting the frontal or maxillary sinuses.[5]
## Causes[edit]
Fluorescein angiography can reveal arteriovenous malformations.
Bonnet–Dechaume–Blanc syndrome results from arteriovenous malformations. The exact cause of this disorder is unknown, and no specific genetic abnormality has been identified. The syndrome is a congenital disorder that begins to develop around the seventh week of gestation when the maturation of retinal mesenchymal cells do not grow properly.[3][7][9] The abnormal development of vascular tissue leads to arteriovenous malformations, which affect both visual and cerebral structures.[9]
## Diagnosis[edit]
Diagnosis commonly occurs later in childhood and often occurs incidentally in asymptomatic patients or as a cause of visual impairment.[3] The first symptoms are commonly found during routine vision screenings.[citation needed]
A number of examinations can be used to determine the extent of the syndrome and its severity. Fluorescein angiography is quite useful in diagnosing retinal features of the disease, and the use of ultrasonography and optical coherence tomography (OCT) are helpful in confirming the disease.[6] Neuro-ophthalmic examinations reveal pupillary defects (e.g. Marcus Gunn Pupil). Funduscopic examinations, examinations of the fundus of the eye, allow detection of arteriovenous malformations.[2] Neurological examination can determine neurological deficits such as hemiparesis and paresthesias.[2] MRI scans are used in imaging the brain and can allow visualization of the optic nerve and any possible atrophy. MRI, CT, and cerebral angiography may all be used to investigate the extent and location of any vascular lesions affecting the brain.[2][5]
## Treatment[edit]
The treatment for Bonnet–Dechaume–Blanc syndrome is controversial due to a lack of consensus on the different therapeutic procedures for treating arteriovenous malformations.[9] The first successful treatment was performed by Morgan et al.,[8] who combined intracranial resection, ligation of the ophthalmic artery, and selective arterial ligature of the external carotid artery. Notably, the patient did not have retinal vascular malformations.[7]
Lesions are watched closely for changes in size. Prognosis is best when lesions are less than 3 cm in length. Most complications occur when the lesions are greater than 6 cm in size.[2] Surgical intervention for intracranial lesions has been done successfully. Nonsurgical treatments include embolization, radiation therapy, and continued observation.[5]
When pursuing treatment, it is important to consider the size of the malformations, their locations, and neurological involvement.[7] Because it is a congenital disorder, there are no preventative steps to take aside from regular follow-ups with a doctor to monitor symptoms so that future complications are avoided.[citation needed]
## Epidemiology[edit]
The syndrome was first described in 1943 and believed to be associated with racemose hemangiomatosis of the retina and arteriovenous malformations of the brain. It is non-hereditary and considered a phakomatosis but rarely involves the skin.[citation needed]
## References[edit]
1. ^ Liu, Anthony; Chen, Yi-Wen; Chang, Steven; Liao, Yaping Joyce (March 2012). "Junctional Visual Field Loss in a Case of Wyburn-Mason Syndrome". Journal of Neuro-Ophthalmology. 32 (1): 42–44. doi:10.1097/WNO.0b013e31821aeefb. PMID 21613961.
2. ^ a b c d e f g h i SINGH, A; RUNDLE, P; RENNIE, I (March 2005). "Retinal Vascular Tumors". Ophthalmology Clinics of North America. 18 (1): 167–176. doi:10.1016/j.ohc.2004.07.005. PMID 15763202.
3. ^ a b c d e f g h i j Kim, Jeonghee; Kim, Ok Hwa; Suh, Jung Ho; Lew, Ho Min (20 March 1998). "Wyburn-Mason syndrome: an unusual presentation of bilateral orbital and unilateral brain arteriovenous malformations". Pediatric Radiology. 28 (3): 161. doi:10.1007/s002470050319. PMID 9561534. S2CID 36979750.
4. ^ a b Muthukumar, N; Sundaralingam, MP (October 1998). "Retinocephalic vascular malformation: case report". British Journal of Neurosurgery. 12 (5): 458–60. doi:10.1080/02688699844718. PMID 10070454.
5. ^ a b c d e f g h i j Dayani, P. N.; Sadun, A. A. (18 January 2007). "A case report of Wyburn-Mason syndrome and review of the literature". Neuroradiology. 49 (5): 445–456. doi:10.1007/s00234-006-0205-x. PMID 17235577. S2CID 11516890.
6. ^ a b Singh, ArunD; Turell, MaryE (2010). "Vascular tumors of the retina and choroid: Diagnosis and treatment". Middle East African Journal of Ophthalmology. 17 (3): 191–200. doi:10.4103/0974-9233.65486. PMC 2934709. PMID 20844673.
7. ^ a b c d e f Lester, Jacobo; Ruano-Calderon, Luis Angel; Gonzalez-Olhovich, Irene (July 2005). "Wyburn-Mason Syndrome". Journal of Neuroimaging. 15 (3): 284–285. doi:10.1111/j.1552-6569.2005.tb00324.x. PMID 15951414. S2CID 1922375.
8. ^ a b Bhattacharya, JJ; Luo, CB; Suh, DC; Alvarez, H; Rodesch, G; Lasjaunias, P (30 March 2001). "Wyburn-Mason or Bonnet-Dechaume-Blanc as Cerebrofacial Arteriovenous Metameric Syndromes (CAMS). A New Concept and a New Classification". Interventional Neuroradiology. 7 (1): 5–17. doi:10.1177/159101990100700101. PMC 3621461. PMID 20663326.
9. ^ a b c Schmidt, D; Pache, M; Schumacher, M (2008). "The congenital unilateral retinocephalic vascular malformation syndrome (bonnet-dechaume-blanc syndrome or wyburn-mason syndrome): review of the literature". Survey of Ophthalmology. 53 (3): 227–49. doi:10.1016/j.survophthal.2007.10.001. PMID 18501269.
## External links[edit]
Classification
D
* ICD-10: Q28.2
* MeSH: C536752
External resources
* Orphanet: 53719
* v
* t
* e
Congenital abnormality syndromes
Craniofacial
* Acrocephalosyndactylia
* Apert syndrome
* Carpenter syndrome
* Pfeiffer syndrome
* Saethre–Chotzen syndrome
* Sakati–Nyhan–Tisdale syndrome
* Bonnet–Dechaume–Blanc syndrome
* Other
* Baller–Gerold syndrome
* Cyclopia
* Goldenhar syndrome
* Möbius syndrome
Short stature
* 1q21.1 deletion syndrome
* Aarskog–Scott syndrome
* Cockayne syndrome
* Cornelia de Lange syndrome
* Dubowitz syndrome
* Noonan syndrome
* Robinow syndrome
* Silver–Russell syndrome
* Seckel syndrome
* Smith–Lemli–Opitz syndrome
* Snyder–Robinson syndrome
* Turner syndrome
Limbs
* Adducted thumb syndrome
* Holt–Oram syndrome
* Klippel–Trénaunay–Weber syndrome
* Nail–patella syndrome
* Rubinstein–Taybi syndrome
* Gastrulation/mesoderm:
* Caudal regression syndrome
* Ectromelia
* Sirenomelia
* VACTERL association
Overgrowth syndromes
* Beckwith–Wiedemann syndrome
* Proteus syndrome
* Perlman syndrome
* Sotos syndrome
* Weaver syndrome
* Klippel–Trénaunay–Weber syndrome
* Benign symmetric lipomatosis
* Bannayan–Riley–Ruvalcaba syndrome
* Neurofibromatosis type I
Laurence–Moon–Bardet–Biedl
* Bardet–Biedl syndrome
* Laurence–Moon syndrome
Combined/other,
known locus
* 2 (Feingold syndrome)
* 3 (Zimmermann–Laband syndrome)
* 4/13 (Fraser syndrome)
* 8 (Branchio-oto-renal syndrome, CHARGE syndrome)
* 12 (Keutel syndrome, Timothy syndrome)
* 15 (Marfan syndrome)
* 19 (Donohue syndrome)
* Multiple
* Fryns syndrome
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Bonnet–Dechaume–Blanc syndrome
|
c0265321
| 27,514 |
wikipedia
|
https://en.wikipedia.org/wiki/Bonnet%E2%80%93Dechaume%E2%80%93Blanc_syndrome
| 2021-01-18T18:38:36 |
{"mesh": ["C536752"], "umls": ["C0265321"], "icd-10": ["Q28.2"], "orphanet": ["53719"], "wikidata": ["Q892776"]}
|
A number sign (#) is used with this entry because of evidence that X-linked congenital bilateral aplasia of the vas deferens (CBAVDX) is caused by mutation in the ADGRG2 gene (300572) on chromosome Xp22.
Description
Congenital bilateral absence of the vas deferens (CBAVD) is found in more than 25% of men with obstructive azoospermia, involving a complete or partial defect of the Wolffian duct derivatives. In 80% of men with CBAVD (see 277180), mutations are identified in the CFTR gene (602421). The forms caused by mutations in the CFTR and ADGRG2 genes are clinically indistinguishable (summary by Patat et al., 2016).
Clinical Features
In their 10-year retrospective series of 379 azoospermic men with CBAVD, Patat et al. (2016) noted that 81 (21%) of the patients did not have a mutation in the CFTR gene. The authors selected 12 of 26 patients with CBAVD and no renal malformations from that cohort for further study. The epididymis caput was present in all 12 patients, whereas the corpus was absent in 3 patients and the cauda was absent in 6; all but 4 patients showed dilation of part or all of the epididymis. The vas deferens was absent in all but 1 of the patients, in whom it was present unilaterally; and seminal vesicles were hypoplastic or absent in all but 1 patient. Testicular volumes were reported as normal in all but 3 patients, who had volumes less than 13 mL. All patients were azoospermic with low semen volume, and 4 patients were also reported to have an acid pH of the semen. Histologic examination of an epididymal biopsy, obtained during an assisted reproduction procedure in 1 of the patients, revealed enlarged sections of the epididymal head containing spermatic material, lined by a cuboidal epithelium due to sperm stasis. Some sections of the efferent ducts appeared dilated with spermatozoa in the lumen, whereas other sections appeared normal.
Pathogenesis
In cases of CBAVD caused by mutation in the CFTR gene, it is generally presumed that the genital tract abnormality is due to progressive atrophy related to abnormal electrolyte balance and fluid transport in the male excurrent ducts rather than agenesis. Azoospermic men with ADGRG2-associated CBAVD are clinically indistinguishable from those with CFTR-associated CBAVD, suggesting that mutations of these 2 genes might result in obstructive azoospermia through a similar pathophysiologic mechanism (summary by Patat et al., 2016).
Molecular Genetics
By exome sequencing in 12 men with obstructive azoospermia due to CBAVD who had no renal malformations and were negative for mutation in the CFTR gene, Patat et al. (2016) identified hemizygosity for 2 truncating mutations in the ADGRG2 gene (300572): a 1-bp deletion (300572.0001) in 1 man, and a deletion/insertion frameshift mutation (300572.0002) in an affected uncle and nephew. Targeted sequencing of the ADGRG2 gene in 14 additional men with CBAVD and no renal malformations from the same cohort identified another man with a truncating mutation, a 1-bp duplication (300572.0003). No mutations in ADGRG2 were found in 28 men with CBAVD and unilateral renal agenesis, suggestive of a different pathophysiologic mechanism in those cases.
INHERITANCE \- X-linked GENITOURINARY Internal Genitalia (Male) \- Reduced testicular volume (in some patients) \- Azoospermia \- Low semen volume \- Acid pH of semen (in some patients) \- Absent vas deferens \- Absent or hypoplastic seminal vesicles \- Absent corpus epididymis (in some patients) \- Absent cauda epididymis (in some patients) MOLECULAR BASIS \- Caused by mutation in the adhesion G protein-coupled receptor G2 gene (ADGRG2, 300572.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
VAS DEFERENS, CONGENITAL BILATERAL APLASIA OF, X-LINKED
|
c0403814
| 27,515 |
omim
|
https://www.omim.org/entry/300985
| 2019-09-22T16:19:01 |
{"mesh": ["C535984"], "omim": ["300985"], "orphanet": ["48"]}
|
Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.
The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.
In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.
Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.
Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).
Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.
## Frequency
It is difficult to determine the prevalence of limb-girdle muscular dystrophy because its features vary and overlap with those of other muscle disorders. Prevalence estimates range from 1 in 14,500 to 1 in 123,000 individuals.
## Causes
The various forms of limb-girdle muscular dystrophy are caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in muscle maintenance and repair.
Some of the proteins produced from these genes assemble with other proteins into larger protein complexes. These complexes maintain the physical integrity of muscle tissue and allow the muscles to contract. Other proteins participate in cell signaling, cell membrane repair, or the removal of potentially toxic wastes from muscle cells.
Limb-girdle muscular dystrophy is classified on the basis of its inheritance pattern and genetic cause. Limb-girdle muscular dystrophy type 1 includes forms of the disorder that have an inheritance pattern called autosomal dominant. Limb-girdle muscular dystrophy type 2 includes forms of the disorder that have an inheritance pattern called autosomal recessive.
Calpainopathy, or limb-girdle muscular dystrophy type 2A, is caused by mutations in the CAPN3 gene. Type 2A is the most common form of limb-girdle muscular dystrophy, accounting for about 30 percent of cases. Dysferlinopathy, also called limb-girdle muscular dystrophy type 2B, is caused by mutations in the DYSF gene.
Sarcoglycanopathies are forms of limb-girdle muscular dystrophy caused by mutations in the SGCA, SGCB, SGCG, and SGCD genes. These sarcoglycanopathies are known as limb-girdle muscular dystrophy types 2D, 2E, 2C, and 2F respectively.
A TTN gene mutation causes limb-girdle muscular dystrophy type 2J, which has been identified only in the Finnish population. Mutations in the ANO5 gene cause limb-girdle muscular dystrophy type 2L. Mutations in several other genes cause forms of limb-girdle muscular dystrophy called dystroglycanopathies, including limb-girdle muscular dystrophy types 2I, 2K, 2M, and 2N.
Other rare forms of limb-girdle muscular dystrophy are caused by mutations in several other genes, some of which have not been identified. In addition, for certain forms that are classified by some researchers as limb-girdle muscular dystrophy, other researchers propose grouping them with different, related disorders, such as myofibrillar myopathy, Emery-Dreifuss muscular dystrophy, rippling muscle disease, or Pompe disease.
### Learn more about the genes associated with Limb-girdle muscular dystrophy
* ANO5
* CAPN3
* CAV3
* COL6A1
* COL6A2
* COL6A3
* CRPPA
* DYSF
* FKRP
* FKTN
* LAMA2
* LMNA
* MYOT
* PLEC
* POGLUT1
* POMT1
* POMT2
* SGCA
* SGCB
* SGCD
* SGCG
* TTN
Additional Information from NCBI Gene:
* DAG1
* DNAJB6
* GMPPB
* HNRNPDL
* POMGNT1
* POMGNT2
* TCAP
* TNPO3
* TRAPPC11
* TRIM32
## Inheritance Pattern
Limb-girdle muscular dystrophy can have different inheritance patterns.
Most forms of this condition are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Several rare forms of limb-girdle muscular dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Limb-girdle muscular dystrophy
|
c3148763
| 27,516 |
medlineplus
|
https://medlineplus.gov/genetics/condition/limb-girdle-muscular-dystrophy/
| 2021-01-27T08:24:52 |
{"gard": ["6907"], "mesh": ["C566589"], "omim": ["603511", "608423", "609115", "618129", "253600", "608807", "611307", "613723", "615356", "253601", "617232", "608099", "604286", "253700", "601287", "601954", "254110", "613530", "609308", "616094", "615352", "613158", "613157", "611588", "607155", "616052", "618135", "613818"], "synonyms": []}
|
Moral insanity referred to a type of mental disorder consisting of abnormal emotions and behaviours in the apparent absence of intellectual impairments, delusions, or hallucinations. It was an accepted diagnosis in Europe and America through the second half of the 19th century.
The physician James Cowles Prichard first used the phrase to describe a mental disorder in 1835 in his Treatise on insanity and other disorders affecting the mind.[1] He defined moral insanity as: "madness consisting in a morbid perversion of the natural feelings, affections, inclinations, temper, habits, moral dispositions, and natural impulses, without any remarkable disorder or defect of the interest or knowing and reasoning faculties, and particularly without any insane illusion or hallucinations."[2][3][4]
The concept of moral insanity was indebted to the work of physician Philippe Pinel, which was acknowledged by Prichard. Pinel had described mental diseases of only partial, affective, insanity. His concept Manie sans délire (Latin – mania sine delirio; French – folie raisonnante or folie lucide raisonnante, monomanie affective; German – Moralisches Irresein[5]) referred to insanity without delusion. That is, the sufferer was thought to be mad in one area only and thus the personality of the individual might be distorted but his or her intellectual faculties were unimpaired.[6]
The term 'moral', at that time and taken originally from French, could mean emotional rather than necessarily referring to ethics.
## Contents
* 1 Diagnostic schemes
* 2 Context
* 3 Implications
* 4 See also
* 5 References
* 6 External links
## Diagnostic schemes[edit]
The term 'moral insanity' had been used earlier by Thomas Arnold (physician) and Benjamin Rush in referring to what they saw as a result of madness – a disruption or perversion of the emotions or moral sense. This usage had little to do with Prichard's diagnostic definition of the term as a form of madness itself, however.[7]
Overall, Prichard defined insanity as a, "chronic disease, manifested by deviations from the healthy and natural state of the mind." He then proposed four broad categories. Moral insanity was for disorders that only seemed to arise from a person's feelings and habits, not his intellect. The other three types involved increasing degrees of intellectual abnormality: a partial derangement that was limited to certain trains of thought; a full mania, by which was meant 'raving madness' regardless of topic; and lastly, a breakdown of any connections between ideas, referred to as incoherence or dementia.
Prichard considered that some early nosologists, namely Sauvages, Sagar and Linnaeus, had distinguished between medical conditions with hallucinations and those involving depraved appetites or feelings. But he credits Pinel as the first in psychiatry to clearly distinguish madness without delerium, in opposition to Locke's widely accepted axiom that insanity always stemmed from faulty intellectual connections or mistaken perceptions. However, Pinel's concept focused on a frenzy of the passions, particularly involving rage and violence. For Prichard the typical syndrome was more a form of extreme eccentricity, and he would later refer to Pinel's type as a madness of the instincts.[7]
Prichard was an adherent of what was known faculty psychology, which attempted to divide the mind into different functions or abilities, but not phrenology, which attempted to locate them below specific parts of the skull. He was also influenced by a school of thought associated with the physician Nasse, which posited disorders of emotions or temperament rather than intellect.[7] Prichard also considered a complex categorical scheme developed by Heinroth, concluding that a number of disorders in different divisions of that scheme would be more simply gathered under the heading 'moral insanity'. He suggested the category could also be termed 'parapathia', or alternatively 'pathomania' by analogy with monomania.
The latter term had been introduced by the physician Esquirol, who had succeeded Pinel, to refer to a form of insanity where there is a fixation or excess in only one area. It was also used widely by Étienne-Jean Georget. It was theorized to be caused by a split in the faculties of the mind. Prichard considered his first category of intellectual (rather than moral) insanity, to be equivalent to monomania. This in turn meant that the symptoms of moral insanity could increase, causing an overall degeneration into monomania.[8] "On the surface, monomania can thus appear even more circumscribed a form of derangement than moral insanity."[9] However, Esquirol by contrast considered moral insanity to be simply one form of monomania.[10]
## Context[edit]
Contemporary misunderstanding of the term derives from the double meaning of the word "moral" in the nineteenth century context. According to Erdmann Mueller in a comprehensive 1899 treatise on moral insanity: "the word moral in the concept moral insanity is derived from the word affective in Esquirol's terminology, and the translation of moral as virtuous or ethical is the result of a misunderstanding due to the double meaning of the word."[11] According to Pinel, manie sans délire (mania without delusion) had no relation to the moral faculty.[12] Moral insanity was a form of mental derangement in which the intellectual faculties were unaffected, but the affects or emotions were damaged, causing patients to be carried away by some kind of furious instinct (instincte fureur).[12]
Likewise, the term moral treatment referred to a set of psychosocial techniques rather than necessarily defined as ethical practice.[13] Under Pinel's guidance, patients were freed from chains and shackles.[14] Prichard used a mixture of moral treatment techniques as well as traditional medical treatments of bleeding, purging, vomiting etc.
Prichard appeared to view the disorder in terms of both affect and morality. As a religious and conservative man, he shared in some gloom about a perceived decline in morals and religion, and increase of selfishness. Some attributed this to socioeconomic developments related to industrialization or capitalism. Prichard saw it as an issue within human consciousness, identity and judgement; he was also influenced by theories that natural human emotions could become unbalanced in conditions of civilisation far removed from nature. However, he also linked moral insanity to a debasement of the more refined emotions, which he in turn saw as more associated with the affluent classes, such that a person still knew right from wrong but became unable to conduct themselves "with decency and propriety in the business of life". Prichard was also concerned to challenge the development of phrenology, which attempted to localise aspects of the mind and personality to particular areas of the brain, as assessed by the size of bumps in the skull. The alternative was to locate mental disorder in temperament, abstractly located in the visceral organs or nervous system in a then modern form of humorism, while maintaining that powers of judgement were a metaphysical or religious component.[7]
Later, Maudsley discussed moral insanity as a sign of poor moral willpower or moral sense. DH Tuke asserted that while it may appear to stem from the emotions, it was often due to a weakening of the 'higher centres' of will, and he thus suggested a new name 'inhibitory insanity'.
Both moral insanity and monomania were depicted in Victorian novels and movies of the time. They were similar in that they were both abnormalities of an otherwise normal mind, though the former was a systemic malfunction and the latter an isolated aberration.[15]
The context leading to the conceptualization of this diagnostic category was undoubtedly borne out of the frustration of alienists (the term is approximately equivalent to the modern day one of psychiatrist) by the definition of madness provided by John Locke in which delusional symptoms were required. In legal trials this definition had proved to be a great source of embarrassment to alienists because unless delusional symptoms could be clearly shown judges would not consider a plea of insanity.[16]
In terms of involuntary commitment of individuals alleged to be insane, Prichard was cautious in using the diagnosis of moral insanity, partly because the educated classes that were typical clients tended to hold the asylum system in very low regard. Prichard tended to suggest it came down to an assessment of individual mental state and ability. He emphasized property and social order as the rationale for confinement: "Of all these arrangements the maintenance of public order is the principal object, and the second is the preservation of the property belonging to the lunatic and the interest of his family."[7]
## Implications[edit]
Ultimately, the concept of moral insanity did not change the orthodox legal defense of insanity which required the clear presence of delusion, as embodied in the M'Naghten rules in 1842 which are still referenced today.[7] Nevertheless, modern conceptions of responsibility have been forged in part through the medical and legal exchanges over moral insanity, including anticipations of the diagnosis in the writings of Benjamin Rush, in the context of concepts of free will associated with religious Common Sense Realism.[17]
Moral insanity came to be increasingly seen as a form of genetically-inherited degeneracy,[11] and toward the end of the 19th century and into the 20th century converged with ideas of moral imbecility and deficiency, as well as with an anti-vice moral hygiene movement.[18]
Several writers have sounded caution over the notion that the diagnostic category of moral insanity was a direct forerunner of psychopathic disorder. As stated by the historian F.A. Whitlock: "there [is] not the remotest resemblance between their examples [Pinel's and Prichard's] and what today would be classed as psychopathic personality."[16] Prichard's "moral insanity" was a catch-all term of behavioural disorders whose only feature in common was an absence of delusions: it is not cognate with the modern diagnostic category of antisocial personality disorder.[19] However, Whitlock has suggested that the diagnosis gradually changed into moral imbecility over the turn of the century and that in turn transformed into something like the current concept of psychopathy.[20]
The psychiatrist Koch sought to make the moral insanity concept more scientific and suggested in 1891 the phrase 'psychopathic inferiority' (later personality) be used instead. This referred to continual and rigid patterns of misconduct or dysfunction in the absence of apparent mental retardation or illness. The diagnosis was meant to imply a congenital disorder, and to be made without moral judgement, though Koch has been described as deeply rooted in a Christian faith.[21] Toward the mid 20th century the terminology of the 'psychopathic' would become specifically associated with an aggressive and anti-social personality. A more general concept of character disorders came into use by psychoanalysts, and psychiatry later adopted the current terminology of personality disorders.[22]
## See also[edit]
* Insanity
* Moral treatment
## References[edit]
1. ^ James Cowles Prichard (1837) A Treatise on Insanity and Other Disorders Affecting the Mind, Carey & Hart, Philadelphia
2. ^ John Macpherson (1899). Mental affections; an introduction to the study of insanity. Macmillan. p. 300.
3. ^ Berrios GE (March 1999). "J.C. Prichard and the concept of 'moral insanity'". Hist Psychiatry. Classic text no.37. 10 (37): 111–26. doi:10.1177/0957154X9901003706. PMID 11623816.
4. ^ Quoted in: Sass & Herpertz 1995, p. 635
5. ^ Tuke, Daniel Hack (ed.) (1892). A Dictionary of Psychological Medicine. Volume 2. J. & A. Churchill. p. 813.
6. ^ Porter, Roy (1999). The Greatest Benefit to Mankind: A Medical History of Humanity from Antiquity to the Present. Fontana. pp. 495–6. ISBN 0393319806.
7. ^ a b c d e f Augstein HF (July 1996). "J C Prichard's concept of moral insanity—a medical theory of the corruption of human nature". Med Hist. 40 (3): 311–43. doi:10.1017/S0025727300061329. PMC 1037128. PMID 8757717.
8. ^ James Cowles Prichard (1837). "Case 2 & Case 3". A treatise on insanity and other disorders affecting the mind. E.L. Carey & A. Hart. p. 37.
9. ^ Sally Shuttleworth (1996). Charlotte Brontë and Victorian psychology. Cambridge University Press. p. 51. ISBN 0-521-55149-8.
10. ^ Leigh D (August 1955). "James Cowles Prichard, M.D., 1786–1848". Proc. R. Soc. Med. 48 (8): 586–90. PMC 1919190. PMID 13254722.
11. ^ a b Quoted in Verplaetse 2009, p. 195
12. ^ a b Verplaetse, Jan (2009). "Ch. 7: Moral insanity as a disorder of the moral sense". Localizing the Moral Sense: Neuroscience and the Search for the Cerebral Seat of Morality, 1800–1930. Springer. pp. 193 ff. ISBN 978-1-4020-6321-3.
13. ^ Sass, H.; Herpertz, S. (1995). "Personality Disorders: Clinical Section". In Berrios, Germán E.; Porter, Roy S. (eds.). History of Clinical Psychiatry: The Origin and History of Psychiatric Disorders. Athlone Press. p. 635. ISBN 978-0-485-24211-9.
14. ^ Vincent Mark Durand, David H. Barlow (2005). Essentials Of Abnormal Psychology (4th ed.). Cengage Learning. p. 16. ISBN 0-495-03128-3.
15. ^ Patrick Brantlinger, William B. Thesing (2002). A companion to the Victorian novel. Wiley-Blackwell. p. 76. ISBN 0-631-22064-X.
16. ^ a b Berrios, G.E. (1996). The History of Mental Symptoms: Descriptive Psychopathology Since the Nineteenth Century. Cambridge University Press. p. 426. ISBN 978-0-521-43736-3.
17. ^ Blumental, S.L. The Mind of a Moral Agent: Scottish Common Sense and the Problem of Responsibility in Nineteenth-Century American Law Archived 2008-10-12 at the Wayback Machine Law and History Review, 2008
18. ^ Rimke, H. & Hunt, A From sinners to degenerates: the medicalization of morality in the 19th century History of the Human Sciences February 2002 vol. 15 no. 1 59-88 doi:10.1177/0952695102015001073
19. ^ Berrios, German E. (1996). The History of Mental Symptoms: Descriptive Psychopathology Since the Nineteenth Century. Cambridge: p. 427.
20. ^ Whitlock, F. A. (1 April 1982). "A Note on Moral Insanity and Psychopathic Disorders". Psychiatric Bulletin. 6 (4): 57–59. doi:10.1192/pb.6.4.57.
21. ^ Gutmann, Philipp (2007). "Julius Ludwig August Koch (1841–1908)". American Journal of Psychiatry. 164: 35. doi:10.1176/appi.ajp.164.1.35.
22. ^ Millon, Theodore; Simonsen, Erik; Birket-Smith, Morten; Davis, Roger D. (2003). Psychopathy: Antisocial, Criminal, and Violent Behavior. Guilford Press. ISBN 978-1-57230-864-0.
## External links[edit]
* Bouvier, John (1856). "Moral insanity". A Law Dictionary, Adapted to the Constitution and Laws of the United States.
* Finney, Charles G. (10 September 1856). "Moral Insanity" (PDF). The Oberlin Evangelist.
* Ozarin L (18 May 2001). "Moral Insanity: A Brief History". Psychiatric News. 36 (10): 21. doi:10.1176/pn.36.10.0021.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Moral insanity
|
None
| 27,517 |
wikipedia
|
https://en.wikipedia.org/wiki/Moral_insanity
| 2021-01-18T18:34:25 |
{"wikidata": ["Q955922"]}
|
Flat face-microstomia-ear anomaly syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by dysmorphic facial features, including high forehead, elongated and flattened midface, arched and sparse eyebrows, short palpebral fissures, telecanthus, long nose with hypoplastic nostrils, long philtrum, high and narrow palate and microstomia with downturned corners. Ears are characteristically malformed, large, low-set and posteriorly rotated and nasal speech is associated. There have been no further descriptions in the literature since 1994.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Flat face-microstomia-ear anomaly syndrome
|
c1866962
| 27,518 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1968
| 2021-01-23T18:46:43 |
{"gard": ["4873"], "mesh": ["C537339"], "omim": ["182150"], "umls": ["C1866962"], "icd-10": ["Q87.0"], "synonyms": ["Blepharophimosis-telecanthus-microstomia syndrome", "Simosa craniofacial syndrome", "Simosa-Penchaszadeh-Bustos syndrome"]}
|
This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (January 2017) (Learn how and when to remove this template message)
Testicular dysgenesis syndrome
SpecialtyUrology
Testicular dysgenesis syndrome is a male reproduction-related condition characterized by the presence of symptoms and disorders such as hypospadias, cryptorchidism, poor semen quality, and testicular cancer. The concept was first introduced by N.E. Skakkaebaek in a research paper along with the department of Growth and Reproduction in Copenhagen University.[1] The paper suggests the origin and underlying cause of TDS can be detected as early as in fetal life, where environmental and genomic factors could affect the development of the male reproductive system.[2]
## Contents
* 1 Causes
* 1.1 Genetic
* 1.2 Environmental
* 1.3 Lifestyle
* 2 Pathogenesis
* 3 Diagnosis
* 3.1 Hypospadias
* 3.2 Cryptorchidism
* 3.3 Poor semen quality
* 3.4 Testicular cancer
* 4 Treatment
* 5 References
## Causes[edit]
Central to the cause of irreversible TDS are disruptions to early fetal testes development. This has both genetic, environmental, and lifestyle components, however the rapid increase in the incidence of the disorders associated with TDS in the last decades[3] indicates that it is under a powerful environmental influence. The fetal origins of TDS are reinforced by the high incidence of TDS disorders found occurring together in one individual.
### Genetic[edit]
Many genes have been implicated in the disorders of TDS, with genome wide association studies (GWAS) regularly identifying new gene variants that play a role in abnormal testes development. Some of these are specific to certain disorders, and some are part of a 'risk factor network' that connect TGCC, hypospadias, cryptorchidism, poor semen quality. The majority of these genes are involved in fetal gonad development. Mutations in androgen receptor genes are highly implicated, as these are involved in penile development, testes descent, and testes development.[4] Testicular germ cell cancer (TGCC) shows a strong genetic disposition, with the most significant gene variants being those linked to gonad formation and germ cell function.[5]
### Environmental[edit]
Exposure of a male fetus to substances that disrupt hormone systems, particularly chemicals that inhibit the action of androgens (male sex hormones) during the development of the reproductive system, has been shown to cause many of the characteristic TDS disorders. These include environmental estrogens and anti-androgens found in food and water sources that have been contaminated with synthetic hormones and pesticides used in agriculture.[6] In historical cases, medicines given to pregnant women, like diethylstilbestrol (DES), have caused many of the features of TDS in fetuses exposed to this chemical during gestation.[7] The impact of environmental chemicals is well documented in animal models.[8] If a substance affects Sertoli and Leydig cell differentiation (a common feature of TDS disorders) at an early developmental stage, germ cell growth and testosterone production will be impaired.[9] These processes are essential for testes descent and genitalia development, meaning that genital abnormalities like cryptorchidism or hypospadias may be present from birth, and fertility problems and TGCC become apparent during adult life. Severity or number of disorders may therefore be dependent on the timing of the environmental exposure.[10] Environmental factors can act directly, or via epigenetic mechanisms, and it is likely that a genetic susceptibility augmented by environmental factors is the primary cause of TDS.
### Lifestyle[edit]
Links between maternal smoking and TDS are tenuous, but there are stronger associations between maternal alcohol consumption and incidences of cryptorchidism in sons. Smoking does however affect the growth of a fetus, and low birth weight is shown to increase the likelihood of all the disorders encompassed by TDS. Maternal obesity, resulting in gestational diabetes, has also been shown to be a risk factor for impaired testes development and TDS symptoms in sons.
## Pathogenesis[edit]
Schematic diagram illustrating the pathogenic links that lead to TDS. CIS = carcinoma in situ; GC = Germ Cell
The TDS hypothesis proposes that testicular dysgenesis, which has various primary causes, can lead to abnormalities in Sertoli and/or Leydig cell function. This leads to both impaired germ cell development and hormonal changes during male sexual differentiation. For instance, insufficient production of testosterone can result in incomplete masculinisation, whilst reduced expression of insulin-like factor 3 can lead to incomplete testes descent.[11] The downstream disorders of such abnormalities can include both genital malformations (e.g. hypospadias and cryptorchidism) and delayed reproductive disorders (e.g. testicular cancer and poor semen quality) which comprise TDS.[12]
## Diagnosis[edit]
Hypospadias
Cryptorchidism - Can see one missing testicle
### Hypospadias[edit]
Hypospadias presents as an abnormal location for the end of the urethra which is typically found on the distal end of the penis.[13] It is generally diagnosed at birth from visual confirmation of the hallmark features. As well as an unusual location of the urethra, the prepuce (foreskin) is typically incomplete as well. The abnormal ‘hooded’ prepuce is what often draws attention to the condition but can occur separately to hypospadias.
### Cryptorchidism[edit]
In Cryptorchidism a diagnosis is made from a physical examination which is performed when the baby is lacking one or both testes in the dependant portion of the scrotal sac.[14] 70% of cryptorchid testes can be felt and are unable to be pulled into the scrotum or retreats quickly after being pulled into a higher position. In 30% of cases the testes cannot be felt indicating an intra-abdominal location. The risk factors for Cryptorchidism are:
* A family history of the condition
* Low birth weight
* Prematurity
### Poor semen quality[edit]
Human sperm stained for semen analysis
Poor semen quality is measured not only by the number of sperm a man produces but also by how effective the sperm is at fertilising an egg. The motility and shape of the sperm are important for this role. A man with poor semen quality will often present with fertility problems which is defined as a couple trying to conceive for over 1 year with no success.[15] Diagnosis can be made from semen analysis, taking a sample of the man's semen and running tests to count numbers and quality of the individual sperm.
### Testicular cancer[edit]
The most common presentation of testicular cancer is a hard, painless lump which can be felt on one of the testis. It is either noticed by a clinician during a routine examination, or the patient themselves.[16] Risk factors for TC include:
* Cryptorchidism
* Family history
* Previous testicular cancer
The diagnosis is confirmed in different ways. An ultrasound scan can be used to diagnose to a 90-95% accuracy. Bloods can also be taken to look for elevated tumour markers which is also used to analyse the patient's response to treatment. 80% of testicular cancer cases are from the 20-34 year old age range[17]
## Treatment[edit]
This section is empty. You can help by adding to it. (November 2016)
## References[edit]
1. ^ Skakkebæk, N. E.; Meyts, E. Rajpert-De; Main, K. M. (2001-05-01). "Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion". Human Reproduction. 16 (5): 972–978. doi:10.1093/humrep/16.5.972. ISSN 0268-1161. PMID 11331648.
2. ^ VIRTANEN, H; RAJPERTDEMEYTS, E; MAIN, K; SKAKKEBAEK, N; TOPPARI, J (1 September 2005). "Testicular dysgenesis syndrome and the development and occurrence of male reproductive disorders". Toxicology and Applied Pharmacology. 207 (2): 501–505. doi:10.1016/j.taap.2005.01.058. PMID 16005920.
3. ^ Toppari, J; Larsen, J C; Christiansen, P; Giwercman, A; Grandjean, P; Guillette, L J; Jégou, B; Jensen, T K; Jouannet, P (1996-08-01). "Male reproductive health and environmental xenoestrogens". Environmental Health Perspectives. 104 (Suppl 4): 741–803. doi:10.1289/ehp.96104s4741. ISSN 0091-6765. PMC 1469672. PMID 8880001.
4. ^ Skakkebæk, N. E.; Meyts, E. Rajpert-De; Main, K. M. (2001-05-01). "Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion". Human Reproduction. 16 (5): 972–978. doi:10.1093/humrep/16.5.972. ISSN 0268-1161. PMID 11331648.
5. ^ Skakkebaek, Niels E.; Meyts, Ewa Rajpert-De; Louis, Germaine M. Buck; Toppari, Jorma; Andersson, Anna-Maria; Eisenberg, Michael L.; Jensen, Tina Kold; Jørgensen, Niels; Swan, Shanna H. (2016-01-01). "Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility". Physiological Reviews. 96 (1): 55–97. doi:10.1152/physrev.00017.2015. ISSN 0031-9333. PMC 4698396. PMID 26582516.
6. ^ Meyts, Ewa Rajpert-De (2006-05-01). "Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects". Human Reproduction Update. 12 (3): 303–323. doi:10.1093/humupd/dmk006. ISSN 1355-4786. PMID 16540528.
7. ^ Gill, W. B.; Schumacher, G. F.; Bibbo, M.; Straus, F. H.; Schoenberg, H. W. (1979-07-01). "Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities". The Journal of Urology. 122 (1): 36–39. doi:10.1016/s0022-5347(17)56240-0. ISSN 0022-5347. PMID 37351.
8. ^ Skakkebæk, N. E.; Meyts, E. Rajpert-De; Main, K. M. (2001-05-01). "Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion". Human Reproduction. 16 (5): 972–978. doi:10.1093/humrep/16.5.972. ISSN 0268-1161. PMID 11331648.
9. ^ Skakkebaek, Niels E.; Meyts, Ewa Rajpert-De; Louis, Germaine M. Buck; Toppari, Jorma; Andersson, Anna-Maria; Eisenberg, Michael L.; Jensen, Tina Kold; Jørgensen, Niels; Swan, Shanna H. (2016-01-01). "Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility". Physiological Reviews. 96 (1): 55–97. doi:10.1152/physrev.00017.2015. ISSN 0031-9333. PMC 4698396. PMID 26582516.
10. ^ Skakkebæk, N. E.; Meyts, E. Rajpert-De; Main, K. M. (2001-05-01). "Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion". Human Reproduction. 16 (5): 972–978. doi:10.1093/humrep/16.5.972. ISSN 0268-1161. PMID 11331648.
11. ^ Sharpe, Richard M.; Skakkebaek, Niels E. (2008). "Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects". Fertility and Sterility. 89 (2): e33–e38. doi:10.1016/j.fertnstert.2007.12.026. PMID 18308057.
12. ^ Bay, Katrine; Asklund, Camilla; Skakkebaek, Niels E.; Andersson, Anna-Maria (2006-03-01). "Testicular dysgenesis syndrome: possible role of endocrine disrupters". Best Practice & Research Clinical Endocrinology & Metabolism. Endocrine Disrupters. 20 (1): 77–90. doi:10.1016/j.beem.2005.09.004. PMID 16522521.
13. ^ "BMJ Best Practice: Anatomical Penile Abnormalities".
14. ^ "BMJ Best Practice: Cryptorchidism".
15. ^ "NHS Choices: Infertility - Diagnosis". 2017-10-23.
16. ^ "BMJ Best Practice: Testicular Cancer".
17. ^ Jemal, A; Siegel, R; Ward, E; Murray, T; Xu, J; Thun, MJ (2007). "Cancer Statistics, 2007". CA: A Cancer Journal for Clinicians. 57 (1): 43–66. doi:10.3322/canjclin.57.1.43. PMID 17237035.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Testicular dysgenesis syndrome
|
c2919755
| 27,519 |
wikipedia
|
https://en.wikipedia.org/wiki/Testicular_dysgenesis_syndrome
| 2021-01-18T19:03:18 |
{"umls": ["C2919755"], "wikidata": ["Q3508714"]}
|
Not to be confused with Cytokine storm.
Bodily reaction
Cytokine release syndrome
Other namesInfusion-related reaction (IRR), infusion reaction,[1] cytokine storm[2]
SpecialtyImmunology
Cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome (SIRS) that can be triggered by a variety of factors such as infections and certain drugs.[3] It refers to cytokine storm syndromes (CSS)[4] and occurs when large numbers of white blood cells are activated and release inflammatory cytokines, which in turn activate yet more white blood cells. CRS is also an adverse effect of some monoclonal antibody medications, as well as adoptive T-cell therapies.[5][6] When occurring as a result of a medication, it is also known as an infusion reaction.[1]
The term cytokine storm is often used interchangeably with CRS but, despite the fact that they have similar clinical phenotype, their characteristics are different. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset CRS is a cytokine storm,[7] although severe cases of CRS have also been called cytokine storms.[2]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Medications
* 3 Diagnosis
* 3.1 Classification
* 4 Prevention
* 5 Management
* 6 Epidemiology
* 7 Research
* 8 See also
* 9 References
## Signs and symptoms[edit]
Symptoms include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination.[5]
Lab tests and clinical monitoring show low blood oxygen, widened pulse pressure, increased cardiac output (early), potentially diminished cardiac output (late), high levels of nitrogen compounds in the blood, elevated D-dimer, elevated transaminases, factor I deficiency and excessive bleeding, higher-than-normal level of bilirubin.[5][8]
## Cause[edit]
CRS occurs when large numbers of white blood cells, including B cells, T cells, natural killer cells, macrophages, dendritic cells, and monocytes are activated and release inflammatory cytokines, which activate more white blood cells in a positive feedback loop of pathogenic inflammation.[5] Immune cells are activated by stressed or infected cells through receptor-ligand interactions.[9]
This can occur when the immune system is fighting pathogens, as cytokines produced by immune cells recruit more effector immune cells such as T-cells and inflammatory monocytes (which differentiate into macrophages) to the site of inflammation or infection. In addition, pro-inflammatory cytokines binding their cognate receptor on immune cells results in activation and stimulation of further cytokine production.[10] This process, when dysregulated, can be life-threatening due to systemic hyper-inflammation, hypotensive shock, and multi-organ failure.[citation needed]
Adoptive cell transfer of autologous T-cells modified with chimeric antigen receptors (CAR-T cell therapy) also causes CRS.[5] Serum samples of patients with CAR-T associated CRS have elevated levels of IL-6, IFN-γ, IL-8 (CXCL8), IL-10, GM-CSF, MIP-1α/β, MCP-1 (CCL2), CXCL9, and CXCL10 (IP-10).[11] The most predictive biomarkers 36h after CAR-T infusion of CRS are a fever ≥38.9°C (102°F) and elevated levels of MCP-1 in serum.[12] Many of the cytokines elevated in CRS are not produced by CAR-T cells, but by myeloid cells that are pathogenically licensed through T-cell-mediated activating mechanisms. For example, in vitro co-culture experiments have demonstrated IL-6, MCP-1, and MIP-1 are not produced by CAR-T cells, but rather by inflammatory myeloid lineage cells.[13] In vivo models have demonstrated NSG (NOD/SCID/γ-chain deficient mice) with defects of both lymphocyte and myeloid lineage compartments do not develop CRS after CAR-T cell infusion.[14]
In addition to adoptive T-cell therapies, severe CRS or cytokine reactions can occur in a number of infectious and non-infectious diseases including graft-versus-host disease (GVHD), coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), sepsis, Ebola, avian influenza, smallpox, and systemic inflammatory response syndrome (SIRS).[15]
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficiently cleared by the early acute phase anti-viral response in most individuals, some progress to a hyperinflammatory condition, often with life-threatening pulmonary involvement. This systemic hyperinflammation results in inflammatory lymphocytic and monocytic infiltration of the lung and the heart, causing ARDS and cardiac failure.[16] Patients with fulminant COVID-19 and ARDS have classical serum biomarkers of CRS including elevated CRP, LDH, IL-6, and ferritin.[17]
Hemophagocytic lymphohistiocytosis and Epstein-Barr virus-related hemophagocytic lymphohistiocytosis are caused by extreme elevations in cytokines and can be regarded as one form of severe cytokine release syndrome.[18]
### Medications[edit]
Cytokine reaction syndrome may also be induced by certain medications, such as the CD20 antibody rituximab and the CD19 CAR T cell tisagenlecleucel. The experimental drug TGN1412—also known as Theralizumab—caused extremely serious symptoms when given to six participants in a Phase I trial.[2] A controlled and limited CRS is triggered by active fever therapy with mixed bacterial vaccines (MBV) according to Coley; it is used for oncological and certain chronic diseases.[19] CRS has also arisen with biotherapeutics intended to suppress or activate the immune system through receptors on white blood cells. Muromonab-CD3, an anti-CD3 monoclonal antibody intended to suppress the immune system to prevent rejection of organ transplants; alemtuzumab, which is anti-CD52 and used to treat blood cancers as well as multiple sclerosis and in organ transplants; and rituximab, which is anti-CD20 and used to treat blood cancers and auto-immune disorders, all cause CRS.[5]
## Diagnosis[edit]
CRS needs to be distinguished from symptoms of the disease itself and, in the case of drugs, from other adverse effects—for example tumor lysis syndrome requires different interventions. As of 2015, differential diagnoses depended on the judgement of doctor as there were no objective tests.[5]
### Classification[edit]
CRS is a form of systemic inflammatory response syndrome and is an adverse effect of some drugs.[5]
The Common Terminology Criteria for Adverse Events classifications for CRS as of version 4.03 issued in 2010 were:[5][20]
Grades Toxicity
Grade 1 Mild reaction, infusion interruption not indicated; intervention not indicated
Grade 2 Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for <=24 hrs
Grade 3 Prolonged (e.g., not rapidly responsive to symptomatic medication or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)
Grade 4 Life-threatening consequences; pressor or ventilatory support indicated
Grade 5 Death
## Prevention[edit]
Severe CRS caused by some drugs can be prevented by using lower doses, infusing slowly, and administering anti-histamines or corticosteroids before and during administration of the drug.[5]
In vitro assays have been developed to understand the risk that pre-clinical drug candidates might cause CRS and guide dosing for Phase I trials, and regulatory agencies expect to see results of such tests in investigational new drug applications.[2][21]
A modified Chandler loop model can be used as a preclinical tool to assess infusion reactions.[22]
## Management[edit]
Treatment for less severe CRS is supportive, addressing the symptoms like fever, muscle pain, or fatigue. Moderate CRS requires oxygen therapy and giving fluids and antihypotensive agents to raise blood pressure. For moderate to severe CRS, the use of immunosuppressive agents like corticosteroids may be necessary, but judgment must be used to avoid negating the effect of drugs intended to activate the immune system.[5]
Tocilizumab, an anti-IL-6 monoclonal antibody, was FDA approved for steroid-refractory CRS based on retrospective case study data.[5][6]
Lenzilumab, an anti-GM-CSF monoclonal antibody, may also be effective at managing cytokine release by reducing activation of myeloid cells and decreasing the production of IL-1, IL-6, MCP-1, MIP-1, and IP-10. Additionally, as a soluble cytokine blockade, it will not increase serum levels of GM-CSF (a phenomenon seen with tocilizumab and IL-6).[23]
Although frequently used to treat severe CRS in people with ARDS, corticosteroids and NSAIDs have been evaluated in clinical trials and have shown no effect on lung mechanics, gas exchange, or beneficial outcome in early established ARDS.[15]
## Epidemiology[edit]
Severe CRS is rare. Minor and moderate CRS are common side effects of immune-modulating antibody therapies and CAR-T therapies.[6]
## Research[edit]
Key therapeutic targets to abrogate hyper-inflammation in CRS are IL-1, IL-6, and GM-CSF. An in vivo model found that GM-CSF knockout CAR-T cells do not induce CRS in mice. However, IL-1 knockout and IL-6 knockout hosts (whose myeloid cells are deficient in IL-1 and IL-6, respectively) were susceptible to CRS after the administration of wild-type CAR-T cells.[14] It is thought this may be because while blockade of IL-1 and IL-6 are myeloid-derived cytokines are thus too far downstream of the inflammatory cascade. Moreover, while tocilizumab (anti-IL-6R monoclonal antibody) may have an anti-inflammatory and antipyretic effect, it has been shown to increase serum levels of IL-6 by saturating the receptor, thus driving the cytokine across the blood brain barrier (BBB) and worsening neurotoxicity.[24] Monoclonal antibody blockade of GM-CSF with lenzilumab has been demonstrated to protect mice from CAR-T associated CRS and neurotoxicity while maintaining anti-leukemic efficacy.[25]
## See also[edit]
* Macrophage activation syndrome
* sHLH
## References[edit]
1. ^ a b Vogel WH (April 2010). "Infusion reactions: diagnosis, assessment, and management". Clinical Journal of Oncology Nursing. 14 (2): E10-21. doi:10.1188/10.CJON.E10-E21. PMID 20350882.
2. ^ a b c d Vidal JM, Kawabata TT, Thorpe R, Silva-Lima B, Cederbrant K, Poole S, et al. (August 2010). "In vitro cytokine release assays for predicting cytokine release syndrome: the current state-of-the-science. Report of a European Medicines Agency Workshop". Cytokine. 51 (2): 213–5. doi:10.1016/j.cyto.2010.04.008. PMID 20471854.
3. ^ Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, et al. (June 2018). "Cytokine release syndrome". Journal for Immunotherapy of Cancer. 6 (1): 56. doi:10.1186/s40425-018-0343-9. PMC 6003181. PMID 29907163.
4. ^ Behrens EM, Koretzky GA (June 2017). "Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era". Arthritis & Rheumatology. 69 (6): 1135–1143. doi:10.1002/art.40071. PMID 28217930. S2CID 21925082.
5. ^ a b c d e f g h i j k l Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. (July 2014). "Current concepts in the diagnosis and management of cytokine release syndrome". Blood. 124 (2): 188–95. doi:10.1182/blood-2014-05-552729. PMC 4093680. PMID 24876563.
6. ^ a b c Kroschinsky F, Stölzel F, von Bonin S, Beutel G, Kochanek M, Kiehl M, Schellongowski P (April 2017). "New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management". Critical Care. 21 (1): 89. doi:10.1186/s13054-017-1678-1. PMC 5391608. PMID 28407743.
7. ^ Porter D, Frey N, Wood PA, Weng Y, Grupp SA (March 2018). "Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel". Journal of Hematology & Oncology. 11 (1): 35. doi:10.1186/s13045-018-0571-y. PMC 5833070. PMID 29499750.
8. ^ Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ (2016). "Toxicity and management in CAR T-cell therapy". Molecular Therapy Oncolytics. 3: 16011. doi:10.1038/mto.2016.11. PMC 5008265. PMID 27626062.
9. ^ Liu Q, Zhou YH, Yang ZQ (January 2016). "The cytokine storm of severe influenza and development of immunomodulatory therapy". Cellular & Molecular Immunology. 13 (1): 3–10. doi:10.1038/cmi.2015.74. PMC 4711683. PMID 26189369.
10. ^ Murphy K, Travers P, Walport M (2007). "Signaling Through Immune System Receptors". Janeway's Immunobiology (7th ed.). London: Garland. ISBN 978-0-8153-4123-9.
11. ^ Teachey DT, Lacey SF, Shaw PA, Melenhorst JJ, Maude SL, Frey N, et al. (June 2016). "Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia". Cancer Discovery. 6 (6): 664–79. doi:10.1158/2159-8290.CD-16-0040. PMC 5448406. PMID 27076371.
12. ^ Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. (November 2017). "Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy". Blood. 130 (21): 2295–2306. doi:10.1182/blood-2017-06-793141. PMC 5701525. PMID 28924019.
13. ^ Barrett DM, et al. (2016). "Interleukin 6 Is Not Made By Chimeric Antigen Receptor T Cells and Does Not Impact Their Function". Blood. 128 (22): 654. doi:10.1182/blood.V128.22.654.654.
14. ^ a b Sentman ML, Murad JM, Cook WJ, Wu MR, Reder J, Baumeister SH, et al. (December 2016). "Mechanisms of Acute Toxicity in NKG2D Chimeric Antigen Receptor T Cell-Treated Mice". Journal of Immunology. 197 (12): 4674–4685. doi:10.4049/jimmunol.1600769. PMC 5136298. PMID 27849169.
15. ^ a b Drazen JM, Cecil RL, Goldman L, Bennett JC (2000). Cecil Textbook of Medicine (21st ed.). Philadelphia: W.B. Saunders. ISBN 978-0-7216-7996-9.
16. ^ Wadman M, Couzin-Frankel J, Kaiser J, Matacic C (April 2020). "A rampage through the body". Science. 368 (6489): 356–360. Bibcode:2020Sci...368..356W. doi:10.1126/science.368.6489.356. PMID 32327580. S2CID 216110951.
17. ^ Zhang C, Wu Z, Li JW, Zhao H, Wang GQ (March 2020). "The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality". International Journal of Antimicrobial Agents. 55 (5): 105954. doi:10.1016/j.ijantimicag.2020.105954. PMC 7118634. PMID 32234467.
18. ^ Rezk SA, Zhao X, Weiss LM (September 2018). "Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408.
19. ^ E. Göhring: Active Fever Therapy with MBV – Coley's Toxins: The Perfect Storm of Cytokines, Epubli, Berlin 2019, ISBN 978-3748530596.
20. ^ "Common Terminology Criteria for Adverse Events (CTCAE) Version v4.03" (PDF). National Institutes of Health and National Cancer Institute. June 14, 2010. p. 66. Archived from the original (PDF) on August 30, 2017. Retrieved October 16, 2017.
21. ^ "Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products" (PDF). FDA. August 2014.
22. ^ Fletcher EA, Eltahir M, Lindqvist F, Rieth J, Törnqvist G, Leja-Jarblad J, Mangsbo SM (January 2018). "Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanism-of-action of immunotherapeutics". International Immunopharmacology. 54: 1–11. doi:10.1016/j.intimp.2017.10.021. PMID 29100032.
23. ^ Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T (November 2008). "Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease". Blood. 112 (10): 3959–64. doi:10.1182/blood-2008-05-155846. PMID 18784373.
24. ^ Santomasso BD, Park JH, Salloum D, Riviere I, Flynn J, Mead E, et al. (August 2018). "Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia". Cancer Discovery. 8 (8): 958–971. doi:10.1158/2159-8290.CD-17-1319. PMC 6385599. PMID 29880584.
25. ^ Sterner RM, Sakemura R, Cox MJ, Yang N, Khadka RH, Forsman CL, et al. (February 2019). "GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts". Blood. 133 (7): 697–709. doi:10.1182/blood-2018-10-881722. PMC 6376281. PMID 30463995.
This article incorporates public domain material from the United States Department of Health and Human Services document: "Common Terminology Criteria for Adverse Events (CTCAE) Version v4.03" (PDF).
Classification
D
* MeSH: D000080424
* DiseasesDB: 34296
* SNOMED CT: 710027002
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Cytokine release syndrome
|
c0948245
| 27,520 |
wikipedia
|
https://en.wikipedia.org/wiki/Cytokine_release_syndrome
| 2021-01-18T19:04:13 |
{"mesh": ["D000080424"], "umls": ["C0948245"], "wikidata": ["Q3961647"]}
|
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-8 (LCCS8) is caused by homozygous mutation in the ADCY6 gene (600294) on chromosome 12q13. One such family has been reported.
Description
Lethal congenital contracture syndrome-8, an axoglial form of arthrogryposis multiplex congenita, is characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period (Laquerriere et al., 2014).
For a general phenotypic description and a discussion of genetic heterogeneity of lethal congenital contracture syndrome, see LCCS1 (253310).
Clinical Features
Laquerriere et al. (2014) reported 2 sibs from a consanguineous family (A649) who were diagnosed with distal arthrogryposis multiplex congenita at 32 weeks' gestation by fetal ultrasound. Both sibs had fetal hypo- or akinesia. At birth, they were noted to have hypotonia, respiratory distress, facial diplegia, areflexia, and swallowing defect. Neither sib had polyhydramnios, pterygium, cleft palate, or hygroma. Severe motor paralysis at birth led to death within the first 3 months of life. No response was found on motor nerve conduction velocity testing. Nerve immunohistochemistry using an S100 protein antibody revealed Schwann cells, but all nerve fascicles were negative for myelin basic protein antibodies. Transmission electron microscopic analysis of nerve showed no myelinated axons and some redundant basal lamina of Schwann cells.
Inheritance
The transmission pattern of lethal arthrogryposis multiplex congenita in the consanguineous family reported by Laquerriere et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 sibs, born of consanguineous parents, with an axoglial form of lethal arthrogryposis multiplex congenita, Laquerriere et al. (2014) identified a homozygous missense mutation in the ADCY6 gene (R1116C; 600294.0001). The parents were heterozygous for the mutation, which was not found in the Exome Variant Server or the dbSNP (build 138) databases.
Animal Model
Laquerriere et al. (2014) knocked down ADCY6 orthologs in zebrafish and found loss of myelin basic protein expression in the peripheral nervous system but normal expression in the central nervous system when compared with wildtype. No defects in Schwann cell migration and axonal growth were found in the morphants.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial diplegia RESPIRATORY \- Respiratory distress secondary to motor nerve paralysis ABDOMEN Gastrointestinal \- Difficulty swallowing SKELETAL \- Arthrogryposis multiplex congenita, distal Limbs \- Contractures, distal NEUROLOGIC Peripheral Nervous System \- Hypotonia \- Areflexia \- No response on motor nerve conduction velocity testing PRENATAL MANIFESTATIONS Movement \- Fetal hypokinesia/akinesia Amniotic Fluid \- No polyhydramnios MISCELLANEOUS \- One consanguineous family has been reported (last curated March 2015) \- Death within 3 months of life MOLECULAR BASIS \- Caused by mutation in the adenylate cyclase 6 gene (ADCY6, 600294.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
LETHAL CONGENITAL CONTRACTURE SYNDROME 8
|
c4225385
| 27,521 |
omim
|
https://www.omim.org/entry/616287
| 2019-09-22T15:49:22 |
{"omim": ["616287"], "orphanet": ["2680"], "synonyms": []}
|
Phosphoglycerate dehydrogenase deficiency is a condition characterized by an unusually small head size (microcephaly); impaired development of physical reactions, movements, and speech (psychomotor retardation); and recurrent seizures (epilepsy). Different types of phosphoglycerate dehydrogenase deficiency have been described; they are distinguished by their severity and the age at which symptoms first begin. Most affected individuals have the infantile form, which is the most severe form, and are affected from infancy. Symptoms of the juvenile and adult types appear later in life; these types are very rare.
In phosphoglycerate dehydrogenase deficiency there is a progressive loss of brain cells leading to a loss of brain tissue (brain atrophy), specifically affecting the fatty tissue known as myelin that surrounds nerve cells (hypomyelination). Frequently, the tissue that connects the two halves of the brain (corpus callosum) is small and thin, and the fluid-filled cavities (ventricles) near the center of the brain are enlarged. Because development of the brain is disrupted, the head does not grow at the same rate as the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Poor brain growth leads to an inability to achieve many developmental milestones such as sitting unsupported and speaking. Many affected infants also have difficulty feeding.
The seizures in phosphoglycerate dehydrogenase deficiency can vary in type. Recurrent muscle contractions called infantile spasms are typical early in the disorder. Without early treatment, seizures may progress to tonic-clonic seizures, which involve a loss of consciousness, muscle rigidity, and convulsions; myoclonic seizures, which involve rapid, uncontrolled muscle jerks; or drop attacks, which are sudden episodes of weak muscle tone.
Individuals with the infantile form of phosphoglycerate dehydrogenase deficiency develop many of the features described above. Individuals with the juvenile form typically have epilepsy as well as mild developmental delay and intellectual disability. Only one case of the adult form has been reported; signs and symptoms began in mid-adulthood and included mild intellectual disability; difficulty coordinating movements (ataxia); and numbness, tingling, and pain in the arms and legs (sensory neuropathy).
## Frequency
This condition is likely a rare disorder, but its prevalence is unknown. At least 15 cases have been described in the scientific literature.
## Causes
Mutations in the PHGDH gene cause phosphoglycerate dehydrogenase deficiency. The PHGDH gene provides instructions for making the parts (subunits) that make up the phosphoglycerate dehydrogenase enzyme. Four PHGDH subunits combine to form the enzyme. This enzyme is involved in the production of the protein building block (amino acid) serine. Specifically, the enzyme converts a substance called 3-phosphoglycerate to 3-phosphohydroxypyruvate in the first step in serine production. Serine is necessary for the development and function of the brain and spinal cord (central nervous system). Serine is a part of chemical messengers called neurotransmitters that transmit signals in the nervous system. Proteins that form cell membranes and myelin also contain serine. Serine can be obtained from the diet, but brain cells must produce their own serine because dietary serine cannot cross the protective barrier that allows only certain substances to pass between blood vessels and the brain (the blood-brain barrier).
PHGDH gene mutations result in the production of an enzyme with decreased function. As a result, less 3-phosphoglycerate is converted into 3-phosphohydroxypyruvate than normal and serine production is stalled at the first step. The lack of serine likely prevents the production of proteins and neurotransmitters in the brain and impairs the formation of normal cells and myelin. These disruptions in normal brain development lead to the signs and symptoms of phosphoglycerate dehydrogenase deficiency.
### Learn more about the gene associated with Phosphoglycerate dehydrogenase deficiency
* PHGDH
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Phosphoglycerate dehydrogenase deficiency
|
c1866174
| 27,522 |
medlineplus
|
https://medlineplus.gov/genetics/condition/phosphoglycerate-dehydrogenase-deficiency/
| 2021-01-27T08:25:30 |
{"mesh": ["C566618"], "omim": ["601815"], "synonyms": []}
|
Invasive non-typhoidal salmonellosis is a rare, bacterial, infectious disease caused by extraintestinal infection of non-typhoidal serotypes of Salmonella enterica in patients with underlying HIV infection, malaria or malignancy. It has a high mortality rate and patients typically present with fever, pallor and respiratory signs (cough, tachypnea, pneumonia). Gastrointestinal manifestations (diarrhea, vomit, abdominal pain) are not common. Occasionally, organ abscesses, septic shock and meningitis may be observed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Invasive non-typhoidal salmonellosis
|
c4706572
| 27,523 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324648
| 2021-01-23T17:33:48 |
{"icd-10": ["A02.0", "A02.1", "A02.2", "A02.8", "A02.9"], "synonyms": ["Invasive non-typhoidal salmonella disease", "iNTS disease"]}
|
A number sign (#) is used with this entry because of evidence that this form of peroxisome biogenesis disorder (PBD4B) is caused by homozygous or compound heterozygous mutation in the PEX6 gene (601498) on chromosome 6p21.1, or overexpression of a heterozygous mutation in PEX6 due to allelic expression imbalance (AEI) resulting from a polymorphism on the mutant allele in the PEX6 3-prime UTR.
Mutations in the PEX6 gene also cause Zellweger syndrome (PBD4A; 614862) and Heimler syndrome-2 (HMLR2; 616617).
Description
Peroxisome biogenesis disorder-4B (PBD4B) includes the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders (PBDs). The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012).
For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539.
Individuals with mutations in the PEX6 gene have cells of complementation group 4 (CG4, equivalent to CG6 and CGC). For information on the history of PBD complementation groups, see 214100.
Clinical Features
Najmabadi et al. (2011) studied 5 sibs (family M331) with moderate intellectual disability, retinitis pigmentosa, hearing loss, and ataxia. Their parents, who were second cousins, had 6 healthy children.
Falkenberg et al. (2017) studied 7 unrelated patients and 1 half-brother who all exhibited characteristic features of a Zellweger spectrum disorder. Most had visual impairment and/or sensorineural hearing loss, and liver dysfunction was also frequently noted. One patient had adrenal insufficiency. All affected individuals showed neurologic involvement, including profound hypotonia, gait abnormalities, developmental delay, and neuropathy, as well as white matter abnormalities on brain MRI. Biochemical analysis revealed aberrant peroxisomal metabolite levels in patient blood and fibroblasts, and patient fibroblasts showed an import defect of peroxisomal matrix proteins. The clinical course was progressive, without a clear episode of rapid deterioration. Four patients died between 8 and 20 years of age, whereas 4 patients were still alive and in their first decade of life at the time of the study.
Molecular Genetics
Matsumoto et al. (2001) found compound heterozygosity for mutations in the PEX6 gene (601498.0007, 601498.0008) in a patient with a diagnosis of neonatal adrenoleukodystrophy (NALD) of PBD complementation group 6. This patient was Patient 6 of Kelley et al. (1986).
The 5 sibs in the study of Najmabadi et al. (2011) carried a homozygous frameshift mutation in the PEX6 gene (601498.0009).
In 4 unrelated patients with a phenotype consistent with a Zellweger spectrum disorder (ZSD), Falkenberg et al. (2017) performed functional genetic complementation of patient fibroblasts or fused cell complementation and identified defective PEX6 as the cause of the disease. Sanger sequencing identified a heterozygous R860W mutation (601498.0015) in the PEX6 gene in all 4 individuals, but no second mutation was detected. Heterozygosity for the same R860W mutation was independently identified by Sanger sequencing in 3 more unrelated patients with a similar phenotype and 1 affected half-brother. Peroxisome-specific gene-panel sequencing in 4 of the patients and whole-exome sequencing in 2 other patients did not reveal additional pathogenic variants in other genes encoding peroxisomal proteins. In 2 patients, the PEX6 mutation was shown to have occurred de novo, but in 3 families, it was inherited from an unaffected parent (parental DNA was unavailable in the remaining 2 families). Analysis of PEX6 mRNA from affected individuals demonstrated allelic expression imbalance (AEI), with levels of mutant cDNA that were consistently 3 to 5 times higher than those of wildtype PEX6. In contrast, the cDNA levels of wildtype and mutant PEX6 alleles were equal in an unaffected mother who carried the R860W mutation. Comparison of common variants in PEX6 between the affected individuals and the unaffected carrier parents identified a c.*442_445delTAAA polymorphism (rs144286892) in the 3-prime UTR that correlated with AEI of PEX6 when present in heterozygosity but not homozygosity; the polymorphism was heterozygous and in cis with the R860W mutation in all 8 affected individuals, but homozygous in the 3 unaffected carrier parents. Functional analysis indicated that the PEX6 R860W mutation has a negative effect on PEX1 (602136)-PEX6 complex function, but results in a disease phenotype only when PEX6 R860W is at least 2 to 3 times more abundant than wildtype PEX6.
INHERITANCE \- Autosomal recessive \- Autosomal dominant GROWTH Other \- Growth retardation, postnatal HEAD & NECK Head \- Large head \- Widely open fontanels Ears \- Hearing loss Eyes \- Hypertelorism \- Nystagmus \- Optic atrophy, bilateral \- Retinitis pigmentosa Nose \- Small nose ABDOMEN Liver \- Hepatomegaly, mild \- Liver dysfunction GENITOURINARY Kidneys \- Oxalate stone, unilateral Ureters \- Ureterocele, bilateral SKIN, NAILS, & HAIR Skin \- Single transverse palmar crease, bilateral NEUROLOGIC Central Nervous System \- Intellectual disability \- Developmental delay \- Hypotonia \- Ataxia \- Gait abnormalities \- Central auditory defect by brainstem auditory-evoked response (BAER) \- Seizures \- White matter disease seen on CT \- Decreased nerve conduction velocities METABOLIC FEATURES \- Recurrent fever ENDOCRINE FEATURES \- Adrenal insufficiency (in 1 patient) LABORATORY ABNORMALITIES \- Elevated spinal fluid protein \- Elevated very long chain fatty acids (VLCFAs) in serum and fibroblasts \- Random serum ACTH of 100 units \- Low serum albumin \- Catalase import deficiency MISCELLANEOUS \- Appropriate development until 6 months of age \- Progressive disease leading to death at age 4 \- Autosomal dominant inheritance occurs with a heterozygous mutation in PEX6 in conjunction with a 3-prime UTR polymorphism in cis causing allelic expression imbalance (AEI) MOLECULAR BASIS \- Caused by mutation in the peroxisome biogenesis factor 6 gene (PEX6, 601498.0007 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
PEROXISOME BIOGENESIS DISORDER 4B
|
c0282527
| 27,524 |
omim
|
https://www.omim.org/entry/614863
| 2019-09-22T15:53:56 |
{"mesh": ["D052919"], "omim": ["614863"], "orphanet": ["772", "44"]}
|
Intraocular medulloepithelioma is a rare eye tumor characterized by a white, gray or yellow-colored cystic mass that arises from the primitive neuroectodermal, nonpigmented epithelium of the ciliary body, or occasionally from the optic nerve, optic disc, retina or iris. Typically it has a benign clinical course with good prognosis and generally presents with childhood onset of poor vision and pain, glaucoma, and/or cataract. Leukocoria, exotropia, exophthalmos, strabismus, epiphora, change in eye color, hyphema, and raised intraocular pressure are also remarkable manifestations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Intraocular medulloepithelioma
|
c1883694
| 27,525 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268139
| 2021-01-23T18:01:28 |
{"synonyms": ["Orbital medulloepithelioma"]}
|
A rare primary bone dysplasia characterized by the association of multiple epiphyseal dysplasia with macrocephaly and dysmorphic facial features (such as frontal bossing, hypertelorism, flat malar region, low-set ears, and short neck). Patients are of normal stature and present with joint swelling and genu valgum. Additional reported manifestations include clinodactyly, spindle-shaped fingers, and pectus excavatum.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Multiple epiphyseal dysplasia, Al-Gazali type
|
c1846722
| 27,526 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166024
| 2021-01-23T17:01:53 |
{"mesh": ["C564621"], "omim": ["607131"], "umls": ["C1846722"], "icd-10": ["Q77.3"], "synonyms": ["Multiple epiphyseal dysplasia-macrocephaly-distinctive facies syndrome"]}
|
Bouffée délirante (BD) is an acute and transient psychotic disorder.[1] It is a uniquely French psychiatric diagnostic term with a long history in France[2] and various French speaking nations: Caribbean, e.g. Haiti, Guadeloupe, Antilles and Francophone Africa.[3] The term BD was originally coined and described by Valentin Magnan (1835-1916), fell into relative disuse and was later revived by Henri Ey (1900-1977).[4]
## Contents
* 1 Terminology
* 2 Description
* 3 Formal classification
* 4 Incidence
* 5 Treatment
* 6 Prognosis
* 7 Society
* 8 Summary
* 9 See also
* 10 References
## Terminology[edit]
The French word bouffée is often translated as a puff or waft (as of air), but can also mean a flash, rush or surge. Chabrol translates the word délirante as 'delusional'.[5] Other common dictionary definitions include less useful meanings such as 'crazy or incoherent'. A reasonable English translation of the term bouffée délirante is a 'delusional flash'.
## Description[edit]
Bouffée délirante is "an acute, brief nonorganic psychosis that typically presents with a sudden onset of fully formed, thematically variable delusions and hallucinations against a background of some degree of clouding of consciousness, unstable and fluctuating affect, and spontaneous recovery with some probability of relapse." [6] The following criteria have been suggested for a diagnosis of BD: a) abrupt onset, b) polymorphic delusions, emotional changes, mood swings, depersonalization, derealization and/or hallucinations, c) complete remission within weeks or a few months, d) exclusion of organic causation, alcohol or drug use, e) no psychiatric antecedents with the exception of a previous episode of bouffée délirante.[7] American academic investigators proposed the following definition in 2011: "The French concept of bouffée délirante refers to conditions with a sudden onset marked by prominent delusions with hallucinations, confusion, anxiety and affective symptoms. Symptoms vary rapidly, perhaps even by the hour, and there is a rapid return to the premorbid state of health." [8] A frequently quoted authority on BD, P. Pichot (Hôpital Sainte Anne, Paris) provides this description of BD:
1. sudden onset: 'a bolt from the blue'
2. manifold delusions without recognizable structure and cohesiveness with/without hallucinations
3. clouding of consciousness associated with emotional instability
4. absence of physical signs.
5. rapid return to pre-morbid level of functioning.[9]
Pichot's criteria can be refined further with these typical clinical characteristics:
* age: usually between 20 and 40 years of age
* onset: acute without prior mental illness (with the exception of previous episodes of bouffée délirante)
* past history: no chronic mental disturbance after resolution of the BD episode.
* typical symptoms: delusions and/or hallucinations of any type. Depersonalization/derealization and/or confusion
* depression and/or elation
* symptoms quite variable from day to day and even hour to hour.
* not due to alcohol, drug use, or organic mental disorder.[10]
## Formal classification[edit]
In 1968 the French national organization INSERM (Institut National de la Santé et de la Recherche Médicale) classification of mental illness referenced two types of BD in their category 'acute delusional psychoses and confusional states' viz. reactive bouffée délirante and bouffée délirante (Magnan's type).[11] This classification scheme has been largely replaced by the two nosological systems discussed below.
