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Platelet storage pool deficiencies (SPD) comprise a range of disorders encompassing variable degrees of reduction in the numbers and contents of dense granules (delta-granules), alpha-granules, or both (Weiss et al., 1979). In addition to the more frequently occurring disorders of dense granules only (delta-SPD), 2 disorders involving alpha-granule deficiencies have been characterized: alpha/delta-SPD, which includes patients with marked deficiencies of dense granules as well as more variable deficiencies of alpha-granules; and alpha-SPD, or the gray platelet syndrome (139090), in which severe reductions occur only in the alpha-granules and their contents. Both disorders are associated with impaired platelet function as indicated by decreased aggregation responses. Weiss et al. (1969) described a kindred in which 10 members in 4 generations had a bleeding diathesis. There were several instances of male-to-male transmission. Six of the affected members were studied and found to have impaired release of platelet adenosine diphosphate (ADP). The platelets were smaller than normal. The major symptom was easy bruising. Ingestion of aspirin interferes with release of ADP even though the storage pool is normal. In a later paper on the same family, Holmsen and Weiss (1970) postulated that these patients lack the storage, or nonmetabolic, pool of ADP. Because of reduced release of ADP, collagen-induced platelet aggregation was impaired. By electron microscopy, Weiss and Ames (1973) showed a marked decrease in platelet dense bodies. Since both serotonin and the storage pool of adenine nucleotides are deficient in these platelets, the dense bodies may normally store them. Willis and Weiss (1973) showed that prostaglandin production is impaired in this disorder. In studies of 18 patients, Weiss et al. (1979) identified several defects, indicating heterogeneity. In 7 patients with albinism (Hermansky-Pudlak syndrome; 203300) and in 4 other unrelated patients, they found a deficiency of dense granules and dense granule substances. They termed this delta-SPD. In 7 other patients, they observed variable deficiencies of alpha-granules and of heparin-neutralized activity (HNA), platelet factor 4 (PF4), beta-thromboglobulin, fibrinogen, and platelet-derived growth factor (PDGF) in addition to dense granule defects. The disorder in one of these with the greatest alpha-granule defects was designated as alpha-delta-SPD. The partial deficiency in alpha granules and granule-bound substances, observed in 6 members of 2 unrelated families, was designated alpha(P)-delta-SPD. The two types of granules are observed by electron microscopy: the more numerous alpha-granules of variable electron density and the less numerous, smaller granules of highest electron density. Delta-storage pool disease appears to be an autosomal recessive (see 203300). The 2 families with alpha(P)-delta-SPD had, in one, affected mother and 2 children and in the second (Iranian in extraction) affected father and daughter and son. In the first family, the platelets of the affected persons showed also a unique lipid defect and increased amounts of glycoprotein IV. Secretable acid hydrolases were normal in all these patients, a finding consistent with their storage in lambda granules (lysosomes). The fact that in delta-SPD with normal alpha-granules, HNA, PF4, beta-thromboglobulin, fibrinogen, and PDGF were normal supports the conclusion that these substances are stored in the alpha-granules. Dense granules store serotonin, calcium, pyrophosphate, ATP, and ADP. Weiss et al. (1980) pointed out that storage pool deficiency can be an acquired disorder. The proband in the family reported by Caen et al. (1968) died of primary pulmonary hypertension (178600). Herve et al. (1990) suggested that the pulmonary hypertension was a consequence of the inherited platelet storage deficiency associated with a high level of 5-hydroxytryptamine (5-HT) in plasma. Administration of ketanserin, a 5-HT antagonist, substantially reduced pulmonary hypertension. The proband had had episodes of excessive bleeding since infancy. Lages et al. (1991) demonstrated heterogeneity in SPD patients. Some with severe alpha/delta-SPD had only about half normal amounts of the alpha-granule membrane protein GMP-140 (173610) while others had normal GMP-140 content, as measured immunologically. Rosa et al. (1987) found that both the content and the surface expression of GMP-140 were similar to that in normal platelets in 2 patients with alpha-SPD. INHERITANCE \- Autosomal dominant HEMATOLOGY \- Mild-moderate prolonged bleeding time \- Decreased platelet aggregation \- Mild-moderate bleeding tendencies \- Absent platelet dense bodies \- Small platelets \- Impaired release of platelet adenosine diphosphate (ADP) LABORATORY ABNORMALITIES \- Mild-moderate prolonged bleeding time \- Decreased platelet aggregation MISCELLANEOUS \- Syndromic forms of dense granule only platelet storage pool deficiencies (delta-SPD) include Hermansky-Pudlak syndrome ( 203300 ) and Chediak-Hygashi syndrome ( 214500 ) \- Aquired delta-SPD seen in myeloproliferative disorders, myelodysplasia, and acute leukemia ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	STORAGE POOL PLATELET DISEASE	c0032197	28,900	omim	https://www.omim.org/entry/185050	2019-09-22T16:34:08	{"doid": ["2223"], "mesh": ["D010981"], "omim": ["185050"], "orphanet": ["734"], "synonyms": ["Alpha dense granule deficiency", "Combined alpha-delta platelet storage pool deficiency"]}
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (December 2010) (Learn how and when to remove this template message) Limbal nodule Limbus SpecialtyOphthalmology A limbal nodule is any nodular lesion at the limbus (junction of the cornea and sclera) of the eye. The differential diagnosis for a limbal nodule can include: * Pinguecula * Early Pterygium * Foreign body / foreign body granuloma * Phlycten, an inflamed nodule of lymphoid tissue * Episcleritis * Scleritis * Granuloma * Limbal dermoid, a kind of choristoma (NB: in other organs dermoid can refer to a teratoma) * malignant melanoma * naevus ## References[edit] * Hampton Roy; Daljit Singh; Richard J. Fugo (2010). Ocular Applications of the Fugo Blade. Lippincott Williams & Wilkins. p. 42. ISBN 1-60547-888-1. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Limbal nodule	None	28,901	wikipedia	https://en.wikipedia.org/wiki/Limbal_nodule	2021-01-18T18:44:45	{"wikidata": ["Q16965572"]}
Pelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system) that primarily affects males. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, Pelizaeus-Merzbacher disease involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. As a result, overall neurological function is reduced. Pelizaeus-Merzbacher disease is divided into classic and connatal (present from birth) types. Although these two types differ in severity, their features can overlap. Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills, such as sitting or grasping objects. Some individuals are able to walk with assistance. Despite these neurological problems, intellectual and motor skills develop throughout childhood, but development usually stops around adolescence, and these skills are slowly lost (developmental regression). As the condition worsens, nystagmus usually goes away but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), head and neck tremors (titubation), involuntary tensing of the muscles (dystonia), and jerking (choreiform) movements. Connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms can begin in infancy and include problems with feeding, poor weight gain and slow growth, high-pitched breathing caused by an obstructed airway (stridor), nystagmus, progressive speech difficulties (dysarthria), severe ataxia, hypotonia, and seizures. As the condition worsens, affected children develop spasticity leading to joint deformities (contractures) that restrict movement. Individuals with connatal Pelizaeus-Merzbacher disease are never able to walk, and many are not able to purposefully use their arms. They also have problems producing speech (expressive language) but can generally understand speech (receptive language). ## Frequency The prevalence of Pelizaeus-Merzbacher disease is