The World Health Organization edition of the International Classification of Disease 10th edition:version 2019 (ICD-10, CIM-10 en français), lists BD as the subentry "Bouffée délirante without symptoms of schizophrenia or unspecified" under diagnosis code F23: Acute and Transient Psychotic Disorders subsection, F23.0: Acute polymorphic psychotic disorder without symptoms of schizophrenia. [12]It is likely that the use of the term BD in French clinical psychiatry will decline further with the proposed 2022 implementation of ICD-11 (which was released in May 2019.) In contrast to the ICD-10, the term BD does not appear anywhere in ICD-11. The closest clinical match for BD in the ICD-11 is code 6A23, 'Acute and transient psychotic disorder' which is defined as "...acute onset of psychotic symptoms that emerge without a prodrome and reach their maximal severity within two weeks. Symptoms may include delusions, hallucinations, disorganization of thought processes, perplexity or confusion, and disturbances of affect and mood. Catatonia-like psychomotor disturbances may be present. Symptoms typically change rapidly, both in nature and intensity, from day to day, or even within a single day. The duration of the episode does not exceed 3 months, and most commonly lasts from a few days to 1 month. The symptoms are not a manifestation of another health condition (e.g., a brain tumor) and are not due to the effect of a substance or medication on the central nervous system (e.g., corticosteroids), including withdrawal (e.g., alcohol withdrawal)."[13]
The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnostic category brief psychotic disorder is probably the closest analog of BD.[14] The French term BD is nowhere mentioned in DSM-5.[15]
## Incidence[edit]
The frequency of BD diagnoses in French hospitals has been declining due to the widespread acceptance of international classification systems such as the ICD-10 and DSM-5. However, the BD diagnosis has been used as recently as 2019 in Le Groupe Hospitalier Universitaire Paris psychiatrie & neurosciences (GHU Paris), Maison Blanche Bichat XVIII.[16] Older estimates of the incidence of BD in psychiatric hospitalizations ranges from 1-5%.[17][18] Psychiatric admission reviews show that 2-7% of first episode psychotic episodes are due to brief psychotic disorder; here serving as a surrogate diagnosis for BD. [19] Some authors state that the diagnostic category of BD can be eliminated because it can be fully integrated into the 'Polymorphic subgroup of Acute and Transient Psychotic Disorders' of the ICD-10.[20]
## Treatment[edit]
There are no current published guidelines in the English language psychiatric literature that discuss treatment for BD. A 2019 case of BD from GHU Paris treated the patient with largactil (chlorpromazine).[21] Assuming that BPD is an equivalent diagnosis, treatment depends on the severity of the episode. Mildly affected patients may receive supportive management and observation with additional outpatient therapy. More severe illness may require inpatient hospitalization and pharmacologic treatment with benzodiazepines and/or antipsychotic medication, for example: risperidone, though no clinical trials have examined the efficacy of therapy for BPD.[22]
## Prognosis[edit]
It is difficult to firmly establish the prognosis of first episode BD patients with respect to progression to other psychiatric illness or relapse to another psychotic episode. This is due to the fact that high quality follow-up studies of large cohorts of BD patients are unavailable in part because of the uncommon nature of the illness and non-standardization of diagnostic methods. Investigators attempting to define the prognosis in BD have used data from similar conditions, i.e. acute transient psychotic disorder (ATPD) and brief psychotic disorder (BPD). A meta-analysis involving 11,000 patients estimated the rate of recurrent psychotic episodes in ATPD and BPD patients was 51% at 30 months compared to first episode schizophrenia patients who had an 84% recurrence rate at 36 months. As suggested by the various definitions of BD discussed above, rapid recovery and return to pre-morbid level of function is expected, though quantitative data is lacking. [23]
## Society[edit]
Psychiatric illnesses comparable to the unique French BD can be seen in the cycloid psychosis of German speaking countries and the psychogenic psychosis in Scandinavia.[24] It has been argued that acute and transient psychoses are more common in African and Afro-Caribbean populations and may be attributable to socio-cultural factors. This has led to the term "culture-bound syndrome." It must be stressed that the term BD long predates any such socio-cultural, ethnic, or regional uses. The African and Caribbean nuances of the diagnosis and presentation of BD has been extensively reviewed by Henry MB Murphy.[25] Note that DSM-5 does not use the term culture-bound and the term BD is not listed in the "Glossary of Cultural Concepts of Distress" in DSM-5.
## Summary[edit]
BD is a psychotic disorder of short duration generally considered to have a relatively good prognosis. The diagnosis has undergone numerous changes and re-evaluations since its description by Magnan in 1886. Though becoming replaced by more internationally recognized terminology, BD as a diagnostic category is still in use in France and other French speaking nations.
## See also[edit]
* Brief psychotic disorder
## References[edit]
1. ^ Chabrol, Henri (2003) Chronic Hallucinatory Psychosis, Bouffée Délirante, and the Classification of Psychosis in French Psychiatry, Curr Psychiatry Rep, Jul;5(3):187-91.
2. ^ Crocq, Marc-Antoine (2015) French perspectives on psychiatric classification Dialogues Clin Neurosci.;17:51-57.
3. ^ Eynaud, Michel (2015) Histoire des représentations de la santé mentale aux Antilles. La migration des thérapeutes Dans L'information psychiatrique 2015/1 (Volume 91).
4. ^ Schioldann, Johan (2011) Classic Text No. 87 ‘Psychogenic Psychoses’ by August Wimmer (1936): Part 1, History of Psychiatry 22(3) 344– 367.
5. ^ Chabrol, op.cit.
6. ^ Jablensky, Assen (2001) Classification of Nonschizophrenic Psychotic Disorders: A Historical Perspective Current Psychiatry Reports 2001, 3:326–331.
7. ^ Castagnini, Augusto & Gian Maria Galeazzi (2016) Acute and transient psychoses: clinical and nosological issues BJPsych Advances, vol. 22, 292–300.
8. ^ Nugent, Katie et al., (2011) Non-affective acute psychoses: Uncertainties on the way to DSM-V and ICD-11 Curr Psychiatry Rep.June ; 13(3): 203–210.
9. ^ Pichot, P (1986) The Concept of 'Bouffée délirnate' with Special Reference to the Scandinavian Concept of Reactive Psychosis. Psychopathology 19, 35-43.
10. ^ Pillmann, Frank et al., (2003) Bouffée délirante and ICD-10 acute and transient psychoses: a comparative study, Australian and New Zealand Journal of Psychiatry, 37:327–333.
11. ^ Garrabé, Jean (2013) « La Classification française des troubles mentaux et la Classification internationale des maladies : historique comparatif », L'information psychiatrique, 2013/4 (Volume 89), p. 319-326. DOI : 10.3917/inpsy.8904.0319. URL : https://www.cairn.info/revue-l-information-psychiatrique-2013-4-page-319.htm
12. ^ International Edition ICD-10 (2019) URL : https://icd.who.int/browse10/2019/en#/F23.1
13. ^ https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f284410555
14. ^ Castagnini, op.cit.
15. ^ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders. (5th Edition). Washington, DC.
16. ^ Chafaï MD, Sofiane, Attending Psychiatrist (2019), Lettre de liaison (personal correspondence 07/17/2019), GHU Paris, Site Bichat, Maison Blanche.
17. ^ Marneros, Andreas and Pillmann, Frank (2004) Acute and Transient Psychoses, Cambridge: Cambridge University Press
18. ^ Pillmann (2003)op.cit.
19. ^ Castagnini, Augusto & Gian Maria Galeazzi (2016) Acute and transient psychoses: clinical and nosological issues BJPsych Advances, vol. 22, 292–300
20. ^ Marneros, op.cit.
21. ^ Chafaï, op.cit.
22. ^ Mojtabai, Ramin (2018) Brief psychotic disorder, UpToDate, http://www.uptodate.com (accessed 03/24/20)
23. ^ Fusar-Poli, P.,et al. (2016) Prognosis of Brief Psychotic Episodes: A Meta-analysis. JAMA Psychiatry, 73(3), 211-220
24. ^ Nugent,op.cit.
25. ^ Murphy, Henry BM, (1982) Comparative Psychiatry, The International and Intercultural Distribution of Mental Illness. Berlin:Springer Verlag
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Bouffée délirante
|
c1318017
| 27,527 |
wikipedia
|
https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante
| 2021-01-18T18:48:22 |
{"umls": ["C1318017"], "icd-10": ["F23.0", "F23.1"], "wikidata": ["Q4949373"]}
|
A rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by onset of slowly progressive proximal lower limb weakness and exercise intolerance in the first decade of life, followed by weakness of neck flexor, shoulder, and distal leg muscles. Facial muscles become involved still later in the disease course. Additional manifestations are restrictive pulmonary function and short stature. Laboratory studies reveal lactic acidemia and increased serum creatine kinase.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Autosomal dominant mitochondrial myopathy with exercise intolerance
|
c4015513
| 27,528 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=457050
| 2021-01-23T17:05:25 |
{"omim": ["616209"], "icd-10": ["G71.3"]}
|
Hypotonic-hyporesponsive episode (HHE)
SymptomsHypotonia, hyporesponsiveness, pallor, cyanosis.[1][2]
Usual onset1 minute to 48 hours post-vaccination.[1]
Duration1 minute to 14 days (median 10 hours).[1]
CausesVaccination, most commonly pertussis vaccine.[1]
Diagnostic methodBased on symptoms.[1][3]
Differential diagnosisVasovagal syncope, seizure
PreventionThose who experience an HHE after pertussis vaccination may avoid further pertussis vaccines.[1][4]
TreatmentUsually resolves on its own, management involves checking the airway, breathing, and circulation, and hospitalization for observation and to rule out other conditions.[5][1][6]
DeathsNone reported
A hypotonic-hyporesponsive episode (HHE) is defined as sudden onset of poor muscle tone, reduced consciousness, and pale or bluish skin occurring within 48 hours after vaccination, most commonly pertussis vaccination.[2] An HHE is estimated to occur after 1 in 4,762 to 1 in 1,408 doses of whole cell pertussis vaccine, and after 1 in 14,286 to 1 in 2,778 doses of acellular pertussis vaccine.[3]
## References[edit]
1. ^ a b c d e f g "Hypotonic, hyporesponsive episode (HHE)" (PDF). 7 January 2006. Retrieved 2018-01-24.
2. ^ a b "Hypotonic–Hyporesponsive Episodes Reported to the Vaccine Adverse Event Reporting System (VAERS), 1996–1998 | ELECTRONIC ARTICLE". Pediatrics. Retrieved 2018-01-22.
3. ^ a b "Hypotonic-hyporesponsive episode (HHE) as an adverse event following immunization in early childhood: Case definition and guidelines for data collection, analysis, and presentation | Jan Bonhoeffer". Academia.edu. Retrieved 2018-02-01.
4. ^ "Pinkbook | Pertussis | Epidemiology of Vaccine Preventable Diseases". CDC. Retrieved 2018-01-24.
5. ^ http://www.medsafe.govt.nz/profs/puarticles/8.htm
6. ^ "Hypotonic–Hyporesponsive Episodes Reported to the Vaccine Adverse Event Reporting System (VAERS), 1996–1998 | ELECTRONIC ARTICLE". Pediatrics. Retrieved 2018-01-24.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Hypotonic-hyporesponsive episode
|
c0549384
| 27,529 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypotonic-hyporesponsive_episode
| 2021-01-18T18:53:40 |
{"wikidata": ["Q48989748"]}
|
"VVF" redirects here. For the health and nutrition charity, see The Vegetarian and Vegan Foundation.
Vesicovaginal fistula
SpecialtyUrology
Vesicovaginal fistula (VVF) is a subtype of female urogenital fistula (UGF).
## Contents
* 1 Presentation
* 2 Causes
* 3 Treatment
* 3.1 Possible complications of surgical treatment
* 4 History
* 5 See also
* 6 References
* 7 External links
## Presentation[edit]
Vesicovaginal fistula, or VVF, is an abnormal fistulous tract extending between the bladder (vesica) and the vagina that allows the continuous involuntary discharge of urine into the vaginal vault.[citation needed]
In addition to the medical sequela from these fistulas, they often have a profound effect on the patient's emotional well-being.[citation needed]
## Causes[edit]
It may be the result of a congenital birth condition such as VATER or VACTERL. It is often caused by childbirth (in which case it is known as an obstetric fistula), when a prolonged labor presses the unborn child tightly against the pelvis, cutting off blood flow to the vesicovaginal wall. The affected tissue may necrotize (die), leaving a hole.[citation needed]
Vaginal fistulas can also result from particularly violent cases of rape, especially those involving multiple rapists and/or foreign objects. Some health centers in countries such as the Democratic Republic of Congo have begun to specialize in the surgical repair of vaginal fistulas.[1][2]It can also be associated with hysterectomy,[3] cancer operations, radiation therapy and cone biopsy.
## Treatment[edit]
Vesicovaginal fistulae are typically repaired either transvaginally or laparoscopically, although patients who have had multiple transvaginal procedures sometimes attempt a final repair through a large abdominal incision, or laparotomy.[citation needed]
The laparoscopic (minimally invasive) approach to VVF repair has become more prevalent due to its greater visualization, higher success rate, and lower rate of complications.[4]
### Possible complications of surgical treatment[edit]
* Recurrent formation of the fistula[5]
* Injury to ureter, bowel, or intestines
* Vaginal shortening
## History[edit]
Before the 19th century, women who suffered from VVF were judged harshly and rejected by society. Throughout the 19th century, treatment for VVF was limited because the practice of gynecology was perceived as taboo. Doctors were almost entirely male at this time and looking at a nude female, even for medical purposes, was seen as divergent from 19th-century values.[6]
One of the most famous gynecological surgeons of this time was Dr. J. Marion Sims, who developed a successful technique for treating VVF in the mid-1800s, for which he is hailed as a pioneer of gynecology.[7]
Black enslaved women in the American South were particularly prone to VVF because they were denied proper nutrients and medical care. Sims performed on these women without anesthesia, which had not been introduced until after he started his experiments, and which in its infancy Dr. Sims hesitated to use.[7] (Ether anesthesia was publicly demonstrated in Boston in 1846, a year after Sims began his experimentation.) Sims did not have a white female patient until he made ether available to them, although he publicly noted that he never resorted to using anesthetics because he believed that the pain did not justify the risks.[7] A detailed case study of Dr. Sims even discusses the case of a white woman who underwent three operations, all without anesthesia.[7] It was considered acceptable to operate on them without anesthetic because, Sims claimed, African-American women have a naturally higher pain tolerance.[8]
The healing process of the VVF procedure is still arduous. To have a successful recovery from the surgery, it must be successful on the first attempt. [9] Dr. J. Marion Sims' operations on African-American enslaved women showcase the dangerous nature of the procedure. [10] There still have not been clear instructions on how to properly recover from the procedure other than taking prescribed antibiotics.[11]
## See also[edit]
* Colposcopy
* Double dye test
* Rectovaginal fistula
* Urinary incontinence
## References[edit]
1. ^ Bhatia J (8 January 2010). "Rape epidemic fuels fistula cases in the Democratic Republic of Congo". Conversations for a Better World. Archived from the original on 28 August 2010.
2. ^ Nordland R (12 November 2006). "Congo: More Vicious Than Rape". Newsweek.
3. ^ Kochakarn W, Pummangura W (October 2007). "A new dimension in vesicovaginal fistula management: an 8-year experience at Ramathibodi hospital". Asian Journal of Surgery. 30 (4): 267–71. doi:10.1016/S1015-9584(08)60037-8. PMID 17962130.[permanent dead link]
4. ^ Miklos JR (20 October 2010). "Fistula Repair Overview". Bladder - Vaginal Fistula Surgeons. Retrieved 11 September 2013.
5. ^ Miklos JR, Sobolewski C, Lucente V (1999). "Laparoscopic management of recurrent vesicovaginal fistula" (PDF). International Urogynecology Journal and Pelvic Floor Dysfunction. 10 (2): 116–7. doi:10.1007/s001920050029. PMID 10384974. S2CID 21633111. Archived from the original (PDF) on 6 August 2013.
6. ^ Ojanuga D (March 1993). "The medical ethics of the 'father of gynaecology', Dr J Marion Sims". Journal of Medical Ethics. 19 (1): 28–31. doi:10.1136/jme.19.1.28. PMC 1376165. PMID 8459435.
7. ^ a b c d Wall LL (June 2006). "The medical ethics of Dr J. Marion Sims: a fresh look at the historical record". Journal of Medical Ethics. 32 (6): 346–50. doi:10.1136/jme.2005.012559. PMC 2563360. PMID 16731734.
8. ^ Spettel S, White MD (June 2011). "The portrayal of J. Marion Sims' controversial surgical legacy". The Journal of Urology. 185 (6): 2424–7. doi:10.1016/j.juro.2011.01.077. PMID 21511295.
9. ^ Stamatakos, M., Sargedi, C., Stasinou, T., & Kontzoglou, K. (2014). Vesicovaginal Fistula: Diagnosis and Management. The Indian Journal of Surgery, 76(2), 131–136. http://doi.org/10.1007/s12262-012-0787-y
10. ^ Wall, L. L. (2006). The medical ethics of Dr J Marion Sims: a fresh look at the historical record. Journal of Medical Ethics, 32(6), 346–350. http://doi.org/10.1136/jme.2005.012559
11. ^ Stamatakos, M., Sargedi, C., Stasinou, T., & Kontzoglou, K. (2014). Vesicovaginal Fistula: Diagnosis and Management. The Indian Journal of Surgery, 76(2), 131–136. http://doi.org/10.1007/s12262-012-0787-y
## External links[edit]
Classification
D
* ICD-10: N82.0
* ICD-9-CM: 619.0
* MeSH: D014719
* DiseasesDB: 13837
External resources
* eMedicine: med/3321
* v
* t
* e
Female diseases of the pelvis and genitals
Internal
Adnexa
Ovary
* Endometriosis of ovary
* Female infertility
* Anovulation
* Poor ovarian reserve
* Mittelschmerz
* Oophoritis
* Ovarian apoplexy
* Ovarian cyst
* Corpus luteum cyst
* Follicular cyst of ovary
* Theca lutein cyst
* Ovarian hyperstimulation syndrome
* Ovarian torsion
Fallopian tube
* Female infertility
* Fallopian tube obstruction
* Hematosalpinx
* Hydrosalpinx
* Salpingitis
Uterus
Endometrium
* Asherman's syndrome
* Dysfunctional uterine bleeding
* Endometrial hyperplasia
* Endometrial polyp
* Endometriosis
* Endometritis
Menstruation
* Flow
* Amenorrhoea
* Hypomenorrhea
* Oligomenorrhea
* Pain
* Dysmenorrhea
* PMS
* Timing
* Menometrorrhagia
* Menorrhagia
* Metrorrhagia
* Female infertility
* Recurrent miscarriage
Myometrium
* Adenomyosis
Parametrium
* Parametritis
Cervix
* Cervical dysplasia
* Cervical incompetence
* Cervical polyp
* Cervicitis
* Female infertility
* Cervical stenosis
* Nabothian cyst
General
* Hematometra / Pyometra
* Retroverted uterus
Vagina
* Hematocolpos / Hydrocolpos
* Leukorrhea / Vaginal discharge
* Vaginitis
* Atrophic vaginitis
* Bacterial vaginosis
* Candidal vulvovaginitis
* Hydrocolpos
Sexual dysfunction
* Dyspareunia
* Hypoactive sexual desire disorder
* Sexual arousal disorder
* Vaginismus
* Urogenital fistulas
* Ureterovaginal
* Vesicovaginal
* Obstetric fistula
* Rectovaginal fistula
* Prolapse
* Cystocele
* Enterocele
* Rectocele
* Sigmoidocele
* Urethrocele
* Vaginal bleeding
* Postcoital bleeding
Other / general
* Pelvic congestion syndrome
* Pelvic inflammatory disease
External
Vulva
* Bartholin's cyst
* Kraurosis vulvae
* Vestibular papillomatosis
* Vulvitis
* Vulvodynia
Clitoral hood or clitoris
* Persistent genital arousal disorder
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Vesicovaginal fistula
|
c0042582
| 27,530 |
wikipedia
|
https://en.wikipedia.org/wiki/Vesicovaginal_fistula
| 2021-01-18T18:30:51 |
{"mesh": ["D014719"], "umls": ["C0042582"], "icd-9": ["619.0"], "icd-10": ["N82.0"], "wikidata": ["Q3702211"]}
|
Eyebrow duplication-syndactyly syndrome is characterised by partial duplication of the eyebrows and syndactyly of the fingers and toes. It has been described in three patients (a brother and sister and an isolated case). Skin hyperelasticity, hypertrichosis and long eyelashes, and abnormal periorbital wrinkling were also reported in some of the patients. Transmission is autosomal recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Eyebrow duplication-syndactyly syndrome
|
c1856896
| 27,531 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3172
| 2021-01-23T18:28:10 |
{"gard": ["2216"], "mesh": ["C536383"], "omim": ["227210"], "umls": ["C1856896"]}
|
Enterotoxigenic Escherichia coli
SpecialtyInfectious disease
Enterotoxigenic Escherichia coli (ETEC) is a type of Escherichia coli and one of the leading bacterial causes of diarrhea in the developing world,[1] as well as the most common cause of travelers' diarrhea.[2] Insufficient data exist, but conservative estimates suggest that each year, about 157,000 deaths occur, mostly in children, from ETEC.[3][4][5] A number of pathogenic isolates are termed ETEC, but the main hallmarks of this type of bacteria are expression of one or more enterotoxins and presence of fimbriae used for attachment to host intestinal cells. The bacteria was identified by the Bradley Sack lab in Kolkata in 1968.
## Contents
* 1 Signs and symptoms
* 2 Enterotoxins
* 3 Prevention and treatment
* 4 See also
* 5 References
* 6 External links
## Signs and symptoms[edit]
Infection with ETEC can cause profuse, watery diarrhea with no blood or leukocytes and abdominal cramping. Fever, nausea with or without vomiting, chills, loss of appetite, headache, muscle aches and bloating can also occur, but are less common.[2]
## Enterotoxins[edit]
Enterotoxins produced by ETEC include heat-labile enterotoxin (LT) and heat-stable enterotoxin (ST).[6]
## Prevention and treatment[edit]
To date, no licensed vaccines specifically target ETEC, though several are in various stages of development.[1][7] Studies indicate that protective immunity to ETEC develops after natural or experimental infection, suggesting that vaccine-induced ETEC immunity should be feasible and could be an effective preventive strategy.[1][8] Prevention through vaccination is a critical part of the strategy to reduce the incidence and severity of diarrheal disease due to ETEC, particularly among children in low-resource settings. The development of a vaccine against this infection has been hampered by technical constraints, insufficient support for coordination, and a lack of market forces for research and development. Most vaccine development efforts are taking place in the public sector or as research programs within biotechnology companies.[9] ETEC is a longstanding priority and target for vaccine development for the World Health Organization.
Treatment for ETEC infection includes rehydration therapy and antibiotics, although ETEC is frequently resistant to common antibiotics.[2] Improved sanitation is also key. Since the transmission of this bacterium is fecal contamination of food and water supplies, one way to prevent infection is by improving public and private health facilities. Another simple prevention of infection is by drinking factory bottled water—this is especially important for travelers and traveling military—though it may not be feasible in developing countries, which carry the greatest disease burden.
## See also[edit]
* Gastroenteritis
## References[edit]
1. ^ a b c Bourgeois, A Louis; Wierzba, Thomas F; Walker, Richard I (2016). "Status of vaccine research and development for enterotoxigenic Escherichia coli". Vaccine. 34 (26): 2880–2886. doi:10.1016/j.vaccine.2016.02.076. PMID 26988259.
2. ^ a b c US Centers for Disease Control and Prevention (2014). "Enterotoxigenic E. coli (ETEC)".
3. ^ Lozano, Rafael; Naghavi, Mohsen; Foreman, Kyle; et al. (2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". The Lancet. 380 (9859): 2095–2128. doi:10.1016/S0140-6736(12)61728-0. hdl:10536/DRO/DU:30050819. PMID 23245604.
4. ^ Gupta, SK; Keck J; Ram PK; et al. (2008). "Analysis of Data Gaps Pertaining to Enterotoxigenic Escherichia coli Infections in Low and Medium Human Development Index Countries, 1984-2005". Epidemiology and Infection. 136 (6): 721–738. doi:10.1017/S095026880700934X. PMC 2870873. PMID 17686197.
5. ^ Kotloff, Karen L; Nataro, James P; Blackwelder, William C; et al. (2013). "Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study". The Lancet. 382 (9888): 209–222. doi:10.1016/s0140-6736(13)60844-2. PMID 23680352.
6. ^ Qadri, F.; Svennerholm, A. M.; Faruque, A. S. G.; Bradley Sack, R. (2005). "Enterotoxigenic Escherichia coli in Developing Countries: Epidemiology, Microbiology, Clinical Features, Treatment, and Prevention". Clinical Microbiology Reviews. 18 (3): 465–483. doi:10.1128/CMR.18.3.465-483.2005. PMC 1195967. PMID 16020685.
7. ^ "WHO vaccine pipeline tracker". World Health Organization. Retrieved 2016-07-21.
8. ^ Girard, M.; Steele, D.; Chaignat, C. L.; Kieny, M. P. (2006). "A review of vaccine research and development: human enteric infections". Vaccine. 24 (15): 2732–2750. doi:10.1016/j.vaccine.2005.10.014. PMID 16483695.
9. ^ PATH, bvgh (March 2011). "The Case for Investment in Enterotoxigenic Escherichia coli Vaccines" (PDF). Retrieved 2 May 2012. Cite journal requires `|journal=` (help)
## External links[edit]
Classification
D
* ICD-10: A04.1
* ICD-9-CM: 008.02
* MeSH: D054307
* US Centers for Disease Control and Prevention: Enterotoxigenic Escherichia coli
* Vaccine Resource Library: Shigellosis and enterotoxigenic Escherichia coli (ETEC)
* v
* t
* e
Escherichia coli
Outbreaks
* 1993 Jack in the Box
* 1996 Odwalla
* 2000 Walkerton
* 2005 South Wales (O157)
* 2006 North American (spinach; O157:H7)
* 2006 North American (multiple; O157:H7)
* 2009 United Kingdom
* 2011 Germany (O104:H4)
* 2015 United States
Genes
* CPS operon
* DnaG
* Fis
* FNR regulon
* OmpT
* RecBCD
* RpoE
* RpoF
* RpoN
* RpoS
Strains
* Enterohemorrhagic
* Enteroinvasive
* Enterotoxigenic
* O104:H21
* O104:H4
* O121
* O157:H7
* Verotoxin-producing
Related
* Aerobactin
* Coliform index
* Long-term evolution experiment
* EcoCyc
* Enteroaggregative
* Molecular biology
* Hok/sok system
* LacUV5
* Min System
* Pathogenic
* EnvZ/OmpR
* Rho factor
* T4 rII system
* Theodor Escherich
* v
* t
* e
Proteobacteria-associated Gram-negative bacterial infections
α
Rickettsiales
Rickettsiaceae/
(Rickettsioses)
Typhus
* Rickettsia typhi
* Murine typhus
* Rickettsia prowazekii
* Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus
Spotted
fever
Tick-borne
* Rickettsia rickettsii
* Rocky Mountain spotted fever
* Rickettsia conorii
* Boutonneuse fever
* Rickettsia japonica
* Japanese spotted fever
* Rickettsia sibirica
* North Asian tick typhus
* Rickettsia australis
* Queensland tick typhus
* Rickettsia honei
* Flinders Island spotted fever
* Rickettsia africae
* African tick bite fever
* Rickettsia parkeri
* American tick bite fever
* Rickettsia aeschlimannii
* Rickettsia aeschlimannii infection
Mite-borne
* Rickettsia akari
* Rickettsialpox
* Orientia tsutsugamushi
* Scrub typhus
Flea-borne
* Rickettsia felis
* Flea-borne spotted fever
Anaplasmataceae
* Ehrlichiosis: Anaplasma phagocytophilum
* Human granulocytic anaplasmosis, Anaplasmosis
* Ehrlichia chaffeensis
* Human monocytotropic ehrlichiosis
* Ehrlichia ewingii
* Ehrlichiosis ewingii infection
Rhizobiales
Brucellaceae
* Brucella abortus
* Brucellosis
Bartonellaceae
* Bartonellosis: Bartonella henselae
* Cat-scratch disease
* Bartonella quintana
* Trench fever
* Either B. henselae or B. quintana
* Bacillary angiomatosis
* Bartonella bacilliformis
* Carrion's disease, Verruga peruana
β
Neisseriales
M+
* Neisseria meningitidis/meningococcus
* Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia
M−
* Neisseria gonorrhoeae/gonococcus
* Gonorrhea
ungrouped:
* Eikenella corrodens/Kingella kingae
* HACEK
* Chromobacterium violaceum
* Chromobacteriosis infection
Burkholderiales
* Burkholderia pseudomallei
* Melioidosis
* Burkholderia mallei
* Glanders
* Burkholderia cepacia complex
* Bordetella pertussis/Bordetella parapertussis
* Pertussis
γ
Enterobacteriales
(OX−)
Lac+
* Klebsiella pneumoniae
* Rhinoscleroma, Pneumonia
* Klebsiella granulomatis
* Granuloma inguinale
* Klebsiella oxytoca
* Escherichia coli: Enterotoxigenic
* Enteroinvasive
* Enterohemorrhagic
* O157:H7
* O104:H4
* Hemolytic-uremic syndrome
* Enterobacter aerogenes/Enterobacter cloacae
Slow/weak
* Serratia marcescens
* Serratia infection
* Citrobacter koseri/Citrobacter freundii
Lac−
H2S+
* Salmonella enterica
* Typhoid fever, Paratyphoid fever, Salmonellosis
H2S−
* Shigella dysenteriae/sonnei/flexneri/boydii
* Shigellosis, Bacillary dysentery
* Proteus mirabilis/Proteus vulgaris
* Yersinia pestis
* Plague/Bubonic plague
* Yersinia enterocolitica
* Yersiniosis
* Yersinia pseudotuberculosis
* Far East scarlet-like fever
Pasteurellales
Haemophilus:
* H. influenzae
* Haemophilus meningitis
* Brazilian purpuric fever
* H. ducreyi
* Chancroid
* H. parainfluenzae
* HACEK
Pasteurella multocida
* Pasteurellosis
* Actinobacillus
* Actinobacillosis
Aggregatibacter actinomycetemcomitans
* HACEK
Legionellales
* Legionella pneumophila/Legionella longbeachae
* Legionnaires' disease
* Coxiella burnetii
* Q fever
Thiotrichales
* Francisella tularensis
* Tularemia
Vibrionaceae
* Vibrio cholerae
* Cholera
* Vibrio vulnificus
* Vibrio parahaemolyticus
* Vibrio alginolyticus
* Plesiomonas shigelloides
Pseudomonadales
* Pseudomonas aeruginosa
* Pseudomonas infection
* Moraxella catarrhalis
* Acinetobacter baumannii
Xanthomonadaceae
* Stenotrophomonas maltophilia
Cardiobacteriaceae
* Cardiobacterium hominis
* HACEK
Aeromonadales
* Aeromonas hydrophila/Aeromonas veronii
* Aeromonas infection
ε
Campylobacterales
* Campylobacter jejuni
* Campylobacteriosis, Guillain–Barré syndrome
* Helicobacter pylori
* Peptic ulcer, MALT lymphoma, Gastric cancer
* Helicobacter cinaedi
* Helicobacter cellulitis
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
* Barrett's esophagus
* Esophageal motility disorder
* Nutcracker esophagus
* Achalasia
* Diffuse esophageal spasm
* Gastroesophageal reflux disease (GERD)
* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
* Atrophic
* Ménétrier's disease
* Gastroenteritis
* Peptic (gastric) ulcer
* Cushing ulcer
* Dieulafoy's lesion
* Dyspepsia
* Pyloric stenosis
* Achlorhydria
* Gastroparesis
* Gastroptosis
* Portal hypertensive gastropathy
* Gastric antral vascular ectasia
* Gastric dumping syndrome
* Gastric volvulus
* Buried bumper syndrome
* Gastrinoma
* Zollinger–Ellison syndrome
Lower GI tract
Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
* Enteritis
* Duodenitis
* Jejunitis
* Ileitis
* Peptic (duodenal) ulcer
* Curling's ulcer
* Malabsorption: Coeliac
* Tropical sprue
* Blind loop syndrome
* Small bowel bacterial overgrowth syndrome
* Whipple's
* Short bowel syndrome
* Steatorrhea
* Milroy disease
* Bile acid malabsorption
Large intestine
(Appendix/Colon)
* Appendicitis
* Colitis
* Pseudomembranous
* Ulcerative
* Ischemic
* Microscopic
* Collagenous
* Lymphocytic
* Functional colonic disease
* IBS
* Intestinal pseudoobstruction / Ogilvie syndrome
* Megacolon / Toxic megacolon
* Diverticulitis/Diverticulosis/SCAD
Large and/or small
* Enterocolitis
* Necrotizing
* Gastroenterocolitis
* IBD
* Crohn's disease
* Vascular: Abdominal angina
* Mesenteric ischemia
* Angiodysplasia
* Bowel obstruction: Ileus
* Intussusception
* Volvulus
* Fecal impaction
* Constipation
* Diarrhea
* Infectious
* Intestinal adhesions
Rectum
* Proctitis
* Radiation proctitis
* Proctalgia fugax
* Rectal prolapse
* Anismus
Anal canal
* Anal fissure/Anal fistula
* Anal abscess
* Hemorrhoid
* Anal dysplasia
* Pruritus ani
GI bleeding
* Blood in stool
* Upper
* Hematemesis
* Melena
* Lower
* Hematochezia
Accessory
Liver
* Hepatitis
* Viral hepatitis
* Autoimmune hepatitis
* Alcoholic hepatitis
* Cirrhosis
* PBC
* Fatty liver
* NASH
* Vascular
* Budd–Chiari syndrome
* Hepatic veno-occlusive disease
* Portal hypertension
* Nutmeg liver
* Alcoholic liver disease
* Liver failure
* Hepatic encephalopathy
* Acute liver failure
* Liver abscess
* Pyogenic
* Amoebic
* Hepatorenal syndrome
* Peliosis hepatis
* Metabolic disorders
* Wilson's disease
* Hemochromatosis
Gallbladder
* Cholecystitis
* Gallstone / Cholelithiasis
* Cholesterolosis
* Adenomyomatosis
* Postcholecystectomy syndrome
* Porcelain gallbladder
Bile duct/
Other biliary tree
* Cholangitis
* Primary sclerosing cholangitis
* Secondary sclerosing cholangitis
* Ascending
* Cholestasis/Mirizzi's syndrome
* Biliary fistula
* Haemobilia
* Common bile duct
* Choledocholithiasis
* Biliary dyskinesia
* Sphincter of Oddi dysfunction
Pancreatic
* Pancreatitis
* Acute
* Chronic
* Hereditary
* Pancreatic abscess
* Pancreatic pseudocyst
* Exocrine pancreatic insufficiency
* Pancreatic fistula
Other
Hernia
* Diaphragmatic
* Congenital
* Hiatus
* Inguinal
* Indirect
* Direct
* Umbilical
* Femoral
* Obturator
* Spigelian
* Lumbar
* Petit's
* Grynfeltt-Lesshaft
* Undefined location
* Incisional
* Internal hernia
* Richter's
Peritoneal
* Peritonitis
* Spontaneous bacterial peritonitis
* Hemoperitoneum
* Pneumoperitoneum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Enterotoxigenic Escherichia coli
|
None
| 27,532 |
wikipedia
|
https://en.wikipedia.org/wiki/Enterotoxigenic_Escherichia_coli
| 2021-01-18T18:31:00 |
{"mesh": ["D054307"], "icd-9": ["008.02"], "icd-10": ["A04.1"], "wikidata": ["Q265214"]}
|
Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency is a rare, genetic, primary immunodeficiency disorder characterized by recurrent bacterial infections (including septic thrombophlebitis and subacute bacterial endocarditis) and neutropenia without lymphopenia or warts, resulting from recessively inherited mutations in CXCR2.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency
|
None
| 27,533 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=420699
| 2021-01-23T16:58:53 |
{"icd-10": ["D70"]}
|
Neuro-cardio-facial-cutaneous-syndromes (NCFC), (also referred to as neuro-craniofacial-cardiac syndromes) is a group of developmental disorders with a genetic ground, affecting the nervous system, circulatory system, (cranio)facial and cutaneous development. These four parts are the common denominator for the syndromes, but are mostly accompanied by disturbances in other parts of the body.
The two most common syndromes under this "umbrella" are: Leopard syndrome (LS) and Noonan syndrome (NS).
Other members are Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC) and Neurofibromatosis type I (NF1). Recently, it has been observed that NCFC syndromes result from de novo germline mutations that alter the Ras/Raf/Mek signal transduction pathway.[1] These are called RASopathies.
1 percent of autistic children have either a loss or duplication in a region of Chromosome 16 that encompasses the gene for ERK 1. Mutations within the ERK signal transduction pathway appears to be a common cause for NCFC syndromes. Some autistic children also have craniofacial and cardiac defects.[2]
## See also[edit]
* SPRED1 gene
* Legius syndrome
## References[edit]
1. ^ http://www.jci.org/articles/view/34385
2. ^ https://www.sciencedaily.com/releases/2009/02/090209094403.htm
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Neuro-cardio-facial-cutaneous syndromes
|
None
| 27,534 |
wikipedia
|
https://en.wikipedia.org/wiki/Neuro-cardio-facial-cutaneous_syndromes
| 2021-01-18T18:33:21 |
{"wikidata": ["Q17074582"]}
|
Inflammation of the aorta
Syphilitic aortitis
Other namesSA
Aneurysm,a common complication of SA
SpecialtyCardiology, Infectious disease
SymptomsOften none
ComplicationsAneurysm
Usual onset40-55 years old, (initial infection is generally earlier in life)[1]
CausesTreponema pallidum
Risk factorsUnprotected sex, HIV, Drug use[2]
PreventionCondoms,avoinding drug use
Syphilitic aortitis is inflammation of the aorta associated with the tertiary stage of syphilis infection. SA begins as inflammation of the outermost layer of the blood vessel, including the blood vessels that supply the aorta itself with blood, the vasa vasorum.[3] As SA worsens, the vasa vasorum undergo hyperplastic thickening of their walls thereby restricting blood flow and causing ischemia of the outer two-thirds of the aortic wall. Starved for oxygen and nutrients, elastic fibers become patchy and smooth muscle cells die. If the disease progresses, syphilitic aortitis leads to an aortic aneurysm. Overall, tertiary syphilis is a rare cause of aortic aneurysms.[3] Syphilitic aortitis has become rare in the developed world with the advent of penicillin treatments after World War II.[citation needed]
## Contents
* 1 Signs and symptoms
* 2 Pathogenesis
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
The infection often has no symptoms until the patient develops an aneurysm because of the aortic dilatation.The disease is often discovered after a routine checkup of the heart and aorta. Although is easy to be overlooked, other symptoms of tertiary syphilis might appear such as gummas and symptoms of neurosyphilis (headache, stiff neck, gait abnormality, dementia etc). Additionally, in rare cases, chest pain and shortness of breath might appear as a result of the damage of the aorta and heart valve.[citation needed]
## Pathogenesis[edit]
Inflammatory involvement of tertiary syphilis begins at the adventitia of the aortic arch which progressively causes obliterative endarteritis of the vasa vasorum.[3] This leads to narrowing of the lumen of the vasa vasorum, causing ischemic injury of the medial aortic arch and then finally loss of elastic support and dilation of the vessel.[3] Dissection of the aortic arch is rare due to medial scarring. As a result of this advanced disease process, normal methods of angiography/angioplasty may be impossible for those with suspected coronary artery disease.[citation needed]
## Treatment[edit]
This section is empty. You can help by adding to it. (September 2020)
## References[edit]
1. ^ "What is tertiary syphilis? (Video)".
2. ^ Paulo, Nelson; Cascarejo, José; Vouga, Luís (2012). "Syphilitic aneurysm of the ascending aorta". Interactive Cardiovascular and Thoracic Surgery. 14 (2): 223–225. doi:10.1093/icvts/ivr067. PMC 3279976. PMID 22159251.
3. ^ a b c d Stone, JR; Bruneval, P; Angelini, A; Bartoloni, G; Basso, C; et al. (September–October 2015). "Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases". Cardiovascular Pathology (Review). 24 (5): 267–78. doi:10.1016/j.carpath.2015.05.001. PMID 26051917.
## External links[edit]
Classification
D
* ICD-10-CM: A52.02
* ICD-9-CM: 093.1
* MeSH: D013589
* v
* t
* e
Proteobacteria-associated Gram-negative bacterial infections
α
Rickettsiales
Rickettsiaceae/
(Rickettsioses)
Typhus
* Rickettsia typhi
* Murine typhus
* Rickettsia prowazekii
* Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus
Spotted
fever
Tick-borne
* Rickettsia rickettsii
* Rocky Mountain spotted fever
* Rickettsia conorii
* Boutonneuse fever
* Rickettsia japonica
* Japanese spotted fever
* Rickettsia sibirica
* North Asian tick typhus
* Rickettsia australis
* Queensland tick typhus
* Rickettsia honei
* Flinders Island spotted fever
* Rickettsia africae
* African tick bite fever
* Rickettsia parkeri
* American tick bite fever
* Rickettsia aeschlimannii
* Rickettsia aeschlimannii infection
Mite-borne
* Rickettsia akari
* Rickettsialpox
* Orientia tsutsugamushi
* Scrub typhus
Flea-borne
* Rickettsia felis
* Flea-borne spotted fever
Anaplasmataceae
* Ehrlichiosis: Anaplasma phagocytophilum
* Human granulocytic anaplasmosis, Anaplasmosis
* Ehrlichia chaffeensis
* Human monocytotropic ehrlichiosis
* Ehrlichia ewingii
* Ehrlichiosis ewingii infection
Rhizobiales
Brucellaceae
* Brucella abortus
* Brucellosis
Bartonellaceae
* Bartonellosis: Bartonella henselae
* Cat-scratch disease
* Bartonella quintana
* Trench fever
* Either B. henselae or B. quintana
* Bacillary angiomatosis
* Bartonella bacilliformis
* Carrion's disease, Verruga peruana
β
Neisseriales
M+
* Neisseria meningitidis/meningococcus
* Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia
M−
* Neisseria gonorrhoeae/gonococcus
* Gonorrhea
ungrouped:
* Eikenella corrodens/Kingella kingae
* HACEK
* Chromobacterium violaceum
* Chromobacteriosis infection
Burkholderiales
* Burkholderia pseudomallei
* Melioidosis
* Burkholderia mallei
* Glanders
* Burkholderia cepacia complex
* Bordetella pertussis/Bordetella parapertussis
* Pertussis
γ
Enterobacteriales
(OX−)
Lac+
* Klebsiella pneumoniae
* Rhinoscleroma, Pneumonia
* Klebsiella granulomatis
* Granuloma inguinale
* Klebsiella oxytoca
* Escherichia coli: Enterotoxigenic
* Enteroinvasive
* Enterohemorrhagic
* O157:H7
* O104:H4
* Hemolytic-uremic syndrome
* Enterobacter aerogenes/Enterobacter cloacae
Slow/weak
* Serratia marcescens
* Serratia infection
* Citrobacter koseri/Citrobacter freundii
Lac−
H2S+
* Salmonella enterica
* Typhoid fever, Paratyphoid fever, Salmonellosis
H2S−
* Shigella dysenteriae/sonnei/flexneri/boydii
* Shigellosis, Bacillary dysentery
* Proteus mirabilis/Proteus vulgaris
* Yersinia pestis
* Plague/Bubonic plague
* Yersinia enterocolitica
* Yersiniosis
* Yersinia pseudotuberculosis
* Far East scarlet-like fever
Pasteurellales
Haemophilus:
* H. influenzae
* Haemophilus meningitis
* Brazilian purpuric fever
* H. ducreyi
* Chancroid
* H. parainfluenzae
* HACEK
Pasteurella multocida
* Pasteurellosis
* Actinobacillus
* Actinobacillosis
Aggregatibacter actinomycetemcomitans
* HACEK
Legionellales
* Legionella pneumophila/Legionella longbeachae
* Legionnaires' disease
* Coxiella burnetii
* Q fever
Thiotrichales
* Francisella tularensis
* Tularemia
Vibrionaceae
* Vibrio cholerae
* Cholera
* Vibrio vulnificus
* Vibrio parahaemolyticus
* Vibrio alginolyticus
* Plesiomonas shigelloides
Pseudomonadales
* Pseudomonas aeruginosa
* Pseudomonas infection
* Moraxella catarrhalis
* Acinetobacter baumannii
Xanthomonadaceae
* Stenotrophomonas maltophilia
Cardiobacteriaceae
* Cardiobacterium hominis
* HACEK
Aeromonadales
* Aeromonas hydrophila/Aeromonas veronii
* Aeromonas infection
ε
Campylobacterales
* Campylobacter jejuni
* Campylobacteriosis, Guillain–Barré syndrome
* Helicobacter pylori
* Peptic ulcer, MALT lymphoma, Gastric cancer
* Helicobacter cinaedi
* Helicobacter cellulitis
* v
* t
* e
Cardiovascular disease (vessels)
Arteries, arterioles
and capillaries
Inflammation
* Arteritis
* Aortitis
* Buerger's disease
Peripheral artery disease
Arteriosclerosis
* Atherosclerosis
* Foam cell
* Fatty streak
* Atheroma
* Intermittent claudication
* Critical limb ischemia
* Monckeberg's arteriosclerosis
* Arteriolosclerosis
* Hyaline
* Hyperplastic
* Cholesterol
* LDL
* Oxycholesterol
* Trans fat
Stenosis
* Carotid artery stenosis
* Renal artery stenosis
Other
* Aortoiliac occlusive disease
* Degos disease
* Erythromelalgia
* Fibromuscular dysplasia
* Raynaud's phenomenon
Aneurysm / dissection /
pseudoaneurysm
* torso: Aortic aneurysm
* Abdominal aortic aneurysm
* Thoracic aortic aneurysm
* Aneurysm of sinus of Valsalva
* Aortic dissection
* Aortic rupture
* Coronary artery aneurysm
* head / neck
* Intracranial aneurysm
* Intracranial berry aneurysm
* Carotid artery dissection
* Vertebral artery dissection
* Familial aortic dissection
Vascular malformation
* Arteriovenous fistula
* Arteriovenous malformation
* Telangiectasia
* Hereditary hemorrhagic telangiectasia
Vascular nevus
* Cherry hemangioma
* Halo nevus
* Spider angioma
Veins
Inflammation
* Phlebitis
Venous thrombosis /
Thrombophlebitis
* primarily lower limb
* Deep vein thrombosis
* abdomen
* Hepatic veno-occlusive disease
* Budd–Chiari syndrome
* May–Thurner syndrome
* Portal vein thrombosis
* Renal vein thrombosis
* upper limb / torso
* Mondor's disease
* Paget–Schroetter disease
* head
* Cerebral venous sinus thrombosis
* Post-thrombotic syndrome
Varicose veins
* Gastric varices
* Portacaval anastomosis
* Caput medusae
* Esophageal varices
* Hemorrhoid
* Varicocele
Other
* Chronic venous insufficiency
* Chronic cerebrospinal venous insufficiency
* Superior vena cava syndrome
* Inferior vena cava syndrome
* Venous ulcer
Arteries or veins
* Angiopathy
* Macroangiopathy
* Microangiopathy
* Embolism
* Pulmonary embolism
* Cholesterol embolism
* Paradoxical embolism
* Thrombosis
* Vasculitis
Blood pressure
Hypertension
* Hypertensive heart disease
* Hypertensive emergency
* Hypertensive nephropathy
* Essential hypertension
* Secondary hypertension
* Renovascular hypertension
* Benign hypertension
* Pulmonary hypertension
* Systolic hypertension
* White coat hypertension
Hypotension
* Orthostatic hypotension
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Syphilitic aortitis
|
c0003511
| 27,535 |
wikipedia
|
https://en.wikipedia.org/wiki/Syphilitic_aortitis
| 2021-01-18T18:56:29 |
{"mesh": ["D013589"], "icd-9": ["093.1"], "wikidata": ["Q666481"]}
|
"Beri beri" redirects here. For the African ethnic group, see Kanuri people.
Thiamine deficiency[1]
Other namesBeriberi, vitamin B1 deficiency, thiamine-deficiency syndrome[1][2]
A person with beriberi during the early twentieth century in Southeast Asia
SpecialtyNeurology, cardiology, pediatrics
Symptoms
* Wet: Fast heart rate, shortness of breath, leg swelling[1]
* Dry: Numbness, confusion, trouble moving the legs, pain[1]
TypesWet, dry, gastrointestinal[3]
CausesNot enough thiamine[1]
Risk factorsDiet of mostly white rice; alcoholism, dialysis, chronic diarrhea, diuretics[1][4]
PreventionFood fortification[1]
TreatmentThiamine supplementation[1]
FrequencyRare (US)[1]
Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1).[1] A severe and chronic form is known as beriberi.[1][5] There are two main types in adults: wet beriberi, and dry beriberi.[1] Wet beriberi affects the cardiovascular system resulting in a fast heart rate, shortness of breath, and leg swelling.[1] Dry beriberi affects the nervous system resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain.[1] A form with loss of appetite and constipation may also occur.[3] Another type, acute beriberi, is found mostly in babies and presents with loss of appetite, vomiting, lactic acidosis, changes in heart rate, and enlargement of the heart.[6]
Risk factors include a diet of mostly white rice, as well as alcoholism, dialysis, chronic diarrhea, and taking high doses of diuretics.[1][4] Rarely it may be due to a genetic condition that results in difficulties absorbing thiamine found in food.[1] Wernicke encephalopathy and Korsakoff syndrome are forms of dry beriberi.[4] Diagnosis is based on symptoms, low levels of thiamine in the urine, high blood lactate, and improvement with treatment.[7]
Treatment is by thiamine supplementation, either by mouth or by injection.[1] With treatment, symptoms generally resolve in a couple of weeks.[7] The disease may be prevented at the population level through the fortification of food.[1]
Thiamine deficiency is rare in the United States.[8] It remains relatively common in sub-Saharan Africa.[2] Outbreaks have been seen in refugee camps.[4] Thiamine deficiency has been described for thousands of years in Asia and became more common in the late 1800s with the increased processing of rice.[9]
## Contents
* 1 Signs and symptoms
* 1.1 Beriberi
* 1.1.1 Dry beriberi
* 1.2 Brain disease
* 1.3 Wet beriberi
* 1.4 Gastrointestinal beriberi
* 1.5 Infants
* 2 Cause
* 2.1 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 Epidemiology
* 7 History
* 7.1 Etymology
* 8 Other animals
* 8.1 Poultry
* 8.2 Ruminants
* 8.3 Snakes
* 8.4 Wild birds and fish
* 9 References
* 9.1 Cited sources
* 10 External links
## Signs and symptoms[edit]
### Beriberi[edit]
Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high-output cardiac failure and death.
Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine-deficiency related condition.
Beriberi is divided into four categories as follows. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:
* Dry beriberi especially affects the peripheral nervous system.
* Wet beriberi especially affects the cardiovascular system and other bodily systems.
* Infantile beriberi affects the babies of malnourished mothers.
* Gastrointestinal beriberi affects the digestive system and other bodily systems.
#### Dry beriberi[edit]
Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:
* Difficulty in walking
* Tingling or loss of sensation (numbness) in hands and feet
* Loss of tendon reflexes[10]
* Loss of muscle function or paralysis of the lower legs
* Mental confusion/speech difficulties
* Pain
* Involuntary eye movements (nystagmus)
* Vomiting
A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.[11]
### Brain disease[edit]
Wernicke's encephalopathy (WE), Korsakoff syndrome (alcohol amnestic disorder), and Wernicke–Korsakoff syndrome are forms of dry beriberi.[4]
Wernicke's encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society,[12][13] though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease,[12] those with HIV/AIDS, and with the injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation.[14] This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.[15]
Korsakoff syndrome is, in general, considered to occur with deterioration of brain function in patients initially diagnosed with WE.[16] This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.[17]
Alcoholics may have thiamine deficiency because of the following:
* Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.
* Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.
* Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.[18]
* Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.
* Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).[19]
Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed, in particular poor brain functionality, although in more severe cases, Wernicke–Korsakoff syndrome leaves permanent damage. (See delirium tremens.)
### Wet beriberi[edit]
Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:
* Increased heart rate
* Vasodilation leading to decreased systemic vascular resistance, and high output heart failure[20]
* Elevated jugular venous pressure[21]
* Dyspnea (shortness of breath) on exertion
* Paroxysmal nocturnal dyspnea
* Peripheral edema[21] (swelling of lower legs)
* Dilated cardiomyopathy
### Gastrointestinal beriberi[edit]
Gastrointestinal beriberi causes abdominal pain. Gastrointestinal beriberi is characterized by:
* Abdominal pain
* Nausea
* Vomiting
* Lactic acidosis[22][23]
### Infants[edit]
Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. It may present as either wet or dry beriberi.[2]
In the acute form, the baby develops dyspnea and cyanosis and soon dies of heart failure. These symptoms may be described in infantile beriberi:
* Hoarseness, where the child makes moves to moan but emits no sound or just faint moans[24] caused by nerve paralysis[10]
* Weight loss, becoming thinner and then marasmic as the disease progresses[24]
* Vomiting[24]
* Diarrhea[24]
* Pale skin[10]
* Edema[10][24]
* Ill temper[10]
* Alterations of the cardiovascular system, especially tachycardia (rapid heart rate)[10]
* Convulsions occasionally observed in the terminal stages[24]
## Cause[edit]
Beriberi may also be caused by shortcomings other than inadequate intake: diseases or operations on the digestive tract, alcoholism,[21] dialysis, genetic deficiencies, etc. All these causes mainly affect the central nervous system, and provoke the development of what is known as Wernicke's disease or Wernicke's encephalopathy.
Wernicke's disease is one of the most prevalent neurological or neuropsychiatric diseases.[25] In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases.[26] Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abusers, autopsy series showed neurological damages at rates of 12.5% or more. Mortality caused by Wernicke's disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries.[27][28] The number of people with Wernicke's disease may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of people can experience fetal damage and subsequent diseases.
### Genetics[edit]
Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia (TRMA) with diabetes mellitus and sensorineural deafness[29] is an autosomal recessive disorder caused by mutations in the gene SLC19A2,[30] a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high-affinity thiamine transporter, SLC19A3.[31][32] Leigh disease (subacute necrotising encephalomyelopathy) is an inherited disorder that affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase complex.[33]
Mutations in the SLC19A3 gene have been linked to biotin-thiamine responsive basal ganglia disease,[34] which is treated with pharmacological doses of thiamine and biotin, another B vitamin.
Other disorders in which a putative role for thiamine has been implicated include subacute necrotising encephalomyelopathy, opsoclonic cerebellopathy (a paraneoplastic syndrome), and Nigerian seasonal ataxia. In addition, several inherited disorders of ThDP-dependent enzymes have been reported,[35] which may respond to thiamine treatment.[17]
## Pathophysiology[edit]
Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate (TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle. The citric acid cycle is a central metabolic pathway involved in the regulation of carbohydrate, lipid, and amino acid metabolism, and its disruption due to thiamine deficiency inhibits the production of many molecules including the neurotransmitters glutamic acid and GABA.[36] Additionally thiamine may also be directly involved in neuromodulation.[37]
## Diagnosis[edit]
Oxidation of thiamine derivatives to fluorescent thiochromes by potassium ferricyanide under alkaline conditions
A positive diagnosis test for thiamine deficiency involves measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte transketolase activation assay). Alternatively, thiamine and its phosphorylated derivatives can directly be detected in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent thiochrome derivatives (Thiochrome assay) and separation by high-performance liquid chromatography (HPLC).[38][39][40] Capillary electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as alternative techniques in quantifying and monitoring thiamine levels in samples.[41] The normal thiamine concentration in EDTA-blood is about 20-100 µg/l.
## Treatment[edit]
Many people with beriberi can be treated with thiamine alone.[42] Given thiamine intravenously (and later orally), rapid and dramatic[21] recovery occurs, generally within 24 hours.[43]
Improvements of peripheral neuropathy may require several months of thiamine treatment.[44]
## Epidemiology[edit]
Beriberi is a recurrent nutritional disease in detention houses, even in this century. In 1999, an outbreak of beriberi occurred in a detention center in Taiwan.[45] High rates of illness and death in overcrowded Haitian jails in 2007 were traced to the traditional practice of washing rice before cooking.[46] In the Ivory Coast, among a group of prisoners with heavy punishment, 64% were affected by beriberi. Before beginning treatment, prisoners exhibited symptoms of dry or wet beriberi with neurological signs (tingling: 41%), cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%), and edemas of the lower limbs (51%). With treatment the rate of healing was about 97%.[47]
Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as refugees from war, are susceptible to micronutritional deficiency, including beriberi.[48] The severe nutritional deprivation caused by famine also can cause beriberis, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems.[49] An extreme weight-loss diet can, rarely, induce a famine-like state and the accompanying beriberi.[21]
## History[edit]
Earliest written descriptions of thiamine deficiency are from Ancient China in the context of Chinese medicine. One of the earliest is by Ge Hong in his book Zhou hou bei ji fang (Emergency Formulas to Keep up Your Sleeve) written sometime during the 3rd century. Hong called the illness by the name jiao qi, which can be interpreted as "foot qi". He described the symptoms to include swelling, weakness and numbness of the feet. He also acknowledged that the illness could be deadly, and claimed that it could be cured by eating certain foods such as fermented soybeans in wine. Better known examples of early descriptions of "foot qi" are by Chao Yuanfang (who lived during 550–630) in his book Zhu bing yuan hou lun (Sources and Symptoms of All Diseases)[50][51] and by Sun Simiao (581–682) in his book Bei ji qian jin yao fang (Essential Emergency Formulas Worth a Thousand in Gold).[52][51][53][54]
In the late 19th century, beriberi was studied by Takaki Kanehiro, a British-trained Japanese medical doctor of the Imperial Japanese Navy.[55] Beriberi was a serious problem in the Japanese navy: Sailors fell ill an average of four times a year in the period 1878 to 1881, and 35% were cases of beriberi.[55] In 1883, Takaki learned of a very high incidence of beriberi among cadets on a training mission from Japan to Hawaii, via New Zealand and South America. The voyage lasted more than nine months and resulted in 169 cases of sickness and 25 deaths on a ship of 376 men. With the support of the Japanese Navy, he conducted an experiment in which another ship was deployed on the same route, except that its crew was fed a diet of meat, fish, barley, rice, and beans. At the end of the voyage, this crew had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause.[55] In 1884, Takaki observed that beriberi was common among low-ranking crew who were often provided free rice and thus ate little else, but not among crews of Western navies, nor among Japanese officers who consumed a more varied diet.
In 1897, Christiaan Eijkman, a Dutch physician and pathologist, demonstrated that beriberi is caused by poor diet, and discovered that feeding unpolished rice (instead of the polished variety) to chickens helped to prevent beriberi. The following year, Sir Frederick Hopkins postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, and salt—that were necessary for the functions of the human body.[56][57] In 1901, Gerrit Grijns, a Dutch physician and assistant to Christiaan Eijkman in the Netherlands, correctly interpreted beriberi as a deficiency syndrome,[58] and between 1910 and 1913, Edward Bright Vedder established that an extract of rice bran is a treatment for beriberi.[citation needed] In 1929, Eijkman and Hopkins were awarded the Nobel Prize for Physiology or Medicine for their discoveries.
### Etymology[edit]
Although according to the Oxford English Dictionary, the term "beriberi" comes from a Sinhalese phrase meaning "weak, weak" or "I cannot, I cannot", the word being duplicated for emphasis,[59] the origin of the phrase is questionable. It has also been suggested to come from Hindi, Arabic and a few other languages, with many meanings like "weakness", "sailor" and even "sheep". Such suggested origins were listed by Heinrich Botho Scheube among others. Edward Vedder wrote in his book Beriberi (1913) that "it is impossible to definitely trace the origin of the word beriberi". Word berbere was used in writing at least as early as 1568 by Diogo do Couto, when he described the deficiency in India.[60]
"Kakke", which is a Japanese synonym for thiamine deficiency, comes from the way "jiao qi" is pronounced in Japanese.[61] "Jiao qi" is an old word used in Chinese medicine to describe beriberi.[50] "Kakke" is supposed to have entered into the Japanese language sometime between the 6th and 8th centuries.[61]
## Other animals[edit]
### Poultry[edit]
As most feedstuffs used in poultry diets contain enough quantities of vitamins to meet the requirements in this species, deficiencies in this vitamin do not occur with commercial diets. This was, at least, the opinion in the 1960s.[62]
Mature chickens show signs three weeks after being fed a deficient diet. In young chicks, it can appear before two weeks of age. Onset is sudden in young chicks. There is anorexia and an unsteady gait. Later on, there are locomotor signs, beginning with an apparent paralysis of the flexor of the toes. The characteristic position is called "stargazing", meaning a chick "sitting on its hocks and the head in opisthotonos".
Response to administration of the vitamin is rather quick, occurring a few hours later.[63][64]
### Ruminants[edit]
Polioencephalomalacia (PEM) is the most common thiamine deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient, diarrhea, listlessness, circling movements, star gazing or opisthotonus (head drawn back over neck), and muscle tremors.[65] The most common cause is high-carbohydrate feeds, leading to the overgrowth of thiaminase-producing bacteria, but dietary ingestion of thiaminase (e.g., in bracken fern), or inhibition of thiamine absorption by high sulfur intake are also possible.[66] Another cause of PEM is Clostridium sporogenes or Bacillus aneurinolyticus infection. These bacteria produce thiaminases that will cause an acute thiamine deficiency in the affected animal.[67]
### Snakes[edit]
Snakes that consume a diet largely composed of goldfish and feeder minnows are susceptible to developing thiamine deficiency. This is often a problem observed in captivity when keeping garter and ribbon snakes that are fed a goldfish-exclusive diet, as these fish contain thiaminase, an enzyme that breaks down thiamine.[68]
### Wild birds and fish[edit]
Thiamine deficiency has been identified as the cause of a paralytic disease affecting wild birds in the Baltic Sea area dating back to 1982.[69] In this condition, there is difficulty in keeping the wings folded along the side of the body when resting, loss of the ability to fly and voice, with eventual paralysis of the wings and legs and death. It affects primarily 0.5–1 kg sized birds such as the herring gull (Larus argentatus), common starling (Sturnus vulgaris) and common eider (Somateria mollissima). Researches noted, "Because the investigated species occupy a wide range of ecological niches and positions in the food web, we are open to the possibility that other animal classes may suffer from thiamine deficiency as well."[69]p. 12006
In the counties of Blekinge and Skåne (southernmost Sweden), mass deaths of several bird species, especially the European herring gull, have been observed since the early 2000s. More recently, species of other classes seems to be affected. High mortality of salmon (Salmo salar) in the river Mörrumsån is reported, and mammals such as the Eurasian Elk (Alces alces) have died in unusually high numbers. Lack of thiamine is the common denominator where analysis is done. In April 2012, the County Administrative Board of Blekinge found the situation so alarming that they asked the Swedish government to set up a closer investigation.[70]
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r "Beriberi". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2015. Archived from the original on 11 November 2017. Retrieved 11 November 2017.
2. ^ a b c Adamolekun, B; Hiffler, L (24 October 2017). "A diagnosis and treatment gap for thiamine deficiency disorders in sub-Saharan Africa?". Annals of the New York Academy of Sciences. 1408 (1): 15–19. Bibcode:2017NYASA1408...15A. doi:10.1111/nyas.13509. PMID 29064578.
3. ^ a b Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 1368. ISBN 9780323529570. Archived from the original on 2017-11-11.
4. ^ a b c d e "Nutrition and Growth Guidelines | Domestic Guidelines - Immigrant and Refugee Health". CDC. March 2012. Archived from the original on 11 November 2017. Retrieved 11 November 2017.
5. ^ Hermann, Wolfgang; Obeid, Rima (2011). Vitamins in the prevention of human diseases. Berlin: Walter de Gruyter. p. 58. ISBN 9783110214482.
6. ^ Gropper, Sareen S. and Smith, Jack L. (2013). Advanced Nutrition and Human Metabolism (6 ed.). Wadsworth, Cengage Learning. p. 324. ISBN 978-1133104056.CS1 maint: multiple names: authors list (link)
7. ^ a b Swaiman, Kenneth F.; Ashwal, Stephen; Ferriero, Donna M.; Schor, Nina F.; Finkel, Richard S.; Gropman, Andrea L.; Pearl, Phillip L.; Shevell, Michael (2017). Swaiman's Pediatric Neurology E-Book: Principles and Practice. Elsevier Health Sciences. p. e929. ISBN 9780323374811. Archived from the original on 2017-11-11.
8. ^ "Thiamin Fact Sheet for Consumers". Office of Dietary Supplements (ODS): USA.gov. Archived from the original on October 29, 2017. Retrieved April 10, 2018.
9. ^ Lanska, DJ (2010). Chapter 30: historical aspects of the major neurological vitamin deficiency disorders: the water-soluble B vitamins. Handbook of Clinical Neurology. 95. pp. 445–76. doi:10.1016/S0072-9752(08)02130-1. ISBN 9780444520098. PMID 19892133.
10. ^ a b c d e f Katsura, E.; Oiso, T. (1976). Beaton, G.H.; Bengoa, J.M. (eds.). "Chapter 9. Beriberi" (PDF). World Health Organization Monograph Series No. 62: Nutrition in Preventive Medicine. Geneva: World Health Organization. Archived from the original (PDF) on 2011-07-08.
11. ^ Spinazzi, Marco; Angelini, Corrado; Patrini, Cesare (2010). "Subacute sensory ataxia and optic neuropathy with thiamine deficiency". Nature Reviews Neurology. 6 (5): 288–93. doi:10.1038/nrneurol.2010.16. PMID 20308997. S2CID 12333200.
12. ^ a b Kril JJ (1996). "Neuropathology of thiamine deficiency disorders". Metab Brain Dis. 11 (1): 9–17. doi:10.1007/BF02080928. PMID 8815394. S2CID 20889916.
13. ^ For an interesting discussion on thiamine fortification of foods, specifically targetting beer, see "Wernicke's encephalopathy and thiamine fortification of food: time for a new direction?". Medical Journal of Australia. Archived from the original on 2011-08-31.
14. ^ Butterworth RF, Gaudreau C, Vincelette J, et al. (1991). "Thiamine deficiency and wernicke's encephalopathy in AIDS". Metab Brain Dis. 6 (4): 207–12. doi:10.1007/BF00996920. PMID 1812394. S2CID 8833558.
15. ^ Harper C. (1979). "Wernicke's encephalopathy, a more common disease than realised (a neuropathological study of 51 cases)". J Neurol Neurosurg Psychiatry. 42 (3): 226–231. doi:10.1136/jnnp.42.3.226. PMC 490724. PMID 438830.
16. ^ McCollum EV A History of Nutrition. Cambridge, MA: Riverside Press, Houghton Mifflin; 1957.
17. ^ a b Butterworth RF. Thiamin. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006.
18. ^ Butterworth RF (1993). "Pathophysiologic mechanisms responsible for the reversible (thiamine-responsive) and irreversible (thiamine non-responsive) neurological symptoms of Wernicke's encephalopathy". Drug Alcohol Rev. 12 (3): 315–22. doi:10.1080/09595239300185371. PMID 16840290.
19. ^ Rindi G, Imarisio L, Patrini C (1986). "Effects of acute and chronic ethanol administration on regional thiamin pyrophosphokinase activity of the rat brain". Biochem Pharmacol. 35 (22): 3903–8. doi:10.1016/0006-2952(86)90002-X. PMID 3022743.
20. ^ Anand, I. S.; Florea, V. G. (2001). "High Output Cardiac Failure". Current Treatment Options in Cardiovascular Medicine. 3 (2): 151–159. doi:10.1007/s11936-001-0070-1. PMID 11242561. S2CID 44475541.
21. ^ a b c d e McIntyre, Neil; Stanley, Nigel N. (1971). "Cardiac Beriberi: Two Modes of Presentation". BMJ. 3 (5774): 567–9. doi:10.1136/bmj.3.5774.567. PMC 1798841. PMID 5571454.
22. ^ Donnino M (2004). "Gastrointestinal Beriberi: A Previously Unrecognized Syndrome". Ann Intern Med. 141 (11): 898–899. doi:10.7326/0003-4819-141-11-200412070-00035. PMID 15583247.
23. ^ Duca, J., Lum, C., & Lo, A. (2015). Elevated Lactate Secondary to Gastrointestinal Beriberi. J GEN INTERN MED Journal of General Internal Medicine
24. ^ a b c d e f Latham, Michael C. (1997). "Chapter 16. Beriberi and thiamine deficiency". Human nutrition in the developing world (Food and Nutrition Series – No. 29). Fao Food and Nutrition Series. Rome: Food and Agriculture Organization of the United Nations (FAO). ISSN 1014-3181. Archived from the original on 2014-02-03.
25. ^ Cernicchiaro, Luis (2007), Enfermedad de Wernicke (o Encefalopatía de Wernicke). Monitoring an acute and recovered case for twelve years. [Wernicke´s Disease (or Wernicke´s Encephalopathy)] (in Spanish), archived from the original on 2013-05-22
26. ^ Salen, Philip N (1 March 2013). Kulkarni, Rick (ed.). "Wernicke Encephalopathy". Medscape. Archived from the original on 12 May 2013.
27. ^ Harper, CG; Giles, M; Finlay-Jones, R (April 1986). "Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy". J Neurol Neurosurg Psychiatry. 49 (4): 341–5. doi:10.1136/jnnp.49.4.341. PMC 1028756. PMID 3701343.
28. ^ Harper, C (March 1979). "Wernicke's encephalopathy: a more common disease than realised. A neuropathological study of 51 cases". J Neurol Neurosurg Psychiatry. 42 (3): 226–31. doi:10.1136/jnnp.42.3.226. PMC 490724. PMID 438830.
29. ^ Slater, PV (1978). "Thiamine Responsive Megaloblastic Anemia with severe diabetes mellitus and sensorineural deafness (TRMA)". The Australian Nurses' Journal. 7 (11): 40–3. PMID 249270.
30. ^ Kopriva, V; Bilkovic, R; Licko, T (Dec 1977). "Tumours of the small intestine (author's transl)". Ceskoslovenska Gastroenterologie a Vyziva. 31 (8): 549–53. ISSN 0009-0565. PMID 603941.
31. ^ Beissel, J (Dec 1977). "The role of right catheterization in valvular prosthesis surveillance (author's transl)". Annales de Cardiologie et d'Angéiologie. 26 (6): 587–9. ISSN 0003-3928. PMID 606152.
32. ^ Online Mendelian Inheritance in Man (OMIM): 249270
33. ^ Butterworth RF. Pyruvate dehydrogenase deficiency disorders. In: McCandless DW, ed. Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Publishing Corp.; 1985.
34. ^ Biotin-Thiamine-Responsive Basal Ganglia Disease - GeneReviews® - NCBI Bookshelf Archived 2018-05-09 at the Wayback Machine
35. ^ Blass JP. Inborn errors of pyruvate metabolism. In: Stanbury JB, Wyngaarden JB, Frederckson DS et al., eds. Metabolic Basis of Inherited Disease. 5th ed. New York: McGraw-Hill, 1983.
36. ^ Sechi, G; Serra, A (May 2007). "Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management". Lancet Neurology. 6 (5): 442–55. doi:10.1016/S1474-4422(07)70104-7. PMID 17434099. S2CID 15523083.
37. ^ Hirsch, JA; Parrott, J (2012). "New considerations on the neuromodulatory role of thiamine". Pharmacology. 89 (1–2): 111–6. doi:10.1159/000336339. PMID 22398704. S2CID 22555167.
38. ^ Bettendorff L, Peeters M, Jouan C, Wins P, Schoffeniels E (1991). "Determination of thiamin and its phosphate esters in cultured neurons and astrocytes using an ion-pair reversed-phase high-performance liquid chromatographic method". Anal. Biochem. 198 (1): 52–59. doi:10.1016/0003-2697(91)90505-N. PMID 1789432.
39. ^ Losa R, Sierra MI, Fernández A, Blanco D, Buesa J (2005). "Determination of thiamine and its phosphorylated forms in human plasma, erythrocytes and urine by HPLC and fluorescence detection: a preliminary study on cancer patients". J Pharm Biomed Anal. 37 (5): 1025–1029. doi:10.1016/j.jpba.2004.08.038. PMID 15862682.
40. ^ Lu J, Frank E (May 2008). "Rapid HPLC measurement of thiamine and its phosphate esters in whole blood". Clin. Chem. 54 (5): 901–906. doi:10.1373/clinchem.2007.099077. PMID 18356241.
41. ^ Shabangi M, Sutton J (2005). "Separation of thiamin and its phosphate esters by capillary zone electrophoresis and its application to the analysis of water-soluble vitamins". Journal of Pharmaceutical and Biomedical Analysis. 38 (1): 66–71. doi:10.1016/j.jpba.2004.11.061. PMID 15907621.
42. ^ Nguyen-Khoa, Dieu-Thu Beriberi (Thiamine Deficiency) Treatment & Management Archived 2014-03-24 at the Wayback Machine. Mescape
43. ^ Tanphaichitr V. Thiamin. In: Shils ME, Olsen JA, Shike M et al., editors. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999
44. ^ Maurice V, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. 2nd ed. Philadelphia: FA Davis, 1989.
45. ^ Chen KT, Twu SJ, Chiou ST, Pan WH, Chang HJ, Serdula MK (2003). "Outbreak of beriberi among illegal mainland Chinese immigrants at a detention center in Taiwan". Public Health Rep. 118 (1): 59–64. doi:10.1093/phr/118.1.59. PMC 1497506. PMID 12604765.
46. ^ Sprague, Jeb; Alexandra, Eunida (17 January 2007). "Haiti: Mysterious Prison Ailment Traced to U.S. Rice". Inter Press Service. Archived from the original on 30 May 2013.
47. ^ Aké-Tano, O.; Konan, E. Y.; Tetchi, E. O.; Ekou, F. K.; Ekra, D.; Coulibaly, A.; Dagnan, N. S. (2011). "Le béribéri, maladie nutritionnelle récurrente en milieu carcéral en Côte-d'Ivoire". Bulletin de la Société de Pathologie Exotique. 104 (5): 347–351. doi:10.1007/s13149-011-0136-6. PMID 21336653.
48. ^ Prinzo, Z. Weise; de Benoist, B. (2009). "Meeting the challenges of micronutrient deficiencies in emergency-affected populations" (PDF). Proceedings of the Nutrition Society. 61 (2): 251–7. doi:10.1079/PNS2002151. PMID 12133207. Archived (PDF) from the original on 2012-10-19.