estimated to be 1 in 200,000 to 500,000 males in the United States. This condition rarely affects females. ## Causes Mutations in the PLP1 gene cause Pelizaeus-Merzbacher disease. The PLP1 gene provides instructions for making proteolipid protein 1 and a modified version (isoform) of that protein called DM20. Proteolipid protein 1 is found primarily in nerves in the central nervous system and DM20 is produced mainly in nerves that connect the brain and spinal cord to muscles (peripheral nervous system). These two proteins are found within the cell membrane of nerve cells, where they make up the majority of myelin and anchor it to the cells. Most mutations that cause Pelizaeus-Merzbacher disease copy (duplicate) the PLP1 gene, which results in increased production of proteolipid protein 1 and DM20. Other mutations lead to production of abnormal proteins that are often misfolded. Excess or abnormal proteins become trapped within cell structures and cannot travel to the cell membrane. As a result, proteolipid protein 1 and DM20 are not available to form myelin. The accumulation of excess proteins leads to swelling and breakdown of nerve fibers. Still other mutations delete the PLP1 gene, which prevents proteolipid protein 1 and DM20 protein production and results in a lack of these proteins in the cell membrane, which causes any myelin that is formed to be unstable and quickly broken down. All of these PLP1 gene mutations lead to hypomyelination, nerve fiber damage, and impairment of nervous system function, resulting in the signs and symptoms of Pelizaeus-Merzbacher disease. It is estimated that 5 to 20 percent of people with Pelizaeus-Merzbacher disease do not have identified mutations in the PLP1 gene. In these cases, the cause of the condition is unknown. ### Learn more about the gene associated with Pelizaeus-Merzbacher disease * PLP1 ## Inheritance Pattern Pelizaeus-Merzbacher disease is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the PLP1 gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the PLP1 gene in each cell can lead to less severe features of the condition, such as muscle stiffness or a decrease in intellectual function, or may cause no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Pelizaeus-Merzbacher disease	c0205711	28,902	medlineplus	https://medlineplus.gov/genetics/condition/pelizaeus-merzbacher-disease/	2021-01-27T08:24:50	{"gard": ["4265"], "mesh": ["D020371"], "omim": ["312080"], "synonyms": []}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs additional citations for verification. Relevant discussion may be found on the talk page. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Salicylate sensitivity" – news · newspapers · books · scholar · JSTOR (December 2010) (Learn how and when to remove this template message) This article's factual accuracy is disputed. Relevant discussion may be found on the talk page. Please help to ensure that disputed statements are reliably sourced. (June 2017) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Salicylate sensitivity Other namesSalicylate intolerance Salicylic acid Salicylate sensitivity is any adverse effect that occurs when a usual amount of salicylate is ingested. People with salicylate intolerance are unable to consume a normal amount of salicylate without adverse effects. Salicylate sensitivity differs from salicylism, which occurs when an individual takes an overdose of salicylates.[1] Salicylate overdose can occur in people without salicylate sensitivity, and can be deadly if untreated. For more information, see aspirin poisoning. Salicylates are derivatives of salicylic acid that occur naturally in plants and serve as a natural immune hormone and preservative, protecting the plants against diseases, insects, fungi, and harmful bacteria. Salicylates can also be found in many medications, perfumes and preservatives. Both natural and synthetic salicylates can cause health problems in anyone when consumed in large doses. But for those who are salicylate intolerant, even small doses of salicylate can cause adverse reactions. ## Contents * 1 Symptoms * 2 Diagnosis * 3 Treatment * 4 History * 5 Terminology * 