49. ^ Golden, Mike (May 1997). "Diagnosing Beriberi in Emergency Situations". Field Exchange (1): 18. Archived from the original on 2012-10-19.
50. ^ a b HA Smith, p. 26-28
51. ^ a b Benedict, CA (2018-10-25). "Forgotten Disease: Illnesses Transformed in Chinese Medicine by Hilary A. Smith (review)". Bulletin of the History of Medicine. 92 (3): 550–551. doi:10.1353/bhm.2018.0059. ISSN 1086-3176. S2CID 80778431.
52. ^ HA Smith, p. 44
53. ^ "TCM history V the Sui & Tang Dynasties". Archived from the original on 2017-07-14. Retrieved 2017-07-11.
54. ^ "Sun Simiao: Author of the Earliest Chinese Encyclopedia for Clinical Practice". Archived from the original on 2007-07-04. Retrieved 2007-06-15.
55. ^ a b c Itokawa, Yoshinori (1976). "Kanehiro Takaki (1849–1920): A Biographical Sketch". Journal of Nutrition. 106 (5): 581–8. doi:10.1093/jn/106.5.581. PMID 772183.
56. ^ Challem, Jack (1997). "The Past, Present and Future of Vitamins". Archived from the original on 8 June 2010.[unreliable medical source?]
57. ^ Christiaan Eijkman, Beriberi and Vitamin B1, Nobelprize.org, Nobel Media AB, archived from the original on 17 January 2010, retrieved 8 July 2013
58. ^ Grijns, G. (1901). "Over polyneuritis gallinarum". Geneeskundig Tijdschrift voor Nederlandsch-Indie. 43: 3–110.
59. ^ Oxford English Dictionary: "Beri-beri ... a Cingalese word, f. beri weakness, the reduplication being intensive ...", page 203, 1937
60. ^ HA Smith, p. 118-119
61. ^ a b HA Smith, p. 149
62. ^ Merck Veterinary Manual, ed 1967, pp 1440-1441.
63. ^ R.E. Austic and M.L. Scott, Nutritional deficiency diseases, in Diseases of poultry, ed. by M.S. Hofstad, Iowa State University Press, Ames, Iowa, USA ISBN 0-8138-0430-2, p. 50.
64. ^ The disease is described more carefully here: merckvetmanual.com Archived 2008-12-22 at the Wayback Machine
65. ^ National Research Council. 1996. Nutrient Requirements of Beef Cattle, Seventh Revised Ed. Washington, D.C.: National Academy Press.
66. ^ Polioencephalomalacia: Introduction Archived 2016-03-03 at the Wayback Machine, Merck Veterinary Manual
67. ^ Polioencephalomacia: Introduction Archived 2010-05-28 at the Wayback Machine, "ACES Publications"
68. ^ "Archived copy". Archived from the original on 2017-09-13. Retrieved 2017-09-13.CS1 maint: archived copy as title (link)
69. ^ a b Balk, L; Hägerroth, PA; Akerman, G; Hanson, M; Tjärnlund, U; Hansson, T; Hallgrimsson, GT; Zebühr, Y; Broman, D; Mörner, T.; Sundberg, H.; et al. (2009). "Wild birds of declining European species are dying from a thiamine deficiency syndrome". Proc Natl Acad Sci U S A. 106 (29): 12001–12006. Bibcode:2009PNAS..10612001B. doi:10.1073/pnas.0902903106. PMC 2715476. PMID 19597145.
70. ^ Blekinge län, Länsstyrelsen (2013). "2012-04-15 500-1380-13 Förhöjd dödlighet hos fågel, lax og älg" (PDF). Archived (PDF) from the original on 2013-12-02. Cite journal requires `|journal=` (help)
### Cited sources[edit]
* HA Smith (2017). Forgotten disease: illnesses transformed in Chinese medicine. doi:10.1093/jhmas/jry029. ISBN 9781503603509. OCLC 993877848.
## External links[edit]
Wikimedia Commons has media related to Beriberi.
* "BERI-BERI". The Encyclopaedia Britannica; A Dictionary of Arts, Sciences, Literature and General Information. III (AUSTRIA LOWER to BISECTRIX ) (11th ed.). Cambridge, England and New York: At the University Press. 1910. pp. 774–775. Retrieved 23 October 2018 – via Internet Archive.
* ARNOLD D (2010). "British India and the beri-beri problem". Medical History. 54 (3): 295–314. doi:10.1017/S0025727300004622. PMC 2889456. PMID 20592882.
Classification
D
* ICD-10: E51
* ICD-9-CM: 265.0
* MeSH: D001602
* DiseasesDB: 14107
External resources
* MedlinePlus: 000339
* eMedicine: ped/229 med/221
* Patient UK: Thiamine deficiency
* v
* t
* e
Malnutrition
Protein-energy
malnutrition
* Kwashiorkor
* Marasmus
* Catabolysis
Vitamin deficiency
B vitamins
* B1
* Beriberi
* Wernicke–Korsakoff syndrome
* Wernicke's encephalopathy
* Korsakoff's syndrome
* B2
* Riboflavin deficiency
* B3
* Pellagra
* B6
* Pyridoxine deficiency
* B7
* Biotin deficiency
* B9
* Folate deficiency
* B12
* Vitamin B12 deficiency
Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
* Osteomalacia
* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
* Potassium
* Magnesium
* Calcium
* Iron
* Zinc
* Manganese
* Copper
* Iodine
* Chromium
* Molybdenum
* Selenium
* Keshan disease
Growth
* Delayed milestone
* Failure to thrive
* Short stature
* Idiopathic
General
* Anorexia
* Weight loss
* Cachexia
* Underweight
Authority control
* LCCN: sh85143963
* NDL: 00564727
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Thiamine deficiency
|
c0005122
| 27,536 |
wikipedia
|
https://en.wikipedia.org/wiki/Thiamine_deficiency
| 2021-01-18T18:49:20 |
{"gard": ["9948"], "mesh": ["D001602"], "umls": ["C0005122"], "wikidata": ["Q184084"]}
|
This article has no lead section. Please help by adding an introductory section to this article. For more information, see the layout guide, and Wikipedia's lead section guidelines to ensure the section will be inclusive of all the essential details. Please discuss this issue on the article's talk page. (December 2020) (Learn how and when to remove this template message)
## Prevalence[edit]
Jordan has low HIV/AIDS prevalence, but if preventive measures are not implemented, HIV/AIDS and other communicable diseases could increase or re-emerge and have significant social and economic consequences.[1]
In 2007, there were an estimated 380,000 people living with HIV/AIDS (PLWHA) in the region, according to UNAIDS. Although figures are low compared with Southern Africa or Asia, they are still a cause for alarm, particularly since they are rising rapidly, especially among high-risk groups, such as injecting drug users (IDUs) and vulnerable youth. Systematic monitoring of the epidemic, however, is far from complete. Surveillance systems remain inadequate in their coverage of at-risk groups and thus fail to reflect risk behaviors or provide incidence and prevalence rates.[1]
In addition to weak surveillance, the adoption of preventive practices is very limited, the participation of PLWHA and civil society in the HIV/AIDS response is still nascent, and despite some progress, general attitudes, institutions, and laws often do not facilitate implementation of an expanded response. The first step in addressing the spread of HIV/AIDS is recognizing the presence of the disease and the sociocultural, political, and economic patterns that fuel and bear the burden of its impact.[1]
Although the Ministry of Health (MOH) reported that 550 cases of HIV/AIDS were diagnosed in Jordan as of December 2007, the actual number is thought to be much higher due to under-reporting. For those cases diagnosed, the routes of transmission included 16.5 percent through blood and blood products, 60 percent through sexual transmission, and 3.3 percent through injection drug use. Perinatal HIV transmission accounted for 1.5 percent, and 18.2 percent of cases were of unknown transmission route. In addition, a significant number of diagnosed HIV/AIDS cases are from foreigners in Jordan (185 Jordanians and 365 non-Jordanians). Since the first case of HIV/AIDS in Jordan was diagnosed in 1986, 85 Jordanians have died of AIDS. Little is known about HIV prevalence rates in high-risk populations in Jordan.[1]
A 2003 assessment conducted of about 1,200 women presenting to obstetrics and gynecological clinics in urban centers in Amman, Zarka, and Rusaifah showed a prevalence of gonorrhea of 0.7 percent, chlamydial infection of 1.2 percent, trichomoniasis of 1.2 percent, bacterial vaginosis of 5.4 percent, and candidiasis of 19.1 percent. Regional variations indicate that rates are much higher in some sites than in others. No syphilis infection was identified.[1]
Stigma and discrimination against PLWHA prevails, as 29 percent of ever-married women surveyed in the 2002 Demographic and Health Survey were unwilling to care for PLWHA at home, while 63.5 percent of young people responding to a knowledge, attitude, practice, and behavior study believed that AIDS patients should be isolated.[1]
Jordan’s cultural sensitivities pose the greatest threat to the country’s low prevalence. Because of difficulties in discussing sexual matters, many Jordanians still harbor misconceptions about HIV/AIDS and PLWHA. A 2005 study of the general population (USAID/JHU/HCP: 2005 Communication Partnership for Family Health Baseline Survey, Key Results) found that talking about HIV/AIDS is still taboo and that PLWHA still face stigma and discrimination. For instance, 65 percent of women and men said people with the AIDS virus should not be allowed to work with others in shops, offices, or on farms, even if they are not feeling sick. Many people responding to the survey did not understand how to prevent HIV/AIDS and did not know that condoms can be used for this purpose.[1]
At an estimated two new cases of tuberculosis (TB) per 100,000 people (WHO 2005), TB incidence in Jordan is relatively low. Currently, fewer than 1 percent of adult TB patients are HIV-positive. However, continued monitoring is necessary because an increase in the incidence of HIV-TB co-infection could add to the complexity of fighting both diseases in Jordan.[1]
## National response[edit]
Jordan’s national response to HIV/AIDS is characterized by strong political commitment to addressing HIV. The response is managed through the MOH National AIDS Program (NAP) and includes the formation of a National AIDS Committee and the appointment of an AIDS program manager. The MOH continues to support the national blood transfusion service, mandatory HIV testing, strong control measures for foreigners who reside in Jordan, and provision of antiretroviral (ARV) drugs for Jordanians who test HIV-positive. There are currently 12 part-time focal point persons who are responsible for HIV/AIDS in all governorates of the country.[1]
In 2005, Jordan launched the National HIV/AIDS Strategy (2005–2009), outlining the key goals, objectives, and initiatives for the response. The key goal is to maintain low HIV prevalence among the population and all vulnerable sub-populations of Jordan.[1]
Jordan has received funding from the Global Fund to Fight AIDS, Tuberculosis and Malaria to strengthen and expand existing HIV/AIDS prevention, care, and support activities since 2003. In July 2007, the MOH was granted $1.25 million from the Global Fund to maintain low HIV prevalence among its population.[1]
## References[edit]
* Jordan portal
1. ^ a b c d e f g h i j k "Health Profile: Jordan" Archived 2008-11-15 at the Wayback Machine. United States Agency for International Development (March 2008). Accessed August 25, 2008. This article incorporates text from this source, which is in the public domain.
* v
* t
* e
HIV/AIDS in Asia
Sovereign states
* Afghanistan
* Armenia
* Azerbaijan
* Bahrain
* Bangladesh
* Bhutan
* Brunei
* Cambodia
* China
* Cyprus
* East Timor (Timor-Leste)
* Egypt
* Georgia
* India
* Indonesia
* Iran
* Iraq
* Israel
* Japan
* Jordan
* Kazakhstan
* North Korea
* South Korea
* Kuwait
* Kyrgyzstan
* Laos
* Lebanon
* Malaysia
* Maldives
* Mongolia
* Myanmar
* Nepal
* Oman
* Pakistan
* Philippines
* Qatar
* Russia
* Saudi Arabia
* Singapore
* Sri Lanka
* Syria
* Tajikistan
* Thailand
* Turkey
* Turkmenistan
* United Arab Emirates
* Uzbekistan
* Vietnam
* Yemen
States with
limited recognition
* Abkhazia
* Artsakh
* Northern Cyprus
* Palestine
* South Ossetia
* Taiwan
Dependencies and
other territories
* British Indian Ocean Territory
* Christmas Island
* Cocos (Keeling) Islands
* Hong Kong
* Macau
* Book
* Category
* Asia portal
* v
* t
* e
HIV/AIDS topics
HIV/AIDS
HIV
* HIV
* Lentivirus
* structure and genome
* subtypes
* CDC classification
* disease progression rates
* HIV/AIDS
* diagnosis
* management
* pathophysiology
* prevention
* research
* vaccination
* PrEP
* WHO disease staging system for HIV infection and disease
* Children
* Teens / Adults
* Countries by AIDS prevalence rate
Conditions
* Signs and symptoms
* AIDS-defining clinical condition
* Diffuse infiltrative lymphocytosis syndrome
* Lipodystrophy
* Nephropathy
* Neurocognitive disorders
* Pruritus
* Superinfection
* Tuberculosis co-infection
* HIV Drug Resistance Database
* Innate resistance to HIV
* Serostatus
* HIV-positive people
* Nutrition
* Pregnancy
History
* History
* Epidemiology
* Multiple sex partners
* Timeline
* AIDS Museum
* Timothy Ray Brown
* Women and HIV/AIDS
Social
* AIDS orphan
* Catholic Church and HIV/AIDS
* Circumcision and HIV
* Criminal transmission
* Discrimination against people
* Economic impact
* Cost of treatment
* HIV-affected community
* HIV/AIDS activism
* HIV/AIDS denialism
* Red ribbon
* Safe sex
* Sex education
* List of HIV-positive people
* People With AIDS Self-Empowerment Movement
* HIV/AIDS in the porn industry
Culture
* Discredited HIV/AIDS origins theories
* International AIDS Conference
* International AIDS Society
* Joint United Nations Programme on HIV/AIDS (UNAIDS)
* Media portrayal of HIV/AIDS
* Misconceptions about HIV/AIDS
* President's Emergency Plan for AIDS Relief (PEPFAR)
* The SING Campaign
* Solidays
* Treatment Action Campaign
* World AIDS Day
* YAA/Youthforce
* "Free Me"
* Larry Kramer
* Gay Men's Health Crisis
* ACT UP
* Silence=Death Project
HIV/AIDS pandemic by region / country
Africa
* Angola
* Benin
* Botswana
* Democratic Republic of the Congo
* Egypt
* Eswatini
* Ethiopia
* Ghana
* Guinea
* Côte d'Ivoire (Ivory Coast)
* Kenya
* Lesotho
* Madagascar
* Malawi
* Mali
* Mozambique
* Namibia
* Niger
* Nigeria
* Rwanda
* Senegal
* Tanzania
* South Africa
* Uganda
* Zambia
* Zimbabwe
North America
* Canada
* Mexico
* El Salvador
* Guatemala
* Honduras
* Nicaragua
United States
* New York City
Caribbean
* Haiti
* Jamaica
* Dominican Republic
South America
* Bolivia
* Brazil
* Colombia
* Guyana
* Peru
Asia
* Afghanistan
* Armenia
* Azerbaijan
* Bahrain
* Bangladesh
* Bhutan
* Cambodia
* China (PRC) (Yunnan)
* East Timor
* India
* Indonesia
* Iran
* Iraq
* Japan
* Jordan
* North Korea
* Laos
* Malaysia
* Myanmar (Burma)
* Nepal
* Pakistan
* Philippines
* Saudi Arabia
* Sri Lanka
* Taiwan (ROC)
* Thailand
* United Arab Emirates
* Turkey
* Vietnam
Europe
* United Kingdom
* Russia
* Ukraine
Oceania
* Australia
* New Zealand
* Papua New Guinea
* List of countries by HIV/AIDS adult prevalence rate
* List of HIV/AIDS cases and deaths registered by region
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
HIV/AIDS in Jordan
|
None
| 27,537 |
wikipedia
|
https://en.wikipedia.org/wiki/HIV/AIDS_in_Jordan
| 2021-01-18T18:42:35 |
{"wikidata": ["Q5629851"]}
|
Functional incontinence is a form of urinary incontinence in which a person is usually aware of the need to urinate, but for one or more physical or mental reasons they are unable to get to a bathroom.[1] The loss of urine can vary, from small leakages to full emptying of the bladder.
## Main causes[edit]
There are a number of causes of functional incontinence. These include confusion, dementia, poor eyesight, impaired mobility or dexterity or unwillingness to use the toilet due to depression or anxiety.[2] Functional incontinence is more common in elderly people as many of the causes are associated with conditions that affect people as they age. For example, a person with Alzheimer's disease may not plan well enough to reach a bathroom in time or may not remember how to get to the bathroom.
## Non-medical causes[edit]
Functional incontinence can also occur at any age in circumstances where there is no underlying medical problem. For example, a person may recognise the need to urinate but are unable to do so because there is no toilet or suitable alternative nearby or access to a toilet is restricted or prohibited.
If a suitable place to urinate does not become available, the person may reach a stage where they are no longer able to refrain from urination and involuntary voiding of the bladder may take place. Instances of this sort will often result in full emptying of the bladder, but are likely to be one-off or rare occurrences. Excessive alcohol consumption can also cause episodes of incontinence in otherwise healthy adults.[3]
## References[edit]
1. ^ http://www.tena.co.uk/Glossary/Functional-Incontinence/
2. ^ http://patient.info/doctor/urinary-incontinence-pro
3. ^ http://www.mayoclinic.com/health/urinary-incontinence/DS00404/DSECTION=causes
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Functional incontinence
|
c0150042
| 27,538 |
wikipedia
|
https://en.wikipedia.org/wiki/Functional_incontinence
| 2021-01-18T18:33:50 |
{"wikidata": ["Q5508826"]}
|
A rare vulvovaginal tumor characterized by intraepithelial neoplastic proliferation of the vulvar epithelium, histologically presenting proliferation of atypical basal cells with basal layer involvement, enlarged nuclei, hyperchromasia, pleomorphic cells and increased numbers of mitotic figures. Patients are frequently asymptomatic, although vulvar pruritis/pain/burning, dysuria and/or dyspareunia may be associated. Concurrent anogenital involvement is frequent. Two subtypes, usual type VIN (uVIN) and differentiated type VIN (dVIN) exist, with uVIN typically being associated with HPV infection and presenting multifocal, elevated lesions around the introitus and/or labia majora, and dVIN being related to chronic inflammation and lesions consisting of poorly demarcated pink or white plaques that are often associated with lichen sclerosis or lichen planus. Diffusely positive p16 immunohistochemistry and high Ki-67 proliferation index in uVIN futher differentiates this subtype from dVIN, this latter being consistently negative for p16 while presenting p53 positivity.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Vulvar intraepithelial neoplasia
|
c0346210
| 27,539 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137583
| 2021-01-23T19:13:08 |
{"umls": ["C0346210"], "icd-10": ["D07.1"], "synonyms": ["VIN", "Vulvar intraepithelial tumor"]}
|
A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-26 (CILD26) is caused by homozygous or compound heterozygous mutation in the C21ORF59 gene (615494) on chromosome 21q22.
Description
Primary ciliary dyskinesia-26 is an autosomal recessive disorder caused by defective ciliary movement. Affected individuals have neonatal respiratory distress, recurrent upper and lower airway disease, and bronchiectasis. About half of patients show laterality defects, including situs inversus totalis. Respiratory cilia from patients show defects in the inner and outer dynein arms (summary by Austin-Tse et al., 2013).
For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400.
Clinical Features
Austin-Tse et al. (2013) reported 4 unrelated patients with primary ciliary dyskinesia. Two of the patients were of Ashkenazi Jewish descent. Clinical features included neonatal respiratory distress, recurrent respiratory infections, and bronchiectasis. Three patients had situs inversus. All had decreased nasal nitric oxide. Ultrastructural analysis of cilia from affected individuals showed an absence of both outer and inner dynein arm components, and video microscopy of patient respiratory epithelial cell cilia showed complete paralysis.
Inheritance
The transmission pattern of CILD26 in the families reported by Austin-Tse et al. (2013) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 unrelated patients with primary ciliary dyskinesia-26 with or without situs inversus, Austin-Tse et al. (2013) identified 3 different truncating mutations in the C21ORF59 gene (615494.0001-615494.0003). The mutations occurred in homozygous or compound heterozygous state. Two patients of Ashkenazi Jewish descent and 1 of Brazilian descent shared the same truncating mutation (Y245X; 615494.0001); haplotype analysis indicated a founder effect common to all 3 patients. Expression of 1 of the truncating mutations in zebrafish C21orf59 mutants showed that the mutant protein was unstable and failed to rescue the phenotype, consistent with a loss of function. The patients were ascertained from a large cohort of 295 individuals with primary ciliary dyskinesia.
Animal Model
Austin-Tse et al. (2013) found that morpholino knockdown of the C21orf59 gene in zebrafish resulted in a strong ciliopathy phenotype, including pronephric cysts, axis curvature, left-right asymmetry defects, and hydrocephalus. Immunostaining for certain ciliary proteins did not detect structural abnormalities, but ultrastructure analysis revealed that the outer dynein arms were missing. High-speed video microscopy showed paralyzed or dyskinetic cilia, consistent with a motility defect.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Sinusitis, recurrent Ears \- Otitis media, recurrent Nose \- Rhinitis, recurrent RESPIRATORY \- Respiratory insufficiency due to defective ciliary clearance \- Respiratory infections, recurrent Airways \- Chronic bronchitis ABDOMEN \- Situs inversus (in about half of patients) GENITOURINARY Internal Genitalia (Male) \- Infertility due to immotile sperm LABORATORY ABNORMALITIES \- Electron microscopy of patient respiratory cells shows absent outer dynein arms \- Variable defects of inner dynein arms \- Severely impaired ciliary motility \- Decreased nasal nitric oxide MISCELLANEOUS \- Onset in infancy or neonatal period MOLECULAR BASIS \- Caused by mutation in the chromosome 21 open reading frame 59 gene (C21ORF59, 615494.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
CILIARY DYSKINESIA, PRIMARY, 26
|
c3809684
| 27,540 |
omim
|
https://www.omim.org/entry/615500
| 2019-09-22T15:51:54 |
{"doid": ["0110627"], "omim": ["615500", "244400"], "orphanet": ["244"], "synonyms": ["Alternative titles", "CILIARY DYSKINESIA, PRIMARY, 26, WITH OR WITHOUT SITUS INVERSUS", "PCD"], "genereviews": ["NBK1122"]}
|
Fungal disease
ʻŌhiʻa lehua flowers
Rapid ʻŌhiʻa Death (ROD) is a fungal disease rapidly killing forests of ʻōhiʻa—the most abundant native tree in the Hawaiian Islands. Initially reported by landowners in Puna in 2010, ROD spread quickly across tens of thousands of acres on Hawaii Island:[1][2] to date, hundreds of thousands of ʻōhiʻa have died from this fungal disease on Hawaii Island alone.[3] In April 2018, the cause of Rapid ʻŌhiʻa Death was identified as two species of Ceratocystis previously unknown to science: Ceratocystis huliohia and Ceratocystis lukuohia.[4] By May 2018, infected ʻōhiʻa trees were found on the island of Kauai, prompting requests that members of the public limit transportation of ʻōhiʻa products within the island.[5] The less aggressive of the two fungus species, C. huliohia, has been confirmed on Hawaii Island, Kauai, Maui, and Oahu.[3] According to experts, the fungus is likely to have been carried between the islands by tourists, on their shoes or hiking boots, but it can also be transmitted by dirty tools, animals or through the wind.[6]
In 2019 a documentary titled Saving ʻŌhiʻ’a: Hawaii's Sacred Tree, produced by Club Sullivan and funded by a grant from the Hawaiʻi Invasive Species Council, was released, providing an in-depth look into the cultural and ecological importance of ʻōhiʻa and the impact of the ROD epidemic. The film was nominated for six Emmys and received three awards from the National Academy of Television Arts and Sciences Pacific Southwest Chapter.[7]
In 2020, the Rapid ʻŌhiʻa Death Working Group released a "Strategic Response Plan for 2020-2024" laying out management, research, and public engagement priorities to contain the disease and calling for $4 million a year in funding over the next five years to “continue progress toward understanding and addressing the fungal disease that has seriously impacted Hawaii’s native forests.”[8]
## References[edit]
1. ^ Nemo, Leslie (2018-09-20). "Hawaii's "rapid ohia death" disease is killing the forest canopy, and there's no end in sight". Newsweek. Archived from the original on 2019-08-05. Retrieved 2020-02-06.
2. ^ "Rapid 'Ōhi'a Death: The Disease That's Killing Native Hawaiian Trees". NPR.org. Archived from the original on 2020-01-30. Retrieved 2020-02-06.
3. ^ a b "Questions and Answers on ROD". cms.ctahr.hawaii.edu. Archived from the original on 2019-11-22. Retrieved 2020-02-06.
4. ^ "Two new species of fungi that kill ohia trees get Hawaiian names | University of Hawaiʻi System News". University of Hawaiʻi System News. 2018-04-17. Retrieved 2020-02-06.
5. ^ Bernardo, Rosemarie (2018-05-11). "Ohia fungus found on Kauai". Honolulu Star-Advertiser. Archived from the original on 2018-05-15. Retrieved 2018-05-14.
6. ^ "Sacred Hawaiian tree is under threat as tourists are asked to help save it". NBC News. Archived from the original on 2019-08-15. Retrieved 2020-02-06.
7. ^ "'Saving ʻŌhiʻa' documentary brings home 3 Emmys". University of Hawaiʻi System News. 2019-06-25. Retrieved 2020-02-06.
8. ^ "Plan to tackle Rapid Ohia Death". The Garden Island. 2020-01-14. Archived from the original on 2020-01-15. Retrieved 2020-02-06.
## External links[edit]
* Rapid ohia death: the official resource on the disease maintained by the University of Hawaii
* Saving ʻŌhiʻa, Hawaii’s Sacred Tree: official website of the documentary
* Rapid ʻOhiʻa Death Video Brochure on Vimeo
This fungal tree disease article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Rapid ʻŌhiʻa Death
|
None
| 27,541 |
wikipedia
|
https://en.wikipedia.org/wiki/Rapid_%CA%BB%C5%8Chi%CA%BBa_Death
| 2021-01-18T18:47:23 |
{"wikidata": ["Q84504375"]}
|
Proximal femoral focal deficiency
Other namesCongenital Femoral Deficiency
13-year-old girl with PFFD
SpecialtyMedical genetics
Proximal femoral focal deficiency (PFFD), also known as Congenital Femoral Deficiency (CFD),[1] is a rare, non-hereditary birth defect that affects the pelvis, particularly the hip bone, and the proximal femur. The disorder may affect one side or both, with the hip being deformed and the leg shortened.
It is commonly linked with the absence or shortening of a leg bone (fibular hemimelia) and the absence of a kneecap. Other linked birth defects include the dislocation or instability of the joint between the femur and the kneecap, a shortened tibia or fibula, and foot deformities.
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Classifications
* 3 Treatment
* 4 References
* 5 External links
## Causes[edit]
The cause of PFFD is uncertain. Two hypotheses have been advanced. The theory of sclerotome subtraction posits injury to neural crest cells that are the precursors to sensory nerves at the level of L4 and L5.[2] Histologic studies of a fetus with unilateral PFFD have prompted an alternative hypothesis that PFFD is caused by a defect in maturation of chondrocytes (cartilage cells) at the growth plate.[3] In either hypothesis, the agent causing the injury is usually not known. Thalidomide is known to cause PFFD when the mother is exposed to it in the fifth or sixth week of pregnancy, and it is speculated that exposure to other toxins during pregnancy may also be a cause. Other etiologies that have been suggested, but not proven, include anoxia, ischemia, radiation, infection, hormones, and mechanical force. PFFD occurs sporadically, and does not appear to be hereditary.[2]
## Diagnosis[edit]
### Classifications[edit]
There are typically four classes (or types) of PFFD, ranging from class A to class D, as detailed by Aitken.[4]
## Treatment[edit]
Depending on the severity of the deformities, the treatment may include the amputation of the foot or part of the leg, lengthening of the femur, extension prosthesis, or custom shoe lifts. Amputation usually requires the use of prosthesis. Another alternative is a rotationplasty procedure, also known as Van Ness surgery. In this situation the foot and ankle are surgically removed, then attached to the femur. This creates a functional "knee joint". This allows the patient to be fit with a below knee prosthesis vs a traditional above knee prosthesis.[citation needed]
In less severe cases, the use of an Ilizarov apparatus can be successful in conjunction with hip and knee surgeries (depending on the status of the femoral head/kneecap) to extend the femur length to normal ranges. This method of treatment can be problematic in that the Ilizarov might need to be applied both during early childhood (to keep the femur from being extremely short at the onset of growth) and after puberty (to match leg lengths after growth has ended). The clear benefit of this approach, however, is that no prosthetics are needed and at the conclusion of surgical procedures the patient will not be biologically or anatomically different from a person born without PFFD.[citation needed]
In some cases the patient may not request treatment and instead elect to use a wheelchair or other aids to assist mobility.[citation needed]
## References[edit]
1. ^ "paleyinstitute.org - Congenital Femoral Deficiency". paleyinstitute. Retrieved 7 September 2014.
2. ^ a b Proximal Femoral Focal Deficiency at eMedicine
3. ^ Boden, SD; Fallon, MD; Davidson, R; Mennuti, MT; Kaplan, FS (1989). "Proximal femoral focal deficiency. Evidence for a defect in proliferation and maturation of chondrocytes". The Journal of Bone and Joint Surgery. 71 (8): 1119–29. doi:10.2106/00004623-198971080-00001. PMID 2777837.
4. ^ "Proximal Femoral Focal Dificiency".
## External links[edit]
Classification
D
* ICD-10: Q72.4
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Proximal femoral focal deficiency
|
c0431996
| 27,542 |
wikipedia
|
https://en.wikipedia.org/wiki/Proximal_femoral_focal_deficiency
| 2021-01-18T18:45:06 |
{"umls": ["C0431996"], "icd-10": ["Q72.4"], "wikidata": ["Q7252853"]}
|
## Description
Thyroglossal duct cysts are common benign cervical masses. They represent a remnant of the thyroglossal duct that fails to regress during fetal development. Nearly all cases present sporadically in young children as slowly enlarging midline neck mass (summary by Greinwald et al., 1996).
Clinical Features
Millikan et al. (1980) reported the condition in a mother, 2 daughters, 1 granddaughter, and 2 great-granddaughters. Two family branches were involved, and there were also other associated thyroid diseases, namely, hypothyroidism and thyroid cancer.
Issa and deVries (1991) reported 2 female sibs, aged 2 and 6 years, with thyroglossal duct cysts and a history of thyroid diseases on the maternal side. The maternal grandmother had autoimmune hypothyroidism (Hashimoto disease; 140300) and the maternal grandfather died of anaplastic carcinoma of the thyroid gland.
Castillo-Taucher and Castillo (1994) reported thyroglossal duct cysts in a father and daughter. The father was asymptomatic until 54 years of age, when an inflammatory mass appeared in the front middle part of his neck. Pathologic examination of the excised specimen confirmed the diagnosis. Late clinical manifestations might escape detection and could explain many undiagnosed cases.
Greinwald et al. (1996) and Schader et al. (2005) found that most reported cases of familial thyroglossal duct cyst are female.
Inheritance
From a review of the medical literature, Greinwald et al. (1996) and Schader et al. (2005) found that most cases of familial thyroglossal duct cysts show a pattern of autosomal dominant inheritance with incomplete penetrance.
Ashworth (1979) reported the disorder in 3 consecutive generations--a grandmother, mother, and daughter.
Klin et al. (1993) described a Moslem Arab family with healthy second-cousin parents in which 3 sibs were affected. In a second family, a father and son were affected.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
THYROGLOSSAL DUCT CYST, FAMILIAL
|
c3495590
| 27,543 |
omim
|
https://www.omim.org/entry/188455
| 2019-09-22T16:32:32 |
{"mesh": ["C536909"], "omim": ["188455"], "orphanet": ["93953"]}
|
Pineocytoma
Other namesPinealocytoma
Micrograph of a pineocytoma. HPS stain.
SpecialtyOncology
Pineocytoma, is a benign, slowly growing tumor of the pineal gland. Unlike the similar condition pineal gland cyst, it is uncommon.
## Contents
* 1 Diagnosis
* 2 Management
* 3 See also
* 4 References
* 5 External links
## Diagnosis[edit]
Pineocytomas are diagnosed from tissue, i.e. a brain biopsy.
They consist of:
* cytologically benign cells (with nuclei of uniform size, regular nuclear membranes, and light chromatin)[citation needed] and,
* have the characteristic pineocytomatous/neurocytic rosettes, which is an irregular circular/flower-like arrangement of cells with a large meshwork of fibers (neuropil) at the centre.[1] Pineocytomatous/neurocytic rosettes are superficially similar to Homer Wright rosettes; however, they differ from Homer Wright rosettes as they have (1) more neuropil at centre of the rosette and, (2) the edge of neuropil meshwork irregular/undulating.
## Management[edit]
This section is empty. You can help by adding to it. (November 2017)
## See also[edit]
* Pineal gland
## References[edit]
1. ^ Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol. 27 (3): 488–92. PMID 16551982.
## External links[edit]
Classification
D
* ICD-10: C75.3
* ICD-O: M9361/1
* MeSH: D010871
* v
* t
* e
Tumours of endocrine glands
Pancreas
* Pancreatic cancer
* Pancreatic neuroendocrine tumor
* α: Glucagonoma
* β: Insulinoma
* δ: Somatostatinoma
* G: Gastrinoma
* VIPoma
Pituitary
* Pituitary adenoma: Prolactinoma
* ACTH-secreting pituitary adenoma
* GH-secreting pituitary adenoma
* Craniopharyngioma
* Pituicytoma
Thyroid
* Thyroid cancer (malignant): epithelial-cell carcinoma
* Papillary
* Follicular/Hurthle cell
* Parafollicular cell
* Medullary
* Anaplastic
* Lymphoma
* Squamous-cell carcinoma
* Benign
* Thyroid adenoma
* Struma ovarii
Adrenal tumor
* Cortex
* Adrenocortical adenoma
* Adrenocortical carcinoma
* Medulla
* Pheochromocytoma
* Neuroblastoma
* Paraganglioma
Parathyroid
* Parathyroid neoplasm
* Adenoma
* Carcinoma
Pineal gland
* Pinealoma
* Pinealoblastoma
* Pineocytoma
MEN
* 1
* 2A
* 2B
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Pineocytoma
|
c0917890
| 27,544 |
wikipedia
|
https://en.wikipedia.org/wiki/Pineocytoma
| 2021-01-18T18:41:20 |
{"gard": ["8207"], "mesh": ["D010871"], "umls": ["C0917890"], "orphanet": ["251912"], "wikidata": ["Q17106360"]}
|
Cerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral).
Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time.
There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation.
## Frequency
Cerebral cavernous malformations affect about 16 to 50 per 10,000 people worldwide.
## Causes
Mutations in at least three genes, KRIT1 (also known as CCM1), CCM2, and PDCD10 (also known as CCM3), cause familial cerebral cavernous malformations.
The precise functions of these genes are not fully understood. Studies show that the proteins produced from these genes are found in the junctions connecting neighboring blood vessel cells. The proteins interact with each other as part of a complex that strengthens the interactions between cells and limits leakage from the blood vessels. Mutations in any of the three genes impair the function of the protein complex, resulting in weakened cell-to-cell junctions and increased leakage from vessels as seen in cerebral cavernous malformations.
Mutations in these three genes account for 85 to 95 percent of all cases of familial cerebral cavernous malformations. The remaining 5 to 15 percent of cases may be due to mutations in unidentified genes or to other unknown causes. Mutations in the KRIT1, CCM2, and PDCD10 genes are not involved in sporadic cerebral cavernous malformations. The cause of this form of the condition is unknown.
### Learn more about the genes associated with Cerebral cavernous malformation
* CCM2
* KRIT1
* PDCD10
## Inheritance Pattern
This condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In the familial form, an affected person inherits the mutation from one affected parent.
Most people with cerebral cavernous malformations have the sporadic form of the disorder. These cases occur in people with no history of the disorder in their family.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Cerebral cavernous malformation
|
c2919945
| 27,545 |
medlineplus
|
https://medlineplus.gov/genetics/condition/cerebral-cavernous-malformation/
| 2021-01-27T08:25:32 |
{"gard": ["1204"], "mesh": ["D020786"], "omim": ["116860"], "synonyms": []}
|
A number sign (#) is used with this entry because familial Mediterranean fever is caused by mutation in the pyrin gene (MEFV; 608107).
Description
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. Amyloidosis with renal failure is a complication and may develop without overt crises (French FMF Consortium, 1997).
See also autosomal dominant FMF (134610), which is caused by heterozygous mutation in the MEFV gene.
Clinical Features
Siegal (1945) reported 'benign paroxysmal peritonitis.' Under the term 'periodic peritonitis,' Reimann et al. (1954) described 72 cases from Lebanon, most of them Armenian. In 1 remarkable family, survivors of the siege of Musa Dagh, 20 affected persons occurred in 5 generations, with 3 instances of skips in the pedigree. The high gene frequency and small breeding group could account for the findings as representing pseudodominant inheritance. Sokmen (1959) noted that many cases of FMF in Turkey were observed in persons without known Armenian ancestry. This condition was called 'familial paroxysmal polyserositis' by Siegal (1964), who was the first to delineate the disorder clearly in the United States and who observed rather numerous cases in Ashkenazim. Barakat et al. (1986) referred to FMF as 'recurrent hereditary polyserositis.'
Armenian (1983) compared the characteristics of 79 patients seen for the first time in a special clinic for FMF in its first 16 months of operation with the characteristics of 79 patients who presented during the last 6 years of its operation. The patients studied during the first period had a more severe form of the disease with multiple clinical manifestations such as proteinuria and amyloidosis. There were more males and more patients with a positive family history in the earlier group. Armenian (1983) emphasized the importance of a population base and 'enrollment bias'--differences in referral pattern, in case selection, and in the sources of data--in accounting for significant variation in the frequency of various clinical manifestations in published series of FMF cases.
In a study of FMF in Kuwait, Barakat et al. (1986) reported on an 11-year experience with 175 Arab patients. The most common manifestation was peritonitis (94%), followed by arthritis (34%) and pleurisy (32%). Amyloidosis, rashes, hepatosplenomegaly, and lymphadenopathy were rare.
Mollaret (1944) described a syndrome of benign, recurrent meningitis with a characteristic spinal fluid picture: pleocytosis of mixed cellular type including endothelial cells (Mollaret cells) during the attack, in the absence of any positive agent. These attacks were separated by symptom-free periods lasting from days to years. Recovery was complete, with no neurologic deficit. Barakat et al. (1988) concluded that Mollaret meningitis is a feature of FMF. Schwabe and Monroe (1988) described a 32-year-old non-Ashkenazi Jewish man in whom meningitis first developed in Morocco at the age of 1 year. Between the ages of 26 and 31 years, he had 6 attacks of fever, frontal headache, nausea, and stiff neck, with positive Kernig and Brudzinski signs. In Saudi Arabia, Majeed and Barakat (1989) found that 48 of 88 affected children had onset before the age of 5 years.
In a 60-year-old Arab man with FMF, Agmon et al. (1984) observed selective amyloid involvement of the zona glomerulosa of the adrenal cortex resulting in isolated hypoaldosteronism. As a rule, the glomerulosa is spared in adrenal amyloidosis of FMF. Knecht et al. (1985) found abnormally high levels of serum amyloid A (SAA; 104750) in attack-free intervals and very high levels at the onset of attacks. Although there is a striking difference in the frequency of amyloid nephropathy in different ethnic groups with FMF, the elevation of SAA during and between attacks is the same, and interethnic marriages produce affected progeny (Pras et al., 1982).
Rawashdeh and Majeed (1996) reviewed findings from the FMF pediatric patient population in northern Jordan (all children were of Jordanian, Palestinian, or Syrian origin). The 192 patients first presented between the age of 4 months and 16 years. The mean delay in diagnosis was 3.7 years and was increased for children who presented before the age of 2 years. Abdominal pain was the most common presenting symptom and occurred in 51%, while arthritis and pleuritis occurred in 26% and 23%, respectively. The investigators noted that family history was positive in 62% of the children, which was not surprising in this autosomal recessive disorder given the 64% consanguinity rate in northern Jordan. Minimum prevalence was given as 1 in 2,600 with an estimated gene frequency in the childhood population of 1 in 50 (calculated on the numbers of diagnosed patients). The authors warned that the frequency of FMF among Jordanian Arab children was greater than previously estimated.
Eshel et al. (1988) suggested that acute, unilateral, short-term orchitis is a feature of FMF; they observed 20 episodes in 13 patients. Ozyilkan et al. (1994) suggested that bronchial asthma is abnormally infrequent in FMF patients. This was the case not only in patients on colchicine because an absence of a history of asthma before the diagnosis of FMF was also found.
In Ankara, Turkey, Saatci et al. (1997) analyzed 425 FMF patients without and 180 with amyloidosis. Of the latter group, 103 had amyloidosis type I and 57 had amyloidosis type II. Type I amyloidosis was defined as amyloidosis developing subsequent to clinical features of FMF, whereas type II was defined as amyloidosis developing as the initial manifestation. The male-to-female ratio was higher in the amyloidosis population (111 to 69) than it was in the FMF population without amyloidosis (225 to 200) (P = 0.048). The consanguinity rate was the same in the 2 groups. A family history of amyloidosis was significantly more frequent in the amyloidosis group (P = 0.0001). The combination of positive family history of amyloidosis and consanguinity increased the risk of amyloidosis more than 6 fold. The 5-year chronic renal failure-free survival was 43.1% and 18.7% in type I and type II amyloidosis, respectively. Saatci et al. (1997) found 10 cases of Henoch-Schonlein purpura and 9 of polyarteritis nodosa among their patients. The significance of the association between FMF and vasculitis was unclear. Among 435 FMF patients treated with colchicine, only 10 (2.3%) developed amyloidosis, thus confirming that this drug protects patients from the complication.
In a retrospective study of 4,000 FMF patients, using a computer chart review, Kees et al. (1997) found that during a 20-year period, one or more episodes of pericarditis were recorded in 27 patients. Each patient experienced 1 to 3 pericarditis attacks, lasting a mean of 4.2 days, accompanied by elevated temperature and symptoms of FMF attack at another site. The pericarditis resolved spontaneously and left no sequelae.
Commenting on a paper by Yazigi and Abou-Charaf (1998), Tutar et al. (1999) noted that recurrent pericarditis can be the initial sole manifestation of FMF and suggested that mutation analysis for FMF be considered in patients with idiopathic recurrent pericarditis, especially if they are of Mediterranean origin.
Pras et al. (1998) compared the clinical features of FMF in North African Jews and Iraqi Jews, the 2 largest population groups suffering from the disease in Israel. North African Jews were found to have more severe disease manifested by earlier age of onset, increase in frequency and severity of joint involvement, higher incidence of erysipelas-like erythema, and higher dose of colchicine required to control symptoms.
Cattan et al. (2000) studied the incidence of inflammatory bowel disease (IBD; 266600) in non-Ashkenazi Jewish patients with FMF. Cattan et al. (2000) estimated a prevalence of at least 3 per 300 (or 3 per 173 if the calculation is done through probands) in non-Ashkenazi Jews with FMF. They postulated that the inflammatory processes of FMF and IBD are additive, resulting in increased severity of disease in the new patients.
Tamir et al. (1999) characterized a late-onset form of FMF with distinct clinical, demographic, and molecular genetic characteristics. This subset of patients experienced their first FMF attack at age 40 years or later. The comparison group consisted of 40 consecutive FMF patients who arrived at the FMF clinic for their regular follow-up visit and were 40 years of age or older at the time of examination. Only 20 of 4,000 (0.5%) patients had late-onset FMF. These patients were mostly men, of non-North African origin (P less than 0.05 compared to controls). All had abdominal attacks and in most these were the only manifestation of their disease (P less than 0.001). None had chronic or prolonged manifestations of FMF such as amyloidosis, chronic arthritis, or protracted myalgia (P less than 0.001). The response to treatment was good despite using low colchicine dosage (P less than 0.05). The overall severity score indicated a mild disease (P less than 0.001). Mutation analysis revealed absence of M694V homozygosity (P less than 0.01), compared to the regular FMF population. Tamir et al. (1999) concluded that the onset of FMF at a late age defines a milder form of disease with typical clinical, demographic, and molecular genetic characteristics.
Other Features
Schwabe and Lehman (1984) reviewed the search for the basic defect in this disorder. Normal peritoneal fluid contains an inhibitor of neutrophil chemotaxis that acts by antagonizing the complement-derived chemotactic anaphylatoxin C5a (113995). The inhibitor resembles a substance found in synovial fluids and is a protein with molecular weight 40,000. Matzner and Brzezinski (1984) found that this inhibitory activity was less than 10% of normal in peritoneal fluid from FMF patients. Inadequate suppression of the inflammatory response to C5a that is released accidentally may be responsible for the inappropriate inflammatory reactions of FMF. Colchicine may prevent attacks by suppressing neutrophil motility and blocking their mobilization to sites of C5a release. Matzner et al. (1984) found a decrease of the C5a inhibitory activity in synovial fluid from patients with FMF. Patients with other forms of inflammatory arthritis and osteoarthritis had normal levels. Ayesh et al. (1990) further characterized the 40-kD inhibitor protein and showed that it is a serine protease. Documentation of a carrier state of reduced C5a-inhibitor activity in unaffected obligatory heterozygotes such as parents or offspring would help establish the inhibitor as the site of the primary defect. The patients studied by Matzner and Brzezinski (1984) were Sephardim; comparable studies in Armenians with FMF would be of interest because of the much lower frequency of amyloidosis with FMF in this ethnic group (Schwabe and Peters, 1974).
Inheritance
Rogers et al. (1989) presented evidence indicating autosomal recessive inheritance of FMF in Armenians. Using extended pedigree data, they calculated an FMF gene frequency of 0.073 and a carrier rate of 1 in 7, which is about 4 times the frequency in non-Ashkenazi Jews. Four of 64 families had 1 parent affected as well as the proband; the high gene frequency could explain this phenomenon. The male/female ratio of 1.7 found in non-Ashkenazi Jews indicates reduced penetrance in females and probably also obtains in Armenians.
Shohat et al. (1992) found concordance for FMF in all 10 monozygotic twin pairs and only 3 of 11 dizygotic twin pairs. However, variability in the clinical manifestations and degree of severity were noted within twin pairs, supporting the contention that the lower than expected incidence of FMF observed in segregation analysis is due to genetically affected but clinically undiagnosed patients.
Yuval et al. (1995) found 77 families, with 240 FMF patients, in which the disorder affected more than one generation. In 75 of these families, the occurrence of FMF in more than one generation was found to be consistent with a recessive mode of inheritance due to a high gene frequency and consanguinity of the parents. In 2 families, however, one of Ashkenazi and the other of Georgian Iraqi origin, in which FMF occurred in 4 consecutive generations, the transmission could be explained only by autosomal dominant inheritance. Aksentijevich et al. (1999) found that the inheritance in the Ashkenazi family reported by Yuval et al. (1995) as an unusual instance of dominantly inherited FMF was in fact recessive inheritance of the E148Q mutation (607108.0005) which has a high frequency and reduced penetrance among Ashkenazi Jews.
Diagnosis
By means of a placebo-controlled, double-blind, crossover study, Barakat et al. (1984) demonstrated that intravenous infusion of 10 mg of metaraminol bitartrate ('Aramine') in 500 ml normal saline over a period of 3 to 4 hrs was followed by a typical attack of FMF in all of 21 persons with the disease and in none of 21 control subjects. The induced attacks were milder and of shorter duration than the spontaneous ones. The metaraminol-induced attacks could be prevented with colchicine. In connection with the metaraminol provocative test for the diagnosis of FMF (Cattan et al., 1984), Barakat et al. (1984) suggested that abdominal tenderness should be included as a feature indicating positive test.
Fischel-Ghodsian et al. (1993) identified 2 flanking markers and microsatellite markers on chromosome 16p that allowed preclinical diagnosis in most pedigrees with affected persons. Dupont et al. (1997) proposed the use of a set of 7 microsatellite markers for diagnosis and heterozygote analysis: D16S283 and D16S3124, telomeric of the FMF disease gene; D16S3070, D16S3082, and D16S3275, which showed no recombination with disease; and D16S2622 and D16S3027, centromeric of the FMF locus. They found this set of markers to be informative in 100% of previously diagnosed non-Ashkenazi Jewish patients. In addition, 73% of patients from this population were homozygous for the 3-3-9 or 3-3-18 haplotype at D16S3070, D16S3082, and D16S3275. Dupont et al. (1997) suggested that these markers could be used for diagnosis of sporadic cases in this population, although absence of homozygosity would not exclude the diagnosis.
Brik et al. (2001) looked for the presence of the 5 most common FMF mutations (M694V, V726A, M694I, M680I, E148Q) in 59 Sephardic Jewish and Israeli Arab children who had been diagnosed with functional abdominal pain. Eight (34.7%) of the Arab children and 4 (11%) of the Sephardic Jewish children were genetically diagnosed as having FMF. Ten children were heterozygous for 1 mutation. The authors suggested that a higher percentage of Arab children were genetically diagnosed since FMF in Arabs is a milder disease and more likely to be undiagnosed clinically. They noted that testing may spare patients from a fruitless workup and allow institution of colchicine therapy to ameliorate the course of the illness and prevent amyloidosis.
Clinical Management
Goldfinger (1972), Wolff et al. (1974), and Ravid et al. (1977) reported benefit from colchicine in reducing painful attacks in FMF.
Zemer et al. (1986) presented evidence that colchicine prevents and ameliorates amyloidosis in FMF. They followed 1,070 patients with FMF for 4 to 11 years after they were advised to take colchicine to prevent febrile attacks. Overall, at the end of the study, the prevalence of nephropathy was one-third of that in a study conducted before colchicine was used to treat FMF. Among 960 patients who initially had no evidence of amyloidosis, proteinuria appeared in 4 who adhered to a prophylactic schedule and in 16 of 54 who admitted noncompliance. Life-table analysis showed that the cumulative rate of proteinuria was 1.7% after 11 years in the compliant patients and 48.9% after 9 years in the noncompliant patients. All 24 patients with nephrosis or uremia had progressive deterioration of renal function. In 86 patients with proteinuria but no nephrotic syndrome, proteinuria resolved in 5 and stabilized in 68 (for more than 8 years in 40 patients). In the experience of Knecht et al. (1985), patients in whom colchicine fails to prevent attacks and SAA spikes enjoy as effective protection against renal amyloidosis as do colchicine-responsive patients. Jones et al. (1977) and Benson et al. (1977) reported recurrence of amyloid in kidney after renal transplant in FMF.
Schwabe and Nishizawa (1987) described a 36-year-old male of pure Japanese ancestry with a classic 20-year history of recurrent FMF manifested by self-limited attacks of fever plus pleuritis, peritonitis, or arthritis. The attacks were completely suppressed by daily prophylactic colchicine but recurred when the drug was briefly discontinued. He had been free of attacks for 10 years while taking 1.2 mg of colchicine daily.
Zemer et al. (1993) reported a family in which 6 of 9 sibs had FMF, the oldest born in 1950 and the youngest in 1970. The youngest was brought for clinical examination at the age of 12 years by his 'painfully experienced and observant mother' because his urine looked suspicious, and proteinuria was found. With continuous colchicine treatment, proteinuria persisted for 3 years and then gradually subsided over the next 2 years. By the age of 22 years, his urine had been free of protein for 5 years.
Ben-Chetrit et al. (1996) measured simultaneous colchicine levels in serum and breast milk in 4 breast-feeding women with a diagnosis of FMF for over 7 years. The authors found that the levels of colchicine in serum and breast milk paralleled each other. The peak concentration of colchicine occurred between 1 to 3 hours in all women. They found no abnormalities in the 4 children after 10 months of follow-up. Although the authors postulated that colchicine did 'no harm to the breast feeding infant,' they also stated that some women may consider breastfeeding 12 hours after the colchicine has been ingested and bottle feed for the other 12 hours.
Milledge et al. (2002) serendipitously found that allogeneic bone marrow transplantation (BMT) can cure FMF. They described a 7-year-old girl with congenital dyserythropoietic anemia (CDA; see 224120) who also had FMF and carried the MEFV M680I mutation (608107.0004), which was inherited from her father. Repeated transfusions required since the age of 6 months to treat her CDA led to iron overload and a persistently high ferritin level. Relapsing FMF made effective iron chelation therapy very difficult. Consequently, at the age of 4 years, she underwent allogeneic BMT from her brother, who did not carry the M680I mutation. During conditioning for her BMT, symptoms of FMF, including splenomegaly, arthritis, and recurrent abdominal pain, began to resolve and she was gradually weaned off colchicine. Two years after the transplantation, she remained free from FMF symptoms and was off all immunosuppressants. Milledge et al. (2002) stated that the findings in this patient demonstrated that symptoms of FMF can be alleviated by the therapy used during allogeneic BMT, and that it was likely that the missing factor in FMF in this patient was provided by granulocytes derived
from the stem cells within transplanted bone marrow. Both the patient and her donor brother had 6 silent polymorphisms of the MEFV gene inherited from the mother. Touitou (2003) suggested that the 'assertion (that through BMT the missing factor in FMF was provided) should be tempered.' Touitou et al. (2003) maintained that BMT has no role in the treatment of FMF, given the morbidity and mortality associated with BMT, and given that FMF is a self-limited disease with an overall good prognosis when colchicine is properly adjusted. They suggested that even in the setting of a well-designed research study, the ethical issue of offering this high-risk, unproven procedure to children is particularly troubling.
Touitou et al. (2007) reported transmission of an FMF mutation via bone marrow transplantation between 2 brothers of Sephardic Jewish origin. One brother had idiopathic aplastic anemia and received allogenic bone marrow transplant from his identical brother at age 5 years. At age 6 years, the donor brother developed clinical features of FMF, which was confirmed by genetic analysis. The transplanted brother, who was born without the FMF mutation, was found to have circulating FMF mutated cells, which fluctuated from 77 to 86.5%. However, by age 8 years, the recipient had not developed symptoms of the disorder.
Pathogenesis
Babior and Matzner (1997) suggested that the pathogenesis of FMF is as follows: pyrin, or marenostrin, is postulated to activate the biosynthesis of a chemotactic factor inactivator, an enzyme that normally occurs in the serosal fluids. They suggested that a chemotactic factor (probably C5a; 113995) can be released by subclinical injury to the serosa during normal activities, but the amounts released are small enough that they are cleared by the inactivating enzyme before they can provoke an inflammatory reaction. In FMF the inactivating enzyme is absent, allowing the chemotactic factors to survive long enough to call in neutrophils, which then release a variety of products, including an enzyme that generates more C5a. The result is an upward spiral that culminates in a full-blown inflammatory reaction: an attack of FMF.
Mapping
In linkage studies in Armenians, Shohat et al. (1990) excluded FMF from those portions of the genome at least 15 cM from 14 genetic markers, and in other linkage studies, Shohat et al. (1990) concluded that the immunogenetic region of chromosome 6 could be excluded from linkage with FMF in Armenian families. By linkage analysis, Gruberg et al. (1991) excluded several candidate genes including lipocortins, dopamine beta-hydroxylase, and interleukins 1 and 6. Kastner et al. (1991) presented a 90-marker exclusion map. With marker D17S74 on chromosome 17, they obtained a maximum multipoint lod score of 3.54 approximately 15 cM telomeric to the marker.
Pras et al. (1992) succeeded in mapping the FMF gene to 16p by linkage studies in 27 non-Ashkenazi Jewish families in Israel. One DNA marker, D16S84, gave a maximum lod score of 9.17 at a recombination frequency of 0.04. A probe associated with the hemoglobin alpha complex (5-prime-HVR) gave a maximum lod score of 14.47 at theta = 0.06. Multipoint analysis indicated that the likely order is as follows: cen--FMF--D16S84--HBA--tel. The maximum multipoint lod score was 19.86. There was a striking degree of homozygosity at chromosome 16p loci in the affected offspring of 8 consanguineous couples, thus supporting linkage by the method of homozygosity mapping. Pras et al. (1992) and Fischel-Ghodsian et al. (1992) found that the FMF gene maps to 16p in all ethnic groups, including Armenians and Ashkenazi and non-Ashkenazi Jews.
Studying 14 Armenian and 9 non-Ashkenazi Jewish families with FMF, Shohat et al. (1992) found linkage to the alpha-globin complex on 16p in both groups, with no evidence for genetic heterogeneity either between the groups or within the groups. Aksentijevich et al. (1992, 1993) observed different haplotypes associated with the disease in strong linkage disequilibrium in Moroccan and Iraqi Jewish families. This, together with the fact that Moroccans had a much more severe form of FMF, suggested that the 2 groups carry different allelic mutations. The mutation in Armenians may also be different from that in Moroccans, accounting for the milder phenotype.
Aksentijevich et al. (1993) attempted more precise mapping of MEFV by the homozygosity method for 8 of 9 markers. The rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEFV more precisely on the basis of homozygosity rates alone would be difficult, they concluded, for 2 reasons: the high FMF carrier frequency increases the chance that inbred offspring have the disease without being homozygous by descent at the MEFV locus; and several of the markers in the MEFV region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location.
Aksentijevich et al. (1993) reexamined the linkage data to ascertain the possible reason for the earlier conclusion that the gene causing FMF is on 17q (Kastner et al., 1991). They found that the data with the chromosome 17 markers alone suggested locus heterogeneity. Nonetheless, the families were not separable into complementary subgroups showing linkage either to chromosome 16 or to chromosome 17. They examined the possibility that the positive lod score for chromosome 17 might reflect a secondary, modifying locus. However, by several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. They concluded that chromosome 17 does not carry a major FMF susceptibility gene for some families and does not encode a disease-modifying gene. Rather, it appeared that linkage to chromosome 17 was a 'false positive' (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive.
FMF in the Arab population is said to be characterized by a low incidence of arthritis, amyloidosis, and erysipeloid erythema. These differences in disease expression raise the possibility of locus heterogeneity. However, Pras et al. (1994) found that the FMF gene maps to 16p in Druze and Moslem Arab families. Shohat et al. (1992) had shown that the gene maps to the same region in Armenians and non-Ashkenazi Jews.
Using linkage disequilibrium mapping in the study of 65 Jewish, Armenian, and Arab families, Levy et al. (1996) obtained a maximum lod score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype using 3 markers was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, Levy et al. (1996) analyzed the Moroccan linkage-disequilibrium data and placed the FMF susceptibility gene within 0.305 cM of D16S246.
The French FMF Consortium (1996) narrowed the location of the FMF gene to a 250-kb interval through the study of non-Ashkenazi Jewish founder haplotypes accomplished by use of 15 microsatellite markers. They concluded that the FMF locus is situated between D16S3070 and D16S3275. Sood et al. (1997) used a high-resolution clone map of the 16p13.3 region to narrow the FMF interval. They identified several founder haplotypes in various ethnic groups.
Akarsu et al. (1997) studied 8 consanguineous Turkish families with at least 2 offspring affected with FMF. In 6 of these families, linkage was observed with a maximum lod score of 9.115 at theta = 0.00 for marker D16S3024. Two families, however, were unlinked to this region. Haplotype construction showed homozygosity for the region bounded by D16S3070 and D16S2617 in 5 families; 80% allelic association was shown with D16S2617.
Molecular Genetics
By screening 165 individuals from 65 families with familial Mediterranean fever, the International FMF Consortium (1997) identified 3 different missense mutations in exon 10 of the MEFV gene (M694V; 608107.0001, V726A; 608107.0003, and M680I; 608107.0004) that accounted for 78 carrier chromosomes.
The French FMF Consortium (1997) identified 4 sequence variations (608107.0001-608107.0004) in the marenostrin gene that correlated with FMF in various ethnic groups. In 72% of the patients in their sample, 1 or 2 of the 4 mutations were found.
For a detailed discussion of GENOTYPE/PHENOTYPE CORRELATIONS, see 608107.
Cazeneuve et al. (2003) analyzed a group of 50 patients with FMF from Karabakh, where the population is mainly of Armenian descent, and reviewed published series of classically affected populations. They found that whereas the distribution of genotypes at the MEFV locus differed dramatically from the Hardy-Weinberg equilibrium (p = 0.0016 and p less than 0.00001, respectively), the distribution of the most common MEFV mutations did not. Based on these results and other population genetics-based data, Cazeneuve et al. (2003) suggested the existence of a novel FMF-like condition that, depending upon the patients' ancestry, would affect 85 to 99% of those with no identified mutation in the MEFV gene.
Population Genetics
For a detailed discussion of particular allele and mutation frequencies of the MEFV gene in different populations, see 608107.
Sohar et al. (1967) estimated that in some Jewish groups the frequency of familial Mediterranean fever is 1 in 2,720 and that the minimal estimates for gene frequency and heterozygote frequency are 1 in 52 and 1 in 26, respectively. The number of Ashkenazi cases observed in Israel by Sohar et al. (1967) explains that a fair number of cases are observed in the large Ashkenazi group in the United States. Familial Mediterranean fever occurs mainly in Armenians and Sephardic Jews (those who left Spain during the Inquisition and settled in various countries bordering the Mediterranean). The possibility that the disorder in Armenians is distinct from that in Sephardic Jews is suggested by the lower frequency of amyloidosis (Schwabe and Peters, 1974) and longer average survival. Schwabe et al. (1977) reported 197 patients: 131 Armenians, 11 Ashkenazim, 27 non-Ashkenazi Jews, and 28 others. In an analysis of 1,327 cases from the literature, Meyerhoff (1980) found that 50% were Sephardic, 22% Armenian, 11% Arabian, 7% Turkish, and 5% Ashkenazi. Rawashdeh and Majeed (1996) reviewed the incidence of amyloidosis complicating FMF among several Mediterranean ethnic groups.
Using extended pedigree data of 90 FMF probands, Daniels et al. (1995) calculated the FMF gene frequency in various ethnic groups in Israel by analyzing the frequency in a total of 2,312 first cousins. The heterozygote frequencies were as follows: 1 in 4.9 (0.2 +/- 0.06) for the Libyan subgroup; 1 in 6.4 (0.16 +/- 0.03) for the subgroup from other North African countries; 1 in 13.3 (0.07 +/- 0.04) for the Iraqi subgroup; 1 in 11.4 (0.09 +/- 0.06) for the Ashkenazi subgroup; and 1 in 29.4 (0.03 +/- 0.03) for the remaining ethnic groups. The observed number of affected parents and affected offspring of probands was in agreement with the estimated gene frequency. Pras et al. (1998) commented that North African Jews and Iraqi Jews were the 2 largest population groups suffering from FMF in Israel. North African Jews were found to have more severe disease manifested by earlier age of onset, increase in frequency and severity of joint involvement, higher incidence of erysipelas-like erythema, and higher dose of colchicine required to control symptoms.
El-Shanti et al. (2006) provided a detailed review of FMF in the Arab population.
In a metaanalysis based on literature reports of 16,756 chromosomes from FMF patients and normal individuals from 14 affected populations, Papadopoulos et al. (2008) demonstrated that MEFV mutations were not distributed uniformly along the Mediterranean Sea area. The most frequent mutations were M694V (39.6%), V726A (13.9%), M680I (11.4%), E148Q (608107.0005) (3.4%), and M694I (608107.0002) (2.9%). However, 28.8% of chromosomes did not have identified mutations, particularly among western Europeans. The mean overall carrier rate was 0.186 with peak values in Arab, Armenian, Jewish, and Turkish populations. The V726A mutation was the only mutation to show Hardy-Weinberg equilibrium, implying that this mutation is the most ancient. Individuals in the Jewish population presented the most intense genetic isolation and drift, suggesting that they might have nested de novo mutations and accelerated evolution. Additional population groups appeared to follow distinct evolutionary lines in Asia Minor, eastern Europe, and western Europe.
Bonyadi et al. (2009) studied 524 unrelated Iranian patients of Azeri Turkish origin with FMF and identified mutations in the MEFV gene in 57% of alleles. The R761H was the most frequent (4.7%) of the rare alleles, and the authors suggested that R761H should be included in routine molecular diagnosis of FMF patients from this ethnic group. Bonyadi et al. (2009) concluded that FMF is no longer a rare disease in Iran.
Among 15,854 ethnically diverse individuals screened for familial Mediterranean fever carrier status, Lazarin et al. (2013) identified 247 carriers (1.6%), for an estimated carrier frequency of 1 in 64. Three individuals were identified as homozygotes or compound heterozygotes. Five 'carrier couples' were identified. Of 745 individuals of southern European origin, a carrier frequency of 1 in 75 was found. Of 392 individuals of Middle Eastern origin, a carrier frequency of 1 in 25 was found.
History
Sack (1988) found novel structural changes in members of the serum amyloid A gene family in 4 FMF patients of varied ethnic backgrounds. He interpreted these observations as suggesting 'that alterations of serum amyloid A genes, their protein products, and/or their regulation may be responsible' for FMF. Shohat et al. (1989, 1990) and Sack et al. (1991) excluded close linkage between FMF and the SAA locus (104750), however. Similarly, Shohat et al. (1989, 1990) demonstrated that the gene for serum amyloid P component (104770) is not closely linked to the locus for FMF. The complication of amyloidosis varies in frequency among various ethnic groups. Although FMF might not be 'caused' primarily by a mutation in the SAA or SAP gene, proneness to amyloidosis might differ according to a particular polymorphic allele at one or the other locus carried by the ethnic group. The failure of Shohat et al. (1990) to find an association of a particular polymorphism with amyloidosis probably rules out this possibility. Shohat et al. (1989) advanced the hypothesis that FMF patients are homozygous for a mutant allele for one of the lipocortin genes (151690), resulting in either lipocortin deficiency or production of an abnormal lipocortin protein. Lipocortin may be especially critical during stress. Its deficiency could result in a lack of feedback inhibition and an increase in the release of arachidonic acid, precursor of the potent mediators of inflammation. The deficiency might result in increased generation of prostaglandins, leukotrienes, and other inflammatory mediators by granulocytes, which then further activate phospholipase A2 by a feedback mechanism.
INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Pericarditis RESPIRATORY Lung \- Pleuritis ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly Gastrointestinal \- Peritonitis \- Abdominal pain GENITOURINARY External Genitalia (Male) \- Tunica vaginalis inflammation (orchitis) Kidneys \- Nephrotic syndrome \- Renal amyloidosis \- Renal failure SKELETAL \- Monarticular or oligoarticular arthritis \- Arthralgia SKIN, NAILS, & HAIR Skin \- Transient painful erysipelas-like lesions on lower leg and ankle NEUROLOGIC Central Nervous System \- Meningitis METABOLIC FEATURES \- Fever, episodic LABORATORY ABNORMALITIES \- Prominent leukocytosis (30,000/ml) \- Elevated erythrocyte sedimentation rate MISCELLANEOUS \- Prevalent in Arabic, Turkish, Armenian, and Sephardic Jewish populations \- Onset often begins in childhood or adolescence \- Acute attacks lasting 24-48 hours \- Attack frequency may occur several times per week to once per year \- See also autosomal dominant FMF ( 134610 ), caused by heterozygous mutations in the MEFV gene MOLECULAR BASIS \- Caused by mutations in the pyrin gene (MEFV, 608107.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
FAMILIAL MEDITERRANEAN FEVER
|
c0031069
| 27,546 |
omim
|
https://www.omim.org/entry/249100
| 2019-09-22T16:25:31 |
{"doid": ["2987"], "mesh": ["D010505"], "omim": ["249100"], "icd-9": ["277.31"], "icd-10": ["M04.1"], "orphanet": ["342"], "synonyms": ["Alternative titles", "FAMILIAL MEDITERRANEAN FEVER, AUTOSOMAL RECESSIVE", "POLYSEROSITIS, RECURRENT", "POLYSEROSITIS, FAMILIAL PAROXYSMAL"], "genereviews": ["NBK1227"]}
|
Chylomicron retention disease is an inherited disorder that impairs the normal absorption of fats, cholesterol, and certain vitamins from food. The features of chylomicron retention disease primarily affect the gastrointestinal system and nervous system.
Chylomicron retention disease begins in infancy or early childhood. Affected children have slow growth and weight gain, frequent (chronic) diarrhea, and foul-smelling stools (steatorrhea). They also have reduced blood cholesterol levels (hypocholesterolemia). Some individuals with chylomicron retention disease develop an abnormal buildup of fats in the liver called hepatic stenosis and can have an enlarged liver.
Other features of chylomicron retention disease develop later in childhood and often impair the function of the nervous system. Affected people may develop decreased reflexes (hyporeflexia) and a decreased ability to sense vibrations. Rarely, affected individuals have heart abnormalities or muscle wasting (amyotrophy).
## Frequency
Chylomicron retention disease is a rare condition with approximately 50 cases described worldwide.
## Causes
Mutations in a gene called SAR1B cause chylomicron retention disease. The SAR1B gene provides instructions for making a protein that is needed for the transport of molecules called chylomicrons. During digestion, chylomicrons are formed within cells called enterocytes that line the small intestine and absorb nutrients. Chylomicrons are needed to absorb fat-soluble vitamins and carry fats and cholesterol from the small intestine into the bloodstream.
SAR1B gene mutations cause the retention of chylomicrons within enterocytes and prevent their release into the bloodstream. Impaired chylomicron transport causes severely decreased absorption (malabsorption) of dietary fats and fat-soluble vitamins, leading to nutritional and developmental problems in people with chylomicron retention disease. Affected individuals are unable to absorb sufficient fats, cholesterol, and vitamins that are necessary for normal growth and development.
### Learn more about the gene associated with Chylomicron retention disease
* SAR1B
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Chylomicron retention disease
|
c0795956
| 27,547 |
medlineplus
|
https://medlineplus.gov/genetics/condition/chylomicron-retention-disease/
| 2021-01-27T08:24:48 |
{"gard": ["9683"], "mesh": ["C535460"], "omim": ["246700"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that Meckel syndrome type 4 (MKS4) is caused by homozygous or compound heterozygous mutation in the CEP290 gene (610142) on chromosome 12q21.
Description
Meckel syndrome is an autosomal recessive pre- or perinatal lethal disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Baala et al., 2007).
For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Clinical Features
Frank et al. (2008) reported a consanguineous family of Kosovar Albanian origin in which 2 male fetuses were found to have ultrasonographic features of Meckel syndrome. Both pregnancies were terminated. Postmortem examination showed enlarged cystic dysplastic kidneys, hepatobiliary ductal plate malformation, postaxial polydactyly, and occipital meningoencephalocele with massively malformed brain. Two fetuses from a second consanguineous family of Kosovar origin were similarly affected.
Mapping
By genomewide analysis of a family with Meckel syndrome, Frank et al. (2008) found linkage to a 3.2-Mb region on chromosome 12q21.31-q21.33 (lod score of 4.32).
Molecular Genetics
### Meckel Syndrome
To identify new Meckel syndrome loci, Baala et al. (2007) performed a genomewide linkage scan in 8 families unlinked to known Meckel syndrome loci and found linkage to chromosome 12. The interval was narrowed to an 8-Mb region containing the CEP290 gene which, in view of the phenotypic overlap between Joubert syndrome (213300) and Meckel syndrome, and the finding of Baala et al. (2007) of allelism of these 2 phenotypes at the MKS3 locus (607361), was considered an excellent candidate gene. Sequencing of the 53 coding exons revealed homozygous truncating mutations in 3 families and compound heterozygous mutations in a fourth family (see, e.g., 610142.0008-610142.0010), confirming that CEP290 is the gene for Meckel syndrome on chromosome 12. Sequencing of 20 additional MKS cases, all negative for mutations in the MKS1 gene (609883) and TMEM67 (609884), identified 2 additional MKS-affected families with affected individuals carrying compound heterozygous mutations of CEP290.
Frank et al. (2008) identified a homozygous mutation in the CEP290 gene (610142.0012) in 4 fetuses with Meckel syndrome type 4 from 2 consanguineous families of Kosovar origin. Haplotype analysis indicated a founder effect.
### Meckel-like Cerebrorenodigital Syndrome
Baala et al. (2007) also identified CEP290 mutations in 4 families presenting a cerebrorenodigital syndrome, with a phenotype between that of Meckel syndrome and Joubert syndrome and thus representing the continuum of the clinical spectrum between these 2 disorders.
INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Head \- Microcephaly (in some patients) Eyes \- Microphthalmia (rare) Mouth \- Cleft palate (in some patients) CARDIOVASCULAR Heart \- Septal defects (in some patients) ABDOMEN Liver \- Bile duct proliferation \- Ductal plate malformations GENITOURINARY Kidneys \- Cystic dysplasia SKELETAL Limbs \- Bowing of the long bones (rare) Hands \- Polydactyly, postaxial Feet \- Polydactyly, postaxial NEUROLOGIC Central Nervous System \- Encephalocele, occipital \- Meningocele, occipital \- Anencephaly (in some patients) \- Hydrocephalus (in some patients) \- Dandy-Walker malformation (in some patients) \- Cerebellar vermis hypoplasia (in some patients) \- Molar tooth sign (in some patients) MISCELLANEOUS \- Lethal in utero or perinatal lethal MOLECULAR BASIS \- Caused by mutation in the 290-kD centrosomal protein gene (CEP290, 610142.0008 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
MECKEL SYNDROME, TYPE 4
|
c0265215
| 27,548 |
omim
|
https://www.omim.org/entry/611134
| 2019-09-22T16:03:36 |
{"doid": ["0070118"], "omim": ["611134"], "orphanet": ["564"], "synonyms": ["Alternative titles", "MECKEL-GRUBER SYNDROME, TYPE 4"]}
|
Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished.
## Epidemiology
The group of diseases is very rare and the prevalence is unknown (around 50 cases have been reported in medical literature, of which 3 had NLSDM) because of the vagueness of the descriptions.
## Clinical description
In NLSDI, generalized ichthyosis occurs in 95% of cases, moderate myopathic syndrome (or abnormal serum muscle enzyme levels), intellectual deficit and moderate hepatomegaly (or functional impairment of the liver) occur in 60% of cases, ocular (cataract, retinopathy) and hearing abnormalities (deafness) occur in 40% of cases, and neuropathy and short stature occur in 20% of cases.