6 See also * 7 References * 8 Further reading * 9 External links ## Symptoms[edit] The most common symptoms of salicylate sensitivity are:[citation needed] * Stomach discomfort or Diarrhea[2] * Itchy skin, hives or rashes[2] * Asthma and other breathing difficulties[2] * Rhinitis, Sinusitis, Nasal polyps[2] * Pseudoanaphylaxis[2] * Angioedema * Headaches * Bed wetting or urgency to urinate * Changes in skin color/skin discoloration * Fatigue * Sore, itchy, puffy or burning eyes * Hyperactivity * Memory loss and poor concentration * Depression * Tinnitus ringing of the ears * Swelling of hands, feet, eyelids, face and/or lips Asthma and nasal polyps are also symptoms of Aspirin Exacerbated Respiratory Disease (AERD, Samter's Triad), which is not believed to be caused by dietary salicylates. ## Diagnosis[edit] There is no laboratory test for salicylate sensitivity. Typically testing is done by an "elimination challenge," to see if symptoms improve, or "provocative challenge," which intends to induce a controlled reaction as a means of confirming diagnosis. During provocative challenge, the person is given incrementally higher doses of salicylates, usually aspirin, under medical supervision, until either symptoms appear or the likelihood of symptoms appearing is ruled out. This only pertains to short-term symptoms such as digestive, respiratory, and skin itching, rather than slower-developing symptoms such as nasal polyps.[2] skin testing can assess for topical salicylate sensitivity. There is a test available called a Functional liver detox test which can tell a person if they are sensitive to salicylates. Drs in Australia can request the kit to be sent out. I believe it comes from the Royal Prince Alfred Hospital in NSW where they also produce a list of foods and their salicylate values. ## Treatment[edit] Salicylate sensitivity can be treated with the use of low-salicylate diets, such as the Feingold Diet and Failsafe Diets. The Feingold Diet removes artificial colors and preservatives and salicylates, whereas the Failsafe Diet removes salicylates, as well as amines and glutamates.[3] The range of foods that have no salicylate content is very limited, and consequently salicylate-free diets are very restricted. Montelukast is one form of treatment used in aspirin-intolerant asthma.[4] ## History[edit] An important salicylate drug is aspirin, which has a long history. Aspirin intolerance was widely known by 1975, when the understanding began to emerge that it is a pharmacological reaction, not an allergy.[5][6] ## Terminology[edit] Salicylate intolerance is a form of food intolerance or of drug intolerance. Salicylate sensitivity is a pharmacological reaction, not a true IgE-mediated allergy. However, it is possible for aspirin to trigger non-allergic hypersensitivity reactions.[7][8] About 5–10% of asthmatics have aspirin hypersensitivity, but dietary salicylates have been shown not to contribute to this. The reactions in AERD (Samter's triad) are due to inhibition of the COX-1 enzyme by aspirin, as well as other NSAIDs that are not salicylates. Dietary salicylates have not been shown to significantly affect COX-1.[9] Samter's triad refers to NSAID sensitivity in conjunction with nasal polyps and asthma.[10] ## See also[edit] * Aspirin-induced asthma * NSAID hypersensitivity reactions ## References[edit] 1. ^ "salicylism" at Dorland's Medical Dictionary 2. ^ a b c d e f Hanns-Wolf Baenkler. "Salicylate Intolerance: Pathophysiology, Clinical Spectrum, Diagnosis and Treatment". Pub Med. Retrieved 17 September 2020. 3. ^ Matthews J. "Feingold Diet / Failsafe Diet". Nourishing Hope. 4. ^ Kim SH, Ye YM, Hur GY, Lee SK, Sampson AP, Lee HY, Park HS (September 2007). "CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients". Pharmacogenomics. 8 (9): 1143–50. doi:10.2217/14622416.8.9.1143. PMID 17924829. 5. ^ Casterline CL (November 1975). "Intolerance to aspirin". American Family Physician. 12 (5): 119–22. PMID 1199905. 6. ^ Patriarca G, Venuti A, Schiavino D, Fais G (1976). "Intolerance to aspirin: clinical and immunological studies". Zeitschrift für Immunitatsforschung. Immunobiology. 151 (4): 295–304. doi:10.1016/s0300-872x(76)80024-8. PMID 936715. 7. ^ Palikhe NS, Kim SH, Park HS (October 2008). "What do we know about the genetics of aspirin intolerance?". Journal of Clinical Pharmacy and Therapeutics. 33 (5): 465–72. doi:10.1111/j.1365-2710.2008.00961.x. PMID 18834360. 8. ^ Narayanankutty A, Reséndiz-Hernández JM, Falfán-Valencia R, Teran LM (May 2013). "Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD)". Review. Clinical Biochemistry. 46 (7–8): 566–78. doi:10.1016/j.clinbiochem.2012.12.005. PMID 23246457. 9. ^ Jang AS, Park JS, Park SW, Kim DJ, Uh ST, Seo KH, Kim YH, et al. (November 2008). "Obesity in aspirin-tolerant and aspirin-intolerant asthmatics". Respirology. 13 (7): 1034–8. doi:10.1111/j.1440-1843.2008.01358.x. PMID 18699807. 10. ^ Kim JE, Kountakis SE (July 2007). "The prevalence of Samter's triad in patients undergoing functional endoscopic sinus surgery". Ear, Nose, & Throat Journal. 86 (7): 396–9. doi:10.1177/014556130708600715. PMID 17702319. ## Further reading[edit] * Parmet S, Lynm C, Glass RM (December 2004). "JAMA patient page. Aspirin sensitivity". JAMA. 292 (24): 3098. doi:10.1001/jama.292.24.3098. PMID 15613676. ## External links[edit] Classification D * ICD-9-CM: E935.3 * "Salicylate Sensitivity Forums and Food/Product Guides". SalicylateSensitivity.com. * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Salicylate sensitivity	c0004058	28,903	wikipedia	https://en.wikipedia.org/wiki/Salicylate_sensitivity	2021-01-18T18:51:32	{"umls": ["C0004058"], "icd-9": ["995.27"], "wikidata": ["Q7404457"]}
A number sign (#) is used with this entry because of evidence that immunodeficiency-43 (IMD43) is caused by homozygous mutation in the B2M gene (109700) on chromosome 15q21. Clinical Features Waldmann et al. (1968), Waldmann (1969), and Waldmann and Terry (1990) investigated a 34-year-old woman and her 17-year-old brother, products of a first-cousin marriage, who had marked reduction in serum concentrations of immunoglobulin and albumin (ALB; 103600). The total circulating and body pools of IgG were less than 28% of normal, although the IgG synthetic rates were in the normal range. IgG survival was short, with a 5-fold increase in catabolic rate. There was proteinuria or abnormality of renal or liver function and no circulating antibodies directed against either immunoglobulin or albumin. Furthermore, Waldmann and Terry (1990) excluded excessive gastrointestinal protein loss by normal fecal (51)Cr-labeled albumin tests. The hypercatabolic hypoproteinemia was associated with chemical diabetes mellitus and a skeletal deformity, i.e., shortened ulnae and bowed radii. Ardeniz et al. (2015) stated that the female sib reported by Waldmann and Terry (1990) reportedly had purple-red spots and ulcerations on her legs after age 21 years, and died of sepsis and bleeding at age 40. Her brother was asymptomatic, but lost to follow-up. Ardeniz et al. (2015) reported 2 sibs, born of consanguineous parents, with B2M deficiency. The proband was a 31-year-old woman with nasal perforation resulting from skin ulceration and diffuse ulcerated brown-violet-colored skin lesions on the extremities. The lesions appeared as subcutaneous nodules at 9 years of age during a flu-like infection and progressed slowly. She also had a history of recurrent lung infections resulting in bronchiectasis, and granulomatous dermatitis without identification of an infectious agent. Her 18-year-old brother was essentially asymptomatic, but had bronchiectasis associated with recurrent respiratory tract infections. Laboratory studies of both patients showed severe hypoproteinemia, decreased IgG with normal IgA and IgM, decreased alpha-beta CD8+ T cells, increased gamma-delta CD8+ T cells, and almost undetectable beta-2-microglobulin. Detailed in vitro studies of patient CD8+ T cells and NK cells showed defects in cytotoxic function. Family history included 3 sibs who died early in life and a sister who died at age 22 years with a diagnosis of 'cutaneous tuberculosis.' The findings were consistent with a complex immunodeficiency. Inheritance The transmission pattern of IMD43 in the family reported by Ardeniz