## Etiology
NLSDI/Dorfman-Chanarin disease is caused by mutations in the ABHD5 gene (3p21), NLSDM by mutations in the PNPLA2/ATGL gene (localized to 11p15.5).
## Diagnostic methods
Biological diagnosis is based on evidence of leukocytes in the vacuoles of neutral lipids and a deficiency in the degradation of cytoplasmic triglycerides in cultured cells (lymphoblasts or fibroblasts), while mitochondrial function (in particular the transport and b-oxidation of fatty acids) is normal. Genetic diagnosis is also possible.
## Differential diagnosis
Differential diagnoses include mitochondrial diseases with accumulation of cytoplasmic triglycerides (deficiencies in carnitine, cartinine palmitoly transferase or fatty acid oxidation enzymes; see these terms).
## Antenatal diagnosis
Prenatal diagnosis is possible by genetic testing (for mutations in chorionic or amniotic cells) when parental mutations have been identified.
## Genetic counseling
Transmission of the disorder is autosomal recessive.
## Management and treatment
There is no treatment to correct the metabolic deficiency.
## Prognosis
For NLSDI/Dorfman-Chanarin disease, the severity of the disease is linked to the myopathy and any associated disorders (which may include ocular and cerebral involvement). The evolution of the disease varies between patients, but is relatively slow because some patients reach late adulthood.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Neutral lipid storage disease
|
c0268238
| 27,549 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=165
| 2021-01-23T18:02:05 |
{"gard": ["3262"], "mesh": ["C536560"], "umls": ["C0268238"], "icd-10": ["E75.5"], "synonyms": ["Lipidosis with triglyceride storage disease"]}
|
Factor XI deficiency is a bleeding disorder that interferes with the body's clotting process. As a result, people affected by this condition may have difficulty stopping the flow of blood following dental extractions, trauma or surgery. Women with factor XI deficiency may also experience heavy menstrual periods or heavy postpartum bleeding. Within affected people and their families, highly variable bleeding patterns occur, and bleeding risk can not be predicted by the level of factor XI (a clotting factor) in the blood. Although the condition can affect people of all heritages, it is most common in people of Ashkenazi Jewish descent. Most cases of factor XI deficiency are inherited and caused by changes (mutations) in the F11 gene. In most cases the condition is inherited in an autosomal recessive manner however, it may follow an autosomal dominant pattern in some families. Treatment is often only recommended during periods of high bleeding risk (i.e. surgery) and may include fresh frozen plasma and/or antifibrinolytics (medications that improve blood clotting). Factor XI concentrates may be available for factor replacement in some countries.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Factor XI deficiency
|
c0015523
| 27,550 |
gard
|
https://rarediseases.info.nih.gov/diseases/9670/factor-xi-deficiency
| 2021-01-18T18:00:36 |
{"mesh": ["D005173"], "omim": ["612416"], "umls": ["C0015523"], "orphanet": ["329"], "synonyms": ["PTA deficiency", "F11 deficiency", "Rosenthal syndrome", "Congenital factor XI deficiency", "Rosenthal factor deficiency", "Plasma thromboplastin antecedent deficiency", "Hemophilia C"]}
|
A number sign (#) is used with this entry because of evidence that encephalocraniocutaneous lipomatosis (ECCL) is caused by postzygotic somatic activating mutation in the FGFR1 gene (136350) on chromosome 8p11.
Description
Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007).
The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, nonscarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).
Clinical Features
Encephalocraniocutaneous lipomatosis was first described by Haberland and Perou (1970) as a new example of ectomesodermal dysgenesis characterized by profound mental retardation, early onset of seizures, unilateral temporofrontal lipomatosis, ipsilateral cerebral and leptomeningeal lipomatosis, cerebral malformation and calcification, and lipomas of the skull, eye, and heart.
Nowaczyk et al. (2000) reported a male infant with ECCL, in whom prenatal sonogram showed normal intracranial structures at 28 weeks of gestation, but at 38 weeks showed asymmetry of the cerebral hemispheres and ventriculomegaly. At birth he had asymmetry of the cranial contour attributed to the presence of fleshy plaques, 1 over the left temple and another extending in a semicircular manner almost to the vertex. He also had a notch in the left upper eyelid, 2 hard excrescences lateral to the notch, and a lipodermoid plaque over the lateral aspect of the sclera of the left eye. In addition, there was a small area of cutaneous focal hypoplasia near the left temple, and a capillary hemangioma over the right antecubital fossa extending onto the upper arm. MRI at age 6 weeks demonstrated a porencephalic cyst on the left, hemiatrophy of the left cerebrum with cortical dystrophy, and a lipoma in the middle cranial fossa. istologic examination of the resected scalp lesion confirmed the presence of a fibrolipoma hamartoma. Nowaczyk et al. (2000) stated that the characteristic lesions of ECCL are typically nonprogressive after birth, but noted that the sonographic evaluation in this patient suggested that there is antenatal progression of intracranial abnormalities. However, calcification of the affected cortex develops postnatally, and this patient showed the characteristic double-contour 'gyriform' calcifications of the affected region of the CNS at 11 months of age.
Moog (2009) reviewed the clinical features of 54 patients with ECCL. Eye anomalies (mainly choristoma) and skin lesions (nonscarring alopecia, nevus psiloliparus, subcutaneous fatty masses, nodular skin tags, and aplastic scalp defects) may be unilateral or bilateral and occur in a consistent pattern. Central nervous system anomalies consist of intracranial and intraspinal lipomas, congenital abnormalities of the meninges, and putative focal vascular defects resulting in highly asymmetric changes. About two-thirds of the patients have normal development or mild retardation only, and half of them have seizures. Aortic coarctation, progressive bone cysts, and jaw tumors may be associated.
Prontera et al. (2009) described a 5-year-old girl with ECCL and a family history of multiple lipomatosis (FML; 151900). The patient had lipomas on the face, alopecia areata, coloboma of iris, chorioretinitis, bilateral epibulbar dermoid, complex partial crises, moderate tricuspid valve insufficiency, increased pulmonary pressure, intracranial lipomas, leptomeningeal angiomatosis, intracranial calcification, hypoplastic corpus callosum, arachnoid cyst of the right temporal lobe, enlargement of the right ventricle, microgyria of the temporal and occipital right lobes, osteolytic lesion in the right jaw, including irregular zones of calcification, ossification and dental elements (odontogenic jaw tumor), moderate speech delay, and macrocephaly. Her father and her paternal grandmother had multiple benign lipomas affecting limbs and trunk that appeared during the second and third decade of life.
Delfino et al. (2011) described 3 unrelated boys with ECCL with typical dermal, ocular, and central nervous system anomalies. One patient also had a sphenoethmoidal lesion that slowly regrew 2 times after surgical resection. Histologic evaluation confirmed the benign nature of the lesion, which was diagnosed as fibrous dysplasia. Delfino et al. (2011) suggested that benign bone tumors may be a component of ECCL.
Kupsik and Brandling-Bennett (2013) reported an infant girl with ECCL who presented at birth with an alopecic plaque on the scalp and corneal lesions. Examination at 3 weeks revealed a soft smooth alopecic plaque on the right scalp near the vertex, extending onto her forehead to the right eyebrow. In addition, she had circular plaques, similar in appearance and texture to the scalp lesion, arranged in a linear configuration on the right temporal region, as well as several yellow to pink papules located on her right upper eyelid, right lateral canthus, and right cheek. In each eye, there was a pink telangiectatic plaque in a limbal distribution extending from the sclera to the cornea; these were diagnosed as limbal dermoids, a form of ocular choristoma. MRI at 2 months showed extraaxial fluid in the anterior portion of the temporal region, with fatty dural thickening along the base of the middle cranial fossa. Neurologic examination was normal.
Bieser et al. (2015) reported a male infant who was noted at birth to have multiple skin tags on his right eyelid and anterior to the right ear, in addition to a region of right parietal alopecia with a pink fluctuant plaque and thin, light hair covering. He had 4 small areas of cutis aplasia on the right side of his head, and a shallow sacral dimple. Echocardiogram revealed ventricular septal defect, and initial brain MRI was normal except for possible parietal lipoma. Repeat MRI at 3 months of age due to failure to thrive showed a homogeneous enhancing mass in the hypothalamic region with extension into the suprasellar cistern and the posterior aspect of the optic chiasm, consistent with low-grade glioma. The patient underwent partial debulking of the tumor; pathology revealed a grade II pilocytic astrocytoma with pilomyxoid features. Bieser et al. (2015) stated that this was the fourth case of low-grade glioma in a patient with ECCL.
Diagnosis
### Differential Diagnosis
Wiedemann and Burgio (1986) reviewed cases of ECCL and concluded that the disorder is a variant of Proteus syndrome (176920). Dean and Cole (1988) also raised this possibility. On the other hand, McCall et al. (1992) studied 3 patients with an array of defects associated with the Proteus syndrome and related hamartoneoplastic conditions. They compared the findings in these 3 patients with those of 50 others with Proteus syndrome and 9 with ECCL reported in the literature. They concluded that Proteus syndrome and ECCL are distinct entities even though some clinical manifestations are shared and a few patients have manifestations of both disorders.
Rizzo et al. (1993) reported a patient with manifestations of ECCL and Proteus syndrome: multiple lipomas of the head, neck, paravertebral region, and heart; hyperostosis of the skull; rugose, yellow-brown skin pigmentation; vertebral anomalies; and alopecia. From a comparison with other cases, they concluded that these disorders represent a continuum rather than distinct entities, supporting the concept of somatic mosaicism, lethal in the nonmosaic state.
McMullin et al. (1993) described 2 unrelated children with diffuse swelling of one cheek and hypertrophy of the underlying maxilla and mandible. Both developed verrucous pigmented streaks over the area of swelling and had epilepsy and severe mental subnormality. One of the children had a contralateral hemiplegia, and his condition was progressive. The other child had no focal neurologic signs, and his disease seemed to be nonprogressive. Although the facial appearance suggested ECCL syndrome, no lipomata could be demonstrated. McMullin et al. (1993) suggested that the 2 cases may represent part of a spectrum of conditions, including the ECCL syndrome and Proteus syndrome.
Haramoto et al. (1995) described a sporadic case of hemifacial hamartomatous hyperplasia consisting of sebaceous nevus-like skin changes, subcutaneous lipomatous mass, cranial bone hyperplasia, and bony change of the meninges. The lesion involved the anterior half of the face and cranial base and was delimited immediately by the midline. This was thought to represent somatic mosaicism for a dominant mutation, lethal in its nonmosaic state, and to be a variant of Proteus syndrome.
Moog et al. (2007) concluded that although ECCL and Proteus syndrome share several features in common, including lipomas, hyperostosis of the skull, mental retardation, and seizures, they are distinct entities. Moog et al. (2007) stated that lipomas and fatty tissue nevi are nonprogressive and present at birth together with ocular and cerebral anomalies in ECCL. In addition, a cerebriform connective tissue nevus, one of the characteristics of Proteus syndrome, and progressive asymmetric, distorting limb overgrowth are not seen in ECCL.
Ardinger et al. (2007) presented evidence that the oculoectodermal syndrome (OES; 600268) is a mild variant of ECCL, differing primarily by lack of intracranial anomalies on brain imaging.
Inheritance
Moog (2009) suggested that ECCL is caused by mosaicism for a mutated autosomal gene involved in multiple mesenchymal tumors and vasculogenesis, with or without a second hit event.
Pathogenesis
Moog et al. (2007) reported 4 new patients with ECCL and reviewed the brain imaging studies and clinical data of these cases and of 6 previously published ECCL patients. They also reviewed the literature on 42 other patients who had undergone some form of neuroimaging, including 3 cases with probable or uncertain ECCL diagnosis. Thirty-three of the 52 patients showed intracranial lipomas, frequently of cerebellopontine location, and/or spinal lipomatosis. The latter was found in 12 of 13 patients who had imaging studies of the spine. Other frequent findings included congenital anomalies of the meninges, in particular arachnoid cysts, and remarkably asymmetric anomalies caused by putative focal vascular defects, such as partial atrophy of one hemisphere or thin cerebral mantle, porencephalic cysts, and calcifications. Vessel anomalies were found in 9 patients. No correlations between the brain anomalies and the degree of retardation or epilepsy could be established. Moog et al. (2007) stated that these data provide evidence that the brain anomalies in ECCL are not primary brain malformations but arise secondary to a mesenchymal defect affecting mostly neural crest derivatives.
Moog et al. (2007) described 3 boys with characteristic skin, eye, and brain anomalies of ECCL who also had coarctation of the aorta and other congenital heart defects; 2 of them also had recurrent chylothoraces, and 1 also had hyperpigmentation following the lines of Blaschko and leg asymmetry. (All 3 were included in the report of Moog et al. (2007) and 1 had previously been described as having oculocerebrocutaneous syndrome (OCCS; 164180) (patient 2 in Narbay et al. (1996)).) All 3 children developed multiple cystic bone lesions, which progressively spread throughout the skeleton in 1 patient and was shown histologically to be nonossifying fibromas in another. Moog et al. (2007) hypothesized that ECCL may be caused by mosaicism for a mutation in an autosomal gene encoding a factor involved in vasculogenesis and in the development of mesenchymal tumors. They suggested the possible involvement of the HMGA2 gene (600698), which frequently shows cytogenetic alterations in a variety of human mesenchymal tumors and was disrupted by a constitutional rearrangement of 12q in a boy with overgrowth, advanced bone age, cerebellar tumor, and multiple lipomas (Ligon et al., 2005); see familial multiple lipomatosis (FML; 151900).
Prontera et al. (2009) described a child with ECCL and a family history of multiple lipomatosis. They suggested that HMGA2 may be a good candidate for FML and ECCL. They proposed that a germline mutation in a gene like HMGA2 may not only be responsible for dominant FML but also represent a predisposition factor for ECCL.
Molecular Genetics
Bennett et al. (2016) performed exome sequencing on DNA samples from multiple affected tissues of 5 unrelated patients with ECCL, and identified 2 mosaic missense variants in the FGFR1 gene (N546K, 136350.0033; K656E, 136350.0034) in 2 patients each, including a 15-year-old boy previously reported by Nowaczyk et al. (2000) and a 2.75-year-old boy studied by Bieser et al. (2015). Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of 4 ECCL patients revealed the N546K mutation in 1 patient, a 5-year-old girl originally reported by Kupsik and Brandling-Bennett (2013). The alternate allele fraction ranged from 23 to 55% in fibroblasts from affected tissues, but the mutations were not detected in saliva or blood samples. Neither variant was found in the Exome Variant Server, ExAC, or dbSNP databases. Bennett et al. (2016) stated that these 2 residues are the most commonly mutated residues among FGFR1 mutation-containing tumors in the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and noted that most of the tumors associated with substitutions in these 2 residues are central nervous system gliomas, including pilocytic astrocytomas, the same type of tumor seen at increased frequency in patients with ECCL.
INHERITANCE \- Somatic mosaicism HEAD & NECK Ears \- Ear abnormalities Eyes \- Microphthalmia \- Epibulbar dermoids \- Hypertrophic conjunctivae \- Sclerocornea \- Small pupils \- Iris hypoplasia \- Anterior chamber anomalies \- Absent macular reflex \- Eyelid coloboma \- Short/abnormal palpebral fissure \- Irregular eyebrows CARDIOVASCULAR Heart \- Coarctation \- Hypoplasia thoracic aorta \- Bicommissural aortic valve \- Subvalvular aortic stenosis \- Atrial septal defect (ASD) \- Ventricular septal defect (VSD) Vascular \- Peripheral pulmonary stenosis \- Abnormal cerebral vessels \- Meningeal angiomatosis GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Pelvic kidney \- Hydronephrosis SKELETAL Skull \- Turricephalic skull Spine \- Spinal lipoma Limbs \- Leg asymmetry \- Skeletal cysts SKIN, NAILS, & HAIR Skin \- Focal scalp defects with alopecia \- Focal skin hypoplasia in face \- Small nodular skin-tags \- Subcutaneous lipomatous tissue \- Linear hyperpigmentation Hair \- Alopecia \- Irregular eyebrows MUSCLE, SOFT TISSUES \- Subcutaneous lipomatous tissue NEUROLOGIC Central Nervous System \- Intracranial lipoma (cerebello-pontine) \- Cortical dysplasia \- Atrophy, thin hemisphere \- Arachnoid cyst \- Porencephalic cyst \- Enlarged lateral ventricle \- Hydrocephalus \- Agenesis of the corpus callosum \- Thin corpus callosum \- Calcifications \- Dandy-Walker malformation \- Cerebellar hypoplasia \- Enlarged cerebellar cistern \- Subependymal hemorrhage \- Adipose tissue in subarachnoid space \- Defective opercularization \- Extensive melanosis of leptomeninges, amygdala, and cerebellar hemispheres \- Psychomotor retardation \- Refractory epilepsy NEOPLASIA \- Low-grade glioma (in some patients) \- Pilocytic astrocytoma (in some patients) MOLECULAR BASIS \- Caused by postzygotic somatic mutation of the fibroblast growth factor receptor 1 (FGFR1, 136350.0033 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS
|
c0406612
| 27,551 |
omim
|
https://www.omim.org/entry/613001
| 2019-09-22T16:00:05 |
{"mesh": ["C535736"], "omim": ["613001"], "orphanet": ["2396"]}
|
Unspecified paraphilic disorder is a DSM-5 category of paraphilic disorders that is used when a specified paraphilic disorder cannot be identified or the clinician chooses not to specify it for some other reason.[1] Along with other specified paraphilic disorder, it replaced the DSM-IV-TR category of paraphilia not otherwise specified (PNOS).
## See also[edit]
* List of paraphilias
## References[edit]
1. ^ American Psychiatric Association, ed. (2013). "Unspecified Paraphilic Disorder, 302.9 (F65.9)". Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. American Psychiatric Publishing. p. 705.
* v
* t
* e
Paraphilias
List
* Abasiophilia
* Acrotomophilia
* Agalmatophilia
* Algolagnia
* Apotemnophilia
* Autassassinophilia
* Biastophilia
* Capnolagnia
* Chremastistophilia
* Chronophilia
* Coprophagia
* Coprophilia
* Crurophilia
* Crush fetish
* Dacryphilia
* Dendrophilia
* Emetophilia
* Eproctophilia
* Erotic asphyxiation
* Erotic hypnosis
* Erotophonophilia
* Exhibitionism
* Formicophilia
* Frotteurism
* Gerontophilia
* Homeovestism
* Hybristophilia
* Infantophilia
* Kleptolagnia
* Klismaphilia
* Lactaphilia
* Macrophilia
* Masochism
* Mechanophilia
* Microphilia
* Narratophilia
* Nasophilia
* Necrophilia
* Object sexuality
* Odaxelagnia
* Olfactophilia
* Omorashi
* Paraphilic infantilism
* Partialism
* Pedophilia
* Podophilia
* Plushophilia
* Pyrophilia
* Sadism
* Salirophilia
* Scopophilia
* Somnophilia
* Sthenolagnia
* Tamakeri
* Telephone scatologia
* Transvestic fetishism
* Trichophilia
* Troilism
* Urolagnia
* Urophagia
* Vorarephilia
* Voyeurism
* Zoophilia
* Zoosadism
See also
* Other specified paraphilic disorder
* Erotic target location error
* Courtship disorder
* Polymorphous perversity
* Sexual fetishism
* Human sexual activity
* Perversion
* Sexology
* Book
* Category
This psychiatry-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Unspecified paraphilic disorder
|
c4237478
| 27,552 |
wikipedia
|
https://en.wikipedia.org/wiki/Unspecified_paraphilic_disorder
| 2021-01-18T19:04:32 |
{"wikidata": ["Q85812360"]}
|
## Clinical Features
Longman et al. (2003) reported 3 sibs, offspring of phenotypically normal first-cousin Pakistani parents, who were variably affected by craniosynostosis, calcification of the basal ganglia, and mild facial dysmorphism comprising prominent eyes and a prominent nasal bridge. The children had normal intelligence and no limb abnormalities.
Inheritance
Longman et al. (2003) suggested that the disorder in the sibs they reported was a novel autosomal recessive craniosynostosis syndrome.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Reduced head circumference Face \- Prominent supraorbital ridges \- Maxillary hypoplasia Eyes \- Proptosis, mild Nose \- Prominent nasal bridge SKELETAL Skull \- Craniosynostosis NEUROLOGIC Central Nervous System \- Calcification of the basal ganglia \- Normal intelligence ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
CRANIOSYNOSTOSIS, CALCIFICATION OF BASAL GANGLIA, AND FACIAL DYSMORPHISM
|
c1842058
| 27,553 |
omim
|
https://www.omim.org/entry/608432
| 2019-09-22T16:07:49 |
{"mesh": ["C564241"], "omim": ["608432"], "orphanet": ["52054"], "synonyms": ["Longman-Tolmie syndrome"]}
|
Triphalangeal thumb
Finger-like appearance
SpecialtyMedical genetics, plastic surgery
Triphalangeal thumb (TPT) is a congenital malformation where the thumb has three phalanges instead of two. The extra phalangeal bone can vary in size from that of a small pebble to a size comparable to the phalanges in non-thumb digits. The true incidence of the condition is unknown, but is estimated at 1:25,000 live births.[1] In about two-thirds of the patients with triphalangeal thumbs, there is a hereditary component.[2] Besides the three phalanges, there can also be other malformations. It was first described by Columbi in 1559.[3]
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 2 Cause
* 2.1 Syndromes
* 3 Diagnosis
* 3.1 Classifications
* 4 Treatment
* 5 References
* 6 External links
## Signs and symptoms[edit]
In combination with polydactyly
Delta shaped extra phalanx
The triphalangeal thumb has a different appearance than normal thumbs. The appearance can differ widely; the thumb can be a longer thumb, it can be deviated in the radio-ulnar plane (clinodactyly), thumb strength can be diminished. In the case of a five fingered-hand it has a finger-like appearance, with the position in the plane of the four fingers, thenar muscle deficiency, and additional length. There is often a combination with radial polydactyly.
### Complications[edit]
Generally, triphalangeal thumbs are non-opposable. In contrast to most people with opposable thumbs, a person suffering from TPT cannot easily place his or her thumb opposite the other four digits of the same hand. The opposable thumb's ability to effortlessly utilize fingers in a "pinch" formation is critical in precision gripping. For the thumb to adequately grip, certain thumb criteria must be met (e.g. suitable position and length, stable joints and good thenar muscle strength).[4] Because triphalangeal thumbs cannot easily oppose and do not possess many of the optimal qualities found in most opposable thumbs, they tend to cause the hand to be less effective in use and, therefore, prove to be more problematic in daily life.
## Cause[edit]
Malformations of the upper extremities can occur In the third to seventh embryonic week.[5] In some cases the TPT is hereditary. In these cases, there is a mutation on chromosome 7q36.[6] If the TPT is hereditary, it is mostly inherited as an autosomal dominant trait,[7] non-opposable and bilateral.[2] The sporadic cases are mostly opposable and unilateral.[8]
### Syndromes[edit]
Triphalangeal thumb can occur in syndromes but it can also be isolated. The triphalangeal thumb can appear in combination with other malformations or syndromes.[5]
Syndromes include:
* Holt-Oram syndrome
* Aase syndrome
* Diamond-Blackfan anemia
* Townes-Brocks syndrome
Malformations include:[5]
* Radial polydactyly
* Syndactyly
* Claw-like hand or foot
## Diagnosis[edit]
### Classifications[edit]
There are multiple classifications for the triphalangeal thumb. The reason for these different classifications is the heterogeneity in appearance of the TPT. The classification according to Wood [9] describes the shape of the extra phalanx: delta (Fig. 4), rectangular or full phalanx (Table 1). With the classification made by Buck-Gramcko a surgical treatment can be chosen (Table 1). Buck-Gramcko differentiates between six different shapes of the extra phalanx and associated malformations.[10]
Table 1: Classifications of Wood [9] and Buck-Gramcko [10]
Classification according to Wood by shape of the extra phalanx Shape Classification according to Buck-Gramcko by shape/size of extra phalanx and associated malformations Shape
I Delta I Rudimentary triphalangism
II Short triangular middle phalanx (brachymesophalangeal)
II Rectangular III Trapezoidal middle phalanx (intermediate)
IV Long rectangular middle phalanx (dolichophalangeal)
III Full V Hypoplastic triphalangeal thumb
VI Triphalangeal thumb associated with polydactyly
## Treatment[edit]
The goals of surgical treatment are: reducing length of the thumb, creating a good functioning, a stable and non deviated joint and improving the position of the thumb if necessary. Hereby improving function of the hand and thumb.
In general the surgical treatment is done for improvement of the thumb function. However, an extra advantage of the surgery is the improvement in appearance of the thumb. In the past, surgical treatment of the triphalangeal thumb was not indicated,[11] but now it is generally agreed that operative treatment improves function and appearance. Because an operation was not indicated in the past, there’s still a population with an untreated triphalangeal thumb. The majority of this population doesn’t want surgery, because the daily functioning of the hand is good.[11] The main obstacle for the untreated patients might not be the diminished function, but the appearance of the triphalangeal thumb.[11] The timing of surgery differs between Wood and Buck-Gramcko. Wood advises operation between the age of six months and two years,[12] while Buck-Gramcko advises to operate for all indications before the age of six years.[13]
* For TPT types I and II of the Buck-Gramcko classification, the surgical treatment typically consists of removing the extra phalanx and reconstructing the ulnar collateral ligament and the radial collateral ligament if necessary.[8]
* For type III of Buck-Gramcko classification proposable surgical treatments:
\- smaller trapezoidal phalanx and under six years: removal of the extra phalanx and reconstruction of the ulnar collateral ligament. Lengthening of the radial collateral ligament is only indicated when the clinodactyly is still present after reconstruction of the ulnar collateral ligament.[8]
\- trapezoidal phalanx and older than six years: partial removal of the extra phalanx with correction of the angle. Arthrodesis of the distal interphalangeal joint (DIP).[8]
* For type IV of Buck-Gramcko classification the surgical treatment typically consists of an osteotomy which reduces the middle phalanx and arthrodesis of the DIP. This gives a shortening of 1 to 1.5 cm. In most cases, this technique is combined with a shortening, rotation and palmar abduction osteotomy at metacarpal level to correct for position and length of the thumb.[8] The extensor tendons and the intrinsic muscles are shortened as well.[8]
* For type V of the Buck-Gramcko classification the surgical treatment proposably consists of a "pollicization". With a pollicization the malpositioned thumb is repositioned, rotated and shortened,[8] the above-described rotation reduction osteotomy of the first metacarpal can be performed as well.
* For type VI of the Buck-Gramcko classification, the surgical treatment typically consists of removing the additional mostly hypoplastic thumb(s). Further procedures of reconstruction of the triphalangeal thumb are performed according to the shape of the extra phalanx as described above.
## References[edit]
1. ^ Lapidus PW, Guidotti FP, Coletti CJ, Triphalageal thumb. Surg Gynecol Obstet, 1943
2. ^ a b Temtamy SA, McKusick VA, the genetics of hand malformations, Birth defects Orig Artic Ser, 1978
3. ^ H. Kelikian, Hyperphalangism, congenital deformities of the hand and forearm, 1974
4. ^ Zguricas J, Raeymaecker DM, Snijder PJ, Psychomotor development in children with triphalangeal thumbs, J Hand Surg Br Vol, 1998
5. ^ a b c Qazi Q, Kassner EG, Triphalangeal thumb, J Med Genet, 1988
6. ^ Heutink, P; Zguricas, J; van Oosterhout, L; et al. (March 1994). "The gene for triphalangeal thumb maps to the subtelomeric region of chromosome 7q". Nature Genetics. 6 (3): 287–92. doi:10.1038/ng0394-287. hdl:1765/57316. PMID 8012392.
7. ^ Zguricas, J; Snijders, PJ; Hovius, SE; et al. (June 1994). "Phenotypic analysis of triphalangeal thumb and associated hand malformations". Journal of Medical Genetics. 31 (6): 462–7. doi:10.1136/jmg.31.6.462. PMC 1049924. PMID 8071973.
8. ^ a b c d e f g Hovius, SE; Zuidam, JM; de Wit, T (December 2004). "Treatment of the triphalangeal thumb". Techniques in Hand & Upper Extremity Surgery. 8 (4): 247–56. doi:10.1097/00130911-200412000-00008. PMID 16518099.
9. ^ a b Wood, treatment of the triphalangeal thumb, Clin Orthop, 1976
10. ^ a b Buck-Gramcko, congenital and development conditions, the interphalangeal joints- hand and upper limb, 1987
11. ^ a b c Zuidam JM, de Kraker M, Selles RW, Hovius SE, Evaluation of function and appearance of adults with untreated triphalangeal thumbs, J Hand Surg Am, 2010
12. ^ Wood VE, The triphalangeal thumb, Operated hand surgery, 1998
13. ^ Buck-Gramcko, The triphalangeal thumb, Congenital malformations of the hand and forearm, 1998
## External links[edit]
Classification
D
* MeSH: C573898
Wikimedia Commons has media related to Triphalangeal thumb.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Triphalangeal thumb
|
c0241397
| 27,554 |
wikipedia
|
https://en.wikipedia.org/wiki/Triphalangeal_thumb
| 2021-01-18T19:05:34 |
{"mesh": ["C573898"], "umls": ["C0241397"], "wikidata": ["Q3539484"]}
|
In cardiology, ventricular dyssynchrony is a difference in the timing, or lack of synchrony, of contractions in different ventricles in the heart. Large differences in timing of contractions can reduce cardiac efficiency and is correlated with heart failure.[1][2][3]
## Contents
* 1 Types of dyssynchrony
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
## Types of dyssynchrony[edit]
Three chief presentations of dyssynchrony can occur. Atrioventricular (AV) dyssynchrony occurs when there is an unfavorable difference in timing between atrial and ventricular contractions. Interventricular dyssynchrony occurs when there is a difference in timing between right ventricular (RV) and left ventricular (LV) Systole. Intraventricular dyssynchrony occurs when the timing in a sequence of activations and contractions of segments of the LV wall becomes abnormal.[3] In all three types, changes in timing lead to changes in the dynamic behavior of the myocardial tissues, leading to mechanical dyssynchrony.[2] All three presentations allow distinct and easily reproducible electrical signatures as illustrated by left and right bundle branch blocks, hemiblocks, etc. The concise measurement of the time and morphology of the QRS interval allows the interventional ability to manipulate this interval with biventricular pacemakers. It is important to distinguish ventricular dyssynchrony from ventricular dyssynergy. Dyssynergy refers to changes in relative strength of contractions, whereas dyssynchrony is a change in relative timing of contractions.[1] Once again the terms inotropy and chronotropy apply to the pathology under examination. Biventricular pacing strongly favors chronotropy over inotropy.
## Diagnosis[edit]
Echocardiography and tissue Doppler echocardiography are both needed to fully diagnose the different types of ventricular dyssynchrony.[2]
## Treatment[edit]
Recent studies suggest that cardiac resynchronization therapy can reduce the incidence of ventricular dyssynchrony and thus increase cardiac efficiency.[1][3]
## See also[edit]
* Bundle branch block
* Ejection fraction
* Pacemaker syndrome
* Speckle tracking echocardiography
* Transthoracic echocardiogram
## References[edit]
1. ^ a b c Nagueh, MD, Sherif F. (2008). "Mechanical Dyssynchrony in Congestive Heart Failure". J Am Coll Cardiol. 51 (1): 18–22. doi:10.1016/j.jacc.2007.08.052. Retrieved 13 February 2013.
2. ^ a b c Ghio, Stefano; Cristina Constantin; Catherine Klersy; Alessandra Serio; Alessandra Fontana; Carlo Campana; Luigi Tavazzi (2004). "Interventricular and intraventricular dyssynchrony are common in heart failure patients, regardless of QRS duration" (PDF). European Heart Journal. 25: 571–578. doi:10.1016/j.ehj.2003.09.030. PMID 15120054. Retrieved 13 February 2013.
3. ^ a b c "Review - The Pathology of Ventricular Dyssynchrony and the Role of Cardiac Resynchronization Therapy". Medscape. Retrieved 13 February 2013.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Ventricular dyssynchrony
|
c3160931
| 27,555 |
wikipedia
|
https://en.wikipedia.org/wiki/Ventricular_dyssynchrony
| 2021-01-18T18:28:11 |
{"umls": ["C3160931"], "wikidata": ["Q7920314"]}
|
A rare genetic neuromuscular disease characterized by neonatal or infancy onset of delayed motor development, generalized muscle weakness involving also the facial muscles, pseudohypertrophy of lower limb muscles, and joint contractures, associated with childhood onset of rapidly progressive dilated cardiomyopathy with arrhythmias leading to sudden cardiac death. Muscle biopsy in early childhood shows minicore-like lesions and centralized nuclei, with dystrophic features being more conspicuous in the second decade of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Early-onset myopathy with fatal cardiomyopathy
|
c2673677
| 27,556 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=289377
| 2021-01-23T19:06:05 |
{"mesh": ["C567129"], "omim": ["611705"], "umls": ["C2673677"], "icd-10": ["G71.8"], "synonyms": ["EOMFC", "Salih myopathy"]}
|
## Summary
### Clinical characteristics.
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, cervical spine malformation and/or instability), craniofacial features (widely spaced eyes, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant.
### Diagnosis/testing.
The diagnosis of LDS is established in individuals based on characteristic clinical findings in the proband and family members and/or by the identification of a heterozygous pathogenic variant in SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, or TGFBR2.
### Management.
Treatment of manifestations: Important considerations when managing cardiovascular features of LDS: aortic dissection can occur at smaller aortic diameters and at younger ages than observed in Marfan syndrome; vascular disease is not limited to the aortic root; angiotensin receptor blockers, beta-adrenergic receptor blockers, or other medications are used to reduce hemodynamic stress; and aneurysms are amenable to early and aggressive surgical intervention. Surgical fixation of cervical spine instability may be necessary to prevent spinal cord damage. Treatment is standard for clubfeet and severe pes planus. Management by a craniofacial team is preferred for treatment of cleft palate and craniosynostosis. Standard treatment for allergic complications with consideration of referral to an allergy/immunology specialist in severe cases. Careful and aggressive refraction and visual correction is mandatory in young children at risk for amblyopia. Hernias tend to recur after surgical intervention. A supporting mesh can be used during surgical repair to minimize recurrence risk. Optimal management of pneumothorax to prevent recurrence may require chemical or surgical pleurodesis or surgical removal of pulmonary blebs.
Prevention of secondary complications: Consider subacute bacterial endocarditis (SBE) prophylaxis in those undergoing dental work or other procedures expected to contaminate the bloodstream with bacteria. Because of high risk for cervical spine instability, a flexion/extension x-ray of the cervical spine should be performed prior to intubation or any other procedure involving manipulation of the neck.
Surveillance: All individuals with LDS require echocardiography at frequent intervals to monitor the status of the ascending aorta; the frequency of magnetic resonance angiography (MRA) or computerized tomography angiography (CTA) evaluation to image the entire arterial tree depends on clinical findings. Individuals with cervical spine instability and severe or progressive scoliosis should be followed by an orthopedist.
Agents/circumstances to avoid: Contact sports, competitive sports, and isometric exercise; agents that stimulate the cardiovascular system including routine use of decongestants or triptan medications for the management of migraine headache; activities that cause joint injury or pain; for individuals at risk for recurrent pneumothorax, breathing against a resistance (e.g., playing a brass instrument) or positive pressure ventilation (e.g., SCUBA diving).
Evaluation of relatives at risk: If the pathogenic variant in the proband is known, molecular genetic testing can be used to clarify genetic status of at-risk family members; if the pathogenic variant is not known, relatives at risk should be evaluated for signs of LDS, including echocardiography and extensive vascular imaging if findings suggest LDS or if findings were subtle in the index case.
Pregnancy management: Pregnancy and the postpartum period can be dangerous for women with LDS because of increased risk of aortic dissection/rupture and uterine rupture. Increased frequency of aortic imaging is recommended, both during pregnancy and in the weeks following delivery.
Therapies under investigation: The safety and efficacy of angiotensin II receptor type 1 blockers (ARBs) has not been addressed for persons with LDS in a clinical trial setting, but ARBs have proven safe and comparable or superior to beta blockers in treating other vascular connective tissue disorders, such as Marfan syndrome.
### Genetic counseling.
LDS is inherited in an autosomal dominant manner. Approximately 25% of individuals diagnosed with LDS have an affected parent; approximately 75% of probands have LDS as the result of a de novo pathogenic variant. Each child of an individual with LDS has a 50% chance of inheriting the pathogenic variant and the disorder. Prenatal diagnosis for pregnancies at increased risk for LDS is possible if the pathogenic variant in the family is known.
## Diagnosis
While various clinical presentations have in the past been labeled as LDS type I (craniofacial features present), LDS type II (minimal to absent craniofacial features), and LDS type III (presence of osteoarthritis) (see Phenotype Correlations by Gene), it is now recognized that LDS caused by a heterozygous pathogenic variant in any of the six known genes (see Table 1) is a continuum in which affected individuals may have various combinations of clinical features.
### Suggestive Findings
Loeys-Dietz syndrome (LDS) should be suspected in individuals with the following vascular, skeletal, craniofacial, cutaneous, allergic/inflammatory, and ocular findings [Loeys et al 2005].
Vascular
* Dilatation or dissection of the aorta and other arteries. Aortic root dilatation is seen in more than 95% of probands; the aortic root is the most common site for a dissection to occur. In rare circumstances, aneurysms or dissections can be seen in other arteries in the head, chest, abdomen, or extremities in the absence of aortic involvement.
* Other arterial aneurysms and tortuosity
* Evaluation is best done with magnetic resonance angiography (MRA) or CT angiogram (CTA) with 3D reconstruction from head to pelvis to identify arterial aneurysms or dissections and arterial tortuosity throughout the arterial tree.
* Tortuosity is often most prominent in head and neck vessels.
* Approximately 50% of individuals with LDS studied had an aneurysm distant from the aortic root that would not have been detected by echocardiography.
Skeletal
* Pectus excavatum or pectus carinatum
* Scoliosis
* Joint laxity or contracture (typically involving the fingers)
* Arachnodactyly
* Talipes equinovarus
* Cervical spine malformation and/or instability
* Osteoarthritis
Craniofacial
* Widely spaced eyes
* Bifid uvula / cleft palate
* Craniosynostosis, in which any sutures can be involved
Cutaneous
* Soft and velvety skin
* Translucent skin with easily visible underlying veins
* Easy bruising
* Dystrophic scars
* Milia, prominently on the face
Allergic/inflammatory disease
* Food allergies
* Seasonal allergies
* Asthma / chronic sinusitis
* Eczema
* Eosinophilic esophagitis/gastritis
* Inflammatory bowel disease
Ocular. Blue or dusky sclerae
### Establishing the Diagnosis
The diagnosis of Loeys-Dietz syndrome is established in a proband (by definition a person without a known family history of LDS) who has a heterozygous pathogenic variant in SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, or TGFBR2 (see Table 1) and EITHER of the following [MacCarrick et al 2014]:
* Aortic root enlargement (defined as an aortic root z-score ≥2.0) or type A dissection
* Compatible systemic features including characteristic craniofacial, skeletal, cutaneous, and/or vascular manifestations found in combination. Special emphasis is given to arterial tortuosity, prominently including the head and neck vessels, and to aneurysms or dissections involving medium-to-large muscular arteries throughout the arterial tree.
Note: In the presence of a family history of documented LDS, the diagnosis can be made in at-risk relatives on the basis of molecular genetic testing even if vascular involvement or other features are not yet apparent (see Evaluation of Relatives at Risk).
Molecular genetic testing approaches can include a combination of gene-targeted testing (serial single-gene testing or a multigene panel) and genomic testing (comprehensive genomic sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because of clinical overlap, it is difficult to predict which of the known LDS-related genes will be causative in any given affected individual. Although individuals with the distinctive findings of LDS described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), those who do not have sufficiently discriminating features to consider the diagnosis of LDS are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the clinical findings suggest the diagnosis of LDS, molecular genetic testing approaches can include serial single-gene testing or use of a multigene panel.
Serial single-gene testing. Sequence analysis of the genes listed in Table 1 can be performed first, typically in order of descending frequency (i.e., TGFBR2, TGFBR1, SMAD3, TGFB2, SMAD2, and TGFB3). Gene targeted deletion/duplication analysis for SMAD3, TGFB2, and TGFB3 should be considered upon strong clinical suspicion and normal sequence analysis.
* Sequencing of SMAD3 could be considered first if early osteoarthritis is evident in the proband or family.
* TGFB2 or TGFB3 can be analyzed first in individuals with milder phenotypes.
A multigene Marfan syndrome / Loeys-Dietz syndrome / familial thoracic aortic aneurysms and dissections panel that includes SMAD2, SMAD3, TGFB2, TGFB3,TGFBR1, and TGFBR2 as well as a number of other genes associated with disorders that include aortic aneurysms and dissections (see Differential Diagnosis) may be offered by clinical laboratories. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For LDS a multigene panel that also includes deletion/duplication analysis may be considered (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from other inherited disorders with features observed in LDS syndrome, molecular genetic testing approaches can include comprehensive genomic testing (exome sequencing and genome sequencing).
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Loeys-Dietz Syndrome
View in own window
Gene 1Proportion of LDS Attributed to Pathogenic Variants in Gene 2Proportion of Pathogenic Variants 3 Detected by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
SMAD2~1%-5%90%-95%Unknown 6
SMAD3~5%-10%90%-95%Rare 7
TGFB2~5%-10%90%-95%Rare 8
TGFB3~1%-5%90%-95%Rare 9
TGFBR1~20%-25%~100%See footnote 10.
TGFBR2~55%-60%~100%See footnote 10.
Unknown 11NA
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
Meester et al [2017b]
3\.
See Molecular Genetics for information on allelic variants detected in this gene.
4\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
No data on gene-targeted del/dup analysis are available.
7\.
Hilhorst-Hofstee et al [2013]
8\.
Lindsay et al [2012], Gaspar et al [2017]
9\.
Deletion of TGFB3 has been observed [Author, personal communication].
10\.
Whole-gene deletion of TGFBR2 [Campbell et al 2011] or TGFBR1 [Redon et al 2006] and duplication of a 14.6-Mb region surrounding TGFBR1 [Breckpot et al 2010] have been reported; however, these individuals lacked aortic involvement. Several other persons with deletions of TGFBR1 or TGFBR2 have not developed aortic aneurysms to date, suggesting that at least some mutated protein needs to be present [Lindsay & Dietz 2011]. As such, whole deletion/duplication of TGFBR1 or TGFBR2 do not present with clear features of Loeys-Dietz syndrome. Smaller deletions/duplications that lead to in frame events are likely to cause an LDS phenotype, whereas events leading to out of frame are not.
11\.
Based on rare individuals with discriminating features of LDS who show no pathogenic variants in the known genes, additional LDS-associated genes remain to be identified [Authors, personal observation].
## Clinical Characteristics
### Clinical Description
Loeys-Dietz syndrome represents a wide phenotypic spectrum in which affected individuals may have various combinations of clinical features ranging from a severe syndromic presentation with significant extravascular systemic findings in young children to predominantly thoracic aortic aneurysm/dissection occurring in adults. Clinical variability is also observed among individuals in the same family who have the same pathogenic variant. The most common findings involve the vascular, skeletal, craniofacial, cutaneous, allergic/inflammatory, and ocular systems [Loeys et al 2005, Loeys et al 2006].
#### Cardiovascular
The major sources of morbidity and early mortality in LDS are dilatation of the aorta at the level of the sinuses of Valsalva, a predisposition for aortic dissection and rupture, mitral valve prolapse (MVP) with or without regurgitation, and enlargement of the proximal pulmonary artery.
Individuals with LDS have a more aggressive vascular course (with routine involvement of vascular segments distant from the aortic root) than that observed in Marfan syndrome. Mean age at death is 26 years [Loeys et al 2006]. Attias et al [2009] reported that the proportion of individuals with aortic dilatation, the age at dissection, and the need for surgery were similar in those with a heterozygous TGFBR2 pathogenic variant and those with a heterozygous FBN1 pathogenic variant causative of Marfan syndrome; however, the rate of death was greater in families with a heterozygous TGFBR2 pathogenic variant. Similarly, a study of 228 families with a heterozygous pathogenic variant in either TGFBR1 or TGFBR2 demonstrated similar aortic risk (dissection or aortic surgery) in both groups [Jondeau et al 2016].
Arterial aneurysms have been observed in almost all side branches of the aorta including (but not limited to) the subclavian, renal, superior mesenteric, hepatic, and coronary arteries.
Aortic dissection has been observed in early childhood (age ≥6 months) and/or at aortic dimensions that do not confer risk in other connective tissue disorders such as Marfan syndrome.
Arterial tortuosity can be generalized but most commonly involves the head and neck vessels:
* The arterial involvement is widespread, and arterial tortuosity is present in a majority of affected individuals.
* Most affected individuals have multiple arterial anomalies.
* Vertebral and carotid artery dissection and cerebral bleeding have been described; however, isolated carotid artery dissection in the absence of aortic root involvement has not been observed.
MVP with mitral regurgitation has been observed in individuals with LDS, although less frequently than in Marfan syndrome.
Other recurrent cardiovascular findings include patent ductus arteriosus, atrial septal defects, and bicuspid aortic valve. Although all of these findings are common in individuals who do not have LDS, the incidence in LDS exceeds by at least five times that seen in the general population.
Aortic histopathology. Histologic examination of aortic tissue reveals fragmentation of elastic fibers, loss of elastin content, and accumulation of amorphous matrix components in the aortic media. Structural analysis shows loss of the intimate spatial association between elastin deposits and vascular smooth muscle cells and a marked excess of aortic wall collagen. These characteristics are observed in young children and in the absence of inflammation, suggesting a severe defect in elastogenesis rather than secondary elastic fiber destruction.
Aortic samples from individuals with LDS had significantly more diffuse medial degeneration than did samples from individuals with Marfan syndrome or control individuals. The changes are not entirely specific for LDS, but in the appropriate clinico-pathologic setting help differentiate it from other vascular diseases [Maleszewski et al 2009].
#### Skeletal
The skeletal findings are characterized by Marfan syndrome-like skeletal features and joint laxity or contractures [Erkula et al 2010]:
Skeletal overgrowth in LDS is less pronounced than in Marfan syndrome and usually affects the digits more prominently than the long bones.
Arachnodactyly is present in some, but true dolichostenomelia (leading to an increase in the arm span-to-height ratio and a decrease in the upper-to-lower segment ratio) is less common in LDS than in Marfan syndrome.
Combined thumb and wrist signs were present in one third of individuals with LDS.
Note: (1) The Walker-Murdoch wrist sign is the overlapping of the complete distal phalanx of the thumb and fifth finger when wrapped around the opposite wrist. (2) The "thumb sign" (Steinberg) is an extension of the entire distal phalanx of the thumb beyond the ulnar border of the hand when apposed across the palm.
Overgrowth of the ribs can push the sternum in (pectus excavatum) or out (pectus carinatum).
Joint hypermobility is common and can include congenital hip dislocation and recurrent joint subluxations. Paradoxically, some individuals can show reduced joint mobility, especially of the hands (camptodactyly) and feet (clubfeet).
Spine anomalies, including congenital malformations of the cervical vertebrae and cervical spine instability, are common, especially in individuals with more severe craniofacial features.
Preliminary data suggest that approximately one third (or more) of affected individuals have structural cervical spine anomalies and at least 50% have cervical spine instability.
Other skeletal findings
* Spondylolisthesis and scoliosis can be mild or severe and progressive.
* Acetabular protrusion, present in one third of individuals, is usually mild but can be associated with pain or functional limitations.
* Pes planus, often associated with inward rotation at the ankle, contributes to difficulty with ambulation, leg fatigue, and muscle cramps.
* Preliminary evidence suggests that individuals with LDS have an increased incidence of osteoporosis with increased fracture incidence and delayed bone healing [Kirmani et al 2010].
Note: Musculoskeletal findings, including hypotonia, have been observed in neonates with LDS [Yetman et al 2007].
#### Craniofacial
In their most severe presentation, craniofacial anomalies in individuals with LDS are characterized by widely spaced eyes and craniosynostosis. Craniosynostosis most commonly involves premature fusion of the sagittal suture (resulting in dolichocephaly). Coronal suture synostosis (resulting in brachycephaly) and metopic suture synostosis (resulting in trigonocephaly) have also been described.
* Bifid uvula is considered the mildest expression of a cleft palate. Sometimes the uvula has an unusual broad appearance with or without a midline raphe.
* Other craniofacial characteristics include malar flattening and retrognathia.
#### Cutaneous
The skin findings, similar to those seen in vascular Ehlers-Danlos syndrome (see Differential Diagnosis), include velvety, thin, translucent skin with visible veins on the chest wall, easy bruising (other than on the lower legs), and slower scar formation and dystrophic scarring.
#### Allergy and Gastrointestinal Disease
Individuals with LDS are predisposed to developing allergic disease including asthma, food allergy, eczema, allergic rhinitis, and eosinophilic gastrointestinal disease. Some affected individuals have exhibited elevated immunoglobulin E levels, eosinophil counts, and T helper 2 (TH2) cytokines in plasma [Frischmeyer-Guerrerio et al 2013, Felgentreff et al 2014].
#### Ocular
Myopia is less frequent and less severe than that seen in Marfan syndrome. Significant refractive errors can lead to amblyopia. Other common ocular features include strabismus and blue sclerae. Retinal detachment has been reported in rare cases. Ectopia lentis is not observed.
#### Other
Life-threatening manifestations include spontaneous rupture of the spleen and bowel, and uterine rupture during pregnancy.
The two most common neuroradiologic findings are dural ectasia (the precise incidence of which is unknown, as only a minority of affected individuals have undergone appropriate examination) and Arnold-Chiari type I malformation, which may be relatively rare.
A minority of affected individuals have developmental delay. When present, developmental delay is most often associated with craniosynostosis and/or hydrocephalus, suggesting that learning disability is an extremely rare primary manifestation of LDS.
Less common associated findings requiring further exploration include submandibular branchial cysts and defective tooth enamel.
Pregnancy. Pregnancy can be dangerous for women with LDS; see Pregnancy Management.
### Phenotype Correlations by Gene
Various clinical presentations have in the past been labeled as LDS type I (craniofacial features present), LDS type II (minimal to absent craniofacial features), LDS type III (presence of osteoarthritis), and so on. These subtype designations provide a general indication of the spectrum of disease severity, from most to least severe: LDS1=LDS2>LDS3>LDS4>LDS5. Note: There is not yet enough information on the spectrum of features of LDS caused by heterozygous pathogenic variants in SMAD2 to place this gene on the continuum or in Table 2.
### Table 2.
Loeys-Dietz Syndrome (LDS): Associated Genes and Subtypes
View in own window
GeneSubtype of LDS 1CommentReference
TGFBR1LDS1 2Loeys et al [2005], Loeys et al [2006]
TGFBR2LDS2 2
SMAD3LDS3 3Strong predisposition for osteoarthritis 4van de Laar et al [2011]
TGFB2LDS4Systemic findings possibly less severe & more like Marfan syndrome 5Lindsay et al [2012], Bertoli-Avella et al [2015]
TGFB3LDS5
1\.
Ordered from most to least severe
2\.
No differences in phenotype are observed between individuals with a heterozygous pathogenic variant in TGFBR1 and those with a heterozygous pathogenic variant in TGFBR2.
3\.
The severity of aortic disease in individuals with a heterozygous pathogenic variant in SMAD3 is similar to that associated with a heterozygous pathogenic variant in TGFBR1 or TGFBR2.
4\.
Several individuals with a heterozygous pathogenic variant in SMAD3 who do not have osteoarthritis have been reported [Wischmeijer et al 2013].
5\.
Boileau et al [2012]
### Genotype-Phenotype Correlations
While the implicated gene can correlate broadly with disease severity (see Phenotype Correlations by Gene), there are few specific genotype-phenotype correlations in LDS. Wide intrafamilial phenotypic variability has been documented. The identical pathogenic variant has also been described in unrelated affected individuals with phenotypes ranging from predominantly thoracic aortic disease to classic and severe LDS. These data suggest the strong influence of genetic modifiers of disease that are independent of the pathogenic variant itself.
### Penetrance
Intrafamilial clinical variability has been described and rare examples of non-penetrance in LDS have been documented. In one case, this was related to somatic mosaicism; in another, no evidence for mosaicism was observed.
Intrafamilial variability likely relates to genetic modification; genes encoding factors that regulate TGFβ signaling are excellent candidates for sites of modifying variation.
### Nomenclature
Marfan syndrome type 2 was a designation initially applied by Mizuguchi et al [2004] to describe individuals with "classic" Marfan syndrome caused by a heterozygous pathogenic variant in TGFBR2. At the time of the report other discriminating features of LDS had not yet been described. There has not been documentation of individuals with a heterozygous pathogenic variant inTGFBR1 or TGFBR2 that satisfied diagnostic criteria for Marfan syndrome including the stipulation requiring absence of discriminating features of LDS [Loeys et al 2006, Van Hemelrijk et al 2010]. The term Marfan syndrome type 2 should not be used to refer to LDS.
### Prevalence
The prevalence of LDS is unknown.
Neither apparent enrichment in any ethnic or racial group nor gender preference has been reported.
### Genetically Related (Allelic) Disorders
No phenotypes other than those discussed in this GeneReview are known to be associated with pathogenic variants in SMAD3, TGFB2, or TGFB3. While pathogenic variants in TGFB3 have been associated with Rienhof syndrome, this phenotype is clinically related to Loeys-Dietz syndrome.
SMAD2. Two pathogenic variants in SMAD2 have been reported in a series of 362 individuals with severe congenital heart disease [Zaidi et al 2013]. These two individuals presented with dextrocardia associated with multiple other congenital heart defects.
TGFBR1 and TGFBR2. A number of disorders have been thought to be caused by a heterozygous pathogenic variant in TGFBR1 or TGFBR2 (see Differential Diagnosis).
The only disorder not clinically related to Loeys-Dietz syndrome that is caused by a heterozygous loss-of-function variant in TGFBR1 is multiple self-healing squamous epithelioma, also known as Ferguson-Smith disease [Goudie et al 2011].
## Differential Diagnosis
### Syndromic Forms of Thoracic Aortic Aneurysms
Marfan syndrome is a systemic disorder with a high degree of clinical variability. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems [Judge & Dietz 2005]. Cardiovascular manifestations include dilatation of the aorta at the level of the sinuses of Valsalva, a predisposition for aortic tear and rupture, mitral valve prolapse with or without regurgitation, tricuspid valve prolapse, and enlargement of the proximal pulmonary artery. Marfan syndrome is caused by mutation of FBN1 and inherited in an autosomal dominant manner.
Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis, distinctive craniofacial features, skeletal changes, neurologic abnormalities, mild-to-moderate intellectual disability, and brain anomalies. Cardiovascular anomalies (mitral valve prolapse, mitral regurgitation, and aortic regurgitation) may occur, but aortic root dilatation is less commonly observed than in LDS, and can be mild. An important feature distinguishing SGS from LDS is the near-uniform incidence of developmental delay in SGS.
Molecular analysis of a series of individuals with typical SGS did not reveal pathogenic variants in TGFBR1 or TGFBR2 [Loeys et al 2005]. Affected individuals are usually simplex cases (i.e., no family history of SGS), although rare instances of apparent autosomal dominant inheritance have been described. Most individuals with SGS have a heterozygous de novo pathogenic missense variant in SKI [Carmignac et al 2012, Doyle et al 2012]. The SKI protein is a known repressor of TGFβ signaling, functionally linking SGS to LDS. Note: An individual reported with SGS by Kosaki et al [2006] was felt to have LDS based on the presence of arterial tortuosity and a bifid uvula [Robinson et al 2006].
### Table 3.
Clinical Features of Loeys-Dietz Syndrome by Associated Gene Compared to the Clinical Features of Marfan Syndrome and Shprintzen-Goldberg Syndrome
View in own window
Clinical FeatureMarfan
SyndromeLoeys-Dietz SyndromeShprintzen
-Goldberg
Syndrome
FBN1TGFBR1/
TGFBR2SMAD3TGFB2TGFB3SMAD2SKI
Developmental delay−−−−−−++
Ectopia lentis+++−−−−−−
Cleft palate / bifid uvula−+++++++
Widely spaced eyes−++++++++
Craniosynostosis−+++−−−+++
Tall stature++++++++++
Arachnodactyly+++++++++++
Pectus deformity++++++++++++
Clubfoot−++++++−+
Osteoarthritis++++++++−
Aortic root aneurysm++++++++++++
Arterial aneurysm−+++++++
Arterial tortuosity−++++++++
Early dissection+++++++++−
Bicuspid aortic valve−+++++++
Mitral valve insufficiency+++++++++
Striae++++++++
Dural ectasia++++−−+
\+
= feature is present; the presence of more than one "+" indicates that a feature is more common, with "+++" indicating most common.
− = feature is absent.
BGN-associated aortic aneurysm syndrome is an X-linked condition caused by a hemizygous pathogenic variant in BGN, coding for biglycan [Meester et al 2017a]. Clinical features significantly overlap with both Marfan syndrome and Loeys-Dietz syndrome, including early-onset aortic root dilatation and dissection, widely spaced eyes, joint hypermobility, contractures, bifid uvula, and pectus deformities. In some families, heterozygous females are also affected. The type of pathogenic variants in BGN suggest loss of function as the mechanism of disease.
MASS phenotype (OMIM 604308) is characterized by mitral valve prolapse, myopia, borderline and non-progressive aortic enlargement, and nonspecific skin and skeletal findings that overlap with those seen in Marfan syndrome. One is most confident in this diagnosis when concordant manifestations are seen in multiple generations in a given family. However, some individuals in such a family could be predisposed to more severe vascular involvement, and thus a regimen of intermittent cardiovascular imaging should be maintained. It is difficult to distinguish MASS phenotype from "emerging" Marfan syndrome when assessing a simplex case (i.e., single occurrence in a family), especially during childhood. Heterozygous variants in FBN1 can be causative. Inheritance is autosomal dominant.
The Ehlers-Danlos syndromes
### Table 4.
Selected Ehlers-Danlos Syndrome (EDS) Subtypes
View in own window
Disease NameGene(s)MOIClinical Features/Comments
Classic EDS (cEDS)COL5A1
COL5A2
COL1A1 1ADIn cEDS & hEDS:
* Some individuals have aortic root enlargement, but progression of the dilatation & predisposition for aortic dissection have not been established. 2
* No history of sudden death also argues against progressive aortic root dilatation.
Hypermobile EDS (hEDS)Unknown/
TNXB 3AD
Vascular EDS (vEDS)COL3A1
COL1A1 4AD 5If:
* vEDS clinically suspected
* Normal collagen biochemistry
* Absence of a COL3A1 or COL1A1 pathogenic variant
Consider LDS/molecular analysis of SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, & TGFBR2. 4
Cardiac-valvular EDS (cvEDS)
OMIM 225320COL1A2ARFeatures of cvEDS 6:
* Joint hypermobility
* Skin hyperextensibility
* Severe cardiac valvular defects
Kyphoscoliotic EDS (kEDS)PLOD1ARIn kEDS:
* Risk for rupture of medium-sized arteries & respiratory compromise if kyphoscoliosis is severe
* Aortic dilation & rupture variably seen
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance
1\.
Mutation of COL1A1 is not a major cause of cEDS [Malfait et al 2005]. See EDS, Classic Type.
2\.
Wenstrup et al [2002]
3\.
In most individuals with hEDS, the gene in which mutation is causative is unknown and unmapped. Haploinsufficiency of tenascin-X (encoded by TNXB) has been associated with hEDS in a small subset of affected individuals.
4\.
Arginine-to-cysteine pathogenic variants in COL1A1 have been identified in a subset of affected individuals who typically present with aneurysms of the abdominal aorta and iliac arteries reminiscent of vEDS. Distinct abnormalities on collagen electrophoresis are observed [Malfait et al 2007].
5\.
vEDS is almost always inherited in an autosomal dominant manner, but rare examples of biallelic inheritance have been reported.
6\.
Schwarze et al [2004]
Congenital contractural arachnodactyly (CCA) is characterized by a Marfan-like appearance (tall, slender habitus in which arm span exceeds height) and long, slender fingers and toes (arachnodactyly). Progressive enlargement of the ascending aorta at the sinuses of Valsalva has been reported, but there is no evidence that the aortic dilatation progresses to dissection or rupture [Gupta et al 2002]. Infants have been observed with a severe/lethal form characterized by multiple cardiovascular and gastrointestinal anomalies in addition to the typical skeletal findings. CCA is caused by mutation of FBN2 and is inherited in an autosomal dominant manner.
Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disorder, mainly characterized by severe tortuosity, stenosis, and aneurysms of the aorta and middle-sized arteries [Wessels et al 2004]. Skeletal and skin involvement is also common. The underlying genetic defect is homozygosity for loss-of-function variants in SLC2A10, the gene encoding solute carrier family 2, facilitated glucose transporter member 10. Although a glucose transporter defect would not be expected to cause abnormal arterial patterning, additional studies indicated upregulation of the TGFβ signaling pathway [Coucke et al 2006], consistent with the pathophysiology in LDS and Marfan syndrome.
### Other Syndromes Associated with Ascending Aortic Aneurysms
Turner syndrome, one of the most common sex chromosome aneuploidy syndromes, is caused by the loss of one of the X chromosomes (45,X). The most important phenotypic features are short stature, gonadal dysgenesis, neck webbing, and an increased incidence of renal and cardiovascular abnormalities. The latter include bicuspid aortic valve (BAV), coarctation of the aorta, and thoracic aortic aneurysms. Aortic root dilation is observed in up to 40% of women with Turner syndrome, but the frequency with which it leads to aortic dissection is unknown. Current health surveillance recommendations for Turner syndrome include echocardiography or MRI for evaluation of the diameter of the aortic root and ascending aorta at least every five years.
Noonan syndrome is characterized by short stature, congenital heart defect, and developmental delay of variable degree. Congenital heart disease occurs in 50%-80% of affected individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of affected individuals. Hypertrophic cardiomyopathy, found in 20%-30% of affected individuals, may be present at birth or appear in infancy or childhood. Other structural defects frequently observed include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Rarely, aortic aneurysms have been described. Noonan syndrome is caused by mutation of BRAF, KRAS, MAP2K1, NRAS, PTPN11, SOS1, RAF1, or RIT1. Inheritance is autosomal dominant.
Cutis laxa. Autosomal dominant cutis laxa (ADCL) was historically considered a strictly cutaneous disorder without systemic involvement, in contrast to autosomal recessive cutis laxa (ARCL), which is associated with high morbidity and mortality resulting from pulmonary emphysema and aortic aneurysms.
### Table 5.
Cutis Laxa Subtypes to Consider in the Differential Diagnosis of Loeys-Dietz Syndrome
View in own window
Disease NameGeneOMIMMOIClinical Findings
Cutis laxaEmphysemaAneurysmsIDGI & GU malformations
FBLN5-related cutis laxaFBLN5219100AR++++++−−+
EFEMP2-related cutis laxaEFEMP2 (FBLN4)614437AR+++++++−−
ADCLELN or FBLN5123700
614434AD+++−−
AD = autosomal dominant; ADCL = autosomal dominant cutis laxa; AR = autosomal recessive; GI = gastrointestinal; GU = genitourinary; ID = intellectual disability; MOI = mode of inheritance
### Nonsyndromic Familial Thoracic Aortic Aneurysms and Dissections
Bicuspid aortic valve with thoracic aortic aneurysm (BAV/TAA). Many cases of a dilated ascending aorta are associated with an underlying BAV. A bicuspid aortic valve is present in 1%-2% of the general population. Among persons with aortic dissection detected at postmortem examination, 8% have BAVs. Histologic studies show elastin degradation and cystic medial necrosis in the aorta above the valve. For a long time, it was believed that the aneurysms were caused by "post-stenotic dilatation" of the ascending aorta. However, echocardiography of young persons with normally functioning BAVs shows that aortic root dilatation is common (52%) [Nistri et al 1999]. Importantly, the aortic dilation often occurs above the sinuses of Valsalva.
BAVs cluster in families and are found in 9% of first-degree relatives of affected individuals. Family members of probands with BAV and aneurysm can show aneurysm and dissection in the absence of the accompanying valve abnormality, suggesting that both BAV and aneurysm represent primary manifestations of the underlying gene defect [Loscalzo et al 2007]. In family studies, reduced penetrance is common.
Thus far, pathogenic variants have been identified in NOTCH1 (OMIM 190198) and SMAD6 (OMIM 602931) in rare individuals with additional congenital cardiac malformations. NOTCH1 pathogenic variants appear specific to individuals and families with significant valve calcification and stenosis, findings not observed in most families with BAV/TAA. Linkage analysis suggests genetic heterogeneity with loci identified on chromosomes 18q, 5q, and 13q [Martin et al 2007]. SMAD6 loss-of-function variants account for about 2% of all cases of BAV/TAA [Gillis et al 2017].
Persistent patent ductus arteriosus with thoracic aortic aneurysm (PDA/TAA). A report describing a single large family with 179 members who have a high incidence of thoracic aortic aneurysm and dissection (TAAD) in conjunction with PDA suggests that a novel genetic defect underlies both vascular conditions in this family. Linkage analysis excluded all known genes or loci implicated in familial TAAD or autosomal recessive PDA. The disease was mapped to chromosome 16p12 [Khau Van Kien et al 2005]. Mutation of MYH11 (encoding myosin-11, a specific contractile protein of smooth muscle cells) is causative. The structural defect leads to lower aortic compliance, smooth muscle cell loss, and elastolysis, but the precise pathophysiology remains unclear [Zhu et al 2006].
Fibromuscular dysplasia (FMD) (OMIM 135580) is a nonatherosclerotic, noninflammatory vascular disease that can affect almost every artery, but most frequently affects the renal and internal carotid arteries. Most commonly, medial hyperplasia leads to a classic "strings of beads" stenotic arterial appearance. Macro-aneurysms and dissections are complications. It is possible that genetic factors play a role in the pathogenesis: the disease is observed among the first-degree relatives of persons with fibromuscular dysplasia of the renal arteries. The underlying genetic cause for nonsyndromic FMD has not been identified, although PHACTR1 has been reported as a genetic susceptibility locus for FMD [Kiando et al 2016].
Familial thoracic aortic aneurysm and dissection (FTAAD). Cardiovascular manifestations of FTAAD include the following:
* Dilatation of the aorta at the level of either the ascending aorta or the sinuses of Valsalva
* Aneurysms and dissections of the thoracic aorta involving either the ascending or descending aorta
TAAD is diagnosed based on the presence of dilatation and/or dissection of the thoracic aorta, absence of Marfan syndrome and other connective tissue abnormalities, and presence of a positive family history.
Cardiovascular manifestations are usually the only findings. Affected individuals typically have progressive enlargement of the ascending aorta leading to either aortic dissection involving the ascending aorta (type A dissection) or consequent tear or rupture. The onset and rate of progression of aortic dilatation is highly variable; however, persons with familial TAAD present with aortic disease at a mean age of 56.8 years, which is younger than that for sporadic TAAD (64.3 years) but significantly older than that for Marfan syndrome (24.8 years) [Coady et al 1999].
### Table 6.
Selected Causes of Heritable Thoracic Aortic Disease (HTAD)
View in own window
Gene/(Locus) 1, 2Proportion of HTAD Attributed to Mutation of GeneFindings
ACTA212%-21% 3In some: livido reticularis, iris flocculi, cerebral aneurysm, bicuspid aortic valve, & persistent patent ductus arteriosus
MYH111% 4Other cardiovascular finding: patent ductus arteriosus 5
MYLK1% 6Aortic dissections w/minimal enlargement but limited experience; no associated features
PRKG11% 7Type A & B aortic dissections associated w/tortuosity & hypertension
MAT2A1% 8Other cardiovascular finding: bicuspid aortic valve
FOXE31% 9Only affected males described; no associated features
MFAP5< 1% 10Mild systemic features; associated w/lone paroxysmal atrial fibrillation
LOX1% 11Associated w/bicuspid aortic valve, mild marfanoid features
(AAT1 or FAA1) 12UnknownMore diffuse vascular disease than in TAAD1, w/aneurysms affecting both thoracic & abdominal aorta & other arteries
(AAT2 or TAAD1) 12Unknown
Heritable thoracic aortic disease (HTAD) refers to thoracic aortic disease caused by mutation of a gene that confers a high risk for thoracic aortic aneurysms and aortic dissections (see Heritable Thoracic Aortic Disease Overview).
1\.
Locus is included when associated gene is not known.
2\.
TGFBR2 pathogenic variants all affecting the same codon (p.Arg460His and p.Arg460Cys) were found in four of 80 unrelated families with familial TAAD. Although the majority of vascular disease in these families involved ascending aortic aneurysms leading to type A dissections, affected family members also had characteristic findings of LDS including descending aortic disease and aneurysms of other arteries (e.g., cerebral, carotid, and popliteal arteries) and other connective tissue findings (e.g., pectus deformity and joint hypermobility). Furthermore, the identical TGFBR2 pathogenic variants reported in FTAAD have been observed in multiple families with typical features of LDS [Loeys et al 2006; Authors, unpublished data]. Currently, it is unclear whether a TGFBR2 pathogenic variant can lead to an isolated aortic aneurysm phenotype (i.e., FTAAD); thus, use of the term FTAAD to refer to families with TAAD and a heterozygousTGFBR2 pathogenic variant does not seem appropriate.
3\.
Guo et al [2007], Morisaki et al [2009], Disabella et al [2011], Hoffjan et al [2011], Renard et al [2013]
4\.
Pannu et al [2007]
5\.
Glancy et al [2001], Khau Van Kien et al [2004], Khau Van Kien et al [2005], Zhu et al [2006], Pannu et al [2007]
6\.
Wang et al [2010], Luyckx et al [2017]
7\.
Guo et al [2013]
8\.
Guo et al [2015]. Two loci designated as AAT1 (FAA1) [Vaughan et al 2001] and AAT2 (TAAD1) [Guo et al 2001] are implicated in TAAD; the genes have not been identified.
9\.
Kuang et al [2016]
10\.
Barbier et al [2014]
11\.
Guo et al [2016]
12\.
Guo et al [2007]
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Loeys-Dietz syndrome (LDS), the following evaluations are recommended if they were not completed as part of the evaluation that led to the diagnosis:
* Echocardiography. Aortic root measurements must be interpreted based on consideration of normal values for age and body size [Roman et al 1989]. Select findings (e.g., severe aortic dilatation) may require the immediate attention of a cardiologist or cardiothoracic surgeon.
* MRA or CT scan with 3D reconstruction from head to pelvis to identify arterial aneurysms and arterial tortuosity throughout the arterial tree
Note: Approximately half of the individuals with LDS studied had an aneurysm distant from the aortic root that would not have been detected by echocardiography.
* Radiographs (including flexion and extension views of the cervical spine) to detect skeletal manifestations that may require attention by an orthopedist (e.g., severe scoliosis, cervical spine instability)
* Craniofacial examination for evidence of cleft palate and craniosynostosis
* Eye examination by an ophthalmologist with expertise in connective tissue disorders, including: slit-lamp examination through a maximally dilated pupil for exclusion of lens (sub)luxation; careful refraction and visual correction, especially in young children at risk for amblyopia; specific assessment for retinal detachment
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Management of LDS is most effective through the coordinated input of a multidisciplinary team of specialists including a clinical geneticist, cardiologist, ophthalmologist, orthopedist, and cardiothoracic surgeon. An extensive review of management guidelines has been published [MacCarrick et al 2014] (full text).
#### Cardiovascular
All individuals with LDS should be managed in a medical center familiar with this condition.
Two important considerations when managing cardiovascular features of LDS:
* Aortic dissection occurs at smaller aortic diameters than observed in Marfan syndrome.
* Vascular disease is not limited to the aortic root. Imaging of the complete arterial tree from the head through the pelvis by MRA or CTA is necessary.
Beta-adrenergic blockers or angiotensin receptor blockers (ARBs) are used to reduce hemodynamic stress. No clinical trials evaluating the efficacy of beta-adrenergic blockers verses ARBs have been completed in individuals with LDS.
Aneurysms are amenable to early and aggressive surgical intervention (in contrast to vascular EDS, in which surgery is used as a last resort because of the extremely high rate of intraoperative complications and death). Many individuals can undergo a valve-sparing procedure that precludes the need for chronic anticoagulation.
Given the safety and the increasing availability of the valve-sparing procedure:
* For young children with the most severe systemic findings of LDS, surgical repair of the ascending aorta should be considered once the maximal dimension exceeds the 99th percentile and the aortic annulus exceeds 1.8-2.0 cm, allowing the placement of a graft of sufficient size to accommodate growth. Additional factors including family history, rate of aortic root growth, and aortic valve function can influence the timing of surgery.
* For adolescents and adults, surgical repair of the ascending aorta should be considered once the maximal dimension approaches 4.0 cm. This recommendation is based on both numerous examples of documented aortic dissection in adults with aortic root dimensions at or below 4.0 cm and the excellent response to prophylactic surgery. An extensive family history of larger aortic dimension without dissection could alter this practice for affected individuals.
* Note: This practice may not eliminate risk of dissection and death, and earlier intervention based on family history or the affected individual's personal assessment of risk versus benefit may be indicated.
#### Skeletal
Surgical fixation of cervical spine instability may be necessary to prevent damage to the spinal cord.
Clubfeet require surgical correction by an orthopedic surgeon.
Bone overgrowth and ligamentous laxity can lead to severe problems (including progressive scoliosis) and should be managed by an orthopedist; surgical stabilization of the spine may be required.
Pectus excavatum can be severe; rarely, surgical intervention is medically (rather than cosmetically) indicated.
Surgical intervention for protusio acetabulae is rarely indicated. Treatment focuses on pain control.
Orthotics are only indicated for severe pes planus. Some individuals prefer use of arch supports; others find them irritating; the choice should be left to personal preference. Surgical intervention is rarely indicated or successful.
#### Craniofacial
Cleft palate and craniosynostosis require management by a craniofacial team. Treatment of cleft palate and craniosynostosis is the same as in all other disorders with these malformations.