et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In the 2 sibs reported by Waldmann (1969), Wani et al. (2006) identified a homozygous mutation in the B2M gene (109700.0001). Both sibs had B2M serum levels that were less than 1.0% of normal as well as soluble HLA levels that were less than 0.2% of normal. The neonatal Fc receptor (FcRn) (FCGRT; 601437) is a heterodimer of a nonclassical MHC class I alpha chain and B2M that binds the 2 most abundant serum proteins, IgG and albumin, after their constitutive cellular uptake. FcRn binds both proteins, thus acting as a salvage pathway, protecting them from lysosomal degradation and extending the catabolic half-lives of both proteins. In these sibs, deficiency of B2M and subsequent deficiency of FcRn resulted in increased catabolism of serum proteins. In 2 Turkish sibs, born of consanguineous parents, with IMD43, Ardeniz et al. (2015) identified a homozygous loss-of-function mutation in the B2M gene (109700.0003). Patient lymphocytes showed no detectable B2M surface protein expression, and serum levels of B2M were undetectable. MHC-I was undetectable on the surface of patient cells, and there was intracellular accumulation of the MHC-I heavy chain (see HLA-A, 142800). Surface expression of CD1A (188370), CD1B (188360), and CD1C (188340) was absent on monocyte-derived dendritic cells, consistent with the notion that B2M also stabilizes the surface expression of these molecules. There was also functional inactivation of NK cells and lack of invariant natural killer T cells (iNKT). Absent FcRn surface expression led to low serum IgG and albumin (103600) in both sibs. INHERITANCE \- Autosomal recessive RESPIRATORY \- Recurrent respiratory infections (family B) Lung \- Bronchiectasis (family B) SKELETAL Limbs \- Short forearms (family A) \- Short ulnae (family A) \- Bowing of the radii (family A) SKIN, NAILS, & HAIR Skin \- Granulomatous dermatitis (in some patients) \- Purple-red skin lesions (in some patients) \- Skin ulcerations (in some patients) IMMUNOLOGY \- Decreased serum IgG \- Decreased B cells (family B) \- Decreased NK cells (in some patients) \- Decreased alpha-beta CD8+ T cells (family B) \- Increased delta-gamma CD8+ T cells (family B) \- Decreased or absent beta-2-microglobulin \- Decreased cell surface expression of MHC-I \- Decreased expression of neonatal Fc receptor LABORATORY ABNORMALITIES \- Hypoproteinemia due to hypercatabolism \- Decreased serum albumin MISCELLANEOUS \- Two unrelated families have been reported (last curated November 2015) \- Variable severity \- Some patients may be asymptomatic MOLECULAR BASIS \- Caused by mutation in the beta-2-microglobulin gene (B2M, 109700.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	IMMUNODEFICIENCY 43	c1858266	28,904	omim	https://www.omim.org/entry/241600	2019-09-22T16:26:32	{"mesh": ["C565759"], "omim": ["241600"], "orphanet": ["34592"], "synonyms": ["Alternative titles", "BETA-2-MICROGLOBULIN DEFICIENCY", "B2M DEFICIENCY", "HYPOPROTEINEMIA, HYPERCATABOLIC"]}
Subacute combined degeneration of spinal cord Diagram of the principal fasciculi of the spinal cord. (In subacute combined degeneration of spinal cord, the "combined" refers to the fact that the dorsal columns and lateral corticospinal tracts are both affected, in contrast to tabes dorsalis which is selective for the dorsal columns.) SpecialtyNeurology Subacute combined degeneration of spinal cord, also known as Lichtheim's disease[1][2] or Putnam-Dana syndrome,[3] refers to degeneration of the posterior and lateral columns of the spinal cord as a result of vitamin B12 deficiency (most common), vitamin E deficiency,[4] and copper deficiency.[5] It is usually associated with pernicious anemia. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] The onset is gradual and uniform. The pathological findings of subacute combined degeneration consist of patchy losses of myelin in the dorsal and lateral columns. Patients present with weakness of the legs, arms, and trunk, and tingling and numbness that progressively worsens. Vision changes and change of mental state may also be present. Bilateral spastic paresis may develop and pressure, vibration and touch sense are diminished. A positive Babinski sign may be seen.