#### Allergic/Inflammatory
Standard treatment for allergic complications such as seasonal allergies, food allergies, asthma, and eczema should apply. Referral to an allergist/immunologist may be considered in severe cases. Inflammatory or allergic gastrointestinal findings are treated in the standard fashion with the guidance of a gastroenterologist.
#### Ocular
The ocular manifestations of LDS should be managed by an ophthalmologist with expertise in connective tissue disorders. Careful and aggressive refraction and visual correction is mandatory in young children at risk for amblyopia.
#### Other
Dural ectasia is usually asymptomatic. No effective therapies for symptomatic dural ectasia currently exist.
Hernias tend to recur after surgical intervention. A supporting mesh can be used during surgical repair to minimize recurrence risk.
Optimal management of pneumothorax to prevent recurrence may require chemical or surgical pleurodesis or surgical removal of pulmonary blebs.
Counseling regarding other life-threatening manifestations including spontaneous rupture of the spleen and bowel and pregnancy-associated risks is recommended.
### Prevention of Secondary Complications
Use of subacute bacterial endocarditis prophylaxis should be considered for individuals with connective tissue disorders and documented evidence of mitral and/or aortic regurgitation who are undergoing dental work or other procedures expected to contaminate the bloodstream with bacteria.
Because of a high risk of cervical spine instability, a flexion and extension x-ray of the cervical spine should be performed prior to intubation or any other procedure involving manipulation of the neck.
### Surveillance
All individuals with LDS require echocardiography at frequent intervals to monitor the status of the ascending aorta. The frequency of MRA or CTA evaluations should be tailored to clinical findings.
Individuals with cervical spine instability and severe or progressive scoliosis should be followed by an orthopedist.
### Agents/Circumstances to Avoid
The following should be avoided:
* Contact sports, competitive sports, and isometric exercise
Note: Individuals can and should remain active with aerobic activities performed in moderation.
* Agents that stimulate the cardiovascular system including routine use of decongestants or triptans for migraine headache management
* Activities that cause joint injury or pain
* For individuals at risk for recurrent pneumothorax, breathing against a resistance (e.g., playing a brass instrument) or positive pressure ventilation (e.g., SCUBA diving)
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those individuals who need regular cardiovascular screening to detect aortic aneurysms and initiate appropriate medical or surgical intervention.
Evaluations can include the following:
* Molecular genetic testing if the pathogenic variant in the family is known
* Signs of the disorder if the pathogenic variant in the family is not known. Echocardiography and extensive vascular imaging of relatives is indicated upon appreciation of any suspicious signs of LDS, and even in apparently unaffected individuals if findings are subtle in the index case.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Pregnancy can be dangerous for women with LDS. Complications include aortic dissection/rupture or uterine rupture during pregnancy or delivery, or aortic dissection/rupture in the immediate postpartum period. Increased frequency of aortic imaging is recommended, both during pregnancy and in the weeks following delivery. However, with appropriate supervision and high-risk obstetric management, women with Loeys-Dietz syndrome can tolerate pregnancy and delivery [Gutman et al 2009, Frise et al 2017].
### Therapies Under Investigation
Experimental evidence suggests that many manifestations of LDS relate to excess activation of and signaling by the growth factor TGFβ.
Animal trials have shown that TGFβ antagonizing agents, such as angiotensin II receptor type 1 blockers (ARBs), can slow or prevent vascular manifestations of LDS [Gallo et al 2014]. ARBs also attenuate the biochemical abnormalities in the aortic wall of mouse models of LDS. The safety and efficacy of such interventions has not been addressed for persons with LDS in a clinical trial setting, but ARBs have proven safe and comparable or superior to beta blockers in treating other vascular connective tissue disorders such as Marfan syndrome.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Loeys-Dietz Syndrome
|
c2697932
| 27,557 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1133/
| 2021-01-18T21:14:26 |
{"mesh": ["D055947"], "synonyms": ["Loeys-Dietz Aortic Aneurysm Syndrome"]}
|
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Psychogenic disease" – news · newspapers · books · scholar · JSTOR (April 2008) (Learn how and when to remove this template message)
Psychogenic disease (or psychogenic illness) is a name given to physical illnesses that are believed to arise from emotional or mental stressors, or from psychological or psychiatric disorders.[1] It is most commonly applied to illnesses where a physical abnormality or other biomarker has not yet been identified. In the absence of such biological evidence of an underlying disease process, it is often assumed that the illness must have a psychological cause, even if the patient shows no indications of being under stress or of having a psychological or psychiatric disorder. Examples of diseases that are believed by many to be psychogenic include psychogenic seizures, psychogenic polydipsia, psychogenic tremor, and psychogenic pain.
There are problems with the assumption that all medically unexplained illness must have a psychological cause. It always remains possible that genetic, biochemical, electrophysiological, or other abnormalities may be present which we do not have the technology or background to identify.[2][3]
The term psychogenic disease is often used in a similar way to psychosomatic disease. However, the term psychogenic usually implies that psychological factors played a key causal role in the development of the illness. The term psychosomatic is often used in a broader way to describe illnesses with a known medical cause where psychological factors may nonetheless play a role (e.g., asthma can be exacerbated by anxiety).
## See also[edit]
* Psychology portal
* Functional symptom
* Habit cough
* Mass psychogenic illness
* Psychogenic amnesia
* Psychological trauma
* Psychoneuroimmunology
## References[edit]
1. ^ Lim, Erle C. H.; Seet, Raymond C. S. (2007). "What Is the Place for Placebo in the Management of Psychogenic Disease?". Journal of the Royal Society of Medicine. 100 (2): 60–61. doi:10.1258/jrsm.100.2.60. PMC 1790983. PMID 17277261.
2. ^ Conversion Disorders at eMedicine
3. ^ Sykes, Richard (2010). "Medically Unexplained Symptoms and the Siren 'Psychogenic Inference'". Philosophy, Psychiatry, & Psychology. 17 (4): 289–299. doi:10.1353/ppp.2010.0034. ISSN 1086-3303.
This psychology-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Psychogenic disease
|
None
| 27,558 |
wikipedia
|
https://en.wikipedia.org/wiki/Psychogenic_disease
| 2021-01-18T18:55:19 |
{"wikidata": ["Q2471453"]}
|
Synkinesis
SpecialtyNeurology
Synkinesis is a neurological symptom in which a voluntary muscle movement causes the simultaneous involuntary contraction of other muscles. An example might be smiling inducing an involuntary contraction of the eye muscles, causing a person to squint when smiling. Facial and extraocular muscles are affected most often; in rare cases, a person's hands might perform mirror movements.
Synkinesis is usually caused by dysfunction of a particular nerve. Potential causes include improper healing after nerve trauma or neurodegeneration, as occurs in Parkinson's disease. In congenital cases, mutations of genes involved in nerve growth, specifically axonal growth have been found. Rarely, it occurs as part of syndromes with neuroendocrine problems, such as Kallman syndrome. The prognosis is usually good with normal intelligence and lifespan. Treatment depends on the cause, but is largely conservative with facial retraining or mime therapy, if needed, while Botox and surgery are used as last resort.
## Contents
* 1 Types
* 1.1 Facial synkinesis
* 1.2 Extra-ocular muscle synkinesis
* 1.3 Bimanual Synkinesis
* 2 Causes
* 3 Mechanism
* 3.1 Aberrant nerve regeneration
* 3.2 Ephaptic transmission
* 3.3 Nuclear hyperexcitability
* 4 Diagnosis
* 4.1 Measurement
* 5 Treatment
* 5.1 Facial retraining
* 5.2 Biofeedback
* 5.3 Mime therapy
* 5.4 Botox
* 5.5 Surgery
* 6 See also
* 7 References
* 8 External links
## Types[edit]
Most cases involve the cranial nerves, which innervate many small cranial muscles, such as the facial muscles and the extraocular muscles. This is in contrast to areas of body where miswiring of the larger muscles is less evident due to the size of the muscles. Synkinesis can also involve the upper limbs, especially hands which is quite rare, at 1 case in 1 million.[1] In some cases, nerves improperly regenerate into glands, such as lacrimal glands, leading to a condition known as crocodile tears or Bogorad's syndrome.
### Facial synkinesis[edit]
Facial synkinesis is a common sequela to Idiopathic Facial Nerve Paralysis, also called Bell's Palsy or Facial Palsy.[2] Bell's Palsy, which is thought to occur due to a viral reactivation which can lead (through unknown mechanisms) to diffuse axon demyelination and degeneration of the seventh cranial nerve, results in a hemifacial paralysis due to non-functionality of the nerve. As the nerve attempts to recover, nerve miswiring results (see Mechanism of Action below). In patients with severe facial nerve paralysis, facial synkinesis frequently develops.[3] Additionally, a common treatment option for facial palsy is to use electrical stimulation. Unfortunately, this has been shown to be disruptive to normal re-innervation and can promote the development of synkinesis.[4] The most common symptoms of facial synkinesis include:[5]
* Eye closure with volitional contraction of mouth muscles
* Midfacial movements with volitional eye closure
* Neck tightness (Platysmal contraction) with volitional smiling
* Hyperlacrimation (also called Crocodile Tears)
* A case where eating provokes excessive lacrimation. This has been attributed to neural interaction between the salivary glands and the lacrimal glands.[6]
### Extra-ocular muscle synkinesis[edit]
The six muscles around the eye (extraocular muscles) are innervated by three different cranial nerves: Abducens (6th nerve), Trochlear (4th nerve), and Oculomotor (3rd nerve). After nerve trauma around the eye, a combination of any two of these three cranial nerves have been shown to be involved with extra-ocular synkinesis. Moreover, while the abducens and the trochlear nerve each innervate one specific muscle, the oculomotor nerve has many functions including eyelid retraction and pupil constriction. Thus, during synkinesis, one of these functions may be involved. Examples include:
* On attempted abduction of an affected eye, the eye adducts and the eyelid retracts.
* This is an interaction between the abducens nerve and a branch of the oculomotor nerve. Voluntary activation of the abducens nerve (eye abduction) causes involuntary activation of the oculomotor nerve (eye adduction and eyelid elevation).[7]
* On attempted abduction, the eye's unreactive pupil constricts
* Another interaction, yet different, is between eye abduction (abducens nerve) and pupil constriction (the oculomotor nerve).[8]
* On attempted adduction with eye depression, the eyelid retracts.
* In this case voluntary activation of the trochlear nerve (eye depression + eye abduction) is involuntarily activating a branch of the oculomotor nerve responsible for eyelid retraction.[9]
* Focusing to the near (accommodation) is accompanied by involuntary convergence of the eyes. This accommodation-convergence synkinesis can result in esotropia, or eyes that turn in when the ratio between accommodation and convergence is unusually high.[10]
Other less common variations of synkinesis involving the cranial nerves include:
* Trigeminal-Abducens Synkinesis
* After physical trauma to the skull, the muscle involved in eye abduction can become reinnervated by the branch of the trigeminal nerve involved in innervating the muscles of mastication(chewing muscles). Thus, involuntary abduction of an involved eye will occur upon eating or chewing.[11]
* Trigeminal-Facial Synkinesis
* After surgical trauma, the muscles of mastication can become reinnervated by the facial nerve as opposed to the trigeminal nerve. This causes weakness in voluntary chewing; also, facial movements such as blinking cause the muscles to contract.[12]
### Bimanual Synkinesis[edit]
Bimanual Synkinesis occurs when left and right upper limbs, especially the hands and fingers execute exactly the same movement even though only one hand is intentionally moved. It is also called "mirror hand movements" and persists throughout life. When it occurs by itself without other associated signs and symptoms it is associated with normal intelligence and lifespan. It can also develop in the course of Parkinson's disease.[1] In association with other abnormalities, mirror hand movements are a hallmark of Kallmann syndrome.
Genetic mutations associated with (congenital) mirror hand movements are in the DCC (gene) or RAD51 gene, which account for about 35 percent of cases.[1] In DCC mutation, impaired or missing netrin 1 receptor protein impairs control of axon growth during nervous system development.[1]
## Causes[edit]
Almost all cases of synkinesis develop as a sequel to nerve trauma. (The exception is when it is congenitally acquired as in Duane-Retraction Syndrome and Marcus Gunn phenomenon.) Trauma to the nerve can be induced in cases such as surgical procedures, nerve inflammation, neuroma,[12] and physical injury.[7]
## Mechanism[edit]
There are three proposed mechanisms for synkinesis: aberrant nerve regeneration, interneuronal ephaptic transmission, and nuclear hyperexcitability.
### Aberrant nerve regeneration[edit]
The aberrant nerve regeneration hypothesis is the most widely accepted mechanism for synkinesis.[13] The hypothesis states that, after trauma, axons project from the facial nucleus to incorrect peripheral muscle groups. These aberrant branches can simultaneously innervate different subdivisions of the facial nerve.[3]
For example: compression to the facial nerve causes a lesion and the set of axons that innervates the orbicularis oris (mouth muscle) degenerate. Once the compression has relieved, regeneration of axons from the lesion site begins. This time though, only 50% of the set of axons that innervate the orbicularis oris successfully reinnervate the original site. The other half aberrantly branched off and innervated the orbicularis oculi(eye muscle). Thus, when the patient purses their lips, the ipsilateral eye will squint.
The hypothesis assumes that disorganized regeneration occurs at the site of the lesion. On the contrary, recent research by Choi and Raisman[14] has provided a more thorough understanding of synkinesis through aberrant axonal regeneration. Their study has shown that regenerating axons become disorganized throughout the length of the nerve and not only at the site of the lesion. Previously, many developed treatment strategies (that inevitably failed) were invented based on the original hypothesis by only focusing on the lesion site for improving the organization of regeneration. The new modification to the hypothesis could allow for better success in developing treatments.
### Ephaptic transmission[edit]
Ephaptic transmission is when two nerves communicate with each other via an artificial synapse between nerves. Healthy peripheral nerves are insulated with a myelin sheath that helps to both enhance electric transmission and to prevent cross-talk between parallel nerves. After a lesion, it has been observed that regenerating nerves might not be myelinated effectively. Consequently, the two nerve fibers can come into contact and provide a means for an impulse to be directly conducted through the nerve membrane. An analogy for this is having two uninsulated electrical wires placed adjacent to each other. Thus, the two nerves are able to “cross-talk” and send action potentials in both directions.[15]
### Nuclear hyperexcitability[edit]
The basis of this hypothesis is as follows: after a lesion, axonal degeneration (via Wallerian degeneration) occurs. The post-synaptic cell consequently becomes deprived of input and becomes more sensitive to neurotransmitters (e.g. creating additional receptors). Subsequently, nearby residual undamaged axons can provide a source of neurotransmitter to the deprived post-synaptic cell. Since the post-synaptic cell is hypersensitive, the neurotransmitters that reach it from an axon of another nerve will successfully provide stimulation. This consequently creates undesired peripheral movement (i.e. synkinesis).[16]
* Since synkinesis has been reported in patients within 1–2 months, the nuclear hyper-excitability hypothesis is being supported by more researchers.[13] Furthermore, axonal regeneration is a slow process (~1 mm/day growth) and regeneration at this rate of the facial nerve would roughly take 4–8 months. Since synkinesis is observed much earlier, aberrant regeneration and ephaptic communication fail to explain for this observation thus providing evidence that nuclear hyper-excitability is an important factor in the mechanism of synkinesis development.[17]
Although these three mechanisms have been argued for and against in various ways, it has become more accepted that synkinesis develops through a combination of these mechanisms.
## Diagnosis[edit]
### Measurement[edit]
Until May 2007, there was no clinical scale to measure synkinesis. A study led by Mehta et al.[5] has validated the use of a newly designed instrument to evaluate facial synkinesis called the Synkinesis Assessment Questionnaire (SAQ). The instrument, consisting of nine questions, was found to be both reliable and valid. In addition, it is simple, easy to administer, and inexpensive. Its analyses can allow for treatment options to be evaluated.
## Treatment[edit]
Experimental research for treatment has been mostly focused on facial synkinesis due to its abundant prevalence compared to extra-ocular synkinesis. Additionally, since the extra-ocular muscles are hidden within the orbits, there is a limit on the type of practical treatments that can be established (e.g. massage). Treatments for synkinesis in general include facial retraining, biofeedback, mime therapy, and Botox and surgery, as a last resort.
### Facial retraining[edit]
Facial retraining therapy builds upon the idea that neurons are constantly in a dynamic state. In other words, there is constant growth and regression of neuronal projections dependent on the stimuli produced. To reduce synkinesis, facial retraining teaches the patient techniques for increasing wanted movements while focusing on restricting unwanted movement. If, for example, the mouth moves whenever the eyes blink voluntarily, facial retraining techniques will teach the patient to slowly close the eyes while actively focusing on keeping the mouth muscles still. Facial retraining has shown to be very successful with almost a 60-70% average decrease in synkinesis reported after 7 months.[18]
### Biofeedback[edit]
Biofeedback therapy for facial synkinesis aims to increase the patient's awareness of the facial muscle posture and movement. Facial muscles contain few to none intrinsic muscle sensory receptors (used for proprioceptive feedback) and additionally they do not span movable joints and so lack joint receptors (another source for proprioceptive feedback).[18] Thus, biofeedback allows the patient to actively sense the motion of their muscles. The two common forms of biofeedback used are electromyographic feedback and mirror feedback. Electromyographic feedback includes visual EMG signals (coming from facial muscle sites displayed to the patient from a computer in the form of waveform traces) or auditory signals that indicate strength of muscle contraction.[19] The subsequent role of the patient is to control the movement of undesired muscle during volitional movement by incorporating the information perceived through the EMG. While mirror feedback is a much more basic way of providing the patient feedback on muscle movement, studies have shown that both are very effective options for synkinesis/paresis reduction.[20] Biofeedback is commonly coupled to facial retraining techniques to achieve maximal effectiveness.
A study by Nakamura et al. has shown that biofeedback works better for prevention of synkinesis as opposed to treatment of synkinesis. Due to the extreme efforts needed to achieve improvements during synkinesis, Nakamura et al. observed that patients will often fail to reach their desired goal because of the difficulty of maintaining motivation during training. The desired course of action is to catch the patient shortly after facial nerve trauma and teach the patient biofeedback techniques. This course of action has been experimentally proven to significantly reduce the development of synkinesis.[3]
### Mime therapy[edit]
Mime therapy was introduced in the Netherlands in 1980.[21] It was initially designed to treat facial palsy by improving symmetry of the face both at rest and during movement. It was then later observed that people who had post-facial palsy synkinesis also benefited from this therapy. It wasn't until 2003 that Beurskens and Heymans were able to experimentally conclude that mime therapy was indeed a good treatment choice for synkinesis. Furthermore, later studies by Beurskens et al. have shown that benefits obtained from mime therapy are stable one year after therapy.[22] Current mime therapy consists of a combination of procedures designed to promote symmetry of the face at rest and during movement to control synkinesis. The components include: massage, stretching exercises, exercises to coordinate both halves of the face, etc.[2] The overall aim of mime therapy is to develop a conscious connection between the use of facial muscles and emotional expression. While facial retraining therapy is more focused on treating slight synkinetic movements, mime therapy aims to increase the overall vigor of the muscles through active exercises, while in the process of doing so, teaching the face to decrease unwanted synkinetic movements.
### Botox[edit]
Botox (botulinum toxin) is a new and versatile tool for the treatment of synkinesis. Initially used for reducing hyperkinesis after facial palsy,[23] Botox was later attempted on patients with post-facial palsy synkinesis to reduce unwanted movements. The effects of Botox have shown to be remarkable, with synkinetic symptoms disappearing within 2 or 3 days. The most common treatment targets are the orbicularis oculi, depressor anguli oris (DAO), mentalis, platysma and the contralateral depressor labii inferioris muscles.[24] Due to the short span of Botox effects though, patients must come back to the doctor for re-injection approximately every 3 months. More notable is that in a majority of patients, various synkinetic movements completely disappeared after 2-3 sessions of trimonthly Botox injections.[25] A more specific synkinesis, crocodile tears syndrome (hyperlacrimation upon eating), has been shown to respond exceedingly well to Botox injection. Botox is injected directly into the lacrimal gland and has shown to reduce hyperlacrimation within 24–48 hours. The procedure was shown to be simple and safe with very little chance of side-effects (although on rare occasions ptosis can occur due to botulinum toxin diffusion).[6] Furthermore, reduction in hyper-lacrimation was shown to last longer than the expected 3 months (about 12 months).[25] Since Botox can mimic facial paralysis, an optimized dose has been determined that reduces involuntary synkinesis of the muscle while not affecting muscle tone.[25]
### Surgery[edit]
Practical surgical procedures used for treating synkinesis are neurolysis and selective myectomy. Neurolysis has been shown to be effective in relieving synkinesis but only temporarily and unfortunately symptoms return much worse than originally.[26] Selective myectomy, in which a synkinetic muscle is selectively resected, is a much more effective technique that can provide permanent relief and results in a low recurrence rate; unfortunately, it also has many post-operative complications that can accompany including edema, hematoma, and ecchymosis.[3] Therefore, surgical procedures are very minimally used by doctors and are used only as last-resort options for patients who do not respond well to non-invasive treatments.
## See also[edit]
* Paralysis
* Paresis
## References[edit]
1. ^ a b c d congenital mirror movement disorder April 2015 Genetics Home Reference, National Library of Medicine, accessed June 27, 2017
2. ^ a b Beurskens CH, Heymans PG (2006). "Mime therapy improves facial symmetry in people with long-term facial nerve paresis: a randomised controlled trial". Aust J Physiother. 52 (3): 177–83. doi:10.1016/s0004-9514(06)70026-5. PMID 16942452.
3. ^ a b c d Nakamura K, Toda N, Sakamaki K, Kashima K, Takeda N (2003). "Biofeedback rehabilitation for prevention of synkinesis after facial palsy". Otolaryngol Head Neck Surg. 128 (4): 539–43. doi:10.1016/S0194-5998(02)23254-4. PMID 12707658.
4. ^ Manikandan N. (2007). "Effect of facial neuromuscular re-education on facial symmetry in patients with Bell's palsy: a randomized controlled trial". Clin Rehabil. 21 (4): 338–43. doi:10.1177/0269215507070790. PMID 17613574.
5. ^ a b Mehta RP, WernickRobinson M, Hadlock TA (2007). "Validation of the Synkinesis Assessment Questionnaire". Laryngoscope. 117 (5): 923–6. doi:10.1097/MLG.0b013e3180412460. PMID 17473697.
6. ^ a b Montoya FJ, Riddell CE, Caesar R, Hague S (2002). "Treatment of gustatory hyperlacrimation (crocodile tears) with injection of botulinum toxin into the lacrimal gland". Eye. 16 (6): 705–09. doi:10.1038/sj.eye.6700230. PMID 12439663.
7. ^ a b Buckley EG, Ellis FD, Postel E, Saunders T (2005). "Postraumatic Abducens to Oculomotor Nerve Misdirection". Journal of AAPOS. 9 (1): 12–16. doi:10.1016/j.jaapos.2004.11.011. PMID 15729274.
8. ^ Pfeiffer N, Simonsz HJ, Kommerell G (1992). "Misdirected regeneration of abducens nerve neurons into the parasympathetic pupillary pathway". Graefes Arch Clin Exp Ophthalmol. 230 (2): 150–3. doi:10.1007/BF00164653. PMID 1577295.
9. ^ Kothari M, Hussain A, Kar D, Toshniwal S (2007). "Primary superior oblique muscle-levator muscle synkinesis". J AAPOS. 11 (2): 204–5. doi:10.1016/j.jaapos.2006.12.054. PMID 17416331.
10. ^ Raab, Edward (1982). "Etiologic Factors In Accommodative esodeviation". Transactions of the American Ophthalmological Society. 80: 657–694. PMC 1312281. PMID 7182971.
11. ^ McGovern ST, Crompton JL, Ingham PN (1986). "Trigemino-abducens synkinesis: an unusual case of aberrant regeneration". Aust N Z J Ophthalmol. 14 (3): 275–9. doi:10.1111/j.1442-9071.1986.tb00049.x. PMID 3768184.
12. ^ a b Rubin DI, Matsumoto JY, Suarez GA, Auger RG (1999). "Facial trigeminal synkinesis associated with a trigeminal schwannoma". Neurology. 53 (3): 635–7. doi:10.1212/wnl.53.3.635. PMID 10449135.
13. ^ a b Moran CJ, Neely JG (1996). "Patterns of facial nerve synkinesis". Laryngoscope. 106 (12): 1491–6. doi:10.1097/00005537-199612000-00009. PMID 8948609.
14. ^ Choi D, Raisman G (2004). "After facial nerve damage, regenerating axons become aberrant throughout the length of the nerve and not only at the site of the lesion: an experimental study". Br J Neurosurg. 18 (1): 45–8. doi:10.1080/02688690410001660454. PMID 15040714.
15. ^ Sadjadpour K. (1975). "After Postfacial palsy phenomena: faulty nerve regeneration or ephaptic transmission?". Brain Res. 95 (2–3): 403–6. doi:10.1016/0006-8993(75)90117-1. PMID 168941.
16. ^ Sibony PA, Lessell S, Gittinger JW Jr (1984). "Acquired oculomotor synkinesis". Surv. Ophthalmol. 28 (5): 382–90. doi:10.1016/0039-6257(84)90243-1. PMID 6372143.
17. ^ May, Mark; Barry M. Schaitkin (1999). The Facial Nerve. Thieme. p. 49. ISBN 0-86577-821-3.
18. ^ a b Brach JS, VanSwearingen JM, Lenert J, Johnson PC (1997). "Facial neuromuscular retraining for oral synkinesis". Plast Reconstr Surg. 99 (7): 1922–31. doi:10.1097/00006534-199706000-00017. PMID 9180715.
19. ^ Brudny J, Hammerschlag PE, Cohen NL, Ransohoff J (1988). "Electromyographic rehabilitation of facial function and introduction of a facial paralysis grading scale for hypoglossal-facial nerve anastomosis". Laryngoscope. 98 (4): 405–10. doi:10.1288/00005537-198804000-00010. PMID 3352440.
20. ^ Ross B, Nedzelski JM, McLean JA (1991). "Efficacy of feedback training in long-standing facial nerve paresis". Laryngoscope. 101 (7): 744–50. doi:10.1288/00005537-199107000-00009. PMID 2062155.
21. ^ Beurskens CH, Heymans PG (2003). "Positive effects of mime therapy on sequelae of facial paralysis: stiffness, lip mobility, and social and physical aspects of facial disability". Otol. Neurotol. 24 (4): 677–81. doi:10.1097/00129492-200307000-00024. PMID 12851564.
22. ^ Beurskens CH, Heymans PG, Oostendorp RA (2006). "Stability of benefits of mime therapy in sequelae of facial nerve paresis during a 1-year period". Otol. Neurotol. 27 (7): 1037–42. doi:10.1097/01.mao.0000217350.09796.07. PMID 17006356.
23. ^ de Maio M, Bento RF (2007). "Botulinum toxin in facial palsy: an effective treatment for contralateral hyperkinesis". Plast Reconstr Surg. 120 (4): 917–27. doi:10.1097/01.prs.0000244311.72941.9a. PMID 17805119.
24. ^ D. Markey, Jeffrey (2017). "Latest advances in the management of facial synkinesis". Current Opinion in Otolaryngology & Head and Neck Surgery. 25 (4): 265–272. doi:10.1097/MOO.0000000000000376. PMID 28604403.
25. ^ a b c Ito H, Ito H, Nakano S, Kusaka H (2007). "Low-dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation". Acta Neurol. Scand. 115 (4): 271–4. doi:10.1111/j.1600-0404.2006.00746.x. PMID 17376126.
26. ^ May, Mark; Barry M. Schaitkin (1999). The Facial Nerve. Thieme. p. 467. ISBN 0-86577-821-3.
## External links[edit]
Classification
D
* MeSH: D046608
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
* Spastic gait
* Magnetic gait
* Truncal ataxia
* Muscular
* Myopathic gait
* Trendelenburg gait
* Pigeon gait
* Steppage gait
* Antalgic gait
Coordination
* Ataxia
* Cerebellar ataxia
* Dysmetria
* Dysdiadochokinesia
* Pronator drift
* Dyssynergia
* Sensory ataxia
* Asterixis
Abnormal movement
* Athetosis
* Tremor
* Fasciculation
* Fibrillation
Posturing
* Abnormal posturing
* Opisthotonus
* Spasm
* Trismus
* Cramp
* Tetany
* Myokymia
* Joint locking
Paralysis
* Flaccid paralysis
* Spastic paraplegia
* Spastic diplegia
* Spastic paraplegia
* Syndromes
* Monoplegia
* Diplegia / Paraplegia
* Hemiplegia
* Triplegia
* Tetraplegia / Quadruplegia
* General causes
* Upper motor neuron lesion
* Lower motor neuron lesion
Weakness
* Hemiparesis
Other
* Rachitic rosary
* Hyperreflexia
* Clasp-knife response
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Synkinesis
|
c0234362
| 27,559 |
wikipedia
|
https://en.wikipedia.org/wiki/Synkinesis
| 2021-01-18T18:48:15 |
{"mesh": ["D046608"], "wikidata": ["Q3508182"]}
|
Confused unintelligible jumble of words and phrases
For the album by Fischer-Z, see Word Salad (album).
A word salad, or schizophasia, is a "confused or unintelligible mixture of seemingly random words and phrases",[1] most often used to describe a symptom of a neurological or mental disorder. The term schizophasia is used in particular to describe the confused language that may be evident in schizophrenia.[2] The words may or may not be grammatically correct, but are semantically confused to the point that the listener cannot extract any meaning from them. The term is often used in psychiatry as well as in theoretical linguistics to describe a type of grammatical acceptability judgement by native speakers, and in computer programming to describe textual randomization.
## Contents
* 1 In psychiatry
* 2 In computing
* 3 See also
* 3.1 Similar textual productions or phenomenons
* 3.2 Other
* 4 References
* 5 External links
## In psychiatry[edit]
Word salad may describe a symptom of neurological or psychiatric conditions in which a person attempts to communicate an idea, but words and phrases that may appear to be random and unrelated come out in an incoherent sequence instead. Often, the person is unaware that he or she did not make sense. It appears in people with dementia and schizophrenia,[3] as well as after anoxic brain injury. In schizophrenia it is also referred to as schizophasia.[2] Clang associations are especially characteristic of mania, as seen in bipolar disorder, as a somewhat more severe variation of flight of ideas. In extreme mania, the patient's speech may become incoherent, with associations markedly loosened, thus presenting as a veritable word salad.
It may be present as:
* Clanging, a speech pattern that follows rhyming and other sound associations rather than meaning
* Graphorrhea, a written version of word salad that is more rarely seen than logorrhea in people with schizophrenia.[4]
* Logorrhea, a mental condition characterized by excessive talking (incoherent and compulsive)
* Receptive aphasia,[5] fluent in speech but without making sense, often a result of a stroke or other brain injury
## In computing[edit]
Word salad can be generated by a computer program for entertainment purposes by inserting randomly chosen words of the same type (nouns, adjectives, etc.) into template sentences with missing words, a game similar to Mad Libs. The video game company Maxis, in their seminal SimCity 2000, used this technique to create an in-game "newspaper" for entertainment; the columns were composed by taking a vague story-structure, and using randomization, inserted various nouns, adjectives, and verbs to generate seemingly unique stories.
Another way of generating meaningless text is mojibake, also called Buchstabensalat ("letter salad") in German, in which an assortment of seemingly random text is generated through character encoding incompatibility in which one set of characters are replaced by another, though the effect is more effective in languages where each character represents a word, such as Chinese.
More serious attempts to automatically produce nonsense stem from Claude Shannon's seminal paper A Mathematical Theory of Communication from 1948[6] where progressively more convincing nonsense is generated first by choosing letters and spaces randomly, then according to the frequency with which each character appears in some sample of text, then respecting the likelihood that the chosen letter appears after the preceding one or two in the sample text, and then applying similar techniques to whole words. Its most convincing nonsense is generated by second-order word approximation, in which words are chosen by a random function weighted to the likeliness that each word follows the preceding one in normal text:
> The Head And In Frontal Attack On An English Writer That The Character Of This Point Is Therefore Another Method For The Letters That The Time Of Who Ever Told The Problem For An Unexpected.
Markov chains can be used to generate random but somewhat human-looking sentences. This is used in some chat-bots, especially on IRC-networks.
Nonsensical phrasing can also be generated for more malicious reasons, such as the Bayesian poisoning used to counter Bayesian spam filters by using a string of words which have a high probability of being collocated in English, but with no concern for whether the sentence makes sense grammatically or logically.
## See also[edit]
### Similar textual productions or phenomenons[edit]
* Dissociated press, a computer program that applies a Markov chain to generate word salad
* Gibberish, nonsensical language
* Lorem ipsum, test text which does not have any meaning
* Nonsense verse, verse which is nonsensical
* Paragrammatism, inability to produce or create grammatically correct sentences
* Thought disorder, disorder of thought
### Other[edit]
* Glossolalia, phenomenon in which people speak in languages which are unfamiliar to them
* Mad Libs, a phrasal template word game that sometimes results in word salad
* Scat singing, vocal improvisation with nonsensical words
## References[edit]
1. ^ "Definition of "word salad". Oxford University Press. 2012.
2. ^ a b "Medical Definition of SCHIZOPHASIA". www.merriam-webster.com. Retrieved 29 December 2019.
3. ^ Shives, Louise Rebraca (2008). Basic concepts of psychiatric-mental health nursing. Philadelphia: Wolters Kluwer / Lippincott Williams & Wilkins. p. 112. ISBN 978-0-7817-9707-8.
4. ^ Geschwind, Norman (1974). Selected papers on language and the brain (2. print. ed.). Dordrecht; Boston: Reidel. p. 80. ISBN 9789027702623.
5. ^ "Merck Manual". merckmanuals.com. Merck Publishing. Retrieved 6 December 2014.
6. ^ Shannon, C. E. (1948). "A Mathematical Theory of Communication" (PDF). The Bell System Technical Journal. 27: 379–423. ISSN 1538-7305. Retrieved 19 July 2017.
## External links[edit]
* The dictionary definition of word salad at Wiktionary
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Word salad
|
c0233648
| 27,560 |
wikipedia
|
https://en.wikipedia.org/wiki/Word_salad
| 2021-01-18T18:37:12 |
{"umls": ["C0233648"], "wikidata": ["Q4384351"]}
|
A number sign (#) is used with this entry because mal de Meleda is caused by homozygous mutation in the SLURP1 gene (606119) on chromosome 8q24.
Clinical Features
Congenital symmetrical cornification of the palms and soles, with ichthyotic changes elsewhere, characterizes this disorder which derives its name from its relatively high frequency among inhabitants of the Island of Meleda, Dalmatia, Yugoslavia. Bosnjakovic (1938) studied the family in Mljet (or Meleda). Schnyder et al. (1969) provided more recent observations. Hyperhidrosis, perioral erythema, and lichenoid plaques were also noted. Franceschetti et al. (1972) reported on Meleda disease and stated that Neumann (1898) was the first to report the disorder, in 5 families from Meleda. Fischer et al. (1998) described the clinical characteristics of Meleda disease as transgressive palmoplantar keratoderma, hyperhidrosis, and perioral erythema.
During clinical assessment of MDM families in Tunisia, Mokni et al. (2004) detected minor clinical signs in the palms and soles of women who were obligate carriers of this autosomal recessive disorder. They illustrated cobblestone changes in the skin of the palms of 2 women, each of whom was heterozygous for a mutation in the SLURP1 gene (see 606119.0008-606119.0009). Two women heterozygous for the 82delT mutation (606119.0001) were also described; both had mild palmoplantar keratodermas, and one had interdigital fissures.
Mapping
Fischer et al. (1998) performed linkage analysis of 2 large consanguineous families from Algeria, including 10 affected individuals, and found strong evidence for localization of a gene for Meleda disease on 8qter with a maximum 2-point lod score for D8S1751 of 8.21 at theta = 0.0. Analysis of homozygosity regions and recombination events placed the gene in a region of at least 3 cM, telomeric to D8S1727. A common haplotype was observed in the 2 families, suggesting a founder effect.
Molecular Genetics
Fischer et al. (2001) refined the critical region on chromosome 8qter and identified mutations in affected individuals in the ARS component B gene, encoding a protein named SLURP1 (606119), for secreted Ly6/uPAR related protein-1. Three different homozygous mutations (82delT, 606119.0001; 178G+1G-A, 606119.0002; and R96X, 606119.0003) were detected in 19 families of Algerian and Croatian origin, suggesting founder effects. Moreover, one of the common haplotypes presenting the same mutation was shared by families from both populations.
Charfeddine et al. (2003) identified homozygous mutations in the SLURP1 gene (606119.0001; 606119.0008-606119.0009) in 17 affected members of 8 consanguineous families segregating mal de Meleda from northern Tunisia.
Heterogeneity
Lestringant et al. (2001) examined 5 patients with autosomal recessive mal de Meleda from 3 unrelated consanguineous families from the United Arab Emirates. The patients had diffuse erythrodermic PPK and transgressive erythrodermic keratosis, often with scaly borders, plaques of erythrodermic keratosis on the knees, and red nails with preserved lunulae; none had hyperhidrosis. The MDM interval on chromosome 8q was excluded by homozygosity mapping in all 3 families. Lestringant et al. (2001) concluded that the MDM phenotype is due to at least 2 different genotypes.
Van Steensel et al. (2002) reported a 7-year-old Dutch girl with MDM, born of nonconsanguineous parents, who had transgredient erythroderma and hyperkeratosis of the palms and soles with slight scaling, hyperhidrosis, brachydactyly, and beginning pseudoainhum of the right middle finger. Sequence analysis of exons and intron-exon junctions of the SLURP1, E48 (LY6D; 606204), and GML (602370) genes showed no deviation from wildtype sequence. Van Steensel et al. (2002) suggested that genetic heterogeneity exists in Meleda disease.
Charfeddine et al. (2006) studied 3 affected and 4 unaffected members of a 6-generation consanguineous Tunisian family with MDM. Screening the SLURP1 gene in 1 of the patients revealed no mutations, and multipoint haplotype analysis excluded linkage to the MDM interval on chromosome 8 in this family. Charfeddine et al. (2006) noted that the keratoderma in these patients was cracked rather than waxy yellow as seen in classic MDM, and concluded that MDM is a clinically and genetically heterogeneous disease.
Pathogenesis
The high degree of structural similarity between SLURP1 and the 3-finger motif of snake neurotoxins and LYNX1 (606110) suggested that SLURP1 may interact with neuronal acetylcholine receptors. Chimienti et al. (2003) found that SLURP1 potentiated the human alpha-7 nicotinic acetylcholine receptors (CHRNA7; 118511) present in keratinocytes. The authors concluded that SLURP1 acts as a secreted epidermal neuromodulator that may be essential for both epidermal homeostasis and inhibition of TNF-alpha (191160) release by macrophages during wound healing. This may explain both the hyperproliferative as well as the inflammatory clinical phenotype of mal de Meleda.
INHERITANCE \- Autosomal recessive HEAD & NECK Mouth \- Perioral erythema SKELETAL Hands \- Brachydactyly SKIN, NAILS, & HAIR Skin \- Congenital symmetrical palmoplantar keratosis \- Transgressive keratosis \- Ichthyosis \- Hyperhidrosis \- Lichenoid plaques Nails \- Fragile, lustreless nails MISCELLANEOUS \- Onset in early infancy MOLECULAR BASIS \- Caused by mutations in the secreted LY6/uPAR-related protein 1 gene (SLURP1, 606119.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
MAL DE MELEDA
|
c0025221
| 27,561 |
omim
|
https://www.omim.org/entry/248300
| 2019-09-22T16:25:40 |
{"doid": ["0060862"], "mesh": ["D007645"], "omim": ["248300"], "orphanet": ["87503"], "synonyms": ["Alternative titles", "MELEDA DISEASE", "KERATOSIS PALMOPLANTARIS TRANSGREDIENS OF SIEMENS"]}
|
A number sign (#) is used with this entry because mucopolysaccharidosis type IIIA (MPS3A) is caused by homozygous or compound heterozygous mutation in the gene encoding N-sulfoglucosamine sulfohydrolase (SGSH; 605270) on chromosome 17q25.
Description
The Sanfilippo syndrome, or mucopolysaccharidosis III, is an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate (Esposito et al., 2000). The disorder is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. Type A has been reported (van de Kamp et al., 1981) to be the most severe, with earlier onset and rapid progression of symptoms and shorter survival.
### Genetic Heterogeneity of Mucopolysaccharidosis Type III
MPS III includes 4 types, each due to the deficiency of a different enzyme: heparan N-sulfatase (type A); alpha-N-acetylglucosaminidase (type B; 252920); acetyl CoA:alpha-glucosaminide acetyltransferase (type C; 252930); and N-acetylglucosamine 6-sulfatase (type D; 252940).
Clinical Features
In the Sanfilippo syndrome, of which 4 enzymatically distinct forms are recognized, only heparan sulfate is excreted in the urine. The clinical features are severe mental defect with relatively mild somatic features (moderately severe claw hand and visceromegaly, little or no corneal clouding or skeletal, e.g., vertebral, change). The presenting problem may be marked overactivity, destructive tendencies, and other behavioral aberrations in a child of 4 to 6 years of age. Maroteaux et al. (1966) reported a kindred in which 3 separate consanguineous marriages resulted in a total of 4 cases. The radiologic findings in the skeleton are relatively mild and include persistent biconvexity of the vertebral bodies and very thick calvaria. Kresse et al. (1971) recognized 3 forms of Sanfilippo syndrome by cocultivation experiments on fibroblasts. Type A has deficiency of heparan sulfate sulfatase (EC 3.10.1.1.) (Kresse and Neufeld, 1972). Neufeld (1987) suggested that for the sake of simplicity the enzyme deficient in this disorder be termed heparan sulfatase.
Van de Kamp (1979) studied 75 cases of Sanfilippo syndrome identified in the Netherlands. Of these, 32 were type A, 18 were type B, and 12 were type C. Six had died before enzymatic studies for classification were performed. The author concluded that the clinical picture was more severe in type A than in types B and C, with shorter life expectancy. The incidence at birth was thought to be about 1 in 24,000. Van de Kamp et al. (1981) reiterated the milder course in type B with less severe dementia, and the earlier onset, greater severity, and earlier death in type A. They studied 73 patients (36 with type A, 23 with type B, 14 with type C).
Lindor et al. (1994) described an adult sister and brother with milder manifestations of MPS IIIA than in most cases. The family came to attention because of psychiatric manifestations in the sister at age 24 requiring admission to a closed psychiatric ward. A brother, then 30 years old, had required special education from the first grade and had worn hearing aids from the age of 7. The parents were nonconsanguineous, the mother being of French and Irish ancestry and the father of German ancestry. Neither sib had strikingly coarse facial characteristics.
Valstar et al. (2010) retrospectively reviewed the clinical features of 92 patients with MPS IIIA, including 32 living and 60 deceased individuals. There was wide phenotypic variability, and patients could be divided into 3 main groups: a severe, intermediate, and attenuated phenotype. Those with a severe phenotype became completely dependent of care and wheelchair-bound in their teenage years, whereas those with the intermediate phenotype had a slower regression of abilities and could live into adulthood. Those with the attenuated form reached much higher developmental levels and could achieve some speech and walking, lasting well into adulthood. Among the whole cohort, most had normal development in the first year of life, with onset of clinical symptoms at a mean age of 2.5 years. Symptoms included developmental delay, delayed speech development and behavioral problems. Behavioral problems included restlessness, temper tantrums, and crying fits, but these tended to decline with age as neurologic deterioration progressed. Other symptoms included sleeping and hearing problems, recurrent upper airway infections, diarrhea, and epilepsy. The median age at death was 18 years, most commonly due to pneumonia.
Diagnosis
Toone and Applegarth (1988) used an enzymatic method to identify heterozygotes by studying leukocytes or fibroblasts. Stone et al. (1990) found that in an assay at 55 degrees C heterozygous carriers could be distinguished with complete certainty from normal controls. Twenty-one obligate carriers in 12 families were studied.
For the sulfamidase assay in chorionic villi and amniotic fluid cells, Kleijer et al. (1996) used an artificial substrate and a 2-step assay. Unequivocal assignment of the fetal status in 5 affected pregnancies and 7 pregnancies with a normal outcome confirmed the reliability of the test, which in every respect was more convenient than the conventional method using (35)S-radiolabeled heparin.
Clinical Management
Severe behavioral disturbance is a very common feature of Sanfilippo syndrome, and one of the more difficult aspects of the disorder to manage. Robertson et al. (1998) described a series of 6 patients with MPS III who had cerebrospinal shunts inserted in an attempt to ameliorate behavior that had proved refractory to conventional treatment. Symptoms improved significantly in all 6.
Sivakumur and Wraith (1999) found that bone marrow transplantation did not affect the prognosis favorably, even though neurologic manifestations were not evident.
McDowell et al. (1993) described a family in which sibs with comparable deficiencies of sulfamidase had rather different clinical severity and disease progression. The cases underscored the need for caution in counseling and the limitations of using sibs as controls in evaluating the outcome of treatment.
Population Genetics
In British Columbia, between 1952 and 1986, 4 cases of MPS IIIA were observed, giving a frequency of 1 in 324,617 live births (Lowry et al., 1990).
Using multiple ascertainment sources, Nelson et al. (2003) obtained an incidence rate for Sanfilippo syndrome (all forms combined) in western Australia for the period 1969 to 1996 of approximately 1 in 58,000 live births; there was a total of 11 cases, including 5 of type A, 5 of type B, and 1 of type C.
In the Netherlands, the incidence of MPS IIIA is estimated at 1.16 to 0.88 per 100,000 live births (Poorthuis et al., 1999).
Khan et al. (2017) analyzed the epidemiology of the mucopolysaccharidoses in Japan and Switzerland and compared them to similar data from other countries. Data for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II (309900), accounting for 55% of all MPS. MPS I (see 607014), III, and IV (see 253000) accounted for 15%, 16%, and 10%, respectively. MPS VI (253200) and VII (253220) were more rare and accounted for 1.7% and 1.3%, respectively. A retrospective epidemiologic data collection was performed in Switzerland between 1975 and 2008 (34 years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12%, 24%, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3% and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS was also reported to be higher in these countries.
Molecular Genetics
For a discussion of the molecular genetics of Sanfilippo syndrome A, and a listing of disease-causing allelic variants of the N-sulfoglucosamine sulfohydrolase gene (SGSH), see 605270.
Genotype/Phenotype Correlations
Valstar et al. (2010) retrospectively reviewed the clinical features of 92 patients with MPS IIIA, including 32 living and 60 deceased individuals. There was wide phenotypic variability that correlated with genotype. In particular, those with 1 or more S298P (605270.0013) mutant alleles had an attenuated phenotype, with a significantly longer preservation of psychomotor functions and a longer survival. The most frequent pathogenic mutations were R245H (605270.0001), Q380R, S66W (605270.0003), and 1080delC, all of which were associated with the classic severe phenotype.
Animal Model
Fischer et al. (1998) identified sulfamidase deficiency in 2 adult wire-haired dachshund littermates. Clinical and pathologic features paralleled the human disorder. Both dogs exhibited progressive neurologic disease without apparent somatic involvement. Pelvic limb ataxia was observed when the dogs were 3 years old and gradually progressed within 1 to 2 years to severe generalized spinocerebellar ataxia. Mentation remained normal throughout the course of the disease. A positive toluidine blue spot test of urine indicated a mucopolysaccharide storage disorder in both dogs; the diagnosis of MPS IIIA was confirmed by documentation of urinary excretion and tissue accumulation of heparan sulfate and decreased sulfamidase activity in fibroblasts and hepatic tissue.
To identify the molecular defect in the type A Sanfilippo syndrome identified by Fischer et al. (1998), Aronovich et al. (2000) determined the nucleotide sequence of the normal canine heparan sulfate sulfamidase gene and cDNA, using PCR-based approaches. The coding region showed 89% amino acid sequence homology with human HSS. All exon-intron borders were conserved. The authors identified a 3-bp deletion, 737-739delCCA, resulting in loss of threonine at position 246 in both alleles of an affected animal. The same mutation was found in 1 allele of a healthy littermate. The canine model should be useful in the evaluation of gene therapy for this disorder.
Bhattacharyya et al. (2001) described a spontaneous mouse mutant of MPS IIIa resulting from an asp31-to-asn (D31N) mutation in the murine sulfatase gene. Affected mice die at about 10 months of age exhibiting a distended bladder and hepatosplenomegaly. Brain sections show distended lysosomes, some with typical zebra body morphology, and many containing periodic-acid Schiff positive storage material. Urinalysis revealed an accumulation of heparan sulfate. Assays of a variety of lysosomal hydrolases in brain, liver, and kidney extracts uncovered a specific defect in sulfamidase activity, which was reduced by about 97%.
Hemsley and Hopwood (2005) found that the MPS IIIA mouse developed impaired open-field locomotor activity at 3 weeks of age. Abnormalities in tests of gait, grip strength, and in the assessment of the negative geotaxis response were observable from about 15 weeks of age. Behavioral changes were often detected in male MPS IIIA mice before they appeared in females. The authors postulated that axonal degeneration was responsible for the deficits. The observations provided insight into the chronology of pathologic changes within the murine MPS IIIA brain.
In brain tissue of MPS IIIA mice, Settembre et al. (2008) observed increased autophagosomes resulting from impaired autophagosome-lysosome fusion. Cells showed a decreased ability to degrade aggregation-prone proteins. There was also an accumulation of ubiquitin-positive inclusions and increased numbers of dysfunctional mitochondria. Similar findings were observed in a mouse model of another lysosomal storage disorder, multiple sulfatase deficiency (MSD; 272200). The findings were consistent with these diseases being disorders of autophagy, which may be a common mechanism in neurodegenerative lysosomal storage diseases.
Hassiotis et al. (2014) studied the development of cerebellar pathology in a canine model of MPS3A (Huntaway dog model) and observed that Purkinje cells were present in affected dogs aged up to and including 30.9 months; however, by 40.9 months, only approximately 12% remained, coincident with the onset of clinical signs. Primary and secondary substrate accumulation and inflammation were detected as early as 2.2 months, and axonal spheroids were observed from 4.3 months in deep cerebellar nuclei and later (11.6 months) in cerebellar white matter tracts. Degenerating neurons and apoptotic cells were not observed at any time. Hassiotis et al. (2014) suggested that cell-autonomous mechanisms may contribute to Purkinje cell death in the MPS3A dog.
INHERITANCE \- Autosomal recessive GROWTH Other \- Usually normal stature HEAD & NECK Face \- Mild coarse facies Ears \- Hearing loss Eyes \- Clear corneas \- Synophrys CARDIOVASCULAR Heart \- Asymmetric septal hypertrophy RESPIRATORY Nasopharynx \- Frequent upper respiratory tract infections ABDOMEN Liver \- Mild hepatomegaly Spleen \- Mild splenomegaly Gastrointestinal \- Diarrhea SKELETAL \- Mild dysostosis multiplex Skull \- Dense calvaria Spine \- Ovoid thoracolumbar vertebrae Limbs \- Mild joint stiffness SKIN, NAILS, & HAIR Hair \- Hirsutism \- Synophrys \- Coarse hair NEUROLOGIC Central Nervous System \- Severe behavioral problems at age 3-4 \- Mental retardation \- Hyperactivity \- Seizures \- Slowing mental development by 1.5 to 3 years \- Sleep disturbances common LABORATORY ABNORMALITIES \- Heparan N-sulfatase deficiency in fibroblasts and amniocytes \- Heparan sulfate excretion in urine MISCELLANEOUS \- Four clinically indistinguishable biochemically distinct forms MOLECULAR BASIS \- Caused by mutations in the heparan sulfate sulfatase gene (SGSH, 605270.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
MUCOPOLYSACCHARIDOSIS, TYPE IIIA
|
c0026706
| 27,562 |
omim
|
https://www.omim.org/entry/252900
| 2019-09-22T16:24:57 |
{"doid": ["12801"], "mesh": ["D009084"], "omim": ["252900"], "icd-10": ["E76.22"], "orphanet": ["581", "79269"], "synonyms": ["Alternative titles", "MPS IIIA", "SANFILIPPO SYNDROME A", "HEPARAN SULFATE SULFATASE DEFICIENCY", "SULFAMIDASE DEFICIENCY"]}
|
Human disease
Neonatal infection
26-week gestation, premature infant, weighing <990gm with ventilator
SpecialtyInfectious disease, Pediatrics
Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or in the first four weeks of life (neonatal period).[1] Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or contracted after birth.[2] Some neonatal infections are apparent soon after delivery, while others may develop in the postnatal period. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later.
There is a higher risk of infection for preterm or low birth weight neonates. Infant respiratory distress syndrome is often a condition of preterm neonates that can have long-term negative consequences, it can also arise following an infection. In some instances, neonatal respiratory tract diseases may increase the susceptibility to future respiratory infections and inflammatory responses related to lung disease.[3]
Antibiotics can be effective for neonatal infections, especially when the pathogen is quickly identified. Instead of relying solely on culturing techniques, pathogen identification has improved substantially with advancing technology; however, neonate mortality reduction has not kept pace and remains 20% to 50%.[4] While preterm neonates are at a particularly high risk, all neonates can develop infection. Neonatal infection may also be associated with premature rupture of membranes (breakage of the amniotic sac) which substantially increases the risk of neonatal sepsis by allowing passage for bacteria to enter the womb prior to the birth of the infant.[5][6] Neonatal infection can be distressing to the family and it initiates concentrated effort to treat it by clinicians. Research to improve treatment of infections and prophylactic treatment of the mother to avoid infections of the infant is ongoing.
## Contents
* 1 Causes
* 1.1 Bacteria
* 1.2 Viruses
* 1.2.1 HIV
* 1.2.2 Cytomegalovirus
* 1.2.3 HSV
* 1.2.4 Zika
* 1.2.5 Rubella
* 1.2.6 Other
* 1.3 Fungi
* 1.4 Protozoans
* 2 Risk factors
* 3 Mechanism
* 3.1 Pathogenesis
* 4 Diagnosis
* 4.1 Viral infection
* 4.2 Protozoan infection
* 4.3 Neonatal sepsis
* 5 Prevention
* 6 Treatment
* 7 Epidemiology
* 7.1 Early-onset infections
* 7.2 Late onset infections
* 8 Research
* 9 See also
* 10 References
* 11 Further reading
* 12 External links
## Causes[edit]
In industrialized countries, treatment for neonatal infections takes place in the neonatal intensive care unit (NICU). The causes and reasons for neonatal infection are many. The origin of infectious bacteria and some other pathogens is often the maternal gastrointestinal and genitourinary tract. Many of the maternal infections with these organisms are asymptomatic in the mother. Other maternal infections that may be transmitted to the infant in utero or during birth are bacterial and viral sexually transmitted infections.[7] The infant's ability to resist infection is limited by its immature immune system. The causative agents of neonatal infection are bacteria, viruses, and fungi. In addition, the immune system of the neonate may respond in ways that can create problems that complicate treatment, such as the release of inflammatory chemicals. Congenital defects of the immune system also affect the infants ability to fight off the infection.[8][9]
### Bacteria[edit]
Listeria monocytogenes
Group B streptococcus are typically identified as the cause of the majority of early-onset infections in the neonate.[7][10][11] This pathogen is vertically transmitted (transmitted directly from the mother) to the infant.[12] Enteric bacilli that originate from the digestive system of the mother have become as prevalent as the group B streptococcus pathogens and are currently as likely to cause infection. With the advances in preventing group B streptococcus infections, β-lactam-resistant Escherichia coli infections have increased in causing neonatal deaths in very low birthweight and premature infants.[12] Infections with Staphylococcus aureus are also diagnosed, but not as frequently as group B streptococcus infections.[5]
Listeria monocytogenes can also cause infection acquired from tainted food and present in the mother.[4][13] The presence of this pathogen can sometimes be determined by the symptoms that appear as a gastrointestinal illness in the mother. The mother acquires infection from ingesting food that contains animal products such as hot dogs, unpasteurized milk, delicatessen meats, and cheese.[citation needed]
Neonatal infection can also occur in term and post-term infants.[14] Infections that develop one month after the birth of the infant are more likely due to Gram-positive bacteria and coagulase positive staphylococci.[15] Acquired maternal infection and subsequent inflammation from Ureaplasma urealyticum is accompanied by a strong immune response and is correlated with the need for prolonged mechanical ventilation.[3][7]
Clostridium tetani can cause a generalised form of tetanus in the neonate. This usually occurs when the mother has not been vaccinated against tetanus and the baby has not acquired passive immunity. The umbilical cord region is the most susceptible.[16]
Other bacterial pathogens include Streptococcus agalactiae, Streptococcus pyogenes, Viridans streptococci, Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa.[17]
### Viruses[edit]
#### HIV[edit]
Human immunodeficiency virus type I (HIV) infection can occur during labor and delivery, in utero through mother-to-child transmission or postnatally by way of breastfeeding.[18] Transmission can occur during pregnancy, delivery or breastfeeding. Most transmission occurs during delivery. In women with low detectable levels of the virus, the incidence of transmission is lower.[19] Transmission risk can be reduced by:
* providing antiretroviral therapy during pregnancy and immediately after birth
* delivery by caesarean section
* not breastfeeding
* antiretroviral prophylaxis in infants born to mothers with HIV.[19]
A low number of women whose HIV status are unknown until after the birth, do not benefit from interventions that could help lower the risk of mother-to-child HIV transmission.[20]
#### Cytomegalovirus[edit]
Sixty percent of mothers of preterm infants are infected with cytomegalovirus (CMV). Infection is asymptomatic in most instances but 9% to 12% of postnatally infected low birth weight, preterm infants have severe, sepsis-like infection. CMV infection duration can be long and result in pneumonitis in association with fibrosis. CMV infection in infants has an unexpected effect on the white blood cells of the immune system causing them to prematurely age. This leads to a reduced immune response similar to that found in the elderly.[3]
#### HSV[edit]
Herpes simplex virus (HSV) can infect the infant during birth. Most women with HVS genital herpes develop asymptomatic infection during pregnancy. HVS inoculation from mother to fetus has a high likelihood of occurring. Mothers who are treated with antiviral prophylaxis are less prone to have an active, symptomatic case at the time of birth. Mothers who have received prophylactic antiviral medication have been shown to be less likely to require a cesarean section. At delivery, mothers treated with antiviral medication are less likely to have a viral shedding at the time of birth.[21]
#### Zika[edit]
Zika fever is caused by a virus that is acquired by the mother and then transmitted to the infant in utero. The CDC is concerned with the potential that this viral infection may cause microcephaly in newborns.[22][23][24]
#### Rubella[edit]
Congential rubella is still a risk with higher risk among immigrant women from countries without adequate vaccination programs.[20]
#### Other[edit]
Other viral infections such as respiratory syncytial virus (RSV), metapneumovirus (hMPV), rhinovirus, parainfluenza (PIV), and human coronavirus in the neonatal period are associated with recurrent wheezing in later childhood. RSV infections can be prolonged. Premature infants born at less than 32 weeks gestation have more days of cough and wheeze at 1 year of age than those uninfected with RSV.[3]
### Fungi[edit]
In very low birth weight infants (VLBWI), systemic fungus infection is a hospital-acquired infection with serious consequences. The pathogens are usually Candida albicans and Candida parapsilosis. A small percentage of fungal infections are caused by Aspergillus, Zygomycetes, Malassezia, and Trichosporon.[25][26] Infection is usually late-onset. Up to 9% of VLBWI with birth weights of <1,000 g develop these fungus infections leading to sepsis or meningitis. As many as one-third of these infants can die. Candidiasis is associated with retinopathy, prematurity and negative neurodevelopmental consequences. Candida can colonize the gastrointestinal tract of low birthweight infants (LBI). This gastrointestinal colonization is often a precursor to a more serious invasive infection. The risk of serious candida infection increases when multiple factors are present. These are: thrombocytopenia, the presence of candidal dermatitis, the use of systemic steroids, birth weights of <1,000 g, presence of a central catheter, postponing enteral feeding, vaginal delivery, and the amount of time broad-spectrum antibiotics were given.[26]
### Protozoans[edit]
Infants born with malaria can be infected with a variety of species; Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium falciparum. In most instances of congenital malaria is caused by P. vivax and P. falciparum. Women living in areas where malaria is prevalent and common are repeatedly exposed to malaria. In response to maternal infection, mothers develop antimalarial antibodies. It is probable that the antibodies present in the mother offers protection for the baby. Bacterial infection can develop with malaria.[25]
Infants that are infected by the protozoanToxoplasma gondii in utero can be born with chorioretinitis or ocular toxoplasmosis. Globally, it is the most common cause of infections of the back of the eye. (posterior segment). The most common sign is decreased vision in one eye. Other signs and symptoms may appear after the neonatal period and include: chorioretinitis development later in life, intracranial calcification hydrocephalus or central nervous system abnormalities.[27]
## Risk factors[edit]
Risk factors are those conditions which increase the likelihood that an infant will be born with or develop an infection.
Risk factors for neonatal infection within the first week Factor Notes References
prematurity birth before 40 weeks gestation [8]
meconium aspiration inspiration of stool in utero [14]
Postpartum endometritis inflammation of the uterus after the birth [14]
low birth weight < 40 weeks gestation [8][15]
premature rupture of membranes <12 hours [5][8][15][28]
prolonged premature rupture of membranes >12 hours [5][28]
pre-term onset of labor labor begins before 40 weeks gestation [8][15]
chorioamnionitis inflammation of the fetal membranes(amnion and chorion) due to a bacterial infection [8]
vaginal discharge abnormal discharge can be a result of an infection [8]
tender uterus discomfort when the uterus is examined [29]
rupture of membranes <12 hours [5]
prolonged rupture of membranes >12 hours) [8][29]
in utero infection with pathogens the period of infection
allows for the logarithmic growth
of pathogens [7]
maternal urinary tract infection bladder and/or kidney infection [8]
prolonged labor [29]
vaginal examinations during labor risk increases with the number of vaginal examinations during labor [8][29]
maternal colonization with group B streptococcus the presence of this bacterium is usually asymptomatic [5][8]
previous baby with early-onset GBS infection [8][29]
gender males are more susceptible;This risk declines
after respiratory distress syndrome is treated [15]
multiples risk is increased for the firstborn [15]
iron supplementation iron is a growth factor for
some bacteria [15]
maternal intrapartum fever > 38 °C [8][28]
after insertion of intravenous line may introduce pathogens into the circulation [15]
immature immune system [15]
invasive medical procedures may introduce pathogens into the circulation [15]
hypoxia unexpected resuscitation
after birth [15][29]
low socioeconomic status [15]
hypothermia relatively low blood temperature [15]
metabolic acidosis a pH imbalance in the blood [15]
obstetrical complications [15]
prevalence of resistant bacteria in the neonatal intensive care unit nosomial populations [15]
maternal exposure to Toxoplasmosis gondii a parasite present in cat litter and other animal excrement [27]
Risk factors for late onset for neonatal infection >one week after birth Factor Notes References
after insertion of an intravenous line hypothermia
poor feeding
lethargy
more likely to develop osteoarthritis
soft tissue infection
meningitits [15]
Mother resides in endemic malaria
area [25]
The risk for developing catheter-related infections is offset by the increased survival rate of premature infants that have early onset sepsis. Intravenous administration of prophylactic immunoglobin enhances immunity of the immature infant and is used for treatment.[15]
## Mechanism[edit]
Chorioamnionitis
Inflammation accompanies infection and is likely to complicate treatment and recovery. Inflammation is linked to reduced growth of the lungs of the premature baby.[3]
### Pathogenesis[edit]
The recent identification of the presence of microorganisms in maternal-infant body fluids that were previously thought to be sterile has provided one explanation for the presence of the inflammatory response in both the mother and infant. Sixty-one percent of pregnant women with chorioamnionitis, or inflammation of the amniotic fluid, were found to be infected by microorganisms. Often, more than one pathogen was present. In fifteen percent of pregnant women inflammation was still evident even though there was no evidence of pathogens. This may indicate that there are other causes. A high percentage, 51% to 62%, of pregnant women who had chorioamnionitis also had inflammation of the placenta.[3]
## Diagnosis[edit]
Diagnosis of infection is based upon the recovery of the pathogen or pathogens from the typically sterile sites in the mother or the baby. Unfortunately, as many half of pregnant women are asymptomatic with a gonorrhea infection and other sexually transmitted infections.[30][31][32] Samples are obtained from urine, blood or cerebrospinal fluid. Diagnosis of infection can also be aided by the use of more nonspecific tests such as determining the total white blood cell count, cytokine levels and other blood tests and signs.[15]
Signs of infection Notes References
abnormal complete blood count looking for signs of infection
in the blood:
increased white cell count; presence of immature neutrophils [5][29]
increased C-reactive protein a chemical in the blood that shows
that the baby's immune system is actively reacting
to infection [5][29][33]
accessory muscle use using the intercostal muscles to assist in
breathing [29]
tachycardia a heart rate that is faster than normal [5]
bradycardia a heart rate that is slower than normal [5]
chest recession [29]
respiratory distress the baby has trouble breathing [5][29]
nasal flaring the baby's nostrils expand
when it inhales [29]
expiratory grunt a sound of effort when the baby exhales [29][34]
apnea the baby stops breathing [5][29]
rash [29]
positive urine culture [5]
positive cerebral spinal fluid [5]
other positive cultures from eyes, ear canal, umbilicus
axilla anus [5]
lethargy the baby seems tired and has slow or no movements [5][29]
hypotonia the muscles seem flabby and weak [5][29]
hypothermia [5]
irritability infant appears uncomfortable and
has difficulty being soothed [5][29]
weak cry [29]
pneumonia [5]
poor perfusion poor circulation [5][29]
hypotension low blood pressure [29]
acidosis pH imbalance in the blood [5][29]
diarrhea water-like, unformed stools [29]
poor feeding [5]
oxygen requirement [5]
bulging fontanel the soft spot on the head is bulging [29]
seizures [5][29]
fever [5]
disseminated intravascular coagulation widespread clotting of blood [29]
kidney failure kidneys do not function [29]
bacteremia bacteria cultured from the blood
of the newborn [5]
### Viral infection[edit]
Symptoms and the isolation of the virus pathogen the upper respiratory tract is diagnostic. Virus identification is specific immunologic methods and PCR. The presence of the virus can be rapidly confirmed by the detection of the virus antigen. The methods and materials used for identifying the RSV virus has a specificity and sensitivity approaching 85% to 95%. Not all studies confirm this sensitivity. Antigen detection has comparatively lower sensitivity rates that approach 65% to 75%.[35]
### Protozoan infection[edit]
Congential malaria has its own set of signs:
Signs of congenital malaria infection Notes References
splenomegaly enlarged speen
fever
anemia
jaundice
poor feeding
hepatomegaly enlarged liver
failure to thrive
loose stools
irritability
hyperbilirubinemia
central nervous system infection
splenic rupture
kidney failure
blackwater fever infection with
P. falciparum only [25]
### Neonatal sepsis[edit]
Main article: Neonatal sepsis
Neonatal sepsis of the newborn is an infection that has spread through the entire body. The inflammatory response to this systematic infection can be as serious as the infection itself.[3] In infants that weigh under 1500 g, sepsis is the most common cause of death. Three to four percent of infants per 1000 births contract sepsis. The mortality rate from sepsis is near 25%.[4] Infected sepsis in an infant can be identified by culturing the blood and spinal fluid and if suspected, intravenous antibiotics are usually started. Lumbar puncture is controversial because in some cases it has found not to be necessary while concurrently, without it estimates of missing up to one third of infants with meningitis is predicted.[15]
## Prevention[edit]
To reduce neonatal infection, screening of pregnant women for HIV, hepatitis B, and syphilis, is available in the UK.[36]
Treatment with an vaginal antibiotic wash prior to birth does not prevent infection with group B streptococcus bacteria (GBS).[5][37] Treatment with vaginal chlorhexidine prior to birth does not prevent neonatal infections.[38]
Because GBS bacteria can colonize the lower reproductive tract of 30% of women, typically pregnant women are tested for this pathogen from 35 to 37 weeks of pregnancy. Before delivery treatment of the mother with antibiotics reduces the rate of neonatal infection.[5] Prevention of the infection of the baby is done by treating the mother with penicillin. Since the adoption of this prophylactic treatment, infant mortality from GBS infection has decreased by 80%.[4]
Mothers with symptomatic genital herpes and who are treated with antiviral prophylaxis are less prone to have an active, symptomatic case at the time of birth and it may be able to reduce the risk of passing on HSV during birth. Cesarean delivery reduces the risk of infection of the infant.[21]
Breastfeeding has been shown to protect the neonate from some infections. .[39][40][41][42][43][excessive citations] Breast milk protects against necrotizing enterocolitis.[8]
## Treatment[edit]
Neonatal infection treatment is typically started before the diagnosis of the cause can be confirmed. Neonatal infection can be prophylactically treated with antibiotics.[7] Maternal treatment with antibiotics is primarily used to protect against group B streptococcus.[15]
Women with a history of genital herpes, can be treated with antiviral drugs to prevent symptomatic lesions and viral shedding that could infect the infant at birth. The antiviral medications used include acyclovir, penciclovir, valacyclovir, and famciclovir. Only very small amounts of the drug can be detected in the fetus. There are no increases in drug-related abnormalities in the infant that could be attributed to acyclovir. Long-term effects of antiviral medications have not been evaluated for their effects after growth and development of the child occurs. Neutropenia can be a complication of acyclovir treatment of neonatal HSV infection, but is usually transient.[21] Treatment with immunoglobulin therapy has not been proven to be effective and is not recommended.[44]
## Epidemiology[edit]
Further information: Perinatal mortality
Up to 3.3 million newborns die each year and 23.4% of these die of neonatal infection. About half of the deaths caused by sepsis or pneumonia happen in the first week postpartum. In industrialized countries, prophylactic antibiotic treatment of the mothers identified with group B streptococcus, early identification of sepsis in the newborn, and administration of antibiotics to the newborn has reduced mortality.[5] Neonatal herpes in North America is estimated to be from 5 – 80 per 100,000 live births. HSV has a lower prevalence in mothers outside the United States. In the United Kingdom the incidence is much lower and estimated to be 1.6 per 100,000 live births. Approximately 70% to 80% of infected infants are born to mothers with no reported history of HSV infection.[21]
Regions with low neonatal mortality include Europe, the Western Pacific, and the Americas, which have sepsis rates that account for 9.1% to 15.3% of the total neonatal deaths worldwide. This is in contrast with the 22.5 to 27.2% percentage of total deaths in resource-poor countries such as Nigeria, the Democratic Republic of the Congo, India, Pakistan, and China.[5]
In the UK, the proportions of pregnant women who are newly screened positive for hepatitis B, syphilis, and HIV have remained constant since 2010 at about 0.4%, 0.14% and 0.15%, respectively. Estimated prevalence levels among pregnant women for hepatitis B and HIV, including previous diagnoses, were higher at 0.67% and 0.27%. Pregnant women evaluated as susceptible to rubella due to low antibody levels have increased by over 60%, to about 7.2%. However, this increase is probably due to changes in testing methods and evaluation criteria.[45]
In North America, prior to the 1950s, group A β-hemolytic streptococcus (GAS) was the most common pathogen associated with neonatal sepsis prior to the 1960s. In the past twenty years, the most common pathogen causing sepsis is coagulase-negative staphylococci that exist as biofilms associated with infected central venous or arterial catheters.[7] Infections can be fatal and contribute to long-term morbidity and disability among the infants who survive into childhood.[7] Neonatal sepsis effects 128 cases per 1000 live births. Meningitis can occur in the septic infant.[15] Expectant mothers with HSV have a 75% chance of at least one flare-up during their pregnancy.[21] In limited studies it was found that infants in Africa born to mothers with malaria have a 7% of acquiring congenital malaria.[25]
### Early-onset infections[edit]
Early onset sepsis can occur in the first week of life. It usually is apparent on the first day after birth. This type of infection is usually acquired before the birth of the infant. Premature rupture of membranes and other obstetrical complications can add to the risk of early-onset sepsis. If the amniotic membrane has been ruptured greater than 18 hours before delivery the infant may be at more risk for this complication. Prematurity, low birth weight, chorioamnionitis, maternal urinary tract infection and/or maternal fever are complications that increase the risk for early-onset sepsis. Early onset sepsis is indicated by serious respiratory symptoms. The infant usually suffers from pneumonia, hypothermia, or shock. The mortality rate is 30 to 50%.[15]
### Late onset infections[edit]
Infections that occur after the first week of life but before the age of 30 days are considered late onset infections. Obstetrical and maternal complications are not typically the cause of these late onset infections; they are usually acquired by the infant in the hospital neonatal intensive care unit. The widespread use of broad-spectrum antibiotics in the nursery intensive care unit can cause a higher prevalence of invasive antibiotic resistant bacteria.[15] Meconium aspiration syndrome has a mortality rate just over 4%. This accounts for 2% for all neonatal deaths.[14]
## Research[edit]
The susceptibility to risk of infection and immune deficiencies are active areas of research. Studies regarding the role of viruses in neonatal infections are lacking. Research also continues into the role and protective effect of gut, skin and other human microbiomes and the colonization during the neonatal period.[3][15] The comparison between both resource rich and poor countries makes it difficult to compare the diagnosis success; as industrialized regions are able to confirm the diagnosis and presence of pathogens in the clinical laboratory. Clinical testing may not be available in all settings and clinicians must rely on the signs of infection in the newborn. Research data from Africa and Southeast Asia is scarce.[5]
The result of some research has been the identification of diagnostic tools and procedures that could identify mothers with group B streptococcus infection in resource-poor regions. These procedures would be easy and inexpensive to use. Those mothers who are identified as being infected could then be prophylactly treated prior to the birth of the baby.[5]
Probiotic administration of Lactobacillus species has shown some success.[17]
A GBS vaccine is currently being tested but not currently available. Vaccination is estimated to being able to prevent 4% of GBS infections for preterm births and 60–70% for neonatal GBS infections in the US. The projected benefits of maternal vaccination is the prevention of 899 cases of GBS disease and 35 deaths among infants. The cost savings in the prevention of GBS may be over 43 million dollars. Vaccination may be especially beneficial in low to middle income countries where screening and prophylactic treatment is not possible. Analysts project that GBS vaccination would prevent 30–54% of infant GBS cases. Screening, prophylactic antibiotics and vaccine would prevent 48% of infection.[46]
## See also[edit]
* Preterm birth
## References[edit]
1. ^ Neil K. Kaneshiro; David Zieve; Isla Ogilvie, eds. (December 4, 2013). "Neonate". U.S. National Library of Medicine. Retrieved January 16, 2016.
2. ^ Mary T. Caserta (October 2015). "Overview of Neonatal Infections". Merck Sharp & Dohme Corporation. Retrieved January 16, 2015.
3. ^ a b c d e f g h Pryhuber, Gloria S. (2015). "Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity". Clinics in Perinatology. 42 (4): 697–718. doi:10.1016/j.clp.2015.08.002. ISSN 0095-5108. PMC 4660246. PMID 26593074; Access provided by the University of Pittsburgh.
4. ^ a b c d Florin, Todd (2011). Netter's pediatrics. Philadelphia, PA: Elsevier Saunders. ISBN 978-1-4377-1155-4.
5. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag Santosham, Mathuram; Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E. (2013). "Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis". PLOS Medicine. 10 (8): e1001502. doi:10.1371/journal.pmed.1001502. ISSN 1549-1676. PMC 3747995. PMID 23976885.
6. ^ Ann L Anderson-Berry, Linda L Bellig, Bryan L Ohning (December 31, 2015). "Neonatal Sepsis Clinical Presentation". WebMD LLC. Retrieved January 16, 2016.CS1 maint: uses authors parameter (link)
7. ^ a b c d e f g MacDonald, Mhairi (2015). Avery's neonatology : pathophysiology and management of the newborn. Philadelphia: Wolters Kluwer. ISBN 978-1-4511-9268-1; Access provided by the University of Pittsburgh.
8. ^ a b c d e f g h i j k l m n Isaacs, David (2014). Evidence-based neonatal infections. Chichester, West Sussex, UK: Wiley Blackwell. ISBN 978-0-470-65460-6; Access provided by the University of Pittsburgh.
9. ^ Leveno, Kenneth (2013). Williams manual of pregnancy complications. New York: McGraw-Hill Medical. p. 507. ISBN 9780071765626.
10. ^ Li, Shunming; Huang, Jingya; Chen, Zhiyao; Guo, Dan; Yao, Zhenjiang; Ye, Xiaohua (2017). "Antibiotic Prevention for Maternal Group B Streptococcal Colonization on Neonatal GBS-Related Adverse Outcomes: A Meta-Analysis". Frontiers in Microbiology. 8: 374. doi:10.3389/fmicb.2017.00374. ISSN 1664-302X. PMC 5355432. PMID 28367139.
11. ^ Ohlsson, A; Shah, VS (10 June 2014). "Intrapartum antibiotics for known maternal Group B streptococcal colonization". The Cochrane Database of Systematic Reviews (6): CD007467. doi:10.1002/14651858.CD007467.pub4. PMID 24915629.
12. ^ a b Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4557-4801-3; Access provided by the University of Pittsburgh.
13. ^ "Listeria (Listeriosis)". Centers for Disease Control and Prevention. 22 October 2015. Retrieved 2015-12-23.
14. ^ a b c d Siriwachirachai, Thitiporn; Sangkomkamhang, Ussanee S; Lumbiganon, Pisake; Laopaiboon, Malinee; Siriwachirachai, Thitiporn (2014). "Antibiotics for meconium-stained amniotic fluid in labour for preventing maternal and neonatal infections". Reviews (11): CD007772. doi:10.1002/14651858.CD007772.pub3. PMC 6823264. PMID 25374369; Access provided by the University of Pittsburgh
15. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Fanaroff, Avroy (2013). Klaus & Fanaroff's care of the high-risk neonate. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4160-4001-9; Access provided by the University of Pittsburgh.
16. ^ "Tetanus and neonatal tetanus (NT)". WHO Western Pacific Region. Archived from the original on 2014-05-03.
17. ^ a b Baucells, B.J.; Mercadal Hally, M.; Álvarez Sánchez, A.T.; Figueras Aloy, J. (2015). "Asociaciones de probióticos para la prevención de la enterocolitis necrosante y la reducción de la sepsis tardía y la mortalidad neonatal en recién nacidos pretérmino de menos de 1.500g: una revisión sistemática". Anales de Pediatría. 85 (5): 247–255. doi:10.1016/j.anpedi.2015.07.038. ISSN 1695-4033. PMID 26611880.
18. ^ Polin, Richard (2014). Fetal and neonatal secrets. Philadelphia: Elsevier Saunders. ISBN 978-0-323-09139-8.
19. ^ a b Health, Australian Government Department of. "Human Immunodeficiency virus (HIV)". www.health.gov.au. Retrieved 2017-12-16.
20. ^ a b Ageing, Australian Government Department of Health and. "Australian Paediatric Surveillance Unit annual report, 2010". www.health.gov.au. Retrieved 2017-12-16.
21. ^ a b c d e Hollier, Lisa M; Wendel, George D; Hollier, Lisa M (2008). "Third trimester antiviral prophylaxis for preventing maternal genital herpes simplex virus (HSV) recurrences and neonatal infection". Reviews (1): CD004946. doi:10.1002/14651858.CD004946.pub2. PMID 18254066; Access provided by the University of Pittsburgh.
22. ^ Leonardo Aguiar. "Ministério da Saúde confirma relação entre vírus Zika e microcefalia" [Ministry of Health confirms relationship between Zika virus and microcephaly]. Portal da Saúde – Ministério da Saúde. Archived from the original on 2016-01-29. Retrieved 2016-02-01.
23. ^ Oliveira Melo, A. S.; Malinger, G.; Ximenes, R.; Szejnfeld, P. O.; Alves Sampaio, S.; Bispo de Filippis, A. M. (1 January 2016). "Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?". Ultrasound in Obstetrics & Gynecology. 47 (1): 6–7. doi:10.1002/uog.15831. ISSN 1469-0705. PMID 26731034.
24. ^ "Epidemiological update: Outbreaks of Zika virus and complications potentially linked to the Zika virus infection". European Centre for Disease Prevention and Control. Retrieved 18 January 2016.
25. ^ a b c d e Martin, Richard (2015). Fanaroff and Martin's neonatal-perinatal medicine : diseases of the fetus and infant. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4557-5617-9; Access provided by the University of Pittsburgh.
26. ^ a b Cloherty, John (2012). Manual of neonatal care. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-1-60831-777-6; Access provided by the University of Pittsburgh.
27. ^ a b Torgerson, Paul R; Mastroiacovo, Pierpaolo (2013). "The global burden of congenital toxoplasmosis: a systematic review". Bulletin of the World Health Organization. 91 (7): 501–508. doi:10.2471/BLT.12.111732. ISSN 0042-9686. PMC 3699792. PMID 23825877.
28. ^ a b c Ungerer, Regina LS; Lincetto, Ornella; McGuire, William; Saloojee, Haroon H; Gülmezoglu, A Metin; Ungerer, Regina LS (2004). "Prophylactic versus selective antibiotics for term newborn infants of mothers with risk factors for neonatal infection". Reviews (4): CD003957. doi:10.1002/14651858.CD003957.pub2. PMID 15495071.
29. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Sinha, Sunil (2012). Essential neonatal medicine. Chichester, West Sussex: John Wiley & Sons. ISBN 978-0-470-67040-8; Access provided by the University of Pittsburgh.
30. ^ Kumar, Ritu; Bronze, Michael Stuart (2015). "Pelvic Inflammatory Disease Empiric Therapy". Medscape. Retrieved 23 January 2019.
31. ^ Zakher, Bernadette; Cantor MD, Amy G.; Daeges, Monica; Nelson MD, Heidi (December 16, 2014). "Review: Screening for Gonorrhea and Chlamydia: A Systematic Review for the U.S. Prevententive Services Task Force". Annals of Internal Medicine. 161 (12): 884–894. CiteSeerX 10.1.1.691.6232. doi:10.7326/M14-1022. PMID 25244000. S2CID 207538182.
32. ^ Kenner, Carole (2014). Comprehensive neonatal nursing care (5th ed.). New York, NY: Springer Publishing Company, LLC. ISBN 978-0-8261-0975-0. Access provided by the University of Pittsburgh.
33. ^ van de Laar, Rafli; van der Ham, David P.; Oei, S. Guid; Willekes, Christine; Weiner, Carl P.; Mol, Ben W.J. (2009). "Accuracy of C-reactive protein determination in predicting chorioamnionitis and neonatal infection in pregnant women with premature rupture of membranes: A systematic review". European Journal of Obstetrics & Gynecology and Reproductive Biology. 147 (2): 124–129. doi:10.1016/j.ejogrb.2009.09.017. ISSN 0301-2115. PMID 19819609.
34. ^ "Grunting in Neonates - General Practice Notebook". www.gpnotebook.co.uk. (subscription required)
35. ^ Mayhall, C (2012). Hospital epidemiology and infection control. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-1-60831-300-6; Access provided by the University of Pittsburgh.
36. ^ "Infectious diseases in pregnancy screening: programme overview; Detailed guidance". GOV.UK. 1 January 2015. Retrieved 2016-01-07.
37. ^ Ohlsson, Arne; Shah, Vibhuti S; Stade, Brenda C; Ohlsson, Arne (2014). "Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection". Reviews. 12 (12): CD003520. doi:10.1002/14651858.CD003520.pub3. PMID 25504106.
38. ^ Lumbiganon, Pisake; Thinkhamrop, Jadsada; Thinkhamrop, Bandit; Tolosa, Jorge E. (2014-09-14). "Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV)". The Cochrane Database of Systematic Reviews (9): CD004070. doi:10.1002/14651858.CD004070.pub3. ISSN 1469-493X. PMC 7104295. PMID 25218725.
39. ^ Kunz C, Rodriguez-Palmero M, Koletzko B, Jensen R (June 1999). "Nutritional and biochemical properties of human milk, Part I: General aspects, proteins, and carbohydrates". Clinics in Perinatology. 26 (2): 307–33. doi:10.1016/S0095-5108(18)30055-1. PMID 10394490.
40. ^ Rodriguez-Palmero M, Koletzko B, Kunz C, Jensen R (June 1999). "Nutritional and biochemical properties of human milk: II. Lipids, micronutrients, and bioactive factors". Clinics in Perinatology. 26 (2): 335–59. doi:10.1016/S0095-5108(18)30056-3. PMID 10394491.
41. ^ Hanson LA, Söderström T (1981). "Human milk: Defense against infection". Progress in Clinical and Biological Research. 61: 147–59. PMID 6798576.
42. ^ Van de Perre P (July 2003). "Transfer of antibody via mother's milk". Vaccine. 21 (24): 3374–6. doi:10.1016/S0264-410X(03)00336-0. PMID 12850343.
43. ^ Jackson KM, Nazar AM (April 2006). "Breastfeeding, the immune response, and long-term health". The Journal of the American Osteopathic Association. 106 (4): 203–7. PMID 16627775.
44. ^ Ohlsson, Arne; Lacy, Janet B. (29 January 2020). "Intravenous immunoglobulin for suspected or proven infection in neonates". The Cochrane Database of Systematic Reviews. 1: CD001239. doi:10.1002/14651858.CD001239.pub6. ISSN 1469-493X. PMC 6988993. PMID 31995649.
45. ^ Infection reports; HIV – STIs Antenatal screening for infectious diseases in England: summary report for 2014 (PDF). Infection reports Volume 9 Number 43 Published on: 4 December 2015 HIV – STIs Antenatal screening for infectious diseases in England: summary report for 2014 (Report). 9. Public Health England. 4 December 2015. Retrieved 8 January 2016.
46. ^ Cortese, Francesca; Scicchitano, Pietro; Gesualdo, Michele; Filaninno, Antonella; De Giorgi, Elsa; Schettini, Federico; Laforgia, Nicola; Ciccone, Marco Matteo (2015). "Early and Late Infections in Newborns: Where Do We Stand? A Review". Pediatrics & Neonatology. 57 (4): 265–273. doi:10.1016/j.pedneo.2015.09.007. ISSN 1875-9572. PMID 26750406.
## Further reading[edit]
* Jenster, Meike; Bonifacio, Sonia L.; Ruel, Theodore; Rogers, Elizabeth E.; Tam, Emily W.; Partridge, John Colin; Barkovich, A. James; Ferriero, Donna M.; Glass, Hannah C. (2014-07-01). "Maternal or neonatal infection: association with neonatal encephalopathy outcomes". Pediatric Research. 76 (1): 93–99. doi:10.1038/pr.2014.47. ISSN 0031-3998. PMC 4062582. PMID 24713817.
* "National Guideline Clearinghouse | Antibiotics for early-onset neonatal infection. Antibiotics for the prevention and treatment of early-onset neonatal infection". www.guideline.gov. Archived from the original on 2016-01-06. Retrieved 2016-01-15.
## External links[edit]
* "WHO | Newborn death and illness". www.who.int. Retrieved 2016-01-15.
Classification
D
* ICD-10: P36 A50 P37 P35P23 Y95
* v
* t
* e
Conditions originating in the perinatal period / fetal disease
Maternal factors
complicating pregnancy,
labour or delivery
placenta
* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome
chorion/amnion
* Chorioamnionitis
umbilical cord
* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery
presentation
* Breech birth
* Asynclitism
* Shoulder presentation
Growth
* Small for gestational age / Large for gestational age
* Preterm birth / Postterm pregnancy
* Intrauterine growth restriction
Birth trauma
* scalp
* Cephalohematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus injury
* Erb's palsy
* Klumpke paralysis
Affected systems
Respiratory
* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* Pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia
Cardiovascular
* Pneumopericardium
* Persistent fetal circulation
Bleeding and
hematologic disease
* Vitamin K deficiency bleeding
* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice
* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity
Gastrointestinal
* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis
Integument and
thermoregulation
* Erythema toxicum
* Sclerema neonatorum
Nervous system
* Perinatal asphyxia
* Periventricular leukomalacia
Musculoskeletal
* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia
Infections
* Vertically transmitted infection
* Neonatal infection
* rubella
* herpes simplex
* mycoplasma hominis
* ureaplasma urealyticum
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis
Other
* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal
* v
* t
* e
Vertically transmitted infections
Gestational
* Viruses
* Congenital rubella syndrome
* Congenital cytomegalovirus infection
* Neonatal herpes simplex
* Hepatitis B
* Congenital varicella syndrome
* HIV
* Fifth disease
* Bacteria
* Congenital syphilis
* Other
* Toxoplasmosis
* transplacental
* TORCH complex
During birth
* transcervical
* Candidiasis
* Gonorrhea
* Listeriosis
Late pregnancy
* Listeriosis
* Congenital cytomegalovirus infection
By breastfeeding
* Breastfeeding
* Tuberculosis
* HIV
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Neonatal infection
|
c0158944
| 27,563 |
wikipedia
|
https://en.wikipedia.org/wiki/Neonatal_infection
| 2021-01-18T18:35:28 |
{"umls": ["C0852269", "C0158944"], "icd-9": ["771"], "icd-10": ["P35-P39"], "wikidata": ["Q9386039"]}
|
Hemicrania continua is a rare, indomethacin-responsive, trigeminal autonomic cephalgia characterized by a typically side-locked, continuous, unilateral headache of moderate intensity with recurrent episodes of exacerbations of severe intensity, lasting for more than 3 months, in the absence of structural brain or vascular lesions. Ipsilateral cranial autonomic symptoms (lacrimation, conjunctival injection, nasal congestion or rhinorrhea, ptosis/miosis), restlessness and/or migrainous features are observed during the exacerbations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Hemicrania continua
|
c2349425
| 27,564 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443070
| 2021-01-23T18:19:02 |
{"gard": ["10795"], "icd-10": ["G44.0"]}
|
A number sign (#) is used with this entry because of evidence that Greenberg dysplasia (GRBGD) is caused by homozygous or compound heterozygous mutation in the LBR gene (600024), which encodes the lamin B receptor, on chromosome 1q42.
Homozygous mutation in the LBR gene can also cause Pelger-Huet anomaly with mild skeletal anomalies (618019). Heterozygous mutation in the LBR gene can cause Pelger-Huet anomaly (169400).
Description
Greenberg dysplasia, also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia, is a rare autosomal recessive osteochondrodysplasia characterized by gross fetal hydrops, severe shortening of all long bones with a moth-eaten radiographic appearance, platyspondyly, disorganization of chondroosseous calcification, and ectopic ossification centers. It is lethal in utero. Patient fibroblasts show increased levels of cholesta-8,14-dien-3-beta-ol, suggesting a defect of sterol metabolism (summary by Konstantinidou et al., 2008).
Herman (2003) reviewed the cholesterol biosynthetic pathway and 6 disorders involving enzyme defects in postsqualene cholesterol biosynthesis: Smith-Lemli-Opitz syndrome (SLOS; 270400), desmosterolosis (602398), X-linked dominant chondrodysplasia punctata (CDPX2; 302960), CHILD syndrome (308050), lathosterolosis (607330), and HEM skeletal dysplasia.
Clinical Features
Greenberg et al. (1988) described 2 sibs, the offspring of consanguineous parents, who presented with an apparently 'new' severe form of short-limb dwarfism. The chondroosseus radiologic and histologic features were distinctive. The first sib presented at 30 weeks of gestation with severe hydrops following fetal death; the second was detected by ultrasonography at 20 weeks. Radiologic abnormalities included an unusual 'moth-eaten' appearance of the markedly short long bones, bizarre ectopic ossification centers, and marked platyspondyly with unusual ossification centers. Extensive extramedullary erythropoiesis was found in both fetuses. Chondroosseous histology was characterized by marked disorganization with interspersed masses of cartilage, bone, and mesenchymal tissue. The first fetus was male, the second female. The parents were third cousins of Greek extraction.
Spranger and Maroteaux (1990) reported a third case of the association of hydrops fetalis with ectopic calcifications and 'moth-eaten' skeletal dysplasia.
Chitayat et al. (1993) reported a fourth case in an offspring of consanguineous parents of East Indian origin. They referred to the disorder as Greenberg hydrops-ectopic calcification-moth-eaten skeletal dysplasia, or HEM dysplasia. The radiologic changes included platyspondyly with multiple extra ossification centers, extraneous calcification in the ribs, sternum, pelvis, and epiphyses, and moth-eaten long bones. The histopathologic changes included chondrocytes with dilated rough endoplasmic reticulum and inclusion bodies with homogeneous material of intermediate electron density.
Horn et al. (2000) described several nonskeletal malformations in a case of Greenberg dysplasia: omphalocele, intestinal malformation, abnormal fingernails, and hypolobated lungs.
Trajkovski et al. (2002) reported the prenatal ultrasound diagnosis of a case of Greenberg dysplasia in the male fetus of a nonconsanguineous Macedonian couple. Polyhydramnios, hydrops fetalis, severely short limbs, and cystic hygroma were noted on ultrasound. After the pregnancy was terminated, radiologic examination showed typical features of Greenberg dysplasia. The fetus had a large head with depressed nasal bridge, midface hypoplasia, and prominent orbital arches. Light microscopic examination of ribs and long bones showed severe disorganization, absent cartilage column formation, and abrupt transition from cartilage to normal bone.
Offiah et al. (2003) reported a fetus, born of unrelated Caucasian parents, with HEM skeletal dysplasia. Prenatal ultrasound at 14 weeks' gestation showed severe micromelia, and the pregnancy was terminated. Postmortem examination showed a small thorax, hepatomegaly, severely shortened limbs, and postaxial hexadactyly of the upper limbs. Dysmorphic features included a large forehead, mild mandibular recession, a flattened nose, and mild hypertelorism. Histologic examination of the bones showed disorganization of the growth plate with no chondrocyte column formation, but random, abrupt transition between cartilage and bone. Radiographs showed a moth-eaten appearance of extremely shortened long bones and significant platyspondyly. There was evidence of ectopic calcification. Biochemical analysis of muscle tissue showed increased 8,14-cholestadien-2-beta-ol.
Konstantinidou et al. (2008) reported a fetus, the product of consanguineous Greek parents, with HEM skeletal dysplasia. Prenatal ultrasound at 11 weeks' gestation showed an abnormal fetus with hydrops, micromelia, narrow thorax, and hepatomegaly. Radiographic examination showed a moth-eaten appearance of long bones. Light microscopy showed complete ossification of the femoral diaphysis and abnormal heterotopic ossification centers in the vertebrae and the long bones. The physeal growth zone was virtually absent, with abrupt transition from cartilage to mineralized, hypocellular bone. There was a history of 2 previously affected fetuses detected by prenatal ultrasound. Postmortem examination of 1 of these fetuses showed hydrops fetalis, severe rhizomelic and mesomelic shortening of all long bones, macrocephaly, low-set ears, hypertelorism, depressed nasal bridge, narrow thorax, and postaxial polydactyly of the feet. Radiographic examination showed a moth-eaten appearance of long bones. Light microscopy showed disorganization of the cartilage column and ectopic calcification.
Molecular Genetics
Waterham et al. (2003) conducted chemical and molecular investigations in cells from a fetus with HEM skeletal dysplasia, the product of healthy consanguineous Turkish parents, who presented with intrauterine growth retardation at 17 weeks' gestation on fetal ultrasound performed on the 24-year-old mother. The fetus showed severe hydrops and short-limb skeletal dysplasia. Amniotic fluid examination showed a 46,XY karyotype. Intrauterine death occurred at 18 weeks and delivery was induced. Postmortem examination showed severe hydrops, extremely short edematous limbs, and postaxial polydactyly on both hands. Radiographic examination showed severe platyspondyly, short irregular ribs, a 'moth-eaten' aspect of scapular and pelvic bones, and very short tubular bones with angulated diaphyses. Waterham et al. (2003) found elevated levels of cholesta-8,14-dien-3-beta-ol in cultured skin fibroblasts, compatible with a deficiency of the cholesterol biosynthetic enzyme 3-beta-hydroxysterol delta(14)-reductase. Sequence analysis of 2 candidate genes encoding putative human sterol delta(14)-reductases, TM7SF2 (603414) and LBR, identified homozygosity for a 7-bp substitution in exon 13 of the LBR gene (600024.0003), which resulted in a truncated protein. Functional complementation of the HEM cells by transfection with control LBR cDNA confirmed that LBR encoded the defective sterol delta(14)-reductase. The healthy mother showed hypolobulated nuclei in 60% of her granulocytes. Waterham et al. (2003) suggested that classic Pelger-Huet anomaly (PHA; 169400), which is also caused by mutation in the LBR gene, represents a heterozygous state of 3-beta-hydroxysterol delta(14)-reductase deficiency.
In a fetus, the product of consanguineous Greek parents, with HEM skeletal dysplasia, Konstantinidou et al. (2008) identified a homozygous missense mutation in the LBR gene (N547D; 600024.0008).
In 3 unrelated fetuses with HEM skeletal dysplasia, Clayton et al. (2010) identified homozygous or compound heterozygous mutations in the LBR gene (600024.0008-600024.0011). One of the patients had been reported by Offiah et al. (2003). A parent who was heterozygous for a missense mutation in the sterol reductase domain had no abnormalities of peripheral blood cells, whereas this missense mutation was shown to result in a loss of sterol reductase activity. Cellular studies showed localization of LBR outside of the nuclear membrane, where it colocalized with markers of the endoplasmic reticulum. Nonnuclear LBR was also expressed in lymphoblastoid cells, differentiated osteoclasts, and osteosarcoma cells, as well as in various tissues of developing mouse embryos. These findings suggested to Clayton et al. (2010) that HEM skeletal dysplasia results from defects in the sterol reductase activity of LBR, not from the structural function of LBR as part of the nuclear membrane. The uncoupling of the metabolic and structural functions of LBR explained how mutations in the same gene can cause distinct disorders. The findings also indicated that sterol reductase function is essential for intrauterine development in humans.
Animal Model
Wassif et al. (2007) studied mice with deficits of Lbr and/or Tm7sf2, another sterol delta(14)-reductase, and demonstrated that these proteins provide substantial enzymatic redundancy with respect to cholesterol synthesis; they concluded, therefore, that HEM dysplasia is a laminopathy rather than an inborn error of cholesterol synthesis.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Large head \- Macrocephaly Face \- Micrognathia \- Small maxilla Ears \- Low-set ears Eyes \- Hypertelorism Nose \- Depressed nasal bridge RESPIRATORY Larynx \- Laryngeal calcifications Airways \- Tracheal calcifications CHEST External Features \- Narrow thorax Ribs Sternum Clavicles & Scapulae \- Anterior rib punctate calcifications \- Sternal punctate calcifications \- 11 pairs of ribs ABDOMEN Liver \- Hepatomegaly SKELETAL \- Osteochondrodysplasia \- Ectopic calcification \- Precocious calcification \- Abnormal ossification centers \- Disorganization of the cartilage column \- Abrupt transition from cartilage to bone Skull \- Deficient skull ossification Spine \- Platyspondyly with multiple extra ossification centers Pelvis \- Iliac apophysis, pubis and ischial punctate calcifications Limbs \- Micromelia \- Mesomelia \- Rhizomelia \- Epiphyseal punctate calcifications \- Moth-eaten (fragmented) long bones Hands \- Polydactyly, postaxial HEMATOLOGY \- Extramedullary erythropoiesis PRENATAL MANIFESTATIONS \- Severe hydrops LABORATORY ABNORMALITIES \- Elevated cholesta-8,14-dien-3-beta-ol in cultured fibroblasts MISCELLANEOUS \- Fetal death MOLECULAR BASIS \- Caused by mutation in the lamin B receptor (LBR, 600024.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
GREENBERG DYSPLASIA
|
c2931048
| 27,565 |
omim
|
https://www.omim.org/entry/215140
| 2019-09-22T16:29:40 |
{"mesh": ["C535858"], "omim": ["215140"], "orphanet": ["1426"], "synonyms": ["Alternative titles", "HYDROPS-ECTOPIC CALCIFICATION-MOTH-EATEN SKELETAL DYSPLASIA", "HEM SKELETAL DYSPLASIA", "MOTH-EATEN SKELETAL DYSPLASIA", "CHONDRODYSTROPHY, HYDROPIC AND PRENATALLY LETHAL TYPE"]}
|
A rare syndrome described in three members of a family (a boy, his father, and his paternal grandmother) that is characterized by the association of aniridia with patella aplasia or hypoplasia. The grandmother also had bilateral cataracts and glaucoma. There have been no further descriptions in the literature since 1975.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Aniridia-absent patella syndrome
|
c1862868
| 27,566 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1069
| 2021-01-23T17:35:22 |
{"gard": ["685"], "mesh": ["C566281"], "omim": ["106220"], "umls": ["C1862868"], "icd-10": ["Q87.8"]}
|
Dopa-responsive dystonia (DRD) describes a group of neurometabolic disorders characterized by dystonia that typically shows diurnal fluctuations, that responds excellently to levodopa (L-dopa) and that is comprised of autosomal dominant dopa-responsive dystonia (DYT5a), autosomal recessive dopa-responsive dystonia (DYT5b) and dopa responsive dystonia due to sepiapterin reductase (SR) deficiency.
## Epidemiology
The estimated European prevalence of DRD ranges from 1/1,000,000-1/200,000.
## Clinical description
DRD usually has a pediatric onset, typically with lower limb dystonia that leads to gait disturbances and that usually worsens during the course of the day and is improved in the morning after sleeping. Parkinsonism can develop at a later age in some patients. Anxiety, depression, sleep disturbances and obsessive-compulsive disorders have also been reported in a few patients with DYT5a. Rarer subtypes which are inherited in an autosomal recessive manner typically show a much more severe phenotype, with onset in the first year of life with additional manifestations of global developmental delay, axial hypotonia, oculogyric crises and encephalopathy. DRD responds dramatically and continuously to L-dopa therapy, and patients usually experience a significant improvement of symptoms once treatment is initiated. If untreated, patients can become wheelchair bound.
## Etiology
DRD is due to mutations in genes that encode proteins essential for the biosynthesis of dopamine. DYT5a is due to mutations in the GTP cyclohydrolase 1 (GCH1) gene (14q22.1 to q22.2) which encodes an enzyme needed for the biosynthesis of tetrahydrobiopterin, the essential co-factor for tyrosine hydroxylase. DYT5b is caused by mutations in the tyrosine hydroxylase TH gene (11p15.5) encoding tyrosine hydroxylase, the enzyme responsible for catalyzing the conversion of tyrosine to L-dopa, the precursor of dopamine. Finally, DRD due to an SRD is due to mutations in the SPR gene (2p14-p12), encoding the enzyme sepiapterin reductase (SR), which is also required for the biosynthesis of tetrahydrobiopterin.
## Genetic counseling
DRD can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype. It can also occur due to de novo mutations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Dopa-responsive dystonia
|
c1851920
| 27,567 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=255
| 2021-01-23T17:58:05 |
{"gard": ["12144"], "mesh": ["C538007"], "umls": ["C1851920"], "icd-10": ["G24.8"], "synonyms": ["HPD with diurnal fluctuation", "Hereditary progressive dystonia with diurnal fluctuation"]}
|
Keratosis
Upper arm showing keratosis pilaris
SpecialtyDermatology, medical genetics
Keratosis (from kerat- \+ -osis)[1] is a growth of keratin on the skin or on mucous membranes stemming from keratinocytes, the prominent cell type in the epidermis. More specifically, it can refer to:
* actinic keratosis (also known as solar keratosis)
* chronic scar keratosis
* hydrocarbon keratosis
* keratosis pilaris (KP, also known as follicular keratosis)
* seborrheic keratosis
Actinic keratoses are pre-malignant growths. Seborrheic keratoses are not pre-malignant.
## See also[edit]
* Keratoderma
## References[edit]
1. ^ Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster.
## External links[edit]
Classification
D
* MeSH: D007642
* v
* t
* e
Cutaneous keratosis, ulcer, atrophy, and necrobiosis
Epidermal thickening
* keratoderma: Keratoderma climactericum
* Paraneoplastic keratoderma
* Acrokeratosis paraneoplastica of Bazex
* Aquagenic keratoderma
* Drug-induced keratoderma
* psoriasis
* Keratoderma blennorrhagicum
* keratosis: Seborrheic keratosis
* Clonal seborrheic keratosis
* Common seborrheic keratosis
* Irritated seborrheic keratosis
* Seborrheic keratosis with squamous atypia
* Reticulated seborrheic keratosis
* Dermatosis papulosa nigra
* Keratosis punctata of the palmar creases
* other hyperkeratosis: Acanthosis nigricans
* Confluent and reticulated papillomatosis
* Callus
* Ichthyosis acquisita
* Arsenical keratosis
* Chronic scar keratosis
* Hyperkeratosis lenticularis perstans
* Hydrocarbon keratosis
* Hyperkeratosis of the nipple and areola
* Inverted follicular keratosis
* Lichenoid keratosis
* Multiple minute digitate hyperkeratosis
* PUVA keratosis
* Reactional keratosis
* Stucco keratosis
* Thermal keratosis
* Viral keratosis
* Warty dyskeratoma
* Waxy keratosis of childhood
* other hypertrophy: Keloid
* Hypertrophic scar
* Cutis verticis gyrata
Necrobiosis/granuloma
Necrobiotic/palisading
* Granuloma annulare
* Perforating
* Generalized
* Subcutaneous
* Granuloma annulare in HIV disease
* Localized granuloma annulare
* Patch-type granuloma annulare
* Necrobiosis lipoidica
* Annular elastolytic giant-cell granuloma
* Granuloma multiforme
* Necrobiotic xanthogranuloma
* Palisaded neutrophilic and granulomatous dermatitis
* Rheumatoid nodulosis
* Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction
Foreign body granuloma
* Beryllium granuloma
* Mercury granuloma
* Silica granuloma
* Silicone granuloma
* Zirconium granuloma
* Soot tattoo
* Tattoo
* Carbon stain
Other/ungrouped
* eosinophilic dermatosis
* Granuloma faciale
Dermis/
localized CTD
Cutaneous lupus
erythematosus
* chronic: Discoid
* Panniculitis
* subacute: Neonatal
* ungrouped: Chilblain
* Lupus erythematosus–lichen planus overlap syndrome
* Tumid
* Verrucous
* Rowell's syndrome
Scleroderma/
Morphea
* Localized scleroderma
* Localized morphea
* Morphea–lichen sclerosus et atrophicus overlap
* Generalized morphea
* Atrophoderma of Pasini and Pierini
* Pansclerotic morphea
* Morphea profunda
* Linear scleroderma
Atrophic/
atrophoderma
* Lichen sclerosus
* Anetoderma
* Schweninger–Buzzi anetoderma
* Jadassohn–Pellizzari anetoderma
* Atrophoderma of Pasini and Pierini
* Acrodermatitis chronica atrophicans
* Semicircular lipoatrophy
* Follicular atrophoderma
* Linear atrophoderma of Moulin
Perforating
* Kyrle disease
* Reactive perforating collagenosis
* Elastosis perforans serpiginosa
* Perforating folliculitis
* Acquired perforating dermatosis
Skin ulcer
* Pyoderma gangrenosum
Other
* Calcinosis cutis
* Sclerodactyly
* Poikiloderma vasculare atrophicans
* Ainhum/Pseudo-ainhum
* v
* t
* e
Skin cancer of the epidermis
Tumor
Carcinoma
BCC
* Forms
* Aberrant
* Cicatricial
* Cystic
* Fibroepithelioma of Pinkus
* Infltrative
* Micronodular
* Nodular
* Pigmented
* Polypoid
* Pore-like
* Rodent ulcer
* Superficial
* Nevoid basal cell carcinoma syndrome
SCC
* Forms
* Adenoid
* Basaloid
* Clear cell
* Signet-ring-cell
* Spindle-cell
* Marjolin's ulcer
* Bowen's disease
* Bowenoid papulosis
* Erythroplasia of Queyrat
* Actinic keratosis
Adenocarcinoma
* Aggressive digital papillary adenocarcinoma
* Extramammary Paget's disease
Ungrouped
* Merkel cell carcinoma
* Microcystic adnexal carcinoma
* Mucinous carcinoma
* Primary cutaneous adenoid cystic carcinoma
* Verrucous carcinoma
* Malignant mixed tumor
Benign
tumors
Acanthoma
* Forms
* Large cell
* Fissuring
* Clear cell
* Epidermolytic
* Melanoacanthoma
* Pilar sheath acanthoma
* Seboacanthoma
* Seborrheic keratosis
* Warty dyskeratoma
Keratoacanthoma
* Generalized eruptive
* Keratoacanthoma centrifugum marginatum
* Multiple
* Solitary
Wart
* Verruca vulgaris
* Verruca plana
* Plantar wart
* Periungual wart
Other
Epidermal nevus
* Syndromes
* Epidermal nevus syndrome
* Schimmelpenning syndrome
* Nevus comedonicus syndrome
* Nevus comedonicus
* Inflammatory linear verrucous epidermal nevus
* Linear verrucous epidermal nevus
* Pigmented hairy epidermal nevus syndrome
* Systematized epidermal nevus
* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Keratosis
|
c0022593
| 27,568 |
wikipedia
|
https://en.wikipedia.org/wiki/Keratosis
| 2021-01-18T19:03:17 |
{"mesh": ["D007642"], "umls": ["C0022593"], "icd-9": ["701.1", "757.39"], "icd-10": ["Q82.8", "L86", "L85.1"], "wikidata": ["Q3667186"]}
|
## Summary
### Clinical characteristics.
Most individuals with classic GBE1 adult polyglucosan body disease (GBE1-APBD) present after age 40 years with unexplained progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, autonomic dysfunction (associated with orthostatic hypotension and constipation), and mild cognitive difficulties (often executive dysfunction). Some affected individuals without classic GBE1-APBD have atypical phenotypes including Alzheimer disease-like dementia and axonal neuropathy, stroke-like episodes, and diaphragmatic failure; others may have a history of infantile liver disease.
### Diagnosis/testing.
The diagnosis of GBE1-APBD is established in a proband with suggestive findings and biallelic GBE1 pathogenic variants identified by molecular genetic testing. Note: GBE enzyme assay (in any tissue) is not a first-line diagnostic test for GBE1-APBD.
### Management.
Treatment of manifestations: Optimally, symptomatic care is provided by a multidisciplinary team that includes specialists in physical medicine rehabilitation, urology, and behavioral neurology or psychology. An individualized physical therapy program can improve flexibility, reduce spasticity, maintain or improve joint mobility, and facilitate activities of daily living; antispasmodic drugs may decrease cramps and facilitate walking. Spastic bladder may be managed with anticholinergic drugs and clean intermittent catheterization or an indwelling bladder catheter to prevent urosepsis; treatment of recurrent urinary infections is essential. Treatment of cognitive decline and psychiatric manifestations is per standard practice.
Surveillance: Routine: neurologic assessments to monitor progression of upper motor neuron and lower motor neuron signs and to assess for new manifestations; urologic evaluations for complications of spastic bladder; occupational and physical therapy assessments regarding activities of daily living; and mental health assessments.
### Genetic counseling.
GBE1-APBD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a GBE1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic heterozygote (carrier), and a 25% chance of being unaffected and not a carrier.
Once the GBE1 pathogenic variants have been identified in the family, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing for GBE1-APBD are possible.
## Diagnosis
### Suggestive Findings
GBE1 adult polyglucosan body disease (GBE1-APBD) should be considered in individuals with the following clinical findings, neuroimaging findings, family history, and ethnicity.
Clinical findings
* Onset age ≥40 years
* Progressive neurogenic bladder
* Gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement
* Sensory loss predominantly in the distal lower extremities
* Mild difficulties in cognition (often executive dysfunction)
* A history of infantile liver disease [Paradas et al 2014]
Brain and spinal cord MRI
* Paraventricular, subcortical, and deep white matter slowly progressive changes that may include involvement of the upper pons, superior cerebellar peduncles, dentate nuclei, and anterior medulla (including the olives) often extending to the level of the cervical-medullary junction [Klein et al 2004]
* Cerebral, cerebellar, and spinal cord slowly progressive atrophy
Family history consistent with autosomal recessive inheritance (e.g., affected sibs (including sibs with infantile liver disease) and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.
Ethnicity. Typically (but not necessarily) Ashkenazi Jewish
### Establishing the Diagnosis
The diagnosis of GBE1-APBD is established in a proband with suggestive findings and biallelic GBE1 pathogenic variants identified by molecular genetic testing (see Table 1). Note that GBE enzyme assay (in any tissue) is not a first-line diagnostic test for GBE1-APBD.
Note: Identification of biallelic GBE1 variants of uncertain significance (or identification of one known GBE1 pathogenic variant and one GBE1 variant of uncertain significance) does not establish or rule out a diagnosis of this disorder.
Molecular genetic testing approaches can include a combination of gene-targeted testing (targeted analysis for pathogenic variants or multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas genomic testing does not (see Option 2).
#### Option 1
Targeted analysis for two GBE1 pathogenic variants common in the Ashkenazi Jewish population can be performed first:
* p.Tyr329Ser [Lossos et al 1998]
* c.2053-5289_2053-5297delinsTGTTTTTTACATGACAGGT [Akman et al 2015]
A multigene panel that includes GBE1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
* Sequence analysis. More than 90% of pathogenic variants are identified by sequence analysis.
* Gene-targeted deletion/duplication analysis. More than 5% of pathogenic variants are identified by gene-targeted deletion/duplication analysis.
### Table 1.
Molecular Genetic Testing Used in GBE1 Adult Polyglucosan Body Disease
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
GBE1Sequence analysis 3>90% 4, 5
Gene-targeted deletion/duplication analysis 6>5% 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017]
5\.
Note: Although almost all variants associated with GBE1-APBD to date are detectable by sequence analysis, the second most common variant, c.2053-5289_2053-5297delinsTGTTTTTTACATGACAGGT, is deep intronic and is unlikely to be detected by typical exon-targeted and splice junction-targeted sequencing assays [Akman et al 2015].
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
7\.
Intragenic deletions, such as those reported by Bruno et al [2004], Tay et al [2004], Raju et al [2008], and Li et al [2012] have been associated with glycogen storage disease type IV (see Genetically Related Disorders).
## Clinical Characteristics
### Clinical Description
Most individuals with GBE1 adult polyglucosan body disease (GBE1-APBD) present after age 40 years with unexplained progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, autonomic dysfunction (associated with orthostatic hypotension and constipation), and mild cognitive difficulties (often executive dysfunction). See Table 2.
More than 160 individuals of Ashkenazi and non-Ashkenazi Jewish heritage have been reported [Ziemssen et al 2000, Klein et al 2004, Mochel et al 2012, Hellmann et al 2015, Schiffmann et al 2018].
### Table 2.
Select Features of Classic GBE1 Adult Polyglucosan Body Disease
View in own window
Feature% of Persons w/Feature
Upper motor neuron
involvementNeurogenic bladder100%
Spasticity93%
Lower motor neuron
involvementWeakness100%
Sensory loss in distal lower extremities94%
Autonomic
dysfunctionOrthostatic hypotensionUnknown
Constipation
Cognitive decline / Dementia47%
Based on Mochel et al [2012] and Hellmann et al [2015]
#### Classic GBE1-APBD
Neurogenic bladder. Urinary incontinence is often the first sign. As it progresses, appropriate management is required to prevent recurrent urinary tract infections and other complications.
Gait difficulties. Age of onset and severity vary among affected individuals; most individuals eventually require gait aids and possibly a wheelchair.
Sensory loss in the distal lower extremities is typically mild but can be severe enough to lead to painless foot injuries.
Autonomic dysfunction, identified by orthostatic intolerance, has been occasionally observed in affected individuals.
Mild cognitive difficulty (e.g., executive dysfunction) varies in severity and progression, with many affected individuals having mild involvement and some not having any cognitive involvement at all. Cognitive difficulties have not been well studied to date.
Life expectancy for GBE1-APBD, while not formally studied, is likely shortened.
#### Atypical GBE1-APBD
In their review of 50 individuals with GBE1-APBD from four reference centers, Mochel et al [2012] identified three individuals of non-Ashkenazi heritage who had atypical manifestations: one with Alzheimer disease-like dementia and axonal neuropathy, and two with subacute manifestations including a stroke-like episode in one and diaphragmatic failure in another.
An "intermediate form" of 1,4-alpha-glucan-branching enzyme (GBE) deficiency in two individuals of non-Ashkenazi Jewish heritage was associated with residual GBE activity – a history of infantile hepatomegaly and increased glycogen on liver biopsy that resolved spontaneously (in one individual) and a family history of severe infantile liver disease (in the other individual), and acute onset of neurologic manifestations in their 30s and 40s (about one decade earlier than typical APBD) followed by a relapsing-remitting course of acute neurologic deficits (mimicking multiple sclerosis) with subsequent neurologic impairment [Paradas et al 2014]. Brain MRI revealed non-progressive white matter lesions and spinocerebellar atrophy similar to typical APBD.
#### Other
Electrophysiologic testing
* Specialized autonomic testing (thermoregulatory sweat tests and autonomic reflex testing) shows sudomotor sweating abnormalities often with specific spinal cord level identified.
* Nerve conduction velocity and electromyogram reveal an axonal lumbosacral polyradiculoneuropathy.
Tissues with pathologic polyglucosan accumulation
* Sural nerve biopsy reveals characteristic polyglucosans within nerve sheaths. The extent and characteristics of the identified polyglucosans typically distinguish them from the rare polyglucosans found in normal older individuals [Xu et al 2019].
* Muscle. Diastase-resistant, periodic acid-Schiff (PAS)-positive material is characteristic.
### Genotype-Phenotype Correlations
No clear correlation of clinical severity and GBE1 pathogenic variants is known.
### Prevalence
More than 160 individuals with GBE1-APBD of Ashkenazi Jewish heritage and non-Ashkenazi Jewish heritage (i.e., of Italian and German descent) have been reported in various studies [Ziemssen et al 2000, Klein et al 2004, Hussain et al 2012, Mochel et al 2012, Hellmann et al 2015, Schiffmann et al 2018]. Due to previous misdiagnosis, this is probably an underestimate.
The carrier frequency for GBE1-APBD is relatively high (1:83 deduced from testing 2,776 individuals self-reported to be 100% Ashkenazi Jewish [R Kornreich, unpublished data]) and, therefore, its prevalence is probably underestimated.
## Differential Diagnosis
Delay in diagnosis of GBE1 adult polyglucosan body disease (GBE1-APBD) is common because multiple sclerosis and primary urologic dysfunction are most commonly considered first.
Other disorders that may present similarly to GBE1-APBD include amyotrophic lateral sclerosis, cerebral small vessel disease (e.g., CADASIL, HTRA1 disorder, and COL4A1 and COL4A2-related small vessel disease), and peripheral neuropathies (e.g., Charcot-Marie-Tooth hereditary neuropathy) [Hellmann et al 2015]. These disorders can be excluded based on clinical findings because none exhibits the combination of pyramidal spastic paraparesis and peripheral neuropathy seen in nearly all individuals with GBE1-APBD.
Polyglucosan bodies. In adult polyglucosan body disease (GBE1-APBD), the polyglucosan bodies consist of periodic acid-Schiff (PAS)-positive material with diastase-resistant glucose polymers and are seen in the central and peripheral nervous system. In early infantile-onset glycogen storage disease type IV (see Genetically Related Disorders), polyglucosan bodies most commonly accumulate in the liver, heart, muscle, brain, spinal cord, peripheral nerve, and skin.
Other genes associated with polyglucosans are summarized in Table 3.
### Table 3.
Other Genes Associated with Accumulation of Polyglucosan Bodies
View in own window
Gene(s)DisorderMOI
EPM2A
NHLRC1Progressive myoclonus epilepsy, Lafora typeAR
GYG1 1Polyglucosan body myopathy type 2 (OMIM 616199)AR
Glycogen storage disease type XV (OMIM 613507)AR
PFKMGlycogen storage disease type VII (OMIM 232800)AR
PRKAG2Glycogen storage disease of the heart, lethal congenital (OMIM 261740)AD
RBCK1Polyglucosan body myopathy 1 w/or w/o immunodeficiency (OMIM 615895)AR
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance
Based on Cenacchi et al [2019]
2\.
Tasca et al [2016]
Polyglucosan bodies also occur in double athetosis (Bielschowsky bodies) and normal older persons (corpora amylacea).
White matter changes on MRI. In individuals with GBE1-APBD, MRI shows increased T2*-weighted signal in the periventricular white matter and possibly the brain stem, which may appear similar to that seen in multiple sclerosis; however, the images in GBE1-APBD typically do not enhance [Paradas et al 2014].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with GBE1 adult polyglucosan body disease (GBE1-APBD), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with GBE1 Adult Polyglucosan Body Disease
View in own window
System/ConcernEvaluationComment
NeurologicComplete neurologic exam
* Obtain history for stroke-like episodes.
* Assess for UMN (spasticity) & LMN involvement (weakness & sensory loss).
* Brain & spine MRI (if not obtained at time of diagnosis) to exclude other causes of gait spasticity & neurogenic bladder
MusculoskeletalOrthopedics / physical medicine & rehab / PT evalTo incl assessment of:
* Muscle tone; joint range of motion; posture; mobility; strength, coordination & endurance; pain; bedsores
* Need for adaptive devices
* Footwear needs
* PT needs
OT evalTo assess:
* Small motor function (hands, feet, face, fingers, toes)
* ADL
Bladder functionHistory of spastic bladder symptoms: urgency, frequency, difficulty voiding
* Referral to urologist
* Consider urodynamic eval & imaging of urinary tract & kidneys.
Orthostatic
hypotensionHistory of postural dizziness & syncopeTest blood pressure for postural changes.
ConstipationHistory of constipationGastroenterology eval
Cognitive
abilitiesAssess cognitive function (executive function, language processing, visuospatial/
visuoconstructional skills, emotion regulation).Referral to psychiatrist, psychologist, neuropsychologist if needed
Genetic
counselingBy genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of GBE1-APBD to facilitate medical & personal decision making
Family support/
resourcesAssess:
* Use of community or online resources;
* Need for social work involvement for care-giver support;
* Need for home nursing referral.
ADL = activities of daily living; LMN = lower motor neuron; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy; UMN = upper motor neuron
1\.
Medical geneticist, certified genetic counselor, or certified advanced genetic nurse
### Treatment of Manifestations
Optimally, care is provided by a multidisciplinary team that includes specialists in physical medicine rehabilitation, urology, and behavioral neurology or psychology (i.e., behavioralists) (see Table 5).
### Table 5.
Treatment of Manifestations in Individuals with GBE1 Adult Polyglucosan Body Disease
View in own window
Manifestation/
ConcernTreatmentConsiderations/Other
SpasticityIndividualized PT program
* Stretching exercises to ↑ flexibility, ↓ spasticity, & maintain or ↑ joint range of motion & prevent joint contractures
* Aerobic exercise to ↑ cardiovascular fitness & to maintain & ↑ muscle strength, coordination, & balance
* Strengthening exercises to improve posture, walking, arm strength to improve use of mobility aids, ADL
Reduction of spasticityMassage, ultrasound, electrical stimulation, whirlpool
Antispasmodic drugsBaclofen, Botox®, dantrolene, tizanidine (used 1 at a time), esp early in disease course to ↓ cramps, make leg muscles less tight, & facilitate walking
Bladder
functionAnticholinergic drugs; clean intermittent catheterization to prevent urosepsisConsider indwelling bladder catheter depending on urologic findings.
Treatment of recurrent UTIs
Orthostatic
hypotensionPer standard practice
ConstipationPer standard practice
Activities of
daily livingPT
* Transfers (e.g., from bed to wheelchair, wheelchair to car)
* Training on how to fall to ↓ risk of injury
OT
* To accomplish tasks such as mobility, washing, dressing, eating, cooking, & grooming
* To assist w/household modifications to meet special needs
Cognitive
decline /
DementiaPharmacologic treatmentStandard treatment for psychiatric manifestations (e.g., depression, anxiety, & psychosis)
Psychotherapy /
neuropsychological rehab
ADL = activities of daily living; OT = occupational therapy; PT = physical therapy; UTI = urinary tract infection
### Surveillance
### Table 6.
Recommended Surveillance for Individuals with GBE1 Adult Polyglucosan Body Disease
View in own window
System/ConcernEvaluationFrequency
Neurologic
* Neurologic assessment for progression of UMN & LMN signs
* Monitor for development of new manifestations.
Per treating neurologist
Bladder functionUrology evalFrequent
Orthostatic
hypotensionBlood pressure testing for postural changesUnknown
ConstipationGastroenterology evalUnknown
Activities of daily
livingOT/PT evalPer treating OT/PT
Cognitive declinePer treating mental health cliniciansPer treating mental health clinicians
Genetic counselingUpdate for new therapies, diagnostic methods, concerns of at-risk family membersAs needed
LMN = lower motor neuron; OT = occupational therapy/therapist; PT = physical therapy/therapist; UMN = upper motor neuron
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Clinical trials involve use of guaiacol [Kakhlon et al 2018] and triacyglycerol mimetic 5 (TGM5) [Alvarez et al 2017].
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
GBE1 Adult Polyglucosan Body Disease
|
None
| 27,569 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK5300/
| 2021-01-18T21:24:50 |
{"synonyms": []}
|
A number sign (#) is used with this entry because of evidence that variation in the SLC24A4 gene (609840) influences skin, hair, and eye pigmentation.
For a general phenotypic description and a discussion of genetic heterogeneity of variation in skin, hair, and eye pigmentation, see SHEP1 (227220).
Mapping
In a genomewide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun, and freckling among 2,986 Icelanders, Sulem et al. (2007) identified a 2-SNP (single-nucleotide polymorphism) haplotype in the SLC24A4 gene that was associated with blond versus brown hair and with blue versus green eyes. The haplotype tagged a group of equivalent SNPs which had a frequency of 60% in the CEPH Utah HapMap sample but less than 1% in the Nigerian Yoruba sample. One of the tagged SNPs was rs12896399, the T allele of which showed a similarly strong association with blond versus brown hair (discovery OR = 2.56, P = 1.4 x 10(-48)) and blue versus green eyes (discovery OR = 2.06, P = 4.1 x 10(-38)) in the Icelandic and Dutch replication samples as in the Icelandic discovery sample.
In a study of eye color variation in a cohort of 718 individuals of European descent, Pospiech et al. (2011) used multifactor dimensionality reduction and logistic regression to examine gene-gene interactions based on SNPs in 11 known pigmentation genes. A significant interaction effect was found for rs12913832 in the HERC2 gene (605837) and rs12896399 in SLC24A4 for blue versus nonblue color.
Hair \- Blond Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 6
|
c2673866
| 27,570 |
omim
|
https://www.omim.org/entry/210750
| 2019-09-22T16:30:22 |
{"mesh": ["C567139"], "omim": ["210750"], "synonyms": ["Alternative titles", "SKIN/HAIR/EYE PIGMENTATION 6, BLOND/BROWN HAIR", "SKIN/HAIR/EYE PIGMENTATION 6, BLUE/GREEN EYES"]}
|
Hemoglobin E disease (HbE) is a hemoglobinopathy characterized by production of abnormal variant hemoglobin known as hemoglobin E, with a generally benign, asymptomatic presentation.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Hemoglobin E disease
|
c0238159
| 27,571 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2133
| 2021-01-23T18:18:59 |
{"gard": ["2641"], "umls": ["C0238159"], "icd-10": ["D58.2"]}
|
Annular pancreas
Duodenum and pancreas (normal anatomy)
SpecialtyMedical genetics
Annular pancreas is a rare condition in which the second part of the duodenum is surrounded by a ring of pancreatic tissue continuous with the head of the pancreas. This portion of the pancreas can constrict the duodenum and block or impair the flow of food to the rest of the intestines. It is estimated to occur in 1 out of 12,000 to 15,000 newborns.[1] The ambiguity arises from the fact that not all cases are symptomatic.[2]
## Contents
* 1 Signs and Symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 References
* 6 External links
## Signs and Symptoms[edit]
Early signs of abnormality include polyhydramnios (an excess of amniotic fluid), low birth weight, and feeding intolerance immediately after birth, in particular a tendency to epigastric distention associated with non-biliary vomiting (the obstruction is generally above the papilla of Vater, therefore superior than the junction with the bile ducts). Different chromosomal diseases (for example trisomy 21 and, with a minor frequency, trisomy 18 and trisomy 13) are present in about 33% of subjects affected by annular pancreas.[3][4] In adults, the clinical picture is often dominated by the sensation of postprandial distension, abdominal pain in the epigastric region, nausea and vomiting that may be present for a long time (sometimes for years) before reaching a precise diagnosis.[citation needed]
## Causes[edit]
It is typically associated with abnormal embryological development, however adult cases can develop. It can result from growth of a bifid ventral pancreatic bud around the duodenum, where the parts of the bifid ventral bud fuse with the dorsal bud, forming a pancreatic ring. It can also result if the ventral pancreatic bud fails to fully rotate, so it remains on the right or if the dorsal bud rotates in the wrong direction, such that the duodenum is surrounded by pancreatic tissue. Blockage of the duodenum develops if inflammation (pancreatitis) develops in the annular pancreas.[citation needed]
## Diagnosis[edit]
Postnatal diagnostic procedures include abdominal x-ray and ultrasound, CT scan, and upper GI and small bowel series. Abdominal radiography can show the classic sign of the "double bubble": the presence of air in the stomach and duodenum.[5][6] Unfortunately, this double-bubble sign is not pathognomonic for annular pancreas, as it can also be observed in other conditions, such as duodenal atresia[7] and intestinal malrotation.[8] Upper GI series may be suggestive of annular pancreas, especially if they show a duodenal narrowing of the second portion of the duodenum and the concomitant dilatation of the proximal duodenum. In some cases it is possible to have signs of inverse peristalsis of the duodenal tract which is proximal to the narrowing caused by the annular pancreas, and the dilatation of the duodenal portion distal to the anomaly. An abdominal CT scan or an MRI allows to highlight the narrowing of the descending duodenal tract and the ring of pancreatic tissue surrounding the duodenum: this ring can be complete or, in patients with an incomplete annular pancreas, extended in a postero-lateral or anterolateral direction with respect to the second part of the duodenum. ERCP or MRCP with secretin allow precise delineation of the anatomical structure and in particular a good visualization of pancreatic ducts, as well as a careful analysis of pancreatic secretion into the duodenum lumen.[9]
## Treatment[edit]
In neonates, treatment for relief of obstruction usually is bypassing the obstructed segment of duodenum by duodeno-jejunostomy.[10] In adults, due to the minor duodenal mobility, the approach is laparoscopic gastrojejunostomy or duodenojejunostomy.[11][12]
## References[edit]
1. ^ Lainakis N; Antypas S; Panagidis A; et al. (2005), "Annular pancreas in two consecutive siblings: an extremely rare case", European Journal of Pediatric Surgery, 15 (5): 364–8, doi:10.1055/s-2005-865838, PMID 16254852
2. ^ Ravitch, MM. (1975). "The pancreas in infants and children". Surg Clin North Am. 55 (2): 377–85. doi:10.1016/S0039-6109(16)40587-6. PMID 165579.
3. ^ Sencan A, Mir E, Günsar C, Akcora B (June 2002). "Symptomatic annular pancreas in newborns". Med. Sci. Monit. 8 (6): CR434–7. PMID 12070435. Retrieved 2018-03-12.
4. ^ Yigiter M, Yildiz A, Firinci B, Yalcin O, Oral A, Salman AB (December 2010). "Annular pancreas in children: a decade of experience". Eurasian J Med. 42 (3): 116–9. doi:10.5152/eajm.2010.33. PMC 4261261. PMID 25610139.
5. ^ Dankovcik R, Jirasek JE, Kucera E, Feyereisl J, Radonak J, Dudas M (2008). "Prenatal diagnosis of annular pancreas: reliability of the double bubble sign with periduodenal hyperechogenic band". Fetal Diagn. Ther. 24 (4): 483–90. doi:10.1159/000178759. PMC 2814148. PMID 19047797.
6. ^ Raman VS, Arora M, Khanna SK (2015). "Annular pancreas, type I choledochal cyst and malrotation in a low-birth weight newborn: A case report". J Indian Assoc Pediatr Surg. 20 (3): 155–6. doi:10.4103/0971-9261.154656. PMC 4481632. PMID 26166991.
7. ^ Poki HO, Holland AJ, Pitkin J (June 2005). "Double bubble, double trouble". Pediatr. Surg. Int. 21 (6): 428–31. doi:10.1007/s00383-005-1448-z. PMID 15912365. S2CID 21589667.
8. ^ Imamoglu M, Cay A, Sarihan H, Sen Y (April 2004). "Rare clinical presentation mode of intestinal malrotation after neonatal period: Malabsorption-like symptoms due to chronic midgut volvulus". Pediatr Int. 46 (2): 167–70. doi:10.1046/j.1442-200x.2004.01859.x. PMID 15056243.
9. ^ Cholet F, Bideau K, Nonent M, Nousbaum JB, Gouérou H, Robaszkiewicz M (2004). "Coexistence of annular pancreas with carcinoma in the dorsal part of pancreas divisum: diagnostic value of magnetic resonance cholangiopancreatography". Abdom Imaging. 29 (6): 703–6. doi:10.1007/s00261-004-0178-3. PMID 15185031. S2CID 19701907.
10. ^ Pansini M, Magerkurth O, Haecker FM, Sesia SB (September 2012). "Annular pancreas associated with duodenal obstruction". BMJ Case Rep. 2012: bcr2012006855. doi:10.1136/bcr-2012-006855. PMC 4544741. PMID 22987909.
11. ^ De Ugarte DA, Dutson EP, Hiyama DT (2006). "Annular pancreas in the adult: management with laparoscopic gastrojejunostomy". The American Surgeon. 72 (1): 71–3. PMID 16494188.
12. ^ Cheng L, Tian F, Zhao T, Pang Y, Luo Z, Ren J (October 2013). "Annular pancreas concurrent with pancreaticobiliary maljunction presented with symptoms until adult age: case report with comparative data on pediatric cases". BMC Gastroenterol. 13: 153. doi:10.1186/1471-230X-13-153. PMC 4015270. PMID 24156788.
## External links[edit]
Classification
D
* ICD-10: Q45.1
* ICD-9-CM: 751.7
* OMIM: 167750
* MeSH: C536376 C536376, C536376
External resources
* MedlinePlus: 001142
* v
* t
* e
Congenital malformations and deformations of digestive system
Upper GI tract
Tongue, mouth and pharynx
* Cleft lip and palate
* Van der Woude syndrome
* tongue
* Ankyloglossia
* Macroglossia
* Hypoglossia
Esophagus
* EA/TEF
* Esophageal atresia: types A, B, C, and D
* Tracheoesophageal fistula: types B, C, D and E
* esophageal rings
* Esophageal web (upper)
* Schatzki ring (lower)
Stomach
* Pyloric stenosis
* Hiatus hernia
Lower GI tract
Intestines
* Intestinal atresia
* Duodenal atresia
* Meckel's diverticulum
* Hirschsprung's disease
* Intestinal malrotation
* Dolichocolon
* Enteric duplication cyst
Rectum/anal canal
* Imperforate anus
* Rectovestibular fistula
* Persistent cloaca
* Rectal atresia
Accessory
Pancreas
* Annular pancreas
* Accessory pancreas
* Johanson–Blizzard syndrome
* Pancreas divisum
Bile duct
* Choledochal cysts
* Caroli disease
* Biliary atresia
Liver
* Alagille syndrome
* Polycystic liver disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Annular pancreas
|
c0149955
| 27,572 |
wikipedia
|
https://en.wikipedia.org/wiki/Annular_pancreas
| 2021-01-18T18:35:06 |
{"gard": ["705"], "mesh": ["C536376"], "umls": ["C0149955"], "icd-9": ["751.7"], "orphanet": ["675"], "wikidata": ["Q1601921"]}
|
Rolandic epilepsy-speech dyspraxia syndrome is a rare, genetic epilepsy characterized by speech disorder (including a range of symptoms from dysarthria, speech dyspraxia, receptive and expressive language delay/regression and acquired aphasia to subtle impairments of conversational speech) and epilepsy (mostly focal and secondary generalized childhood-onset seizures, sometimes with aura). Mild to severe intellectual disability may also be observed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Rolandic epilepsy-speech dyspraxia syndrome
|
c0282512
| 27,573 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163721
| 2021-01-23T17:08:07 |
{"mesh": ["D018887"], "omim": ["245570", "300643"]}
|
A number sign (#) is used with this entry because of evidence that Grebe chondrodysplasia is caused by homozygous or compound heterozygous mutation in the CDMP1 gene (GDF5; 601146) on chromosome 20q11.
Description
Grebe chondrodysplasia is an autosomal recessive disorder characterized by severe abnormality of the limbs and limb joints. The severity of limb shortening progresses in a proximal-distal gradient, with the hands and feet being most affected. The fingers and toes lack articulation and appear as skin appendages. In contrast, axial skeletal structures and the craniofacial skeleton are not affected. Heterozygous individuals are of average stature and have mild skeletal abnormalities (summary by Thomas et al., 1997).
Clinical Features
Grebe (1952, 1955) described the disorder in 7- and 11-year-old sisters, offspring of a consanguineous mating. (The name is pronounced GRAY-beh.) The same disorder was found in Brazil by Quelce-Salgado (1964). In these cases, all 4 limbs are markedly shortened and end in tiny digits. The trunk and head are normal. A case with childhood and adult radiographic studies was presented by Scott (1969).
Romeo et al. (1977) described 2 patients, each with an entity similar to but distinct from Grebe chondrodysplasia. Teebi et al. (1986) reviewed the adult case reported by Romeo et al. (1977) and added the case of an infant who, in their view, has the same disorder, a condition separate from Grebe chondrodysplasia. Meera Khan and Khan (1982) described 6 cases distributed in 3 sibships in 3 generations of an inbred kindred in India. The parents were consanguineous in each of the 3 sibships and the entire pedigree gave incontrovertible support to autosomal recessive inheritance. No radiologic or other abnormality was found in heterozygotes by Meera Khan and Khan (1982) or by Garcia-Castro and Perez-Comas (1975), although Quelce-Salgado (1968) mentioned that x-ray studies of the parents of one of his patients showed absence of some phalanges of the toes and changes in other phalanges, as well as talipes equinovarus, polydactyly, and double halluces in more remote relatives.
Curtis (1986) called attention to a report of an inbred Miao Chinese kindred with 6 affected persons. The authors suggested that heterozygotes may have mild skeletal anomalies of the hands and feet. Curtis (1986) concluded that the family that she reported (Kumar et al., 1984) may have been an example of brachydactyly as a heterozygous manifestation of Grebe chondrodysplasia. Feng et al. (1985) reported an inbred kindred living in an isolated village of Yunnan province in China. Six of 13 children in 2 related sibships were affected. They stated that 65 affected individuals, including these 6, have been reported. In the 2 patients they studied in detail, the head and trunk were normal in marked contrast to severely malformed limbs. The anomalies progressed in severity distally in the limbs. The fingers and toes were replaced by small, bud-like or knob-like protrusions. Both patients were polydactylous. The skull and vertebral column were normal roentgenographically.
Costa et al. (1998) reported clinical and radiological findings in 10 affected individuals originating from Bahia, Brazil. The phenotype was characterized by a normal axial skeleton and severely shortened and deformed limbs, with a proximal-distal gradient of severity. The humeri and femora were relatively normal, the radii/ulnae and tibiae/fibulae were short and deformed, carpal and tarsal bones were fused, and several metacarpal and metatarsal bones were absent. The proximal and middle phalanges of the fingers and toes were invariably absent, while the distal phalanges were present. Postaxial polydactyly was found in several affected individuals. Several joints of the carpus, tarsus, hand, and foot were absent. Heterozygotes presented with a variety of skeletal manifestations, including polydactyly, brachydactyly, hallux valgus, and metatarsus adductus.
Other Features
Lin et al. (2001) called attention to Vietnamese sisters pictured in an April 25, 2000 article in The Boston Globe, entitled 'The Agent Orange tragedy continues.' The well illustrated features were typical of Grebe syndrome.
Molecular Genetics
Thomas et al. (1997) used the candidate gene approach to identify the genetic defect in Grebe type chondrodysplasia. They identified 20 members of the original family from the state of Bahia in Brazil described by Quelce-Salgado (1964). The cartilage-derived morphogenetic protein-1 (CDMP1; 601146) maps to 20q11.2 and is tightly linked to D20S191 and D20S195 (Lin et al., 1996). Thomas et al. (1997) demonstrated that 13 of 14 chromosomes from individuals with Grebe chondrodysplasia shared the D20S191:D20S195:CDMP1 2:1:1 haplotype. The fourteenth chromosome was detected in an affected individual with 1 copy of the 2:1:1 haplotype and 1 copy of a 1:1:1 haplotype. All obligate carriers analyzed possessed 1 copy of the 2:1:1 haplotype. They found that affected individuals homozygous for the 2:1:1 haplotype had a G-to-A transition at nucleotide 1199 (1199G-A), predicting a tyrosine for cysteine substitution at amino acid 400 (C400Y; 601146.0003) in the mature region of CDMP1. The affected individual with the 2:1:1/1:1:1 haplotype was found to be a compound heterozygote, possessing 1 allele for the 1199G-A mutation and the other for a deletion of a guanine nucleotide at position 1144 (del1144G), predicting a frameshift and premature stop codon 70 amino acids downstream. This individual was phenotypically identical to homozygotes for the 1199G-A mutation. The del1144G mutation was not present in any of the other 1:1:1 haplotypes analyzed and may have represented a sporadic mutation. Thomas et al. (1997) noted that in affected individuals the severity of limb shortening progressed in a proximal-distal gradient, with the hands and feet being most affected. The fingers and toes lacked articulation and appeared as skin appendages. In contrast, axial skeletal structures and the craniofacial skeleton, including the temporomandibular joint, were not affected. Notably, heterozygous individuals were of average stature and had a variety of mild skeletal abnormalities, including postaxial polydactyly, brachydactyly, delayed bone age, metatarsus adductus, valgus deviation of toes, and flexion contracture of fingers.
Nomenclature
Grebe chondrodysplasia may be a good term for this disorder (Scott, 1977) to distinguish it from other quite different disorders that are also called achondrogenesis. (Before the ninth edition of MIM (1990), this disorder was referred to as type II achondrogenesis. As it turned out, this only complicated the nomenclature inasmuch as this condition bears no similarity to the lethal neonatal chondrodysplasias, which are also referred to as achondrogenesis, and the designation 'type II achondrogenesis' has been used for the Langer-Saldino type of lethal neonatal achondrogenesis (200610).) Superti-Furga (1996) suggested that this disorder should be renamed chondrodysplasia, Grebe type. The definition of achondrogenesis by Grebe (1952) resulted from an incorrect conclusion based on a superficial similarity between the 2 sisters he reported and the original patient of Fraccaro (1952).
INHERITANCE \- Autosomal recessive GROWTH Height \- Short limb dwarfism \- Average adult male height, 100.5cm \- Average adult female height, 99.5cm SKELETAL Limbs \- Limb reduction, especially distally (acromesomelia) \- Legs shorter than arms \- Short humeri \- Short radii \- Short ulna \- Short femurs \- Short tibia \- Short fibulae \- Absent or hypoplastic patellae Hands \- Very short digits \- Rudimentary carpal bones \- Rudimentary phalanges (distal phalanges present) \- Valgus hand deformity \- Postaxial polydactyly \- Absent or hypoplastic metacarpals Feet \- Short feet \- Valgus foot deformity \- Rudimentary phalanges (distal phalanges present) \- Fused tarsal bone \- Absent or hypoplastic metatarsal NEUROLOGIC Central Nervous System \- Normal intelligence MISCELLANEOUS \- Stillborn or death in infancy \- Heterozygote individuals are average stature and can have mild skeletal abnormalities including brachydactyly, delayed bone age, metatarsus adductus, and finger flexion contractures \- Increased frequency in the state of Bahia, Brazil \- Allelic to acromesomelic dysplasia, Hunter-Thompson type ( 201250 ), brachydactyly, type C ( 113100 ), and fibular hypoplasia nd complex brachydactyly ( 228900 ) MOLECULAR BASIS \- Caused by mutations in the growth/differentiation factor-5 gene (GDF5, 601146.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
CHONDRODYSPLASIA, GREBE TYPE
|
c0265260
| 27,574 |
omim
|
https://www.omim.org/entry/200700
| 2019-09-22T16:31:39 |
{"doid": ["0080052"], "mesh": ["C537915"], "omim": ["200700"], "orphanet": ["2098"], "synonyms": ["Alternative titles", "ACHONDROGENESIS, BRAZILIAN", "GREBE CHONDRODYSPLASIA", "GREBE DYSPLASIA", "ACROMESOMELIC DYSPLASIA, GREBE TYPE", "ACHONDROGENESIS, TYPE II, FORMERLY"]}
|
Deficiencies in immunoglobulin (Ig) isotypes (including: isolated IgG subclass deficiency, IgG sublcass deficiency with IgA deficiency and kappa chain deficiency) are primary immunodeficiencies that are often asymptomatic but can be characterized by recurrent, often pyogenic, sinopulmonary infections.
## Epidemiology
Prevalence is unknown.
## Clinical description
Some patients may show an increased frequency of infections in their second year of life, while for others the onset of infections may be later. There are four subclasses of IgG (IgG1, IgG2, IgG3 and IgG4), the levels of which change with age. Deficiency with IgG subclass 2 is most common in children, whereas after puberty deficiency in subclass 3 is more common. Symptomatic patients experience recurrent sinopulmonary infections, particularly with Streptococcus pneumonia and Haemophilus influenza, which present as repeated ear infections, bronchitis, pneumonia, sinusitis and diarrhea. Patients may also present with meningitis, bronchiectasis and severe, recurrent otitis media, which may lead to hearing loss. Patients with kappa chain deficiency are usually asymptomatic but symptoms can include recurrent respiratory infections and diarrhea.
## Etiology
The cause and mode of transmission of deficiencies in IgG subclasses is unknown. Kappa-chain deficiency is produced by mutations in the IGKC gene (2p11).
## Diagnostic methods
IgG subclass deficiency, with or without IgA deficiency, should be suspected in patients suffering from recurrent or chronic infections with encapsulated bacteria. Diagnosis is based on the number of infections (more than 6 courses of antibiotics per year given for upper and lower respiratory tract infections) and a lack of functional antibodies produced in response to vaccines and, in the case of IgG subclass deficiency, measurement of IgG subclass levels. The most common subclass deficiency is in IgG2, which may be accompanied by decreased IgG4 with or without decreased IgA levels. IgG subclass deficiency may still be a possibility even when the total IgG is normal, therefore measurement of all four IgG subclasses is required for an accurate diagnosis of IgG subclass deficiency. Diagnosis of kappa chain deficiency can be confirmed with genetic testing.
## Differential diagnosis
Differential diagnoses include other primary immunodeficiencies, including 22q11 microdeletion syndrome, HLA class II deficiency and ataxia telangiectasia (see these terms). In general, infections are less severe than those in patients with marked deficiencies of IgG (all subclasses), IgA and IgM (such as X-linked agammaglobulinemia and common variable immunodeficiency; see these terms).
## Genetic counseling
Transmission is autosomal recessive and point mutations in one family have been described.
## Management and treatment
Treatment is based on prophylactic antibiotics and/or polyvalent immunoglobulin replacement in cases with severe or recurrent infections. Asymptomatic cases do not require treatment. Treatment in children is restricted to 8-9 months over winter with attempts to stop treatment totally in the summer in order to see if the deficit has corrected itself. For kappa chain deficiency, oral poliovaccine should not be given because of the risk of paralytic disease.
## Prognosis
In children these deficiencies may be transient, while in adults they seem to be permanent. However, there is no evidence at diagnosis to predict their evolution.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Recurrent infections associated with rare immunoglobulin isotypes deficiency
|
c0162539
| 27,575 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=183675
| 2021-01-23T18:38:18 |
{"mesh": ["D017099"], "omim": ["614102"], "umls": ["C0162539", "C3279824"], "synonyms": ["IgG subclass deficiency with IgA subclass deficiency", "Isolated IgG subclass deficiency", "Kappa-chain deficiency", "Selective IgG subclass deficiency"]}
|
Pachyonychia congenita
Pachyonychia congenita has an autosomal dominant pattern of inheritance.
SpecialtyMedical genetics
Pachyonychia congenita (often abbreviated as "PC") is a rare group of autosomal dominant skin disorders that are caused by a mutation in one of five different keratin genes. Pachyonychia congenita is often associated with thickened toenails, plantar keratoderma, and plantar pain.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Inheritance
* 3 Diagnosis
* 3.1 Classification
* 3.2 Clinical Diagnosis
* 3.3 Genetic Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 Research
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
Pachyonychia congenita is characterized by a clinical triad present in 97% of people with PC by the time they turn 10 years old:[1][2]
1. Thickened toenails
2. Plantar keratoderma
3. Plantar pain that may require some patients to use wheelchairs, canes, crutches, and pain medications due to its severity
Other signs and symptoms found in PC include:[1][3]
* Thickened fingernails
* Palmar keratoderma
* Oral leukokeratosis
* Cysts, including steatocystoma multiplex
* Follicular hyperkeratosis
* Natal or prenatal teeth
* Blisters
* Excessive sweating of the palms and soles
* Excess earwax production
* Ear pain
* Hoarseness
* Angular chelitis
* Fingernail and toenail infections
## Cause[edit]
The condition is caused by genetic mutations in one of five genes that encode keratin proteins. Three keratin genes were identified to have a role PC in 1995[4][5] with a fourth keratin gene's role in PC identified in 1998.[6]
### Inheritance[edit]
Pachyonychia congenita follows an autosomal dominant pattern of inheritance, which means the defective gene is located on an autosome, and only one copy of the gene is required to inherit the disorder from a parent who has the disorder. On average, 50% of the offspring of an affected person will inherit the disorder, regardless of gender.
Occasionally, however, a solitary case can emerge in a family with no prior history of the disorder due to the occurrence of a new mutation (often referred to as a sporadic, spontaneous or de novo mutation).
## Diagnosis[edit]
### Classification[edit]
ILDS: Q84.520 ICD-10: Q84.5
Pachyonychia congenita consists of five sub-types, each named after its corresponding genetic mutation and each associated with distinguishing clinical features:[1][7]
1. PC-K6a is caused by a mutation in the KRT6A gene and more often associated with oral leukokeratosis and poor feeding in infants.
2. PC-K6b is caused by a mutation in the KRT6B gene and more commonly associated with an increased age of onset (>14 years).
3. PC-K6c is caused by a mutation in the KRT6C gene and is the least common sub-type. It is not often associated with the additional features of oral leukokeratosis, cysts, follicular hyperkeratosis, and natal teeth.
4. PC-K16 is caused by a mutation in the KRT16 gene and is more commonly associated with severe plantar pain.
5. PC-K17 is caused by a mutation in the KRT17 gene and more commonly associated with the presence of cysts, follicular kyperkeratosis, and natal teeth.
Before the genetic basis of Pachyonychia congenita was identified and described, the disease was historically divided into the following sub-types:[8]:510
* Pachyonychia congenita type I (also known as "Jadassohn–Lewandowsky syndrome"[9]) is an autosomal dominant keratoderma that principally involves the plantar surfaces, but also with nails changes that may be evident at birth, but more commonly develop within the first few months of life.[8]:510[9][10]:569
* Pachyonychia congenita type II (also known as "Jackson–Lawler pachyonychia congenita" and "Jackson–Sertoli syndrome") is an autosomal dominant keratoderma presenting with a limited focal plantar keratoderma that may be very minor, with nails changes that may be evident at birth, but more commonly develop within the first few months of life.[8][10]:569
### Clinical Diagnosis[edit]
In order to clinically diagnose pachyonychia congenita, the clinical triad of toenail thickening, plantar keratoderma, and plantar pain must be present. This triad is present in 97% of individuals with PC by the age of 10 years old.[1]
Pachyonychia congenita can be suspected in patients who do not have the complete clinical triad but who exhibit other symptoms such as cysts, oral leukokeratosis, follicular hyperkeratosis, palmoplantar hyperhidrosis, or natal teeth. Since PC is inherited in an autosomal dominant fashion in 70% of individuals, it should especially be suspected in patients with symptoms who also have a parent with similar symptoms. Histopathological analysis of skin or nail tissue is not helpful in diagnosis of PC, but can be used to rule out some related diseases. If there is a clinical suspicion for PC, genetic testing can confirm the diagnosis.[1]
### Genetic Diagnosis[edit]
The diagnosis of PC can be confirmed by the identification of a mutation in one of the five genes responsible for the condition: KRT6A, KRT6B, KRT6C, KRT16, KRT17. Pachyonychia Congenita Project is a non-profit dedicated to finding a cure for PC. The organization houses a genetic registry (the International PC Research Registry) and offers free genetic testing for individuals suspected to have PC.[11]
## Treatment[edit]
There is currently no cure for pachyonychia congenita. Treatment focuses on symptom relief for any plantar pain, hyperkeratoses, cysts, leukokeratosis, hyperhidrosis, or secondary infections.[12]
Palmoplantar keratoderma can be treated with consistent grooming, including trimming back the callus, applying emollients, and draining blisters. Plantar pain is often treated by reducing pressure on the feet by minimizing walking, wearing cushioned footwear, or using wheelchairs or crutches. Hyperkeratosis can be treated with keratolytic emollients while cysts may be treated with incision and drainage. Patients with hyperhidrosis may need to wear moisture-wicking socks and ventilated shoes. Any secondary infection may need to be treated with antibiotics, though infection can often be prevented with appropriate grooming and vinegar or bleach baths.[12][1][7]
## Epidemiology[edit]
Pachyonychia congenita is a rare disorder with an unknown prevalence. As of 2018, the International PC Research Registry has identified approximately 774 individuals with the disease, but prevalence is estimated to be 5,000–10,000 worldwide.[1][7] The disease affects both males and females.
## Research[edit]
There are several ongoing investigational therapies for pachyonychia congenita, including topical sirolimus, siRNA, botulinum toxin, statins, and anti-TNF biologics.[1] Pachyonychia Congenita Project houses a list of clinical trials and assists with clinical trial recruitment from patients enrolled in their International PC Research Registry.[11][13]
## See also[edit]
* Unilateral palmoplantar verrucous nevus
* List of cutaneous conditions
## References[edit]
1. ^ a b c d e f g h Smith, Frances JD; Hansen, C. David; Hull, Peter R.; Kaspar, Roger L.; McLean, WH Irwin; O’Toole, Edel; Sprecher, Eli (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Pachyonychia Congenita", GeneReviews®, University of Washington, Seattle, PMID 20301457, retrieved 2018-08-01
2. ^ Eliason, Mark J.; Leachman, Sancy A.; Feng, Bing-jian; Schwartz, Mary E.; Hansen, C. David (October 2012). "A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita". Journal of the American Academy of Dermatology. 67 (4): 680–686. doi:10.1016/j.jaad.2011.12.009. ISSN 1097-6787. PMID 22264670.
3. ^ "What Is Pachyonychia Congenita?". www.pachyonychia.org. Retrieved 2018-08-01.
4. ^ McLean W, Rugg E, Lunny D, Morley S, Lane E, Swensson O, Dopping-Hepenstal P, Griffiths W, Eady R, Higgins C, Navsaria H, Leigh I, Strachan T, Kunkeler L, Munro C (1995). "Keratin 16 and keratin 17 mutations cause pachyonychia congenita". Nature Genetics. 9 (3): 273–8. doi:10.1038/ng0395-273. PMID 7539673. S2CID 1873772.
5. ^ Bowden PE, Haley JL, Kansky A, Rothnagel JA, Jones DO, Turner RJ (1995). "Mutation of a type II keratin gene (K6a) in pachyonychia congenita". Nature Genetics. 10 (3): 363–5. doi:10.1038/ng0795-363. PMID 7545493. S2CID 26060130.
6. ^ Smith FJ, Jonkman MF, Van Goor H, Coleman CM, Covello SP, Uitto J, McLean WH (1998). "A Mutation in Human Keratin K6b Produces a Phenocopy of the K17 Disorder Pachyonychia Congenita Type 2". Human Molecular Genetics. 7 (7): 1143–8. doi:10.1093/hmg/7.7.1143. PMID 9618173.
7. ^ a b c "Pachyonychia Congenita - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2018-08-02.
8. ^ a b c Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
9. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 740. ISBN 978-1-4160-2999-1.
10. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
11. ^ a b "International PC Research Registry (IPCRR)". www.pachyonychia.org. Retrieved 2018-08-01.
12. ^ a b Goldberg, I.; Fruchter, D.; Meilick, A.; Schwartz, M.E.; Sprecher, E. (2013-01-30). "Best treatment practices for pachyonychia congenita". Journal of the European Academy of Dermatology and Venereology. 28 (3): 279–285. doi:10.1111/jdv.12098. ISSN 0926-9959. PMID 23363249. S2CID 29684041.
13. ^ "Clinical Trials & Studies". www.pachyonychia.org. Retrieved 2018-08-01.
## External links[edit]
Classification
D
* ICD-10: Q84.5 (ILDS Q84.520), (ILDS Q84.530)
* ICD-9-CM: 703.8 757.5
* OMIM: 167210 167200, 167210
* MeSH: D009264
* DiseasesDB: 32826
* SNOMED CT: 39427000
External resources
* eMedicine: derm/812
* Orphanet: 2309
* GeneReviews/NCBI/NIH/UW entry on Pachyonychia Congenita
* OMIM: 260130 Pachyonychia congenita recessive at NIH's Office of Rare Diseases
* v
* t
* e
Congenital malformations and deformations of skin appendages
Nail disease
* Anonychia
* Leukonychia
* Pachyonychia congenita/Onychauxis
* Koilonychia
Hair disease
* hypotrichosis/abnormalities: keratin disease
* Monilethrix
* IBIDS syndrome
* Sabinas brittle hair syndrome
* Pili annulati
* Pili torti
* Uncombable hair syndrome
* Björnstad syndrome
* Giant axonal neuropathy with curly hair
* hypertrichosis: Zimmermann–Laband syndrome
* v
* t
* e
Diseases of collagen, laminin and other scleroproteins
Collagen disease
COL1:
* Osteogenesis imperfecta
* Ehlers–Danlos syndrome, types 1, 2, 7
COL2:
* Hypochondrogenesis
* Achondrogenesis type 2
* Stickler syndrome
* Marshall syndrome
* Spondyloepiphyseal dysplasia congenita
* Spondyloepimetaphyseal dysplasia, Strudwick type
* Kniest dysplasia (see also C2/11)
COL3:
* Ehlers–Danlos syndrome, types 3 & 4
* Sack–Barabas syndrome
COL4:
* Alport syndrome
COL5:
* Ehlers–Danlos syndrome, types 1 & 2
COL6:
* Bethlem myopathy
* Ullrich congenital muscular dystrophy
COL7:
* Epidermolysis bullosa dystrophica
* Recessive dystrophic epidermolysis bullosa
* Bart syndrome
* Transient bullous dermolysis of the newborn
COL8:
* Fuchs' dystrophy 1
COL9:
* Multiple epiphyseal dysplasia 2, 3, 6
COL10:
* Schmid metaphyseal chondrodysplasia
COL11:
* Weissenbacher–Zweymüller syndrome
* Otospondylomegaepiphyseal dysplasia (see also C2/11)
COL17:
* Bullous pemphigoid
COL18:
* Knobloch syndrome
Laminin
* Junctional epidermolysis bullosa
* Laryngoonychocutaneous syndrome
Other
* Congenital stromal corneal dystrophy
* Raine syndrome
* Urbach–Wiethe disease
* TECTA
* DFNA8/12, DFNB21
see also fibrous proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Pachyonychia congenita
|
c1721007
| 27,576 |
wikipedia
|
https://en.wikipedia.org/wiki/Pachyonychia_congenita
| 2021-01-18T18:38:52 |
{"gard": ["10753"], "mesh": ["D053549"], "umls": ["C1721007", "C0265334", "C1706595"], "icd-9": ["757.5", "703.8"], "icd-10": ["Q84.5"], "orphanet": ["2309"], "wikidata": ["Q3360152"]}
|
A rare head and neck tumor characterized by a malignant epithelial neoplasm most commonly arising in the maxillary sinus or nasal cavity, occurring as a keratinizing, a non-keratinizing, or a spindle cell (sarcomatoid) type. Patients may present with nasal obstruction, epistaxis, rhinorrhea, swelling, or (at more advances stages) with facial pain and/or paralysis, diplopia, and proptosis. Patients with paranasal sinus tumors present later and at a higher stage than patients with nasal cavity carcinomas. Risk factors are smoking and industrial exposures. High-risk HPV is most frequently associated with the non-keratinizing type.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Squamous cell carcinoma of the nasal cavity and paranasal sinuses
|
c1168401
| 27,577 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=500464
| 2021-01-23T16:57:14 |
{"mesh": ["D000077195"], "omim": ["275355"], "synonyms": ["Squamous cell carcinoma of the nasal cavity and sinuses"]}
|
The trait is age- and sex-dependent, being rare in young children and more frequent in males. Instances of involvement in multiple generations were reviewed by Hrdlicka (1935).
Inheritance \- Autosomal dominant Misc \- Age dependent \- More frequent in males Ears \- External auditory canal exostoses ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
EAR EXOSTOSES
|
c0155411
| 27,578 |
omim
|
https://www.omim.org/entry/128300
| 2019-09-22T16:42:02 |
{"omim": ["128300"], "icd-9": ["380.81"], "synonyms": ["Alternative titles", "EXOSTOSES OF EXTERNAL AUDITORY CANAL"]}
|
Cocaine embryofetopathy is a group of clinical signs observed in newborns exposed in utero to cocaine, a short-acting central nervous system stimulant used as a recreational drug through inhalation of the powder or intravenous injection. Cocaine use during pregnancy is associated with intrauterine growth restriction, low birth weight, seizures, respiratory distress (decreased apnea density and periodic breathing), feeding difficulties, irritability and lability of state, decreased behavioral and autonomic regulation, poor alertness and orientation and cognitive impairment (impaired auditory information processing , visual-spatial delay and subtle language delay) in the offspring.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Cocaine embryofetopathy
|
c0432371
| 27,579 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1911
| 2021-01-23T18:31:56 |
{"gard": ["1413"], "umls": ["C0432371"], "icd-10": ["Q86.8"], "synonyms": ["Fetal cocaine syndrome"]}
|
## Summary
### Clinical characteristics.
Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus, and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are depressed nasal bridge and broad flat nasal tip, widely spaced eyes, downslanted palpebral fissures, mild ptosis, short philtrum with prominent philtral ridges with an upward pointing vermilion border resulting in a triangular mouth, and thickened (patulous) everted lips. Less common findings include other types of congenital heart defects, other hand and foot anomalies, hypodontia, hearing loss, myopia and/or strabismus, polythelia, parasomnia, craniosynostosis (involving either the metopic or sagittal suture), and short stature.
### Diagnosis/testing.
The diagnosis of Char syndrome is established in a proband with suggestive clinical findings and/or a heterozygous pathogenic variant in TFAP2B identified by molecular genetic testing.
### Management.
Treatment of manifestations: Management of patent ductus arteriosus after the immediate newborn period is determined by the degree of shunting from the aorta to the pulmonary artery; options are surgical ligation or ductal occlusion at catheterization. Hypodontia/tooth anomalies, vision problems, hearing loss, other hand/foot anomalies, parasomnias, and craniosynostosis are treated in a routine manner.
Surveillance: Assessment for signs and symptoms of sleep problems at each visit; monitoring of head shape and size at each visit during the first year of life; vision and hearing screening annually or as clinically indicated; dental evaluations every six months starting at age three years.
### Genetic counseling.
Char syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by a de novo pathogenic variant is unknown. If a parent of the proband is affected, the risk to the sibs is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. Each child of an individual with Char syndrome has a 50% chance of inheriting the pathogenic variant and having the disorder. If the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
## Diagnosis
Formal clinical diagnostic criteria for Char syndrome have not been published.
### Suggestive Findings
Char syndrome should be suspected in individuals with the following clinical and family history findings.
Clinical features
* Typical facial features with depressed nasal bridge and broad flat nasal tip, widely spaced eyes, downslanted palpebral fissures, mild ptosis, short philtrum with prominent philtral ridges with an upward pointing vermilion border resulting in a triangular mouth, and thickened (patulous) everted lips
* Patent ductus arteriosus
* Aplasia or hypoplasia of the middle phalanges of the fifth fingers
Family history consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis.
### Establishing the Diagnosis
The diagnosis of Char syndrome is established in a proband with suggestive clinical findings and/or a heterozygous pathogenic variant in TFAP2B identified by molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Char syndrome is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of Char syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of Char syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of TFAP2B detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.
* A multigene panel that includes TFAP2B and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the diagnosis of Char syndrome is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Char Syndrome
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
TFAP2BSequence analysis 315/15 probands 4
Gene-targeted deletion/duplication analysis 5None reported 6
UnknownNA
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Satoda & Gelb [2003]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
Because most of the pathogenic variants identified to date result in mutated protein with dominant-negative effects, it is likely that variants will be missense defects in the coding region for critical domains, particularly the basic domain. Rare pathogenic changes altering splice sites & engendering haploinsufficiency have also been reported [Mani et al 2005, Massaad et al 2019].
## Clinical Characteristics
### Clinical Description
Char syndrome is characterized by the triad of typical facial features (see Figure 1), patent ductus arteriosus (PDA), and stereotypic hand anomalies (see Diagnosis).
#### Figure 1.
Typical facial features in a woman with Char syndrome Reprinted with permission from Satoda et al [1999]
### Table 2.
Features of Char Syndrome
View in own window
Feature% of Persons
with FeatureComment
Facial
dysmorphia86%Higher prevalence in those w/missense variants (98%) vs loss-of-function variants (59%) (See Genotype-Phenotype Correlations.)
PDA68%
Other congenital
heart defects6%
Hand anomalies57%Higher prevalence in those w/missense variants altering the basic domain (residues 223-301; 79%) than in the transactivation domain (residues 65-86; 0%) (See Genotype-Phenotype Correlations.)
PDA. The ductus arteriosus, the fetal arterial connection between the aorta and pulmonary artery that shunts blood away from the lungs, constricts shortly after birth. If the ductus arteriosus remains patent, left to right shunting (from the systemic circulation into the pulmonary circulation) occurs, resulting in pulmonary hypertension if not corrected. No information is available concerning the likelihood of spontaneous closure of a PDA after the first weeks of life in individuals with Char syndrome, but it is likely to be rather low.
Less common features associated with Char syndrome:
* Other heart defects (e.g., muscular ventricular septal defects, complex congenital defects)
* Other hand abnormalities including interstitial polydactyly [Slavotinek et al 1997], distal symphalangism of the fifth fingers (fusion of distal interphalangeal joints), and hypoplasia of the third fingers [Babaoğlu et al 2012]
* Foot anomalies including interphalangeal joint fusion or clinodactyly [Sweeney et al 2000], interstitial polydactyly [Slavotinek et al 1997], and syndactyly [Slavotinek et al 1997]
* Hypodontia. Lack of second and/or third molars in all four quadrants [Mani et al 2005; Author, unpublished observation]
* Visual impairment. Myopia [Bertola et al 2000], strabismus [Bertola et al 2000, Sweeney et al 2000]
* Hearing abnormalities including profound bilateral hearing loss in two affected individuals [Edward et al 2019; Author, unpublished observation in a member of the enlarged version of the original family studied by Char]
* Polythelia (supernumerary nipples) [Zannolli et al 2000]
* Parasomnia [Mani et al 2005]
* Craniosynostosis involving either the metopic or sagittal suture reported in four affected individuals [Timberlake et al 2019]
* Short stature (≤3 SD below the mean) reported in two affected individuals [Massaad et al 2019, Timberlake et al 2019]
### Genotype-Phenotype Correlations
Among the 16 different pathogenic variants in TFAP2B described in publications, seven are loss-of-function alleles and nine are missense changes. For the latter, eight of the nine alter residues in the DNA binding domain (basic domain; residues 223-301) and one is in the transactivation domain (residues 65-86).
* Individuals harboring basic domain alleles tend to have the classic form of Char syndrome (97% with facial features, 58% with PDA, and 79% with hand anomalies) [Satoda et al 1999, Satoda et al 2000, Zhao et al 2001].
* For individuals in the one family inheriting the transactivation domain-altering variant, the facial features were prevalent (14/14) but mild, PDA was generally present (10/14), but hand anomalies were not observed in any [Zhao et al 2001].
* The phenotypes associated with loss-of-function pathogenic variants often included PDA (32/40; 80%) but facial features of Char syndrome were less prevalent (23/39; 59%); features in these individuals not observed in those with missense variants included craniosynostosis (n = 3) and short stature (n = 2) [Massaad et al 2019, Timberlake et al 2019].
### Penetrance
The penetrance of Char syndrome has not been formally determined. Two asymptomatic individuals with TFAP2B pathogenic variants have been described [Mani et al 2005, Timberlake et al 2019].
### Prevalence
The prevalence of Char syndrome has not been determined but is thought to be quite low.
## Differential Diagnosis
Facial features. The typical facial features associated with Char syndrome are usually striking and not often confused with facial features observed in other disorders. The facial profile is similar to that of maxillonasal dysplasia (Binder syndrome; OMIM 155050).
Hand anomalies. The hand anomalies associated with Char syndrome can be as minimal as fifth finger clinodactyly, which can be a normal finding and overlaps with numerous other syndromes.
Patent ductus arteriosus (PDA) constitutes about 10% of all congenital heart disease.
Isolated PDA (in the absence of other congenital heart defects) occurs in about one in 2,000 full-term infants. PDA is considerably more common in premature infants. It is one of the cardiac lesions observed in congenital rubella syndrome and may occur in autosomal dominant and recessive disorders that are nonsyndromic [Mani et al 2002].
Note: Screening of a group of individuals with isolated PDA rarely revealed the presence of TFAP2B pathogenic variants [Khetyar et al 2008, Chen et al 2011].
Heart-hand syndromes. See Table 3.
### Table 3.
Genes Associated with Heart-Hand Syndromes in the Differential Diagnosis of Char Syndrome
View in own window
Gene(s)DisorderMOICongenital Heart DefectsHand AbnormalitiesOther Clinical Characteristics
CREBBP
EP300Rubinstein-Taybi syndromeADPresent in ~1/3 of affected persons; CHDs incl ASD, VSD, PDA, CoA.Broad & often angulated thumbs & hallucesDistinctive facial features, short stature, & moderate-to-severe ID
DVL1
DVL3
WNT5AAutosomal dominant Robinow syndromeADPresent in <25% of affected persons; CHDs incl pulmonary valve stenosis/atresia, ASD, VSD, & CoA.BrachydactylySkeletal dysplasia; short stature; dysmorphic facial features resembling a fetal face
EVC
EVC2Ellis-van Creveld syndrome (OMIM 225500)ARPresent in 50-60% of affected persons; CHDs incl common atrium, mitral & tricuspid valve defects, PDA, VSD, & hypoplastic left heart syndrome.Postaxial polydactylyShort stature w/shortening of the long bones; hidrotic ectodermal dysplasia of the nails, hair, & teeth
GPC3
GPC4Simpson-Golabi-Behmel syndrome type 1XL
* CHDs variable; septal defects common
* Pulmonic stenosis, CoA, transposition of the great vessels, & PDA or patent foramen ovale reported
Hand anomalies incl large hands & postaxial polydactyly.Pre- & postnatal macrosomia; distinctive facies; variable visceral, skeletal, & neurodevelopmental abnormalities
RBM8AThrombocytopenia-absent radius syndromeARPresent in 15%-22% of affected persons (usually septal defects rather than complex cardiac malformations)Thumbs of near-normal size but somewhat wider & flatter than usual; they are also held in flexion against the palm, & tend to have limited function.Bilateral absence of the radii & thrombocytopenia (<50 platelets/nL) that is generally transient
ROR2ROR2 Robinow syndromeAR
* Present in 15% of affected persons
* CHDs include pulmonary valve stenosis/ atresia, ASD, VSD, CoA, tetralogy of Fallot, & tricuspid atresia
* CHDs are the major cause of early death.
* Phalanges & carpal bones may be fused.
* Partial cutaneous syndactyly or ectrodactyly (i.e., split hand) may be seen.
Face in early childhood resembling a fetal face at 8 wks' gestation; skeletal abnormalities; short stature
TBX3Ulnar-mammary syndrome (OMIM 181450)ADVSDPostaxial polydactyly; camptodactyly, missing digitsHypoplastic or missing ulnae; hypoplasia of the apocrine & mammary glands; facial dysmorphia
TBX5Holt-Oram syndromeADPresent in 75% of affected persons; CHDs most commonly involving the septumUpper-limb malformations may be unilateral, bilateral/symmetric, or bilateral/asymmetric & range from triphalangeal or absent thumb(s) to phocomelia.Cardiac conduction disease
AD = autosomal dominant; AR = autosomal recessive; ASD = atrial septal defect; CHD = congenital heart disease; CoA = coarctation of the aorta; ID = intellectual disability; MOI = mode of inheritance; PDA = patent ductus arteriosus; VSD = ventricular septal defect; XL = X-linked
Heart-hand disorders of unknown genetic etiology to consider:
* PDA and bicuspid aortic valve with hand anomalies (fifth metacarpal hypoplasia and brachydactyly), but normal facies (OMIM 604381). This disorder is genetically distinct from Char syndrome, documented using linkage exclusion for the TFAP2B locus.
* Tabatznik syndrome [Silengo et al 1990]
* Heart-hand syndrome type III (OMIM 140450)
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Char syndrome, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with Char Syndrome
View in own window
System/ConcernEvaluationComment
DentalDental eval after age 3 yrsTo assess for hypodontia & other tooth anomalies
EyesOphthalmology evalTo assess for strabismus & refractive error
HearingAudiology evalTo assess for hearing loss
CardiovascularCardiac eval, usually incl echocardiogramTo screen for PDA &/or other cardiac anomalies 1
MusculoskeletalPhysical exam for polydactyly, symphalangism, & syndactylyHand &/or foot radiographs may be considered.
SleepAssessment for sleep disorders incl abnormal movements during sleep
CraniofacialAssessment of head shape & sizeImaging may be needed if craniosynostosis suspected.
Miscellaneous/
OtherConsultation w/clinical geneticist &/or genetic counselorTo incl genetic counseling
Family support/resourcesUse of community or online resources such as Parent to Parent
PDA = patent ductus arteriosus
1\.
Evaluation in the newborn nursery may not be completely informative, as the ductus arteriosus may remain open for several days in any neonate.
### Treatment of Manifestations
The most striking external aspects of Char syndrome, namely the dysmorphia and hand anomalies, require no special care early in life. The dysmorphic features do become important as affected individuals go through childhood and adolescence because of their stigmatizing effects. No data on the success of plastic surgical intervention for the facial features in Char syndrome are available.
### Table 5.
Treatment of Manifestations in Individuals with Char Syndrome
View in own window
Manifestation/ConcernTreatmentConsiderations/Other
Hypodontia / Tooth
anomaliesStandard treatment per orthodontist
Strabismus /
Refractive errorStandard treatment per ophthalmologist
Hearing lossHearing aids may be helpful as per otolaryngologistCommunity hearing services through early intervention or school district
PDA / Congenital
heart defectsManagement of PDA after immediate newborn period determined by degree of shunting from aorta to pulmonary arterySurgical ligation or ductal occlusion at catheterization are treatment options.
Polydactyly, symphalangism,
&/or syndactylyStandard treatment per orthopedist
ParasomniasStandard treatment through a sleep disorders clinic
CraniosynostosisStandard treatment through plastic surgery
PDA = patent ductus arteriosus
### Surveillance
Children with Char syndrome need pediatric attention during infancy and childhood.
### Table 6.
Recommended Surveillance for Individuals with Char Syndrome
View in own window
System/ConcernEvaluationFrequency
DentalDental evalEvery 6 mos starting at age 3 yrs
EyesVision screeningAnnually or as clinically indicated in childhood
HearingAudiology evalAnnually or as clinically indicated in childhood
SleepAssessment for signs & symptoms of sleep disorderAt each visit
CraniofacialMonitor head shape & size in infancy.At each visit during 1st yr of life
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Char Syndrome
|
c1868570
| 27,580 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1106/
| 2021-01-18T21:36:03 |
{"mesh": ["C566815"], "synonyms": []}
|
Fibrous papule of the nose (also known as "Benign solitary fibrous papule," and "Fibrous papule of the face") occurs in adults and is characterized by a dome-shaped, sessile, skin-colored, white, or reddish papule 3 to 6mm in diameter on or near the nose.[1]:609
## See also[edit]
* Skin lesion
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Fibrous papule of the nose
|
c0334428
| 27,581 |
wikipedia
|
https://en.wikipedia.org/wiki/Fibrous_papule_of_the_nose
| 2021-01-18T18:58:15 |
{"umls": ["C0334428", "C0346046"], "wikidata": ["Q426962"]}
|
Ocular motor apraxia, Cogan type is characterised by impairment of voluntary horizontal eye movements and compensatory head thrust. Around 50 cases have been described so far. The oculomotor manifestations tend to improve with age but the syndrome may also be associated with learning and speech difficulties, or, in some cases, cerebral malformations. Both sporadic and familial forms have been described, with sporadic forms being more frequent. The mode of transmission of the familial form has not yet been clearly established. A gene located on the long arm of chromosome 2, near to the NPHP1 gene involved in nephronophthisis, may be associated with ocular motor apraxia, Cogan type.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Ocular motor apraxia, Cogan type
|
c0543874
| 27,582 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1125
| 2021-01-23T18:27:35 |
{"gard": ["16"], "mesh": ["C537423"], "omim": ["257550"], "umls": ["C0543874"], "icd-10": ["H51.8"], "synonyms": ["Oculomotor apraxia, Cogan type"]}
|
Autosomal recessive spastic paraplegia type 69 is a rare, complex hereditary spastic paraplegia disorder characterized by infantile onset of progressive lower limb spasticity, global developmental delay, hyperreflexia, clonus and extensor plantar reflexes, associated with dysarthria, intellectual disability, cataracts and hearing impairment.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Autosomal recessive spastic paraplegia type 69
|
None
| 27,583 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401830
| 2021-01-23T17:00:56 |
{"icd-10": ["G11.4"], "synonyms": ["SPG69"]}
|
Self-healing papular mucinosis
SpecialtyDermatology
Self-healing papular mucinosis is a skin condition caused by fibroblasts producing abnormally large amounts of mucopolysaccharides, and may present in adult and juvenile forms.[1]:185 The juvenile variant is also called self-healing juvenile cutaneous mucinosis.[1]:185[2]
## See also[edit]
* Papular mucinosis
* List of cutaneous conditions
## References[edit]
1. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
* v
* t
* e
Mucinosis/Lichen myxedematosus
Localized lichen myxedematosus
* Discrete papular lichen myxedematosus
* Acral persistent papular mucinosis
* Self-healing papular mucinosis/Self-healing juvenile cutaneous mucinosis
* Papular mucinosis of infancy
* Atypical lichen myxedematosus
* Atypical tuberous myxedema
* Nodular lichen myxedematosus
Other primary mucinoses
* Cutaneous focal mucinosis
* Cutaneous lupus mucinosis
* Eccrine mucinosis
* Alopecia mucinosa
* Perifollicular mucinosis
* Stiff skin syndrome
* Generalized lichen myxedematosus
Secondary mucinoses
* Basal-cell carcinoma
* Granuloma annulare
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Self-healing papular mucinosis
|
None
| 27,584 |
wikipedia
|
https://en.wikipedia.org/wiki/Self-healing_papular_mucinosis
| 2021-01-18T18:28:36 |
{"orphanet": ["90397"], "synonyms": [], "wikidata": ["Q7448106"]}
|
Jilek-Aall et al. (1979) studied a seizure disorder called kifafa in an isolated tribe in the interior of Tanzania. About 200 cases were found among 10,000 persons. The disorder often led to severe burns in those afflicted. Many showed parkinsonian features and-or other neurologic abnormalities, as well as mental retardation and transient psychotic episodes. In children, head nodding was a frequent precursor of later grand mal seizures. Familial incidence was high; segregation analysis supported autosomal recessive inheritance. Jilek-Aall and Rwiza (1992) provided a 30-year follow-up. A prevalence of the disorder in the range of 19/1,000-36/1,000 with a mean age at onset of 11.6 years was found. Neuman et al. (1995) collected family data on 26 probands in 20 kifafa families. Of the 127 affected persons in these pedigrees, 23 were first-degree relatives of the 26 probands; 20 were second-degree relatives. When corrected for age, the risk to first degree relatives was 0.15; the risk to second degree relatives was 0.063. Among the mendelian single-locus models, an additive model was favored over either a dominant, recessive, or codominant model. The single-locus model could be rejected when compared with the mixed mendelian model (inclusion of a polygenic background), although the major-gene component tends to be recessive. However, the hypothesis of mendelian transmission could be rejected, suggesting that, although kifafa aggregates in these families, the mode of inheritance is genetically complex.
Neuro \- Seizures \- Parkinsonian features \- Neurologic abnormalities \- Mental retardation \- Transient psychotic episodes \- Head nodding Inheritance \- ? Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
KIFAFA SEIZURE DISORDER
|
c0796010
| 27,585 |
omim
|
https://www.omim.org/entry/245180
| 2019-09-22T16:26:03 |
{"mesh": ["C537708"], "omim": ["245180"]}
|
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (March 2013)
Conjunctival squamous cell carcinoma, NOS
SpecialtyOncology
Conjunctival squamous cell carcinoma (conjunctival SCC) and corneal intraepithelial neoplasia comprise what are called ocular surface squamous cell neoplasias. SCC is the most common malignancy of the conjunctiva in the US, with a yearly incidence of 1-2.8 per 100,000. Risk factors for the disease are exposure to sun (specifically occupational), exposure to UVB, and light-colored skin. Other risk factors include radiation, smoking, HPV, arsenic, and exposure to polycyclic hydrocarbons.[1]
Conjunctival SCC is often asymptomatic at first, but it can present with the presence of a growth, red eye, pain, itching, burning, tearing, sensitivity to light, double vision, and decreased vision.[1] Spread of conjunctival SCC can occur in 1-21% of cases, with the first site of spread being the regional lymph nodes.[1] Mortality for conjunctival SCC ranges from 0-8%.[1] Diagnosis is often made by biopsy, as well as CT (in the case of invasive SCC).
Treatment of conjunctival SCC is usually surgical excision followed by cryotherapy.[1] After this procedure, Conjunctival SCC can recur 8-40% of the time.[1] Radiation treatment, topical Mitomycin C, and removal of the contents of the orbit, or exenteration, are other methods of treatment.[1] Close follow-up is recommended, because the average time to recurrence is 8–22 months.[1]
## Contents
* 1 Classification
* 1.1 Terminology
* 2 Signs and symptoms
* 3 Causes
* 4 Diagnosis
* 5 Management
* 6 In animals
* 7 References
* 8 External links
## Classification[edit]
Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous cell carcinomas comprising one of the largest subsets.[2][3][4]
### Terminology[edit]
All squamous cell carcinoma lesions are thought to begin via the repeated, uncontrolled division of cancer stem cells of epithelial lineage or characteristics. Accumulation of these cancer cells causes a microscopic focus of abnormal cells that are, at least initially, locally confined within the specific tissue in which the progenitor cell resided. This condition is called squamous cell carcinoma in situ, and it is diagnosed when the tumor has not yet penetrated the basement membrane or other delimiting structure to invade adjacent tissues. Once the lesion has grown and progressed to the point where it has breached, penetrated, and infiltrated adjacent structures, it is referred to as "invasive" squamous cell carcinoma. Once a carcinoma becomes invasive, it is able to spread to other organs and cause a metastasis, or "secondary tumor", to form.[citation needed]
## Signs and symptoms[edit]
This section is empty. You can help by adding to it. (March 2013)
## Causes[edit]
Human papilloma virus
## Diagnosis[edit]
The differential for OSSN includes pterygium, pingueculum, papilloma, solar keratosis, lipoma, lymphoma, chronic blepharoconjunctivitis, inflammation, melanoma, ocular pannus, pyogenic granuloma, kaposi sarcoma, keratocanthoma, mucoepidermoid carcinoma, pseudoepitheliomatous hyperplasia, and adenocarcinoma.[5] While confocal microscopy can be used for diagnosis, biopsy is considered the standard, especially before treatment with a cytotoxic medication.[5]
## Management[edit]
Most conjunctival squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas.[citation needed]
## In animals[edit]
Squamous cell carcinoma of eye tissues is one of the most frequent neoplasms of cattle.[6]
* On third eyelid, papilloma-like (see hairs)
* invading conjunctival tissues
## References[edit]
1. ^ a b c d e f g h Mehta, M; Fay, A (Winter 2009). "Squamous cell carcinoma of the eyelid and conjunctiva". International Ophthalmology Clinics. 49 (1): 111–21. doi:10.1097/iio.0b013e3181928fb9. PMID 19125070.
2. ^ Berman JJ (November 2004). "Tumor taxonomy for the developmental lineage classification of neoplasms". BMC Cancer. 4: 88. doi:10.1186/1471-2407-4-88. PMC 535937. PMID 15571625.
3. ^ Berman JJ (March 2004). "Tumor classification: molecular analysis meets Aristotle". BMC Cancer. 4: 10. doi:10.1186/1471-2407-4-10. PMC 415552. PMID 15113444.
4. ^ Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; et al., eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 92-832-2418-3. Archived from the original (PDF) on 23 August 2009. Retrieved 27 March 2010.
5. ^ a b ISSN 0020-8167
6. ^ "Ocular Neoplasia in Cattle - Eye Diseases and Disorders".
## External links[edit]
Classification
D
* ICD-9-CM: 190.3
* ICD-O: M/
* v
* t
* e
Diseases of the skin and appendages by morphology
Growths
Epidermal
* Wart
* Callus
* Seborrheic keratosis
* Acrochordon
* Molluscum contagiosum
* Actinic keratosis
* Squamous-cell carcinoma
* Basal-cell carcinoma
* Merkel-cell carcinoma
* Nevus sebaceous
* Trichoepithelioma
Pigmented
* Freckles
* Lentigo
* Melasma
* Nevus
* Melanoma
Dermal and
subcutaneous
* Epidermal inclusion cyst
* Hemangioma
* Dermatofibroma (benign fibrous histiocytoma)
* Keloid
* Lipoma
* Neurofibroma
* Xanthoma
* Kaposi's sarcoma
* Infantile digital fibromatosis
* Granular cell tumor
* Leiomyoma
* Lymphangioma circumscriptum
* Myxoid cyst
Rashes
With
epidermal
involvement
Eczematous
* Contact dermatitis
* Atopic dermatitis
* Seborrheic dermatitis
* Stasis dermatitis
* Lichen simplex chronicus
* Darier's disease
* Glucagonoma syndrome
* Langerhans cell histiocytosis
* Lichen sclerosus
* Pemphigus foliaceus
* Wiskott–Aldrich syndrome
* Zinc deficiency
Scaling
* Psoriasis
* Tinea (Corporis
* Cruris
* Pedis
* Manuum
* Faciei)
* Pityriasis rosea
* Secondary syphilis
* Mycosis fungoides
* Systemic lupus erythematosus
* Pityriasis rubra pilaris
* Parapsoriasis
* Ichthyosis
Blistering
* Herpes simplex
* Herpes zoster
* Varicella
* Bullous impetigo
* Acute contact dermatitis
* Pemphigus vulgaris
* Bullous pemphigoid
* Dermatitis herpetiformis
* Porphyria cutanea tarda
* Epidermolysis bullosa simplex
Papular
* Scabies
* Insect bite reactions
* Lichen planus
* Miliaria
* Keratosis pilaris
* Lichen spinulosus
* Transient acantholytic dermatosis
* Lichen nitidus
* Pityriasis lichenoides et varioliformis acuta
Pustular
* Acne vulgaris
* Acne rosacea
* Folliculitis
* Impetigo
* Candidiasis
* Gonococcemia
* Dermatophyte
* Coccidioidomycosis
* Subcorneal pustular dermatosis
Hypopigmented
* Tinea versicolor
* Vitiligo
* Pityriasis alba
* Postinflammatory hyperpigmentation
* Tuberous sclerosis
* Idiopathic guttate hypomelanosis
* Leprosy
* Hypopigmented mycosis fungoides
Without
epidermal
involvement
Red
Blanchable
Erythema
Generalized
* Drug eruptions
* Viral exanthems
* Toxic erythema
* Systemic lupus erythematosus
Localized
* Cellulitis
* Abscess
* Boil
* Erythema nodosum
* Carcinoid syndrome
* Fixed drug eruption
Specialized
* Urticaria
* Erythema (Multiforme
* Migrans
* Gyratum repens
* Annulare centrifugum
* Ab igne)
Nonblanchable
Purpura
Macular
* Thrombocytopenic purpura
* Actinic/solar purpura
Papular
* Disseminated intravascular coagulation
* Vasculitis
Indurated
* Scleroderma/morphea
* Granuloma annulare
* Lichen sclerosis et atrophicus
* Necrobiosis lipoidica
Miscellaneous
disorders
Ulcers
*
Hair
* Telogen effluvium
* Androgenic alopecia
* Alopecia areata
* Systemic lupus erythematosus
* Tinea capitis
* Loose anagen syndrome
* Lichen planopilaris
* Folliculitis decalvans
* Acne keloidalis nuchae
Nail
* Onychomycosis
* Psoriasis
* Paronychia
* Ingrown nail
Mucous
membrane
* Aphthous stomatitis
* Oral candidiasis
* Lichen planus
* Leukoplakia
* Pemphigus vulgaris
* Mucous membrane pemphigoid
* Cicatricial pemphigoid
* Herpesvirus
* Coxsackievirus
* Syphilis
* Systemic histoplasmosis
* Squamous-cell carcinoma
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
* v
* t
* e
Skin cancer of the epidermis
Tumor
Carcinoma
BCC
* Forms
* Aberrant
* Cicatricial
* Cystic
* Fibroepithelioma of Pinkus
* Infltrative
* Micronodular
* Nodular
* Pigmented
* Polypoid
* Pore-like
* Rodent ulcer
* Superficial
* Nevoid basal cell carcinoma syndrome
SCC
* Forms
* Adenoid
* Basaloid
* Clear cell
* Signet-ring-cell
* Spindle-cell
* Marjolin's ulcer
* Bowen's disease
* Bowenoid papulosis
* Erythroplasia of Queyrat
* Actinic keratosis
Adenocarcinoma
* Aggressive digital papillary adenocarcinoma
* Extramammary Paget's disease
Ungrouped
* Merkel cell carcinoma
* Microcystic adnexal carcinoma
* Mucinous carcinoma
* Primary cutaneous adenoid cystic carcinoma
* Verrucous carcinoma
* Malignant mixed tumor
Benign
tumors
Acanthoma
* Forms
* Large cell
* Fissuring
* Clear cell
* Epidermolytic
* Melanoacanthoma
* Pilar sheath acanthoma
* Seboacanthoma
* Seborrheic keratosis
* Warty dyskeratoma
Keratoacanthoma
* Generalized eruptive
* Keratoacanthoma centrifugum marginatum
* Multiple
* Solitary
Wart
* Verruca vulgaris
* Verruca plana
* Plantar wart
* Periungual wart
Other
Epidermal nevus
* Syndromes
* Epidermal nevus syndrome
* Schimmelpenning syndrome
* Nevus comedonicus syndrome
* Nevus comedonicus
* Inflammatory linear verrucous epidermal nevus
* Linear verrucous epidermal nevus
* Pigmented hairy epidermal nevus syndrome
* Systematized epidermal nevus
* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
* v
* t
* e
Cancer involving the respiratory tract
Upper RT
Nasal cavity
Esthesioneuroblastoma
Nasopharynx
Nasopharyngeal carcinoma
Nasopharyngeal angiofibroma
Larynx
Laryngeal cancer
Laryngeal papillomatosis
Lower RT
Trachea
* Tracheal tumor
Lung
Non-small-cell lung carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma (Mucinous cystadenocarcinoma)
* Large-cell lung carcinoma
* Rhabdoid carcinoma
* Sarcomatoid carcinoma
* Carcinoid
* Salivary gland–like carcinoma
* Adenosquamous carcinoma
* Papillary adenocarcinoma
* Giant-cell carcinoma
Small-cell carcinoma
* Combined small-cell carcinoma
Non-carcinoma
* Sarcoma
* Lymphoma
* Immature teratoma
* Melanoma
By location
* Pancoast tumor
* Solitary pulmonary nodule
* Central lung
* Peripheral lung
* Bronchial leiomyoma
Pleura
* Mesothelioma
* Malignant solitary fibrous tumor
* v
* t
* e
Tumors of the female urogenital system
Adnexa
Ovaries
Glandular and epithelial/
surface epithelial-
stromal tumor
CMS:
* Ovarian serous cystadenoma
* Mucinous cystadenoma
* Cystadenocarcinoma
* Papillary serous cystadenocarcinoma
* Krukenberg tumor
* Endometrioid tumor
* Clear-cell ovarian carcinoma
* Brenner tumour
Sex cord–gonadal stromal
* Leydig cell tumour
* Sertoli cell tumour
* Sertoli–Leydig cell tumour
* Thecoma
* Granulosa cell tumour
* Luteoma
* Sex cord tumour with annular tubules
Germ cell
* Dysgerminoma
* Nongerminomatous
* Embryonal carcinoma
* Endodermal sinus tumor
* Gonadoblastoma
* Teratoma/Struma ovarii
* Choriocarcinoma
Fibroma
* Meigs' syndrome
Fallopian tube
* Adenomatoid tumor
Uterus
Myometrium
* Uterine fibroids/leiomyoma
* Leiomyosarcoma
* Adenomyoma
Endometrium
* Endometrioid tumor
* Uterine papillary serous carcinoma
* Endometrial intraepithelial neoplasia
* Uterine clear-cell carcinoma
Cervix
* Cervical intraepithelial neoplasia
* Clear-cell carcinoma
* SCC
* Glassy cell carcinoma
* Villoglandular adenocarcinoma
Placenta
* Choriocarcinoma
* Gestational trophoblastic disease
General
* Uterine sarcoma
* Mixed Müllerian tumor
Vagina
* Squamous-cell carcinoma of the vagina
* Botryoid rhabdomyosarcoma
* Clear-cell adenocarcinoma of the vagina
* Vaginal intraepithelial neoplasia
* Vaginal cysts
Vulva
* SCC
* Melanoma
* Papillary hidradenoma
* Extramammary Paget's disease
* Vulvar intraepithelial neoplasia
* Bartholin gland carcinoma
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Conjunctival squamous cell carcinoma
|
c0346359
| 27,586 |
wikipedia
|
https://en.wikipedia.org/wiki/Conjunctival_squamous_cell_carcinoma
| 2021-01-18T19:00:34 |
{"umls": ["C0346359"], "wikidata": ["Q18554890"]}
|
A rare predominantly pure hereditary spastic paraplegia characterized by juvenile or adult onset of slowly progressive spastic paraparesis, gait disturbances, and increased tendon reflexes. Additional variable manifestations include pes cavus, dysarthria, sensory impairment, and urinary symptoms. Cognition is normal.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Autosomal dominant spastic paraplegia type 9B
|
None
| 27,587 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=447757
| 2021-01-23T18:17:00 |
{"icd-10": ["G11.4"], "synonyms": ["AD-SPG9B"]}
|
Hyperdynamic precordium
Other namesHyperdynamic apex
Hyperdynamic precordium is a condition where the precordium (the area of the chest over the heart) moves too much (is hyper dynamic) due to some pathology of the heart. This problem can be hypertrophy of the ventricles, tachycardia, or some other heart problem.[1]
Hyperdynamic precordium can also be due to hyperthyroidism, and thus indicates an increased cardiac contractility, with systolic hypertension. It may also be due to aortic coarctation, and most other congenital heart malformations.
Palpation of the chest wall can be done to assess volume changes within the heart. A hyperdynamic precordium reflects a large volume change.[2]
## References[edit]
1. ^ Sibarjun Ghosh. bedside clinics in paediatrics. Academic Publishers. p. 137. ISBN 978-81-89781-85-9.
2. ^ Lynn Bickley; Peter G. Szilagyi (1 November 2012). Bates' Guide to Physical Examination and History-Taking. Lippincott Williams & Wilkins. pp. 801. ISBN 978-1-60913-762-5.
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Hyperdynamic precordium
|
c1142035
| 27,588 |
wikipedia
|
https://en.wikipedia.org/wiki/Hyperdynamic_precordium
| 2021-01-18T18:56:34 |
{"umls": ["C1142035"], "wikidata": ["Q5957960"]}
|
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-31 (MRD31) is caused by heterozygous mutation in the PURA gene (600473) on chromosome 5q31.
Clinical Features
Lalani et al. (2014) reported 11 unrelated children with a similar neurodevelopmental disorder characterized by neonatal hypotonia, severely delayed psychomotor development, early-onset feeding difficulties, and significant respiratory insufficiency. Almost all had early-onset seizures, often myoclonic, but also generalized. Most had an abnormal EEG pattern, and 2 developed an epileptic encephalopathy consistent with a clinical diagnosis of Lennox-Gastaut syndrome. Hypomyelination or delayed myelination was noted on brain imaging studies in 4 individuals. Most patients were nonverbal and nonambulatory. Dysmorphic facial features were variable and nonspecific except for myopathic facies, often with open mouth and high-arched palate, nystagmus, and strabismus in many patients. Lalani et al. (2014) noted the phenotypic overlap with chromosome 5q31.3 microdeletion syndrome (Brown et al., 2013).
Hunt et al. (2014) reported 4 unrelated girls with neurodevelopmental delay. Two patients were severely affected, with hypotonia and apneic episodes at birth and severely delayed psychomotor development; neither could walk at ages 4 and 6 years, respectively, and both were essentially nonverbal. Both patients also had dysconjugate gaze and either seizures or seizure-like episodes. Brain MRI of both patients showed delayed myelination. The other 2 girls, 12 and 14 years of age, were able to walk with a broad-based gait and could speak with limited vocabulary. One was hypotonic and had seizure-like episodes. Brain imaging was normal in these 2 patients. All patients had mild but variable dysmorphic features, including hypotonic facies, prominent or high forehead, telecanthus, and upslanting palpebral fissures. One girl had gonadotropin-dependent precocious puberty and another had elevated prolactin levels soon after birth as well as blunted cortisol response to stress, suggesting that endocrine abnormalities may be part of the disorder.
The Deciphering Developmental Disorders Study (2015) reported 3 female patients with global developmental delay and various syndromic features who carried heterozygous de novo mutations in the PURA gene. One additionally had generalized hypotonia, cafe-au-lait spot, and unsteady gait; the second had delayed CNS myelination, epicanthus, short nose, deep philtrum, and edema; and the third had microcephaly, facial asymmetry, strabismus, hypertelorism, bilateral ptosis, overlapping toe, and anxiety.
Tanaka et al. (2015) reported 6 unrelated children, ranging from 6 months to 15 years of age, with moderate to severely delayed psychomotor development, lack of speech, and hypotonia. Two patients had seizure-like activity, and 5 had variable visual impairment, mainly esotropia and strabismus, although 1 had cortical visual impairment. Four patients had variable dysmorphic features, such as epicanthal folds, high-arched palate, dolichocephaly, hypertelorism, and broad forehead. Four had variable brain imaging abnormalities, including delayed myelination, enlarged ventricles, thin corpus callosum, and periventricular white matter changes.
Cytogenetics
Brown et al. (2013) reported 2 unrelated children with a severe neurodevelopmental disorder associated with de novo heterozygous deletions of chromosome 5q31.3. Both patients presented at birth with significant hypotonia, central apnea, and myoclonic jerks. One child was conceived by in vitro fertilization. One child was nonverbal and nonambulatory at 6 years of age, whereas the other was standing with support and able to indicate needs with gestures at age 2, both consistent with delayed psychomotor development. Brain imaging in both patients showed diffuse T2-weighted white matter lesions and shallow immature sulcation in the frontal lobes, with evidence of delayed myelination in 1 patient who underwent serial imaging. The shortest region of deletion overlap in these patients was 101 kb, including the PURA gene, which Brown et al. (2013) considered to be the best candidate for the phenotype.
Molecular Genetics
Lalani et al. (2014) identified de novo heterozygous mutations in the PURA gene (see, e.g., 600473.0001-600473.0005) in 11 (0.52%) of 2,117 pediatric patients with various neurodevelopmental disorders who underwent whole-exome sequencing. There were 4 truncating mutations, 5 missense mutations, and 2 in-frame deletions. Functional studies of the variants were not performed, but the presence of truncating mutations suggested at least a partial loss of protein function as responsible for the phenotype.
In 4 unrelated girls with MRD31, Hunt et al. (2014) identified 4 different de novo heterozygous mutations in the PURA gene (see, e.g., 600473.0006-600473.0008). Two mutations were truncating frameshifts, 1 was missense, and 1 was an in-frame deletion. The mutations were found by whole-exome sequencing; functional studies of the variants were not performed.
In 6 unrelated children with MRD31, Tanaka et al. (2015) identified 6 different de novo heterozygous mutations in the PURA gene (see, e.g., 600473.0008-600473.0010). The mutations, which were found by whole-exome sequencing, comprised missense, frameshift, and small intragenic deletions. Functional studies of the variants were not performed.
Animal Model
Khalili et al. (2003) found that Pura -/- mice appeared normal at birth, but at 2 weeks of age, they developed neurologic problems characterized by severe tremor and spontaneous seizures, and they died by 4 weeks. Regions of the hippocampus and cerebellum of Pura -/- mice showed severely lower numbers of neurons compared with wildtype littermates, and lamination of these regions was aberrant at time of death. Immunohistochemical analysis of Mcm7 (600592), a marker for DNA replication, revealed lack of proliferation of precursor cells in these regions in Pura -/- mice. Proliferation was also low or absent in several other tissues of Pura -/- mice, including those of myeloid lineage, whereas those of Pura +/- mice were intermediate. Evaluation of brain sections indicated reduced myelination and pathologic development of oligodendrocytes and astrocytes. At postnatal day 5, a critical time for cerebellar development, Pura and Cdk5 (123831) were both at peak levels in bodies and dendrites of Purkinje cells of wildtype mice, but both proteins were absent in dendrites of Pura -/- mice. Immunohistochemical analysis revealed dramatic reduction in both phosphorylated and nonphosphorylated neurofilaments in dendrites of the Purkinje cell layer and of synapse formation in the hippocampus. Khalili et al. (2003) concluded that PURA has a role in developmentally timed DNA replication in specific cell types.
Lalani et al. (2014) found that mutant Caenorhabditis elegans animals homozygous for a null allele of the PURA ortholog plp-1 were sterile and had defective locomotion compared to wildtype, suggesting a role for PURA in both germline and somatic neuronal tissues.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Myopathic facies \- Prominent forehead Eyes \- Nystagmus \- Strabismus \- Telecanthus (in some patients) Mouth \- Open mouth \- High-arched palate RESPIRATORY \- Respiratory insufficiency ABDOMEN Gastrointestinal \- Feeding difficulties MUSCLE, SOFT TISSUES \- Hypotonia, neonatal NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Poor or absent speech \- Lack of independent ambulation (in some patients) \- Broad-based gait (in some patients) \- Seizures \- Myoclonic jerks \- Hypomyelination \- Delayed myelination ENDOCRINE FEATURES \- Gonadotropin-dependent precocious puberty (1 patient) MISCELLANEOUS \- Onset at birth or early infancy \- Variable severity \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the purine-rich element-binding protein A gene (PURA, 600473.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
MENTAL RETARDATION, AUTOSOMAL DOMINANT 31
|
c4015357
| 27,589 |
omim
|
https://www.omim.org/entry/616158
| 2019-09-22T15:49:45 |
{"doid": ["0070061"], "omim": ["616158"], "orphanet": ["438216", "438213"], "synonyms": [], "genereviews": ["NBK426063"]}
|
Pontocerebellar hypoplasia is a group of related conditions that affect the development of the brain. The term "pontocerebellar" refers to the pons and the cerebellum, which are the brain structures that are most severely affected in many forms of this disorder. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals between the cerebellum and the rest of the brain. The cerebellum, which is located at the back of the brain, normally coordinates movement. The term "hypoplasia" refers to the underdevelopment of these brain regions.
Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size (microcephaly). This microcephaly is usually not apparent at birth but becomes noticeable as brain growth continues to be slow in infancy and early childhood.
Researchers have described at least ten types of pontocerebellar hypoplasia. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.
The two major forms of pontocerebellar hypoplasia are designated as type 1 (PCH1) and type 2 (PCH2). In addition to the brain abnormalities described above, PCH1 causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord, similar to another genetic disorder known as spinal muscular atrophy. Individuals with PCH1 also have very weak muscle tone (hypotonia), joint deformities called contractures, vision impairment, and breathing and feeding problems that are evident from early infancy.
Common features of PCH2 include a lack of voluntary motor skills (such as grasping objects, sitting, or walking), problems with swallowing (dysphagia), and an absence of communication, including speech. Affected children typically develop temporary jitteriness (generalized clonus) in early infancy, abnormal patterns of movement described as chorea or dystonia, and stiffness (spasticity). Many also have impaired vision and seizures.
The other forms of pontocerebellar hypoplasia, designated as type 3 (PCH3) through type 10 (PCH10), appear to be rare and have each been reported in only a small number of individuals. Because the different types have overlapping features, and some are caused by mutations in the same genes, researchers have proposed that the types be considered as a spectrum instead of distinct conditions.
## Frequency
The prevalence of pontocerebellar hypoplasia is unknown, although most forms of the disorder appear to be very rare.
## Causes
Pontocerebellar hypoplasia can result from mutations in several genes. About half of all cases of PCH1 are caused by mutations in the EXOSC3 gene. PCH1 can also result from mutations in several other genes, including TSEN54, RARS2, and VRK1. PCH2 is caused by mutations in the TSEN54, TSEN2, TSEN34, or SEPSECS gene. In addition to causing PCH1 and PCH2, mutations in the TSEN54 gene can cause PCH4 and PCH5. Mutations in the RARS2 gene, in addition to causing PCH1, can result in PCH6. The remaining types of pontocerebellar hypoplasia are caused by mutations in other genes. In some cases, the genetic cause of pontocerebellar hypoplasia is unknown.
The genes associated with pontocerebellar hypoplasia appear to play essential roles in the development and survival of nerve cells (neurons). Many of these genes are known or suspected to be involved in processing RNA molecules, which are chemical cousins of DNA. Fully processed, mature RNA molecules are essential for the normal functioning of all cells, including neurons. Studies suggest that abnormal RNA processing likely underlies the abnormal brain development characteristic of pontocerebellar hypoplasia, although the exact mechanism is unknown. Researchers hypothesize that developing neurons in certain areas of the brain may be particularly sensitive to problems with RNA processing.
Some of the genes associated with pontocerebellar hypoplasia have functions unrelated to RNA processing. In most cases, it is unclear how mutations in these genes impair brain development.
### Learn more about the genes associated with Pontocerebellar hypoplasia
* EXOSC3
* RARS2
* SEPSECS
* TSEN2
* TSEN34
* TSEN54
* VRK1
Additional Information from NCBI Gene:
* AMPD2
* CHMP1A
* CLP1
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Pontocerebellar hypoplasia
|
c4014347
| 27,590 |
medlineplus
|
https://medlineplus.gov/genetics/condition/pontocerebellar-hypoplasia/
| 2021-01-27T08:24:58 |
{"gard": ["10977"], "omim": ["615803", "607596", "614678", "277470", "612389", "612390", "613811", "615851", "608027", "225753", "610204", "611523", "614969", "614961", "615809"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that type Ib glycogen storage disease (GSD1B) is caused by homozygous or compound heterozygous mutation in the G6PT1 gene (SLC37A4; 602671), which encodes glucose-6-phosphate translocase, on chromosome 11q23.
Senior and Loridan (1968) proposed the existence of a second type of von Gierke disease in which, although glucose-6-phosphatase (G6PC; 613742) activity is present on in vitro assay, glucose is not liberated from glucose-6-phosphate in vivo. They referred to this as 'functional deficiency of G6P.' They pointed out that some mutants in Neurospora show impaired enzyme function in the intact fungus despite normal activity in homogenates.
Arion et al. (1975) concluded that G6Pase activity requires 2 components of the microsomal membrane: (1) a glucose-6-phosphate specific transport system that shuttles G6P from the cytoplasm to the lumen of the endoplasmic reticulum (a G6P translocase), and (2) an enzyme, glucose-6-phosphate phosphohydrolase, bound to the luminal surface of the membrane.
Narisawa et al. (1978) described a patient who appeared to have a defect in the transport system. In liver without detergent, enzyme activity was very low but normal activity was obtained by addition of detergent. Kuzuya et al. (1983) reported a 25-year-old patient. Protuberant abdomen and diarrhea were noted at age 1 or 2 years, and short stature and hepatomegaly at age 4 years. At age 18, yellowish-red spots appeared on her legs and hypertension was detected. At age 20, she was 138 cm tall. Eruptive xanthoma and hyperlipidemia were present. Liver scintigraphy suggested the presence of adenomas.
Recurrent infections and neutropenia have been recognized as distinctive features of GSD Ib. Corbeel et al. (1983) provided a 6-year follow-up on the hematologic effects of termino-lateral portacaval anastomosis. Granulocyte counts returned to normal and recurrent infections ceased after the shunt. Platelet dysfunction, evident before surgery, was also corrected. Marked hypochromic anemia, probably caused by sequestration of iron in the spleen and resistant to therapy, was a persistent feature in this patient. The mechanism of the granulocyte defect in this disorder was discussed. Roe et al. (1986) observed Crohn disease in 2 unrelated boys with GSD Ib. Their neutrophils showed severe chronic neutropenia and markedly deficient chemotactic response, whereas the leukocytes were normal in 4 patients with GSD Ia (232200). Thus, chronic inflammatory bowel disease (IBD; see 266600) appears to be an integral part of GSD Ib and the abnormality of leukocytes is probably involved in the pathogenesis of the IBD. Oral lesions and perianal abscesses are common in this disorder (Ambruso et al., 1985). Ueno et al. (1986) found that neutrophils were defective in both motility and respiratory burst, whereas monocytes showed a defect only in respiratory burst. Bashan et al. (1988) showed that the rate of 2-deoxyglucose transport into GSD Ib polymorphonuclear leukocytes was 30% of that into cells of normal controls. Transport was normal in GSD Ib lymphocytes and in GSD Ia polymorphonuclear leukocytes and lymphocytes. The striking limitation of glucose transport across the cell membrane of polymorphonuclear leukocytes probably accounts for the impairment of leukocyte function that is characteristic of GSD Ib but not GSD Ia. Schroten et al. (1991) used granulocyte colony-stimulating factor (CSF3; 138970) to treat successfully the neutropenia in 2 patients with GSD Ib associated with recurrent bacterial infections. Roe et al. (1992) administered granulocyte-macrophage colony stimulating factor (CSF2; 138960) to the 2 adolescent boys whom they had reported in 1986 (Roe et al., 1986). They observed a prompt increase in neutrophil counts to normal, complete relief from abdominal symptoms, and an increase in appetite, energy, and weight, and a feeling of well being. There was radiologic evidence of bowel healing and a decrease in the erythrocyte sedimentation rate. Both patients remained free of oral and anal lesions over a period of 10 and 12 months of treatment. One patient was switched to G-CSF (CSF3) because of a presumed allergic reaction to GM-CSF. In a multicenter study in the United States and Canada, Talente et al. (1994) identified 5 patients with GSD type Ib who were 18 years of age or older. Severe recurrent bacterial infections and gingivitis were present. One patient, a 22-year-old college student, was described in detail. She had severe recurrent stomatitis, recurrent otitis media and externa, perianal and perirectal abscesses, and, at the age of 12 years, 2 brain abscesses due to Staphylococcus aureus. At 18 years of age, she was as tall as an 8-year-old and had not undergone any pubertal changes.
In a patient with GSD Ib, Heyne and Henke-Wolter (1989) found a change in the oligosaccharide side chains of the alpha-1-antitrypsin (107400) glycoprotein suggesting effects of the limited availability of glucose or glucose derivatives for the synthesis of N-glycosidic glycoproteins. Kikuchi et al. (1990) found secondary amyloidosis in a 12-year-old girl with GSD Ib.
In 14 children (aged 4 to 16 years) with GSD Ia and GSD Ib, Lee et al. (1996) found that the use of uncooked cornstarch loads resulted in satisfactory glycemia lasting only a median of 4.25 hours (range 2.5 to 6).
In studies of 5 patients with GSD Ib, Kuijpers et al. (2003) found neutrophils in the circulation that showed signs of apoptosis with increased caspase activity, condensed nuclei, and perinuclear clustering of mitochondria to which the proapoptotic BCL2 member BAX (600040) had translocated already. Granulocyte colony-stimulating factor (GCSF; 138970) added to in vitro cultures did not rescue the GSD Ib neutrophils from apoptosis as occurred with GCSF-treated control neutrophils. Moreover, the 2 GSD Ib patients on GCSF treatment did not show significantly lower levels of apoptotic neutrophils in the bloodstream. Kuijpers et al. (2003) studied neutrophils from children with infections (active pneumonia or septicemia) or with other neutropenic syndromes (Shwachman-Diamond syndrome; 260400), but to date had not observed circulating apoptotic neutrophils in these patients.
Annabi et al. (1998) reported linkage of the GSD Ib locus to genetic markers spanning a 3-cM region on 11q23. The region is located between D11S939 centromerically and D11S4129 telomerically and includes the IL10R (146933), ATP1G1 (601814), and ALL1 (159555) genes. The authors studied 8 consanguineous families and 1 nonconsanguineous family of various ethnic origins. The assignment to chromosome 11 was confirmed by Kure et al. (1998), who showed that the translocase gene that is mutated in this disorder maps to chromosome 11 by study of somatic cell hybrids.
In 2 female patients with GSD Ib, Gerin et al. (1997) found 2 point mutations in the glucose-6-phosphate translocase gene (602671.0001 and 602671.0002). Kure et al. (1998) identified 3 additional mutations, one of which, W118R (602671.0003), may be unusually frequent among Japanese patients with GSD Ib.
Kure et al. (2000) proposed that GSD Ib without neutropenia could be due to glucose-6-phosphate translocase mutations with residual transporter activity based on finding biallelic mutations with normal liver microsomal GTPase activity in 2 Japanese patients; see 602671.0015 and 602671.0016.
Chou and Mansfield (1999) reviewed the molecular genetics of type I glycogen storage diseases.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Delayed puberty HEAD & NECK Face \- 'Doll-like' facies Eyes \- Lipemia retinalis Mouth \- Oral ulcers CARDIOVASCULAR Vascular \- Hypertension ABDOMEN External Features \- Protuberant abdomen Liver \- Hepatomegaly \- Liveradenomas \- Hepatocellular carcinoma Pancreas \- Pancreatitis Gastrointestinal \- Chronic inflammatory bowel disease (IBD) \- Intestinal mucosal ulceration GENITOURINARY Kidneys \- Reduced creatinine clearance \- Focal segmental glomerulosclerosis \- Renal stones \- Renal enlargement SKELETAL \- Osteoporosis \- Gouty arthritis SKIN, NAILS, & HAIR Skin \- Xanthoma HEMATOLOGY \- Neutropenia \- Abnormal leukocyte function LABORATORY ABNORMALITIES \- T1 transport protein (Glucose-6-phosphate translocase) defect \- Hyperlipidemia \- Hyperuricemia \- Lactic acidosis \- Hypoglycemia \- Proteinuria \- Liver transaminases normal to slightly increased MISCELLANEOUS \- Recurrent bacterial infections MOLECULAR BASIS \- Caused by mutation in the glucose-6-phosphate transporter 1 gene (G6PT1, 602671.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
GLYCOGEN STORAGE DISEASE Ib
|
c2919796
| 27,591 |
omim
|
https://www.omim.org/entry/232220
| 2019-09-22T16:27:27 |
{"doid": ["2749"], "mesh": ["C538655"], "omim": ["232220"], "orphanet": ["364", "79259"], "synonyms": ["Alternative titles", "GSD Ib", "GLUCOSE-6-PHOSPHATE TRANSPORT DEFECT"], "genereviews": ["NBK1312"]}
|
Multidrug-resistance tuberculosis
Mycobacterium tuberculosis bacteria seen by microscope
SpecialtyInfectious disease
Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs), isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).[1]
Tuberculosis is caused by infection with the bacteria Mycobacterium tuberculosis. Almost one in four people in the world are infected with TB bacteria.[1] Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person's immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone).[2]
However, beginning with the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see mechanisms.)[2][3][4] Currently the majority of multidrug-resistant cases of TB are due to one strain of TB bacteria called the Beijing lineage.[5][6] This process accelerates if incorrect or inadequate treatments are used, leading to the development and spread of multidrug-resistant TB (MDR-TB). Incorrect or inadequate treatment may be due to use of the wrong medications, use of only one medication (standard treatment is at least two drugs), not taking medication consistently or for the full treatment period (treatment is required for several months).[7][8][9] Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs.[7] Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over US$100,000.[10] If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB.
Resistant strains of TB are already present in the population, so MDR-TB can be directly transmitted from an infected person to an uninfected person. In this case a previously untreated person develops a new case of MDR-TB. This is known as primary MDR-TB, and is responsible for up to 75% of cases.[11] Acquired MDR-TB develops when a person with a non-resistant strain of TB is treated inadequately, resulting in the development of antibiotic resistance in the TB bacteria infecting them. These people can in turn infect other people with MDR-TB.[4][7]
MDR-TB caused an estimated 600,000 new TB cases and 240,000 deaths in 2016 and MDR-TB accounts for 4.1% of all new TB cases and 19% of previously treated cases worldwide.[12] Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.[13]
Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected.[8] Under ideal program conditions, MDR-TB cure rates can approach 70%.[8]
## Contents
* 1 Mechanism of drug resistance
* 2 Extensively drug-resistant TB
* 3 Prevention
* 3.1 DOTS-Plus
* 4 Treatment
* 5 Epidemiology
* 5.1 Somalia
* 5.2 Russian prisons
* 5.2.1 Contributing factors
* 5.2.2 Policy impacts
* 6 See also
* 7 References
* 8 External links
## Mechanism of drug resistance[edit]
The TB bacteria has natural defenses against some drugs, and can acquire drug resistance through genetic mutations. The bacteria does not have the ability to transfer genes for resistance between organisms through plasmids (see horizontal transfer). Some mechanisms of drug resistance include:[14]
1. Cell wall: The cell wall of M. tuberculosis (TB) contains complex lipid molecules which act as a barrier to stop drugs from entering the cell.
2. Drug modifying & inactivating enzymes: The TB genome codes for enzymes (proteins) that inactivate drug molecules. These enzymes are usually phosphorylate, acetylate, or adenylate drug compounds.
3. Drug efflux systems: The TB cell contains molecular systems that actively pump drug molecules out of the cell.
4. Mutations: Spontaneous mutations in the TB genome can alter proteins which are the target of drugs, making the bacteria drug resistant.[15]
One example is a mutation in the rpoB gene, which encodes the beta subunit of the bacteria's RNA polymerase. In non-resistant TB, rifampin binds the beta subunit of RNA polymerase and disrupt transcription elongation. Mutation in the rpoB gene changes the sequence of amino acids and eventual conformation of the beta subunit. In this case rifampin can no longer bind or prevent transcription, and the bacteria is resistant.
Other mutations make the bacterium resistant to other drugs. For example, there are many mutations that confer resistance to isoniazid (INH), including in the genes katG, inhA, ahpC and others. Amino acid replacements in the NADH binding site of InhA apparently result in INH resistance by preventing the inhibition of mycolic acid biosynthesis, which the bacterium uses in its cell wall. Mutations in the katG gene make the enzyme catalase peroxidase unable to convert INH to its biologically active form. Hence, INH is ineffective and the bacteria is resistant.[16][17] The discovery of new molecular targets is essential to overcome drug resistant problems.[18]
In some TB bacteria, the acquisition of these mutations can be explained other mutations in the DNA recombination, recognition and repair machinery.[19] Mutations in these genes allow the bacteria to have a higher overall mutation rate and to accumulate mutations that cause drug resistance more quickly.[20][21]
## Extensively drug-resistant TB[edit]
Main article: Extensively drug-resistant tuberculosis
MDR-TB can become resistant to the major second-line TB drug groups: fluoroquinolones (moxifloxacin, ofloxacin) and injectable aminoglycoside or polypeptide drugs (amikacin, capreomycin, kanamycin). When MDR-TB is resistant to at least one drug from each group, it is classified as extensively drug-resistant tuberculosis (XDR-TB).[7]
In a study of MDR-TB patients from 2005 to 2008 in various countries, 43.7% had resistance to at least one second-line drug.[22] About 9% of MDR-TB cases are resistant to a drug from both classes and classified as XDR-TB.[1][23]
In the past 10 years TB strains have emerged in Italy, Iran, India, and South Africa which are resistant to all available first and second line TB drugs, classified as totally drug-resistant tuberculosis, though there is some controversy over this term.[24][25][26] Increasing levels of resistance in TB strains threaten to complicate the current global public health approaches to TB control. New drugs are being developed to treat extensively resistant forms but major improvements in detection, diagnosis, and treatment will be needed.[25]
## Prevention[edit]
There are several ways that drug resistance to TB, and drug resistance in general, can be prevented:[27][28]
1. Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided.
2. Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete his/her antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB.
3. Patients with HIV/AIDS should be identified and diagnosed as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance.
4. Identify contacts who could have contracted TB: i.e. family members, people in close contact, etc.
5. Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB.
"Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run."— Paul Farmer [29]
### DOTS-Plus[edit]
Community-based treatment programs such as DOTS-Plus, a MDR-TB-specialized treatment using the popular Directly Observed Therapy – Short Course (DOTS) initiative, have shown considerable success in the world. In these locales, these programs have proven to be a good option for proper treatment of MDR-TB in poor, rural areas. A successful example has been in Lima, Peru, where the program has seen cure rates of over 80%.[30]
However, TB clinicians[who?] have expressed concern in the DOTS program administered in the Republic of Georgia because it is anchored in a passive case finding. This means that the system depends on patients coming to health care providers, without conducting compulsory screenings. As medical anthropologists like Erin Koch have shown, this form of implementation does not suit all cultural structures. They urge that the DOTS protocol be constantly reformed in the context of local practices, forms of knowledge and everyday life.[31]
Erin Koch has used Paul Farmer's concept of "structural" violence as a perspective for understanding how "institutions, environment, poverty, and power reproduce, solidify, and naturalize the uneven distribution of disease and access to resources". She has also studied the effectiveness of the DOTS protocol in the widespread disease of tuberculosis in the Georgian prison system.[32] Unlike the DOTS passive case finding used for the general Georgian public, the multiple-level surveillance in the prison system has proven more successful in reducing the spread of tuberculosis while increasing rates of cure.[citation needed]
Koch critically notes that because the DOTS protocol aims to change the individual's behavior without addressing the need to change the institutional, political, and economic contexts, certain limitations arise, such as MDR tuberculosis.[citation needed]
## Treatment[edit]
See also: Tuberculosis treatment
Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs, but these are more expensive than first-line drugs and have more adverse effects.[33] The treatment and prognosis of MDR-TB are much more akin to those for cancer than to those for infection. MDR-TB has a mortality rate of up to 80%, which depends on a number of factors, including:
1. How many drugs the organism is resistant to (the fewer the better)
2. How many drugs the patient is given (patients treated with five or more drugs do better)
3. The expertise and experience of the physician responsible
4. How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient)
5. Whether the patient is HIV-positive or not (HIV co-infection is associated with an increased mortality).
The majority of patients suffering from multidrug-resistant tuberculosis do not receive treatment, as they are found in underdeveloped countries or in poverty. Denial of treatment remains a difficult human rights issue, as the high cost of second-line medications often precludes those who cannot afford therapy.[34]
A study of cost-effective strategies for tuberculosis control supported three major policies. First, the treatment of smear-positive cases in DOTS programs must be the foundation of any tuberculosis control approach, and should be a basic practice for all control programs. Second, there is a powerful economic case for treating smear-negative and extra-pulmonary cases in DOTS programs along with treating smear-negative and extra-pulmonary cases in DOTS programs as a new WHO "STOP TB" approach and the second global plan for tuberculosis control. Last, but not least, the study shows that significant scaling up of all interventions is needed in the next 10 years if the millennium development goal and related goals for tuberculosis control are to be achieved. If the case detection rate can be improved, this will guarantee that people who gain access to treatment facilities are covered and that coverage is widely distributed to people who do not now have access.[35]
In general, treatment courses are measured in months to years; MDR-TB may require surgery, and death rates remain high despite optimal treatment. However, good outcomes for patients are still possible.[36]
The treatment of MDR-TB must be undertaken by physicians experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantly higher to those of patients treated in specialist centers. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. When treating a patient with suspected MDR-TB, pending the result of laboratory sensitivity testing, the patient could be started on SHREZ (Streptomycin\+ isonicotinyl Hydrazine\+ Rifampicin+Ethambutol\+ pyraZinamide) and moxifloxacin with cycloserine. There is evidence that previous therapy with a drug for more than a month is associated with diminished efficacy of that drug regardless of in vitro tests indicating susceptibility.[37] Hence, a detailed knowledge of the treatment history of each patient is essential. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment.
A gene probe for rpoB is available in some countries. This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe (rpoB) are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance).
For treatment of RR- and MDT-TB, WHO treatment guidelines are as follows: "a regimen with at least five effective TB medicines during the intensive phase is recommended, including pyrazinamide and four core second-line TB medicines – one chosen from Group A, one from Group B, and at least two from Group C3 (conditional recommendation, very low certainty in the evidence). If the minimum number of effective TB medicines cannot be composed as given above, an agent from Group D2 and other agents from Group D3 may be added to bring the total to five. It is recommended that the regimen be further strengthened with high-dose isoniazid and/or ethambutol (conditional recommendation, very low certainty in the evidence)." [38] Medicines recommended are the following:
* Group A: Fluoroquinolones (levofloxacin moxifloxicin, gatifloxacin), linezolid, bedaquiline
* Group B: clofazimine, cycloserine/terizidone
* Group C: Other core second-line agents (ethambutol, delamanid, pyrazinamide, imipenem-cilastatin/meropenem, amikacin/streptomycin, ethionamide/prothionamide, p-aminosalicylic acid)
For patients with RR-TB or MDR-TB, "not previously treated with second-line drugs and in whom resistance to fluoroquinolones and second-line injectable agents was excluded or is considered highly unlikely, a shorter MDR-TB regimen of 9–12 months may be used instead of the longer regimens (conditional recommendation, very low certainty in the evidence)." [39]
In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2 mg/l INH, but sensitive at 1.0 mg/l INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available. As of 2008, Cochrane reports that trials of other fluoroquinolones are ongoing.[40]
There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.[41]
Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more.[citation needed]
Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients remain isolated until their sputum is smear-negative, or even culture-negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility, and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (in particular, of the aminoglycosides) both to monitor compliance and to avoid toxic effects.
Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for the purposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will be needed to make five). Supplements are: arginine[42] (peanuts are a good source), vitamin D,[43] Dzherelo,[44] V5 Immunitor.[45]
The drugs listed below have been used in desperation, and it is uncertain as to whether they are effective at all. They are used when it is not possible to find five drugs from the list above. imipenem,[46] co-amoxiclav,[47][48] clofazimine,[49][50][51] prochlorperazine,[52] metronidazole.[53]
On 28 December 2012, the U.S. Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multidrug-resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.[54][55]
The following drugs are experimental compounds that are not commercially available, but may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown: pretomanid[56] (manufactured by Novartis, developed in partnership with TB Alliance),[57] and delamanid.
In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. The center with the largest experience in this is the National Jewish Medical and Research Center in Denver, Colorado. In 17 years of experience, they have performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who were culture-positive before surgery, only 4 were culture-positive after surgery.
The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades—serve to reinforce the thesis that Mycobacterium tuberculosis, the causative organism, makes its own preferential option for the poor.[58] The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.[59]
Treatment success rates remain unacceptably low globally with variation between regions. 2016 data published by the WHO[60] reported treatment success rates of multidrug-resistant TB globally. For those started on treatment for multidrug-resistant TB 56% successfully completed treatment, either treatment course completion or eradication of disease; 15% of those died while in treatment; 15% were lost to follow-up; 8% had treatment failure and there was no data on the remaining 6%. Treatment success rate was highest in the World Health Organization Mediterranean region at 65%. Treatment success rates were lower than 50% in the Ukraine, Mozambique, Indonesia and India. Areas with poor TB surveillance infrastructure had higher rates of loss to follow-up of treatment.[61]
57 countries reported outcomes for patients started on extreme-drug resistant Tuberculosis, this included 9258 patients. 39% completed treatment successfully, 26% of patients died and treatment failed for 18%. 84% of the extreme Drug resistant Cohort was made up of only three countries; India, Russian Federation and Ukraine. Shorter treatment regimes for MDR-TB have been found to be beneficial having higher treatment success rates.[62]
## Epidemiology[edit]
Cases of MDR tuberculosis have been reported in every country surveyed.[34] MDR-TB most commonly develops in the course of TB treatment,[4] and is most commonly due to doctors giving inappropriate treatment, or patients missing doses or failing to complete their treatment. Because MDR tuberculosis is an airborne pathogen, persons with active, pulmonary tuberculosis caused by a multidrug-resistant strain can transmit the disease if they are alive and coughing.[34] TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with HIV).[63][64][65][66][67] Outbreaks among non immunocompromised healthy people do occur,[68] but are less common.[4]
As of 2013, 3.7% of new tuberculosis cases have MDR-TB. Levels are much higher in those previously treated for tuberculosis - about 20%. WHO estimates that there were about 0.5 million new MDR-TB cases in the world in 2011. About 60% of these cases occurred in Brazil, China, India, the Russian Federation and South Africa alone.[23] In Moldova, the crumbling health system has led to the rise of MDR-TB.[69] In 2013, the Mexico–United States border was noted to be "a very hot region for drug resistant TB", though the number of cases remained small.[70]
It has been known for many years that INH-resistant TB is less virulent in guinea pigs, and the epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in Los Angeles, California, found that only 6% of cases of MDR-TB were clustered. Likewise, the appearance of high rates of MDR-TB in New York City in the early 1990s was associated with the explosion of AIDS in that area.[71][72] In New York City, a report issued by city health authorities states that fully 80 percent of all MDR-TB cases could be traced back to prisons and homeless shelters.[73] When patients have MDR-TB, they require longer periods of treatment—about two years of multidrug regimen. Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis. The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs. Most such patients require adjuvant surgery for any hope of a cure.[74]
### Somalia[edit]
MDR-TB is widespread in Somalia, where 8.7% of newly discovered TB cases are resistant to Rifampicin and Isoniazid, in patients which were treated previously the share was 47%.[75]
Refugees from Somalia brought an until then unknown variant of MDR tuberculosis with them to Europe. A few number of cases in four different countries were considered by the European Centre for Disease Prevention and Control to pose no risk to the native population.[76]
### Russian prisons[edit]
One of the so-called "hot-spots" of drug-resistant tuberculosis is within the Russian prison system. Infectious disease researchers Nachega & Chaisson report that 10% of the one million prisoners within the system have active TB.[77] One of their studies found that 75% of newly diagnosed inmates with TB are resistant to at least one drug; 40% of new cases are multidrug-resistant.[77] In 1997, TB accounted for almost half of all Russian prison deaths, and as Bobrik et al. point out in their public health study, the 90% reduction in TB incidence contributed to a consequential fall in the prisoner death rate in the years following 1997.[78] Baussano et al. articulate that concerning statistics like these are especially worrisome because spikes in TB incidence in prisons are linked to corresponding outbreaks in surrounding communities.[79] Additionally, rising rates of incarceration, especially in Central Asian and Eastern European countries like Russia, have been correlated with higher TB rates in civilian populations.[78] Even as the DOTS program is expanded throughout Russian prisons, researchers such as Shin et al. have noted that wide-scale interventions have not had their desired effect, especially with regard to the spread of drug-resistant strains of TB.[80]
#### Contributing factors[edit]
There are several elements of the Russian prison system that enable the spread of MDR-TB and heighten its severity. Overcrowding in prisons is especially conducive to the spread of tuberculosis; an inmate in a prison hospital has (on average) 3 meters of personal space, and an inmate in a correctional colony has 2 meters.[78] Specialized hospitals and treatment facilities within the prison system, known as TB colonies, are intended to isolate infected prisoners to prevent transmission; however, as Ruddy et al. demonstrate, there are not enough of these colonies to sufficiently protect staff and other inmates.[81] Additionally, many cells lack adequate ventilation, which increases likelihood of transmission. Bobrik et al. have also noted food shortages within prisons, which deprive inmates of the nutrition necessary for healthy functioning.[78]
Comorbidity of HIV within prison populations has also been shown to worsen health outcomes. Nachega & Chaisson articulate that while HIV-infected prisoners are not more susceptible MDR-TB infection, they are more likely to progress to serious clinical illness if infected.[77] According to Stern, HIV infection is 75 times more prevalent in Russian prison populations than in the civilian population.[82] Therefore, prison inmates are both more likely to become infected with MDR-TB initially and to experience severe symptoms because of previous exposure to HIV.
Shin et al. emphasize another factor in MDR-TB prevalence in Russian prisons: alcohol and substance use.[80] Ruddy et al. showed that risk for MDR-TB is three times higher among recreational drug users than non-users.[81] Shin et al.'s study demonstrated that alcohol usage was linked to poorer outcomes in MDR-TB treatment; they also noted that a majority of subjects within their study (many of whom regularly used alcohol) were nevertheless cured by their aggressive treatment regimen.[80]
Non-compliance with treatment plans is often cited as a contributor to MDR-TB transmission and mortality. Indeed, of the 80 newly-released TB-infected inmates in Fry et al.'s study, 73.8% did not report visiting a community dispensary for further treatment.[83] Ruddy et al. cite release from facilities as one of the main causes of interruption in prisoner's TB treatment, in addition to non-compliance within the prison and upon reintegration into civilian life.[81] Fry et al.'s study also listed side effects of TB treatment medications (especially in HIV positive individuals), financial worries, housing insecurities, family problems, and fear of arrest as factors that prevented some prisoners from properly adhering to TB treatment.[83] They also note that some researchers have argued that the short-term gains TB-positive prisoners receive, such as better food or work exclusion, may dis-incentivize becoming cured.[83] In their World Health Organization article, Gelmanova et al. posit that non-adherence to TB treatment indirectly contributes to bacterial resistance.[84] Although ineffective or inconsistent treatment does not "create" resistant strains, mutations within the high bacterial load in non-adherent prisoners can cause resistance.
Nachega & Chaisson argue that inadequate TB control programs are the strongest driver of MDR-TB incidence.[77] They note that prevalence of MDR-TB is 2.5 times higher in areas of poorly controlled TB.[77] Russian-based therapy (i.e., not DOTS) has been criticized by Kimerling et al. as "inadequate" in properly controlling TB incidence and transmission.[85] Bobrik et al. note that treatment for MDR-TB is equally inconsistent; the second-line drugs used to treat the prisoners lack specific treatment guidelines, infrastructure, training, or follow-up protocols for prisoners reentering civilian life.[78]
#### Policy impacts[edit]
As Ruddy et al. note in their scholarly article, Russia's recent penal reforms will greatly reduce the number of inmates inside prison facilities and thus increase the number of ex-convicts integrated into civilian populations.[81] Because the incidence of MDR-TB is strongly predicted by past imprisonment, the health of Russian society will be greatly impacted by this change.[81] Formerly incarcerated Russians will re-enter civilian life and remain within that sphere; as they live as civilians, they will infect others with the contagions they were exposed to in prison. Researcher Vivian Stern argues that the risk of transmission from prison populations to the general public calls for an integration of prison healthcare and national health services to better control both TB and MDR-TB.[82] While second-line drugs necessary for treating MDR-TB are arguably more expensive than a typical regimen of DOTS therapy, infectious disease specialist Paul Farmer posits that the outcome of leaving infected prisoners untreated could cause a massive outbreak of MDR-TB in civilian populations, thereby inflicting a heavy toll on society.[86] Additionally, as MDR-TB spreads, the threat of the emergence of totally-drug-resistant TB becomes increasingly apparent.
## See also[edit]
* 2007 tuberculosis scare
* Drug resistance
* MRSA
* Vancomycin-resistant enterococcus (VRE)
* Totally drug-resistant tuberculosis (TDR-TB)
## References[edit]
1. ^ a b c "Diagnosis and notification of multidrug-resistant TB" (PDF). World Health Organization (WHO). Retrieved 7 December 2016.
2. ^ a b Longo, Fausci; et al. (2012). Harrison's Principles of Internal Medicine (18th ed.). New York: McGraw Hill. pp. Chapter 165: Tuberculosis. Retrieved 7 December 2016.
3. ^ "Chapter 168. Antimycobacterial Agents | Harrison's Principles of Internal Medicine, 18e". AccessMedicine | McGraw-Hill Medical. Retrieved 7 December 2016.
4. ^ a b c d Wood, Alastair J.J.; Iseman, Michael D. (1993). "Treatment of Multidrug-Resistant Tuberculosis". New England Journal of Medicine. 329 (11): 784–91. doi:10.1056/NEJM199309093291108. PMID 8350889.
5. ^ Stoffels, Karolien; Allix-Béguec, Caroline; Groenen, Guido; Wanlin, Maryse; Berkvens, Dirk; Mathys, Vanessa; Supply, Philip; Fauville-Dufaux, Maryse (9 May 2013). "From Multidrug- to Extensively Drug-Resistant Tuberculosis: Upward Trends as Seen from a 15-Year Nationwide Study". PLOS ONE. 8 (5): e63128. Bibcode:2013PLoSO...863128S. doi:10.1371/journal.pone.0063128. ISSN 1932-6203. PMC 3650045. PMID 23671662.
6. ^ Parwati, Ida; Crevel, Reinout van; Soolingen, Dick van (February 2010). "Possible underlying mechanisms for successful emergence of the Mycobacterium tuberculosis Beijing genotype strains". The Lancet Infectious Diseases. 10 (2): 103–111. doi:10.1016/s1473-3099(09)70330-5. PMID 20113979.
7. ^ a b c d Millard, James; Ugarte-Gil, Cesar; Moore, David A. J. (26 February 2015). "Multidrug resistant tuberculosis". BMJ. 350: h882. doi:10.1136/bmj.h882. ISSN 1756-1833. PMID 25721508. S2CID 11683912.
8. ^ a b c Adams and Woelke (2014). Understanding Global Health. Chapter 10: TB and HIV/AIDS (12th ed.). McGraw Hill. Retrieved 9 May 2015.
9. ^ Keshavjee, Salmaan; Farmer, Paul E. (6 September 2012). "Tuberculosis, Drug Resistance, and the History of Modern Medicine". New England Journal of Medicine. 367 (10): 931–936. doi:10.1056/NEJMra1205429. ISSN 0028-4793. PMID 22931261.
10. ^ Kaplan, Jeffrey. 2017. "Tuberculosis" American University. Lecture.
11. ^ Nathanson, Eva; Nunn, Paul; Uplekar, Mukund; Floyd, Katherine; Jaramillo, Ernesto; Lönnroth, Knut; Weil, Diana; Raviglione, Mario (9 September 2010). "MDR Tuberculosis — Critical Steps for Prevention and Control" (PDF). New England Journal of Medicine. 363 (11): 1050–1058. doi:10.1056/NEJMra0908076. ISSN 0028-4793. PMID 20825317.
12. ^ "Drug-resistant tuberculosis". World Health Organization. Retrieved 2 October 2018.
13. ^ "Multi-drug-resistant tuberculosis (MDR-TB) – 2015 Update". World Health Organization (WHO). Retrieved 7 December 2016.
14. ^ Sandhu, P; Akhter, Y (26 September 2017). "Evolution of structural fitness and multifunctional aspects of mycobacterial RND family transporters". Archives of Microbiology. 200 (1): 19–31. doi:10.1007/s00203-017-1434-6. PMID 28951954. S2CID 13656026.
15. ^ Louw, G. E.; Warren, R. M.; Gey Van Pittius, N. C.; McEvoy, C. R. E.; Van Helden, P. D.; Victor, T. C. (2009). "A Balancing Act: Efflux/Influx in Mycobacterial Drug Resistance". Antimicrobial Agents and Chemotherapy. 53 (8): 3181–9. doi:10.1128/AAC.01577-08. PMC 2715638. PMID 19451293.
16. ^ Gillespie, S. H. (2002). "Evolution of Drug Resistance in Mycobacterium tuberculosis: Clinical and Molecular Perspective". Antimicrobial Agents and Chemotherapy. 46 (2): 267–74. doi:10.1128/AAC.46.2.267-274.2002. PMC 127054. PMID 11796329.
17. ^ Ramaswamy, S; Musser, JM (1998). "Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update". Tubercle and Lung Disease. 79 (1): 3–29. doi:10.1054/tuld.1998.0002. PMID 10645439.
18. ^ Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis AJ (23 March 2018). "Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products" (PDF). Future Medicinal Chemistry. 10 (7): 811–822. doi:10.4155/fmc-2017-0273. PMID 29569936.
19. ^ Hanekom, M.; Pittius, N.C. Gey van; McEvoy, C.; Victor, T.C.; Helden, P.D. Van; Warren, R.M. (2011). "Mycobacterium tuberculosis Beijing genotype: A template for success". Tuberculosis. 91 (6): 510–523. doi:10.1016/j.tube.2011.07.005. PMID 21835699.
20. ^ Ford, Christopher B.; Shah, Rupal R.; Maeda, Midori Kato; Gagneux, Sebastien; Murray, Megan B.; Cohen, Ted; Johnston, James C.; Gardy, Jennifer; Lipsitch, Marc (July 2013). "Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis". Nature Genetics. 45 (7): 784–790. doi:10.1038/ng.2656. ISSN 1061-4036. PMC 3777616. PMID 23749189.
21. ^ Mestre, Olga; Luo, Tao; Vultos, Tiago Dos; Kremer, Kristin; Murray, Alan; Namouchi, Amine; Jackson, Céline; Rauzier, Jean; Bifani, Pablo (20 January 2011). "Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication, Recombination and Repair". PLOS ONE. 6 (1): e16020. Bibcode:2011PLoSO...616020M. doi:10.1371/journal.pone.0016020. ISSN 1932-6203. PMC 3024326. PMID 21283803.
22. ^ Dalton, Tracy; Cegielski, Peter; Akksilp, Somsak; Asencios, Luis; Caoili, Janice Campos; Cho, Sang-Nae; Erokhin, Vladislav V; Ershova, Julia; Gler, Ma Tarcela; Kazennyy, Boris Y; Kim, Hee Jin; Kliiman, Kai; Kurbatova, Ekaterina; Kvasnovsky, Charlotte; Leimane, Vaira; Van Der Walt, Martie; Via, Laura E; Volchenkov, Grigory V; Yagui, Martin A; Kang, Hyungseok; Global Petts, Investigators; Akksilp, R; Sitti, W; Wattanaamornkiet, W; Andreevskaya, SN; Chernousova, LN; Demikhova, OV; Larionova, EE; Smirnova, TG; Vasilieva, IA (2012). "Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: A prospective cohort study". The Lancet. 380 (9851): 1406–17. doi:10.1016/S0140-6736(12)60734-X. PMID 22938757. S2CID 10446754.
23. ^ a b WHO. "Multidrug-resistant tuberculosis (MDR-TB) 2013 Update" (PDF). World Health Organization. Retrieved 14 June 2013.
24. ^ Velayati, A; Farnia P; Masjedi M (2013). "The totally drug resistant tuberculosis (TDR-TB)". International Journal of Clinical and Experimental Medicine. 6 (4): 307–309. PMC 3631557. PMID 23641309.
25. ^ a b Zumla, Alimuddin; Abubakar, Ibrahim; Raviglione, Mario; Hoelscher, Michael; Ditiu, Lucica; Mchugh, Timothy D.; Squire, S. Bertel; Cox, Helen; Ford, Nathan (15 May 2012). "Drug-Resistant Tuberculosis—Current Dilemmas, Unanswered Questions, Challenges, and Priority Needs". Journal of Infectious Diseases. 205 (suppl 2): S228–S240. doi:10.1093/infdis/jir858. ISSN 0022-1899. PMID 22476720.
26. ^ Parida, S. K.; Axelsson-Robertson, R.; Rao, M. V.; Singh, N.; Master, I.; Lutckii, A.; Keshavjee, S.; Andersson, J.; Zumla, A. (1 April 2015). "Totally drug-resistant tuberculosis and adjunct therapies". Journal of Internal Medicine. 277 (4): 388–405. doi:10.1111/joim.12264. ISSN 1365-2796. PMID 24809736. S2CID 43844933.
27. ^ Gao, Qian; Li, Xia (2010). "Transmission of MDR tuberculosis". Drug Discovery Today: Disease Mechanisms. 7: e61–5. doi:10.1016/j.ddmec.2010.09.006.
28. ^ Lobue, Philip (2009). "Extensively drug-resistant tuberculosis". Current Opinion in Infectious Diseases. 22 (2): 167–73. doi:10.1097/QCO.0b013e3283229fab. PMID 19283912. S2CID 24995375.
29. ^ Farmer 2005, p. 133.
30. ^ Shin, Sonya; Furin, Jennifer; Bayona, Jaime; Mate, Kedar; Kim, Jim Yong; Farmer, Paul (2004). "Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience". Social Science & Medicine. 59 (7): 1529–39. doi:10.1016/j.socscimed.2004.01.027. PMID 15246180.
31. ^ Koch, Erin (2011). "Local Microbiologies of Tuberculosis: Insights from the Republic of Georgia". Medical Anthropology. 30 (1): 81–101. doi:10.1080/01459740.2010.531064. PMID 21218357. S2CID 27735359.
32. ^ Koch, Erin (2006). "Beyond suspicion". American Ethnologist. 33: 50–62. doi:10.1525/ae.2006.33.1.50.
33. ^ "Scientific Facts on Drug-resistant Tuberculosis". GreenFacts. 18 December 2008. Retrieved 26 March 2009.
34. ^ a b c Farmer, Paul (2001). "The Major Infectious Diseases in the World — to Treat or Not to Treat?". New England Journal of Medicine. 345 (3): 208–10. doi:10.1056/NEJM200107193450310. PMID 11463018.
35. ^ Baltussen, R.; Floyd, K; Dye, C (2005). "Cost effectiveness analysis of strategies for tuberculosis control in developing countries". BMJ. 331 (7529): 1364. doi:10.1136/bmj.38645.660093.68. PMC 1309642. PMID 16282379.
36. ^ Mitnick, Carole; Bayona, Jaime; Palacios, Eda; Shin, Sonya; Furin, Jennifer; Alcántara, Felix; Sánchez, Epifanio; Sarria, Madeleny; Becerra, Mercedes; Fawzi, Mary C. Smith; Kapiga, Saidi; Neuberg, Donna; Maguire, James H.; Kim, Jim Yong; Farmer, Paul (2003). "Community-Based Therapy for Multidrug-Resistant Tuberculosis in Lima, Peru" (PDF). New England Journal of Medicine. 348 (2): 119–28. doi:10.1056/NEJMoa022928. PMID 12519922.
37. ^ Goble, Marian; Iseman, Michael D.; Madsen, Lorie A.; Waite, Dennis; Ackerson, Lynn; Horsburgh Jr, C. Robert (1993). "Treatment of 171 Patients with Pulmonary Tuberculosis Resistant to Isoniazid and Rifampin". New England Journal of Medicine. 328 (8): 527–32. doi:10.1056/NEJM199302253280802. PMID 8426619.
38. ^ WHO Treatment Guidelines for Drug-Resistant Tuberculosis, 2016 Update. WHO Guidelines Approved by the Guidelines Review Committee. Geneva: World Health Organization. 2016. ISBN 9789241549639. PMID 27748093.
39. ^ WHO Treatment Guidelines for Drug-Resistant Tuberculosis, 2016 Update. WHO Guidelines Approved by the Guidelines Review Committee. Geneva: World Health Organization. 2016. ISBN 9789241549639. PMID 27748093.
40. ^ Ziganshina, L. E.; Squire, S. B. (23 January 2008). Ziganshina, Lilia E (ed.). "Fluoroquinolones for treating tuberculosis". The Cochrane Database of Systematic Reviews (1): CD004795. doi:10.1002/14651858.CD004795.pub3. ISSN 1469-493X. PMID 18254061.
41. ^ Leimane, Vaira; Riekstina, Vija; Holtz, Timothy H; Zarovska, Evija; Skripconoka, Vija; Thorpe, Lorna E; Laserson, Kayla F; Wells, Charles D (2005). "Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: A retrospective cohort study". The Lancet. 365 (9456): 318–26. doi:10.1016/S0140-6736(05)17786-1. PMID 15664227. S2CID 32752884.
42. ^ Schon, T.; Elias, D.; Moges, F.; Melese, E.; Tessema, T.; Stendahl, O.; Britton, S.; Sundqvist, T. (2003). "Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis". European Respiratory Journal. 21 (3): 483–8. doi:10.1183/09031936.03.00090702. PMID 12662006.
43. ^ Rockett, Kirk A.; Brookes, Roger; Udalova, Irina; Vidal, Vincent; Hill, Adrian V. S.; Kwiatkowski, Dominic (1998). "1,25-Dihydroxyvitamin D3 Induces Nitric Oxide Synthase and Suppresses Growth of Mycobacterium tuberculosis in a Human Macrophage-Like Cell Line". Infection and Immunity. 66 (11): 5314–21. doi:10.1128/iai.66.11.5314-5321.1998. PMC 108664. PMID 9784538.
44. ^ Zaitzeva, S. I.; Matveeva, S. L.; Gerasimova, T. G.; Pashkov, Y. N.; Butov, D. A.; Pylypchuk, V. S.; Frolov, V. M.; Kutsyna, G. A. (2009). "Treatment of cavitary and infiltrating pulmonary tuberculosis with and without the immunomodulator Dzherelo". Clinical Microbiology and Infection. 15 (12): 1154–62. doi:10.1111/j.1469-0691.2009.02760.x. PMID 19456829.
45. ^ Butov, Dmitry A; Pashkov, Yuri N; Stepanenko, Anna L; Choporova, Aleksandra I; Butova, Tanya S; Batdelger, Dendev; Jirathitikal, Vichai; Bourinbaiar, Aldar S; Zaitzeva, Svetlana I (2011). "Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB". Journal of Immune Based Therapies and Vaccines. 9: 3. doi:10.1186/1476-8518-9-3. PMC 3031205. PMID 21244690.
46. ^ Chambers, H. F.; Turner, J.; Schecter, G. F.; Kawamura, M.; Hopewell, P. C. (2005). "Imipenem for Treatment of Tuberculosis in Mice and Humans". Antimicrobial Agents and Chemotherapy. 49 (7): 2816–21. doi:10.1128/AAC.49.7.2816-2821.2005. PMC 1168716. PMID 15980354.
47. ^ Chambers, Henry F.; Kocagöz, Tanil; Sipit, Tugrul; Turner, Joan; Hopewell, Philip C. (1998). "Activity of Amoxicillin/Clavulanate in Patients with Tuberculosis". Clinical Infectious Diseases. 26 (4): 874–7. doi:10.1086/513945. PMID 9564467.
48. ^ Peter r. Donald, Frederick a. Sirge; Sirgel, FA; Venter, A; Parkin, DP; Van De Wal, BW; Barendse, A; Smit, E; Carman, D; Talent, J; Maritz, J (2001). "Early Bactericidal Activity of Amoxicillin in Combination with Clavulanic Acid in Patients with Sputum Smear-positive Pulmonary Tuberculosis". Scandinavian Journal of Infectious Diseases. 33 (6): 466–9. doi:10.1080/00365540152029954. PMID 11450868.
49. ^ Jagannath, C; Reddy, M V; Kailasam, S; O'Sullivan, J F; Gangadharam, P R (1995). "Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis. In vitro, intracellular, and in vivo studies". American Journal of Respiratory and Critical Care Medicine. 151 (4): 1083–6. doi:10.1164/ajrccm.151.4.7697235. PMID 7697235.
50. ^ Adams, Linda B.; Sinha, Indu; Franzblau, Scott G.; Krahenbuhl, James L. Krahenbuhl; Mehta, Reeta T. Mehta (1999). "Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine". Antimicrobial Agents and Chemotherapy. 43 (7): 1638–43. doi:10.1128/AAC.43.7.1638. PMC 89336. PMID 10390215.
51. ^ Janulionis, E.; Sofer, C.; Song, H.-Y.; Wallis, R. S. (2004). "Lack of Activity of Orally Administered Clofazimine against Intracellular Mycobacterium tuberculosis in Whole-Blood Culture". Antimicrobial Agents and Chemotherapy. 48 (8): 3133–5. doi:10.1128/AAC.48.8.3133-3135.2004. PMC 478499. PMID 15273133.
52. ^ Shubin, H; Sherson, J; Pennes, E; Glaskin, A; Sokmensuer, A (1958). "Prochlorperazine (compazine) as an aid in the treatment of pulmonary tuberculosis". Antibiotic Medicine and Clinical Therapy. 5 (5): 305–9. PMID 13521769.
53. ^ Wayne, L G; Sramek, H A (1994). "Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis". Antimicrobial Agents and Chemotherapy. 38 (9): 2054–8. doi:10.1128/AAC.38.9.2054. PMC 284683. PMID 7811018.
54. ^ "FDA Press Release". U.S. Food and Drug Administration. 31 December 2012.
55. ^ Carroll, John (31 December 2012). "J&J wins accelerated OK for first new TB drug in 40 years". fiercebiotech.com. Retrieved 3 January 2013.
56. ^ Stover, C. Kendall; Warrener, Paul; Vandevanter, Donald R.; Sherman, David R.; Arain, Taraq M.; Langhorne, Michael H.; Anderson, Scott W.; Towell, J. Andrew; Yuan, Ying; McMurray, David N.; Kreiswirth, Barry N.; Barry, Clifton E.; Baker, William R. (2000). "A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis". Nature. 405 (6789): 962–6. Bibcode:2000Natur.405..962S. doi:10.1038/35016103. PMID 10879539. S2CID 4428584.
57. ^ Chase, Marilyn (27 October 2004). "Novartis Sets Deal to Seek New Drugs for Fighting TB". TB Alliance. Archived from the original on 6 May 2007. Retrieved 3 January 2013.
58. ^ Farmer 1999, p. [page needed].
59. ^ Farmer 2005, p. 148.
60. ^ https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1
61. ^ https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1
62. ^ https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1
63. ^ Centers for Disease Control (CDC) (August 1991). "Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons—Florida and New York, 1988–1991". Morbidity and Mortality Weekly Report. 40 (34): 585–91. PMID 1870559.
64. ^ Edlin, Brian R.; Tokars, Jerome I.; Grieco, Michael H.; Crawford, Jack T.; Williams, Julie; Sordillo, Emelia M.; Ong, Kenneth R.; Kilburn, James O.; Dooley, Samuel W.; Castro, Kenneth G.; Jarvis, William R.; Holmberg, Scott D. (1992). "An Outbreak of Multidrug-Resistant Tuberculosis among Hospitalized Patients with the Acquired Immunodeficiency Syndrome". New England Journal of Medicine. 326 (23): 1514–21. doi:10.1056/NEJM199206043262302. PMID 1304721.
65. ^ Pitchenik, Arthure; Burr, Janice; Laufer, Marla; Miller, Gary; Cacciatore, Robert; Bigler, Williamj.; Witte, Johnj.; Cleary, Timothy (1990). "Outbreaks of drug-resistant tuberculosis at AIDS centre". The Lancet. 336 (8712): 440–1. doi:10.1016/0140-6736(90)91987-L. PMID 1974967. S2CID 39041093.
66. ^ Centers for Disease Control (CDC) (March 1991). "Transmission of multidrug-resistant tuberculosis from an HIV-positive client in a residential substance-abuse treatment facility—Michigan". Morbidity and Mortality Weekly Report. 40 (8): 129–31. PMID 1900098.
67. ^ Fischl, Margaret A.; Uttamchandani, RB; Daikos, GL; Poblete, RB; Moreno, JN; Reyes, RR; Boota, AM; Thompson, LM; Cleary, TJ; Lai, S (1992). "An Outbreak of Tuberculosis Caused by Multiple-Drug-resistant Tubercle Bacilli among Patients with HIV Infection". Annals of Internal Medicine. 117 (3): 177–83. doi:10.7326/0003-4819-117-3-177. PMID 1616211.
68. ^ Centers for Disease Control (1990). "Outbreak of multidrug-resistant tuberculosis—Texas, California, and Pennsylvania". Morbidity and Mortality Weekly Report. 39 (22): 369–72. PMID 2111434.
69. ^ Rochkind, David (9 August 2010). "Moldova: Fighting a Deadly Disease". Pulitzer Center on Crisis Reporting. Retrieved 23 September 2012.
70. ^ McKay, Betsy (9–10 March 2013). "Risk of Deadly TB Exposure Grows Along U.S.—Mexico Border". The Wall Street Journal (paper). p. A1.
71. ^ Frieden, Thomas R.; Sterling, Timothy; Pablos-Mendez, Ariel; Kilburn, James O.; Cauthen, George M.; Dooley, Samuel W. (1993). "The Emergence of Drug-Resistant Tuberculosis in New York City". New England Journal of Medicine. 328 (8): 521–6. doi:10.1056/NEJM199302253280801. PMID 8381207.
72. ^ Garrett 2000, p. 266ff.
73. ^ Garrett 1994, p. 524.
74. ^ Farmer 2005, p. 118.
75. ^ Ärzteblatt, Deutscher Ärzteverlag GmbH, Redaktion Deutsches (27 December 2016). "MDR-Tuberkulose unter Migranten aus Somalia". Deutsches Ärzteblatt (in German). Retrieved 27 September 2019.
76. ^ Ärzteblatt, Deutscher Ärzteverlag GmbH, Redaktion Deutsches (27 December 2016). "MDR-Tuberkulose unter Migranten aus Somalia". Deutsches Ärzteblatt (in German). Retrieved 27 September 2019.
77. ^ a b c d e Nachega J., Chaisson R. (2003). "Tuberculosis Drug Resistance: A Global Threat". Clinical Infectious Diseases. 36 (1): S24–S30. doi:10.1086/344657. PMID 12516027.
78. ^ a b c d e Bobrik A.; Danishevski K.; Eroshina K.; McKee M. (2005). "Prison Health in Russia: The Larger Picture". Journal of Public Health Policy. 26 (1): 30–59. doi:10.1057/palgrave.jphp.3200002. PMID 15906874. S2CID 2102820.
79. ^ Baussano I.; Williams B.; Nunn P.; Beggiato M.; Fedeli U. (2010). "Tuberculosis Incidence in Prisons: A Systematic Review". PLOS Medicine. 7 (12): e1000381. doi:10.1371/journal.pmed.1000381. PMC 3006353. PMID 21203587.
80. ^ a b c Shin S. S.; Pasechnikov A.; Gelmanova I.; Peremitin G.; Strelis A.; Andreev Y.; Golubchikova V.; Tonkel T.; Yanova G.; Nikiforov M.; Yedilbayev A.; Mukherjee J.; Furin J.; Barry D.; Farmer P.; Rich M.; Keshavjee S. (2006). "Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia". The International Journal of Tuberculosis and Lung Disease. 10 (4): 402–407. PMID 16602404.
81. ^ a b c d e Ruddy M.; Balabanova Y.; Graham C.; Fedorin I.; Malomanova N.; Elisarova E.; Kuznetznov S.; Gusarova G.; Zakharova S.; Melentyev A.; Krukova E.; Golishevskaya V.; Erokhin V.; Dorozhkova I.; Drobniewski F. (2005). "Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samar Region, Russia". Thorax. 60 (2): 130–135. doi:10.1136/thx.2004.026922. PMC 1747303. PMID 15681501.
82. ^ a b Stern, V. (2001). Problems in Prisons Worldwide, with a Particular Focus on Russia. Annals of the New York Academy of Sciences, 953b, 113-119.
83. ^ a b c Fry R.; Khoshnood K.; Vdovichenko E.; Granskaya J.; Sazhin V.; Shpakovskaya L; Zhemkov V.; Zhemkova M.; Rowhani-Rahbar A.; Funk M.; Kozlov A. (2005). "Barriers to completion of tuberculosis treatment among prisoners and former prisoners in St. Petersburg, Russia". The International Journal of Tuberculosis and Lung Disease. 9 (9): 1027–1033. PMID 16158896.
84. ^ Gelmanova I.; Keshavjee S.; Golubchikova V.; Berezina V.; Strelis A.; Yanova G.; Atwood S.; Murray M. (2007). "Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance". Bulletin of the World Health Organization. 85 (9): 703–11. doi:10.2471/BLT.06.038331. PMC 2636414. PMID 18026627.
85. ^ Kimerling M.E.; Kluge H.; Vezhnina N.; Iacovazzi T.; Demeulenaere T.; Portaels F.; Matthys F. (1999). "Inadequacy of the current WHO re-treatment regimen in a central Siberian prison: treatment failure and MDR-TB". The International Journal of Tuberculosis and Lung Disease. 3 (5): 451–453. PMID 10331736.
86. ^ Farmer P (1999). "Pathologies of power: rethinking health and human rights". American Journal of Public Health. 89 (10): 1486–1496. doi:10.2105/ajph.89.10.1486. PMC 1508789. PMID 10511828.
Notes
* Farmer, Paul (1999). Infections and inequalities : the modern plagues. Berkeley, California, United States: University of California Press. ISBN 978-0-520-22913-6.
* Farmer, Paul (2005). Pathologies of Power: health, human rights, and the new war on the poor. Berkeley, California, United States: University of California Press. ISBN 978-0-520-93147-3.
* Garrett, Laurie (1994). The coming plague : newly emerging diseases in a world out of balance. New York, New York, United States: Farrar, Straus and Giroux. ISBN 978-0-374-12646-9.
* Garrett, Laurie (2000). Betrayal of trust: the collapse of global public health. New York, New York, United States: Hyperion Books. ISBN 978-0-7868-6522-2.
## External links[edit]
Classification
D
* ICD-10: Z16.24
* MeSH: D018088
* Video: Drug-Resistant TB in Russia 24 July 2007, Woodrow Wilson Center event featuring Salmaan Keshavjee and Murray Feshbach
* TB Drug Resistance Mutation Database
* MDR-TB : a story of Hope, Struggle & Triumph
* MDR-TB (DOTS Plus) protocol followed under RNTCP in India (PDF)
* "The Strange, Isolated Life of a Tuberculosis Patient in the 21st Century", Buzzfeed
* v
* t
* e
Gram-positive bacterial infection: Actinobacteria
Actinomycineae
Actinomycetaceae
* Actinomyces israelii
* Actinomycosis
* Cutaneous actinomycosis
* Tropheryma whipplei
* Whipple's disease
* Arcanobacterium haemolyticum
* Arcanobacterium haemolyticum infection
* Actinomyces gerencseriae
Propionibacteriaceae
* Propionibacterium acnes
Corynebacterineae
Mycobacteriaceae
M. tuberculosis/
M. bovis
* Tuberculosis: Ghon focus/Ghon's complex
* Pott disease
* brain
* Meningitis
* Rich focus
* Tuberculous lymphadenitis
* Tuberculous cervical lymphadenitis
* cutaneous
* Scrofuloderma
* Erythema induratum
* Lupus vulgaris
* Prosector's wart
* Tuberculosis cutis orificialis
* Tuberculous cellulitis
* Tuberculous gumma
* Lichen scrofulosorum
* Tuberculid
* Papulonecrotic tuberculid
* Primary inoculation tuberculosis
* Miliary
* Tuberculous pericarditis
* Urogenital tuberculosis
* Multi-drug-resistant tuberculosis
* Extensively drug-resistant tuberculosis
M. leprae
* Leprosy: Tuberculoid leprosy
* Borderline tuberculoid leprosy
* Borderline leprosy
* Borderline lepromatous leprosy
* Lepromatous leprosy
* Histoid leprosy
Nontuberculous
R1:
* M. kansasii
* M. marinum
* Aquarium granuloma
R2:
* M. gordonae
R3:
* M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP
* MAI infection
* M. ulcerans
* Buruli ulcer
* M. haemophilum
R4/RG:
* M. fortuitum
* M. chelonae
* M. abscessus
Nocardiaceae
* Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica
* Nocardiosis
* Rhodococcus equi
Corynebacteriaceae
* Corynebacterium diphtheriae
* Diphtheria
* Corynebacterium minutissimum
* Erythrasma
* Corynebacterium jeikeium
* Group JK corynebacterium sepsis
Bifidobacteriaceae
* Gardnerella vaginalis
* v
* t
* e
Tuberculosis
Symptoms, signs and
associated conditions
* Caseous necrosis
* Ghon focus / Ghon's complex
* Giant multinucleated cell
* Pott disease
* Canga's bead symptom
* Prosector's wart
* Latent tuberculosis
* Paronychia
* Lupus vulgaris
* Tuberculous lymphadenitis
* Tuberculous meningitis
* Miliary tuberculosis
Mycobacterium species
* Mycobacterium africanum
* Mycobacterium bovis
* Mycobacterium caprae
* Mycobacterium tuberculosis
Tuberculosis diagnosis
* Ziehl–Neelsen stain
* Auramine phenol stain
* Culture on Löwenstein–Jensen medium and/or MGIT
* Chest photofluorography
* GeneXpert MTB/RIF
* Interferon gamma release assay
* QuantiFERON
* T-SPOT.TB
* Microscopic Observation Drug Susceptibility assay
* Tuberculin
* Heaf test
* Mantoux test
* Tine test
Management
* ATC code J04
* Isoniazid
* 4-Aminosalicylic acid
* Ethambutol
* Capreomycin
* Cycloserine
* Rifampicin
* Thioacetazone
* Streptomycin
* Bedaquiline
* RBCG30
* Pyrazinamide
* MVA85A
* Rifater
* vaccines
* BCG vaccine
Resistance
* Multi-drug-resistant tuberculosis
* Extensively drug-resistant tuberculosis
* Totally drug-resistant tuberculosis
History of tuberculosis
* Manuel de Abreu
* Hermann Brehmer
* Albert Calmette
* Christopher Dye
* Marcos Espinal
* Friedrich Franz Friedmann
* Max Gerson
* Philip D'Arcy Hart
* F. R. G. Heaf
* George M. Heath
* Robert Koch
* Charles Mantoux
* Richard Morton
* Mario Raviglione
* Carl Rüedi
* Lucius Rüedi
* Madonna Swan
* Edward Livingston Trudeau
Organizations
* Adirondack Cottage Sanitarium
* Campaign for Access to Essential Medicines
* Center for Infectious Disease Research
* Cure Cottages of Saranac Lake
* Glen Lake Children's Camp
* Glen Lake Sanatorium
* Glenn Dale Hospital
* The Global Fund to Fight AIDS, Tuberculosis and Malaria
* Global Plan to Stop Tuberculosis
* International Congress on Tuberculosis
* International Union Against Tuberculosis and Lung Disease
* Millennium Foundation
* Mycobacterium Tuberculosis Structural Genomics Consortium
* National Jewish Health
* Phipps Institute for the Study, Treatment and Prevention of Tuberculosis
* Stop TB Partnership
* TB Alliance
* Unitaid
Other
* 2007 tuberculosis scare
* 72F fusion protein vaccine
* Baumgarten-Tangl law
* CFP-10
* ESAT-6
* Iowa Cow War
* List of tuberculosis cases
* Plombage
* Preventorium
* Sanatorium
* Sunshine Way
* Tuberculosis classification
* Tuberculosis in China
* Tuberculosis in popular culture
* Tuberculosis radiology
* Tygerberg score
* World Tuberculosis Day
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Multidrug-resistant tuberculosis
|
c0206526
| 27,592 |
wikipedia
|
https://en.wikipedia.org/wiki/Multidrug-resistant_tuberculosis
| 2021-01-18T18:43:09 |
{"mesh": ["D018088"], "wikidata": ["Q866602"]}
|
Glycogen storage disease type 4 (GSD 4) is part of a group of disorders which lead to abnormal accumulation of glycogen (a storage form of glucose) in various parts of the body. Symptoms of GSD 4 usually begin in infancy and typically include failure to thrive; enlarged liver and spleen (hepatosplenomegaly); and in many cases, progressive liver cirrhosis and liver failure. In rare cases individuals may have a form with non-progressive liver disease, or a severe neuromuscular form. GSD 4 is caused by mutations in the GBE1 gene and is inherited in an autosomal recessive manner. Treatment typically focuses on the specific symptoms that are present in each individual.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Glycogen storage disease type 4
|
c0017923
| 27,593 |
gard
|
https://rarediseases.info.nih.gov/diseases/2520/glycogen-storage-disease-type-4
| 2021-01-18T18:00:16 |
{"mesh": ["D006011"], "omim": ["232500"], "orphanet": ["367"], "synonyms": ["GSD 4", "Andersen disease", "Brancher deficiency", "Amylopectinosis", "Glycogen branching enzyme deficiency", "Cirrhosis, familial, with deposition of abnormal glycogen", "Glycogenosis 4", "Glycogen storage disease type IV", "GSD IV"]}
|
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE syndrome) occurs when the immune system attacks the body by mistake. Symptoms usually develop within the first few months of life and may include recurrent fevers and purple colored spots on the skin particularly around the eyes. Loss of body fat, bone, and joint pain also usually occur. Since so few people have been reported with CANDLE syndrome, it is difficult to know how it affects people in the long term. CANDLE syndrome occurs when the PSMB8 gene is not working correctly. Other genes associated with CANDLE syndrome include PSMB4, PSMA3, and POMP. It is usually inherited in an autosomal recessive pattern; however, when associated with variants in the POMP gene, may be inherited in an autosomal dominant pattern. There is no specific treatment for this condition; however, steroids may help reduce the frequency of symptoms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature
|
c1850568
| 27,594 |
gard
|
https://rarediseases.info.nih.gov/diseases/10811/chronic-atypical-neutrophilic-dermatosis-with-lipodystrophy-and-elevated-temperature
| 2021-01-18T18:01:19 |
{"mesh": ["C538334"], "omim": ["256040"], "orphanet": ["325004"], "synonyms": ["CANDLE syndrome", "Chronic atypical neutrophilic dermatosis-lipodystrophy-elevated temperature syndrome"]}
|
A very rare, benign, cutaneous, slow-growing, vascular tumor mostly developing in infancy or early childhood.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Tufted angioma
|
c0346073
| 27,595 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1063
| 2021-01-23T18:29:59 |
{"gard": ["425"], "mesh": ["C536924"], "omim": ["607859"], "umls": ["C0346073"], "icd-10": ["D18.0"], "synonyms": ["Nakagawa angioblastoma"]}
|
Primary basilar impression (PBI) is a very rare skeletal developmental defect characterized by congenital upward translocation of the upper cervical spine and clivus into the foramen magnum. PBI can be asymptomatic or associated with severe neurological dysfunction.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Primary basilar invagination
|
c1862299
| 27,596 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2285
| 2021-01-23T18:27:28 |
{"gard": ["1037"], "mesh": ["C566226"], "omim": ["109500"], "umls": ["C1862299"], "icd-10": ["Q75.8"], "synonyms": ["Bull-Nixon syndrome"]}
|
Rare genetic disease affecting palate, thumbs, and upper limbs
Adducted thumb syndrome
Other namesChristian syndrome, craniostenosis arthrogryposis cleft palate
Adducted thumb syndrome has a lysosomal recessive pattern of inheritance
Adducted thumb syndrome recessive form is a rare disease affecting multiple systems causing malformations of the palate, thumbs, and upper limbs. The name Christian syndrome derives from Joe. C. Christian, the first person to describe the condition. Inheritance is believed to be autosomal recessive,[1] caused by mutation in the CHST14 (carbohydrate sulfotransferase 14) gene.[2]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
This syndrome is characterised by typical facial appearance, slight build, thin and translucent skin, severely adducted thumbs, arachnodactyly, club feet, joint instability, facial clefting and bleeding disorders, as well as heart, kidney or intestinal defects. Severe psychomotor and developmental delay and decreased muscle tone may also be present during infancy. Cognitive development during childhood is normal.[3]
## Cause[edit]
This section is empty. You can help by adding to it. (April 2017)
## Diagnosis[edit]
The syndrome is associated with microcephaly, arthrogryposis and cleft palate and various craniofacial, respiratory, neurological and limb abnormalities, including bone and joint defects of the upper limbs, adducted thumbs, camptodactyly and talipes equinovarus or calcaneovalgus. It is characterized by craniosynostosis, and myopathy in association with congenital generalized hypertrichosis.[4] Patients with the disease are considered intellectually disabled. Most die in childhood. Patients often suffer from respiratory difficulties such as pneumonia, and from seizures due to dysmyelination in the brain's white matter.[5] It has been hypothesized that the Moro reflex (startle reflex in infants) may be a tool in detecting the congenital clapsed thumb early in infancy.[6] The thumb normally extends as a result of this reflex.
## Treatment[edit]
This section is empty. You can help by adding to it. (April 2017)
## See also[edit]
* Adams–Oliver syndrome
* List of cutaneous conditions
* Tetrasomy 18p
## References[edit]
1. ^ Fitch N, Levy EP (1975). "Adducted thumb syndromes". Clin. Genet. 8 (3): 190–8. doi:10.1111/j.1399-0004.1975.tb01493.x. PMID 1175322.
2. ^ "CHST14". National Center for Biotechnology Information database. NCBI. Retrieved 21 March 2013.
3. ^ "Ehlers-Danlos syndrome, musculocontractural type – Genetic and Rare Diseases Information Center (GARD) – an NCATS Program".
4. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1008. ISBN 978-1-4160-2999-1.
5. ^ Kunze J, Park W, Hansen KH, Hanefeld F (1983). "Adducted thumb syndrome. Report of a new case and a diagnostic approach". Eur. J. Pediatr. 141 (2): 122–6. doi:10.1007/BF00496805. PMID 6662143. S2CID 13243887.
6. ^ Anderson TE, Breed AL (1981). "Congenital clasped thumb and the Moro reflex. (Letter)". The Journal of Pediatrics. 99: 664–665. doi:10.1016/s0022-3476(81)80293-4.
## External links[edit]
* Whonamedit.com entry on Christian syndrome
Classification
D
* OMIM: 201550
* DiseasesDB: 31689
* v
* t
* e
Congenital abnormality syndromes
Craniofacial
* Acrocephalosyndactylia
* Apert syndrome
* Carpenter syndrome
* Pfeiffer syndrome
* Saethre–Chotzen syndrome
* Sakati–Nyhan–Tisdale syndrome
* Bonnet–Dechaume–Blanc syndrome
* Other
* Baller–Gerold syndrome
* Cyclopia
* Goldenhar syndrome
* Möbius syndrome
Short stature
* 1q21.1 deletion syndrome
* Aarskog–Scott syndrome
* Cockayne syndrome
* Cornelia de Lange syndrome
* Dubowitz syndrome
* Noonan syndrome
* Robinow syndrome
* Silver–Russell syndrome
* Seckel syndrome
* Smith–Lemli–Opitz syndrome
* Snyder–Robinson syndrome
* Turner syndrome
Limbs
* Adducted thumb syndrome
* Holt–Oram syndrome
* Klippel–Trénaunay–Weber syndrome
* Nail–patella syndrome
* Rubinstein–Taybi syndrome
* Gastrulation/mesoderm:
* Caudal regression syndrome
* Ectromelia
* Sirenomelia
* VACTERL association
Overgrowth syndromes
* Beckwith–Wiedemann syndrome
* Proteus syndrome
* Perlman syndrome
* Sotos syndrome
* Weaver syndrome
* Klippel–Trénaunay–Weber syndrome
* Benign symmetric lipomatosis
* Bannayan–Riley–Ruvalcaba syndrome
* Neurofibromatosis type I
Laurence–Moon–Bardet–Biedl
* Bardet–Biedl syndrome
* Laurence–Moon syndrome
Combined/other,
known locus
* 2 (Feingold syndrome)
* 3 (Zimmermann–Laband syndrome)
* 4/13 (Fraser syndrome)
* 8 (Branchio-oto-renal syndrome, CHARGE syndrome)
* 12 (Keutel syndrome, Timothy syndrome)
* 15 (Marfan syndrome)
* 19 (Donohue syndrome)
* Multiple
* Fryns syndrome
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Adducted thumb syndrome
|
c0431886
| 27,597 |
wikipedia
|
https://en.wikipedia.org/wiki/Adducted_thumb_syndrome
| 2021-01-18T18:59:01 |
{"mesh": ["C562949"], "umls": ["C0431886"], "orphanet": ["2952"], "wikidata": ["Q4681410"]}
|
Polypoid melanoma
SpecialtyDermatology/oncology
Polypoid melanoma is a rare cutaneous condition, a virulent variant of nodular melanoma.[1]:696Polypoid melanoma is a subtype of nodular melanoma, the most aggressive form of melanoma (a skin cancer).
Polypoid melanoma, like all types of melanoma, starts in the cells that make melanin, which is the protective pigment that gives skin color. Polypoid melanoma is most commonly found on the torso but may be found in unexpected places like the nasal mucous membranes and the rectum. Sometimes polypoid melanoma may develop on moles on your skin, but it usually occurs out of nowhere on normal skin. Polypoid melanoma can be treated if it's diagnosed early, but the disease progresses very rapidly and has a worse prognosis than many other types of melanoma.
## Treatment[edit]
Therapies for metastatic melanoma include the biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.[2]
## See also[edit]
* Melanoma
* List of cutaneous conditions
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
2. ^ Maverakis E, Cornelius LA, Bowen GM, Phan T, Patel FB, Fitzmaurice S, He Y, Burrall B, Duong C, Kloxin AM, Sultani H, Wilken R, Martinez SR, Patel F (2015). "Metastatic melanoma - a review of current and future treatment options". Acta Derm Venereol. 95 (5): 516–524. doi:10.2340/00015555-2035. PMID 25520039.
* v
* t
* e
Medicine
Specialties
and
subspecialties
Surgery
* Cardiac surgery
* Cardiothoracic surgery
* Colorectal surgery
* Eye surgery
* General surgery
* Neurosurgery
* Oral and maxillofacial surgery
* Orthopedic surgery
* Hand surgery
* Otolaryngology
* ENT
* Pediatric surgery
* Plastic surgery
* Reproductive surgery
* Surgical oncology
* Transplant surgery
* Trauma surgery
* Urology
* Andrology
* Vascular surgery
Internal medicine
* Allergy / Immunology
* Angiology
* Cardiology
* Endocrinology
* Gastroenterology
* Hepatology
* Geriatrics
* Hematology
* Hospital medicine
* Infectious disease
* Nephrology
* Oncology
* Pulmonology
* Rheumatology
Obstetrics and gynaecology
* Gynaecology
* Gynecologic oncology
* Maternal–fetal medicine
* Obstetrics
* Reproductive endocrinology and infertility
* Urogynecology
Diagnostic
* Radiology
* Interventional radiology
* Nuclear medicine
* Pathology
* Anatomical
* Clinical pathology
* Clinical chemistry
* Cytopathology
* Medical microbiology
* Transfusion medicine
Other
* Addiction medicine
* Adolescent medicine
* Anesthesiology
* Dermatology
* Disaster medicine
* Diving medicine
* Emergency medicine
* Mass gathering medicine
* Family medicine
* General practice
* Hospital medicine
* Intensive care medicine
* Medical genetics
* Narcology
* Neurology
* Clinical neurophysiology
* Occupational medicine
* Ophthalmology
* Oral medicine
* Pain management
* Palliative care
* Pediatrics
* Neonatology
* Physical medicine and rehabilitation
* PM&R
* Preventive medicine
* Psychiatry
* Addiction psychiatry
* Radiation oncology
* Reproductive medicine
* Sexual medicine
* Sleep medicine
* Sports medicine
* Transplantation medicine
* Tropical medicine
* Travel medicine
* Venereology
Medical education
* Medical school
* Bachelor of Medicine, Bachelor of Surgery
* Bachelor of Medical Sciences
* Master of Medicine
* Master of Surgery
* Doctor of Medicine
* Doctor of Osteopathic Medicine
* MD–PhD
Related topics
* Alternative medicine
* Allied health
* Dentistry
* Podiatry
* Pharmacy
* Physiotherapy
* Molecular oncology
* Nanomedicine
* Personalized medicine
* Public health
* Rural health
* Therapy
* Traditional medicine
* Veterinary medicine
* Physician
* Chief physician
* History of medicine
* Book
* Category
* Commons
* Wikiproject
* Portal
* Outline
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Polypoid melanoma
|
None
| 27,598 |
wikipedia
|
https://en.wikipedia.org/wiki/Polypoid_melanoma
| 2021-01-18T18:39:34 |
{"wikidata": ["Q7226854"]}
|
"Savant" redirects here. For other uses, see Savant (disambiguation).
Savant syndrome
Other namesAutistic savant, idiot savant (historical)[1]
Kim Peek, the savant who was the inspiration for the main character in the movie Rain Man
SpecialtyPsychiatry, Neurology
SymptomsGeneral mental disability with certain abilities far in excess of average[1][2]
TypesCongenital, acquired[3]
CausesNeurodevelopmental disorder such as autism spectrum disorder, brain injury[1]
Frequencyc. 1 in a million people[4]
Savant syndrome is a rare condition in which someone with significant mental disabilities demonstrates certain abilities far in excess of average.[1][2] The skills that savants excel at are generally related to memory.[1] This may include rapid calculation, artistic ability, map making, or musical ability.[1] Usually, only one exceptional skill is present.[1]
Those with the condition generally have a neurodevelopmental disorder such as autism spectrum disorder or have a brain injury.[1] About half of cases are associated with autism, and these individuals may be known as "autistic savants".[1] While the condition usually becomes apparent in childhood, some cases develop later in life.[1] It is not recognized as a mental disorder within the DSM-5.[5]
Savant syndrome is estimated to affect around one in a million people.[4] The condition affects more males than females, at a ratio of 6:1.[1] The first medical account of the condition was in 1783.[1] Among those with autism, 1 in 10 to 1 in 200 have savant syndrome to some degree.[1] It is estimated that there are fewer than a hundred savants with extraordinary skills currently living.[1]
## Contents
* 1 Signs and symptoms
* 1.1 Calendrical savants
* 2 Mechanism
* 2.1 Psychological
* 2.2 Neurological
* 3 Epidemiology
* 4 History
* 5 Society and culture
* 5.1 Notable cases
* 5.2 Fictional cases
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Venice by British artistic savant Stephen Wiltshire
Savant skills are usually found in one or more of five major areas: art, memory, arithmetic, musical abilities, and spatial skills.[1] The most common kinds of savants are calendrical savants,[6][7] "human calendars" who can calculate the day of the week for any given date with speed and accuracy, or recall personal memories from any given date. Advanced memory is the key "superpower" in savant abilities.[6]
Approximately half of savants are autistic; the other half often have some form of central nervous system injury or disease.[1] It is estimated that up to 10% of those with autism have some form of savant abilities.[1][8][9]
### Calendrical savants[edit]
A calendrical savant (or calendar savant) is someone who – despite having an intellectual disability – can name the day of the week of a date, or vice versa, on a limited range of decades or certain millennia.[7][10] The rarity of human calendar calculators is possibly due to the lack of motivation to develop such skills among the general population, although mathematicians have developed formulas that allow them to obtain similar skills.[10] Calendrical savants, on the other hand, may not be prone to invest in socially engaging skills.[11]
## Mechanism[edit]
### Psychological[edit]
No widely accepted cognitive theory explains savants' combination of talent and deficit.[12] It has been suggested that individuals with autism are biased towards detail-focused processing and that this cognitive style predisposes individuals either with or without autism to savant talents.[13] Another hypothesis is that savants hyper-systemize, thereby giving an impression of talent. Hyper-systemizing is an extreme state in the empathizing–systemizing theory that classifies people based on their skills in empathizing with others versus systemizing facts about the external world.[14] Also, the attention to detail of savants is a consequence of enhanced perception or sensory hypersensitivity in these unique individuals.[14][15] It has also been confirmed that some savants operate by directly accessing low-level, less-processed information that exists in all human brains that is not normally available to conscious awareness.[16]
### Neurological[edit]
In some cases, savant syndrome can be induced following severe head trauma to the left anterior temporal lobe.[1] Savant syndrome has been artificially replicated using transcranial magnetic stimulation to temporarily disable this area of the brain.[17]
## Epidemiology[edit]
See also: Epidemiology of autism
There are no objectively definitive statistics about how many people have savant skills. The estimates range from "exceedingly rare"[18] to one in ten people with autism having savant skills in varying degrees.[1] A 2009 British study of 137 parents of autistic children found that 28% believe their children met the criteria for a savant skill, defined as a skill or power "at a level that would be unusual even for 'normal' people".[19] As many as 50 cases of sudden or acquired savant syndrome have been reported.[20][21]
Males with savant syndrome outnumber females by roughly 6:1 (in Finland),[22] slightly higher than the sex ratio disparity for autism spectrum disorders of 4.3:1.[23]
## History[edit]
The term idiot savant (French for "learned idiot") was first used to describe the condition in 1887 by John Langdon Down, who is known for his description of Down syndrome. The term idiot savant was later described as a misnomer because not all reported cases fit the definition of idiot, originally used for a person with a very severe intellectual disability. The term autistic savant was also used as a description of the disorder. Like idiot savant, the term came to be considered a misnomer because only half of those who were diagnosed with savant syndrome were autistic. Upon realization of the need for accuracy of diagnosis and dignity towards the individual, the term savant syndrome became widely accepted terminology.[1][18]
## Society and culture[edit]
### Notable cases[edit]
* Alonzo Clemons, American acquired savant sculptor
* Anthony Cicoria, American acquired savant pianist and medical doctor
* Brian MacGregor, British poet, author, polyglot, musician, artist and pianist[24]
* Daniel Tammet, British author and polyglot
* Derek Amato, American composer and pianist
* Derek Paravicini, British blind musical prodigy and pianist
* Henriett Seth F., Hungarian autistic writer and artist
* Kim Peek, American "megasavant"
* Leslie Lemke, American musician
* Rex Lewis-Clack, American pianist and musical savant
* Matt Savage, American musician
* Orlando Serrell, American acquired savant
* Stephen Wiltshire, British architectural artist
* Temple Grandin,[25] American professor of animal science
* Tom Wiggins, American blind pianist and composer[26]
* Tommy McHugh, British artist and poet
* Flo and Kay Lyman, only identical twin autistic savant sisters known to exist.
* Kodi Lee, 2020 America's Got Talent winner (musician)
* Collin Ennis, American acquired savant after a car accident left him with a traumatic brain injury, graduate of West Chester University, pop culture and sports savant.
### Fictional cases[edit]
* Raymond Babbitt, autistic savant in the 1988 film Rain Man (inspired by Kim Peek)
* Park Shi-on, autistic savant in the 2013 South Korean medical drama Good Doctor
* Shaun Murphy, autistic savant in the 2017 U.S. medical drama The Good Doctor
* Kazan, autistic savant in the 1997 film Cube
* It is implied (but not confirmed) that highly skilled hitman Akira Sato in the 2019 Yakuza-comedy The Fable has Savant Syndrome
## See also[edit]
* Autistic art
* Child prodigy
* Creativity and mental illness
* Mental calculator
* Hyperthymesia
* Ideasthesia
* Twice exceptional
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s t Treffert DA (May 2009). "The savant syndrome: an extraordinary condition. A synopsis: past, present, future". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1351–7. doi:10.1098/rstb.2008.0326. PMC 2677584. PMID 19528017.
2. ^ a b Miller LK (January 1999). "The savant syndrome: intellectual impairment and exceptional skill". Psychological Bulletin. 125 (1): 31–46. doi:10.1037/0033-2909.125.1.31. PMID 9990844.
3. ^ Hughes JR (2012). "The savant syndrome and its possible relationship to epilepsy". Advances in Experimental Medicine and Biology. 724: 332–43. doi:10.1007/978-1-4614-0653-2_25. ISBN 978-1-4614-0652-5. PMID 22411254.
4. ^ a b Hyltenstam, Kenneth (2016). Advanced Proficiency and Exceptional Ability in Second Languages. Walter de Gruyter GmbH & Co KG. p. 258. ISBN 9781614515173.
5. ^ Sperry, Len (2015). Mental Health and Mental Disorders: An Encyclopedia of Conditions, Treatments, and Well-Being [3 volumes]: An Encyclopedia of Conditions, Treatments, and Well-Being. ABC-CLIO. p. 969. ISBN 9781440803833.
6. ^ a b Saloviita T, Ruusila L, Ruusila U (August 2000). "Incidence of Savant Syndrome in Finland". Perceptual and Motor Skills. 91 (1): 120–2. doi:10.2466/pms.2000.91.1.120. PMID 11011882. S2CID 20306664.
7. ^ a b Kennedy DP, Squire LR (August 2007). "An analysis of calendar performance in two autistic calendar savants". Learning & Memory. 14 (8): 533–8. doi:10.1101/lm.653607. PMC 1951792. PMID 17686947.
8. ^ Treffert DA. "The Autistic Savant". Wisconsin Medical Society.
9. ^ "Savant Syndrome Statistics". Health Research Funding. 2014-07-12.
10. ^ a b Conway, Richard; Carney, Daniel P. J. (June 2006). "Calendrical savants: Exceptionality and Practice". Cognition. 100 (2): B1–B9. doi:10.1016/j.cognition.2005.08.001. PMID 16157326. S2CID 34912923. Retrieved 9 October 2020.
11. ^ Cowan R, Frith C (May 2009). "Do calendrical savants use calculation to answer date questions? A functional magnetic resonance imaging study". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1417–24. doi:10.1098/rstb.2008.0323. PMC 2677581. PMID 19528025.
12. ^ Pring, Linda (2005). "Savant talent" (PDF). Developmental Medicine & Child Neurology. 47 (7): 500–503. doi:10.1017/S0012162205000976. PMID 15991873.
13. ^ Happé F, Vital P (May 2009). "What aspects of autism predispose to talent?". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1369–75. doi:10.1098/rstb.2008.0332. PMC 2677590. PMID 19528019. Lay summary – The Economist (April 16, 2009).
14. ^ a b Baron-Cohen S, Ashwin E, Ashwin C, Tavassoli T, Chakrabarti B (May 2009). "Talent in autism: hyper-systemizing, hyper-attention to detail and sensory hypersensitivity". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1377–83. doi:10.1098/rstb.2008.0337. PMC 2677592. PMID 19528020.
15. ^ Mottron L, Dawson M, Soulières I (May 2009). "Enhanced perception in savant syndrome: patterns, structure and creativity". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1385–91. doi:10.1098/rstb.2008.0333. PMC 2677591. PMID 19528021.
16. ^ Snyder A (May 2009). "Explaining and inducing savant skills: privileged access to lower level, less-processed information". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1399–405. doi:10.1098/rstb.2008.0290. PMC 2677578. PMID 19528023. Lay summary – The Economist (April 16, 2009).
17. ^ Snyder A (May 2009). "Explaining and inducing savant skills: privileged access to lower level, less-processed information". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1399–405. doi:10.1098/rstb.2008.0290. PMC 2677578. PMID 19528023.
18. ^ a b "Archived copy". Archived from the original on 2012-10-25. Retrieved 2012-10-06.CS1 maint: archived copy as title (link)
19. ^ Howlin P, Goode S, Hutton J, Rutter M (May 2009). "Savant skills in autism: psychometric approaches and parental reports". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1522): 1359–67. doi:10.1098/rstb.2008.0328. PMC 2677586. PMID 19528018. Lay summary – The Economist (April 16, 2009).
20. ^ Yant-Kinney M (2012-08-20). "An artist is born after car crash". The Inquirer. Philadelphia. Retrieved 2012-11-24.
21. ^ "'A ski accident left me with advanced mental abilities': US woman tells her extraordinary story". Daily Telegraph. 17 April 2015.
22. ^ Treffert, Darold. A Visual Feast
23. ^ Newschaffer CJ, Croen LA, Daniels J, Giarelli E, Grether JK, Levy SE, Mandell DS, Miller LA, Pinto-Martin J, Reaven J, Reynolds AM, Rice CE, Schendel D, Windham GC (2007). "The epidemiology of autism spectrum disorders". Annual Review of Public Health. 28: 235–58. doi:10.1146/annurev.publhealth.28.021406.144007. PMID 17367287.
24. ^ MacGregor, Brian (December 30, 2020). Festive Fun. Tamfourhill Leaflet (December 2020). Retrieved December 30, 2020. British acquired savant
25. ^ McGowan, Kat (March 13, 2013). Exploring Temple Grandin's Brain. Discover Magazine (April 2013). Retrieved June 20, 2018.
26. ^ Badcock, Christopher (2009). The Imprinted Brain: How Genes Set the Balance Between Autism and Psychosis. London: Jessica Kingsley. p. 29. ISBN 9781849050234.
## External links[edit]
* Derek Amato, piano player with Savant Syndrome
Classification
D
* ICD-9-CM: 315.8
External resources
* MedlinePlus: 001526
* GeneReviews: NBK1442
* v
* t
* e
Pervasive developmental disorders and autism spectrum
Main
* Causes
* Comorbid conditions
* Epidemiology
* Heritability
* Societal and cultural aspects
* Medical model
* Therapies
Diagnoses
* Autism spectrum (High-functioning autism
* Classic autism
* Asperger syndrome
* Pervasive developmental disorder not otherwise specified
* Childhood disintegrative disorder
* Rett syndrome)
Related conditions
* Alexithymia
* Attention deficit hyperactivity disorder
* Anxiety disorder (obsessive–compulsive disorder)
* Late talker
* Epilepsy
* Fragile X syndrome
* Hyperlexia
* Savant syndrome
* Sensory processing disorder
* Intellectual disability
* Developmental coordination disorder
* Multiple complex developmental disorder
Controversies
* Autism rights movement
* Autistic enterocolitis
* Facilitated communication
* MMR vaccine
* Rapid prompting method
* Thiomersal (Chelation)
Diagnostic scales
* Gilliam Asperger's disorder scale
* Autism Diagnostic Observation Schedule
* Autism Diagnostic Interview
* Autism-spectrum quotient
* Childhood Autism Rating Scale
Lists
* Autism-related topics
* Fictional characters
* Schools
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-aminobutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: Androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
*[lit.]: literal translation
*[CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
*[No.]: Number
*[XLSMA]: X-linked spinal muscular atrophies
*[DSMA]: Distal spinal muscular atrophies
*[EUA]: emergency use authorization
*[AAS]: anabolic–androgenic steroid
*[hCG]: human chorionic gonadotropin
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[SHBG]: Sex hormone binding globulin
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
*[Pub.L.]: Public Law (United States)
*[CFUs]: Colony-forming units
*[nm]: nanometer
*[CRF]: corticotropin-releasing factor
*[cAMP]: cyclic adenosine monophosphate
*[†]: Extinct
*[VDCCs]: voltage-dependent calcium channels
*[ADHD]: Attention-deficit hyperactivity disorder
*[CNS]: central nervous system
*[PPD]: Paranoid Personality Disorder
*[SzPD]: Schizoid Personality Disorder
*[StPD]: Schizotypal Personality Disorder
*[ASPD]: Antisocial Personality Disorder
*[BPD]: Borderline Personality Disorder
*[HPD]: Histrionic Personality Disorder
*[NPD]: Narcissistic Personality Disorder
*[AvPD]: Avoidant Personality Disorder
*[DPD]: Dependent Personality Disorder
*[OCPD]: Obsessive-Compulsive Personality Disorder
*[PAPD]: Passive-Aggressive Personality Disorder
*[DpPD]: Depressive Personality Disorder
*[SDPD]: Self-Defeating Personality Disorder
*[SaPD]: Sadistic Personality Disorder
*[m.]: married
*[MSM]: Men who have sex with men
*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
*[transl.]: translation
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-gated calcium channel
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
|
Savant syndrome
|
c2316458
| 27,599 |
wikipedia
|
https://en.wikipedia.org/wiki/Savant_syndrome
| 2021-01-18T18:44:07 |
{"umls": ["C2316458"], "wikidata": ["Q467265"]}
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.