[6] Prolonged deficiency of vitamin B12 leads to irreversible nervous system damage. HIV-associated vacuolar myelopathy can present with a similar pattern of dorsal column and corticospinal tract demyelination.[citation needed] It has been thought that if someone is deficient in vitamin B12 and folic acid, the vitamin B12 deficiency must be treated first. However, modern research has shown that folic acid will not exacerbate the symptoms of vitamin B12 deficiency.[7] And that if this were the case, then the mechanism remains unclear.[8] Administration of nitrous oxide anesthesia can precipitate subacute combined degeneration in people with subclinical vitamin B12 deficiency, while chronic nitrous oxide exposure can cause it even in persons with normal B12 levels. Posterior column dysfunction decreases vibratory sensation and proprioception (joint sense). Lateral corticospinal tract dysfunction produces spasticity and dorsal spinocerebellar tract dysfunction causes ataxia. ## Cause[edit] In general, the most common cause of this condition is a deficiency of vitamin B12. This may be due to a dietary deficiency, malabsorption in the terminal ileum, lack of intrinsic factor secreted from gastric parietal cells, or low gastric pH inhibiting attachment of intrinsic factor to ileal receptors.[9] Vitamin E deficiency, which is associated with malabsorption disorders such as cystic fibrosis and Bassen-Kornzweig syndrome,[10] can cause a similar presentation due to the degeneration of the dorsal columns.[4] ## Diagnosis[edit] Serum vitamin B12, methylmalonic acid, Schilling test, and a complete blood count, looking for megaloblastic anemia if there is also folic acid deficiency or macrocytic anemia. The Schilling test is no longer available in most areas.[11] MRI-T2 images may reveal increased signal within the white matter of the spinal cord, predominantly in the posterior columns and possibly in the spinothalamic tracts. ## Treatment[edit] Therapy with vitamin B12 results in partial to full recovery where SACD has been caused by vitamin B12 deficiency, depending on the duration and extent of neurodegeneration. ## References[edit] 1. ^ synd/492 at Who Named It? 2. ^ L. Lichtheim. Zur Kenntnis der perniciösen Anämie. Verhandlungen des Deutschen Kongress für innere Medizin, 1889, 6: 84-96. 42: 1887. 3. ^ Pearce, J. M. S. (June 2008). "Subacute Combined Degeneration of the Cord: Putnam-Dana Syndrome". European Neurology. 60. doi:10.1159/000131715. 4. ^ a b Agamanolis, Dimitri P. (July 2014). "Nutritional CNS Disorders". Retrieved 13 September 2014. "Clinically, vitamin E deficiency causes a sensory peripheral neuropathy, ataxia, retinitis pigmentosa, and skeletal and cardiac myopathy. Neuropathological examination in such cases reveals loss of dorsal ganglionic neurons with degeneration of their peripheral and central axons (peripheral neuropathy and posterior column degeneration respectively). Neuroaxonal swellings are seen in the gracile and cuneate nuclei. Similar changes can be produced in rats and monkeys with experimental vitamin E deprivation." 5. ^ Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology. 2004 Jul 13;63(1):33-9. 6. ^ Hemmera B et al. Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings. J Neurol Neurosurg Psychiatry 1998;65:822-827 doi:10.1136/jnnp.65.6.822 7. ^ https://www.cambridge.org/core/services/aop-cambridge-core/content/view/D8C38CD6D49977957C5B098623459519/S0029665107005873a.pdf/div-class-title-folate-and-vitamin-b-span-class-sub-12-span-friendly-or-enemy-nutrients-for-the-elderly-a-href-fn001-ref-type-fn-a-div.pdf 8. ^ https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/nutritionreviews/74/7/10.1093_nutrit_nuw015/3/nuw015.pdf?Expires=1488023069&Signature=YwLo2YqL~dkimRwBF3eZ3TgB6IdtIU3PutgyACZruOlY9l1oVZhPLmOhkTfvLKX5N7IJWvWKb3rntY3ECOclDE47wHFHkrGpR1HTPYyQdQF55~13228rSMEfY1g1eAtMlqXBfduGQZ7f0Wh6-68eA4zlK4iuRtYbEMjIz8sP~96D8WlNqnjqhIn-AMPOFtKKqVGkYQF8MXtm7~mPzP9SxxmZ09pozWnet6X3pX8yB0Gx11HvNqk8mi2c5tponqc3iJeIHbZFoXHHayyJXrRokg3wXUoEpixgJom2klTTZ05Cs6SoQNxYHphagm0lPuXQ9Ly8G76lWPg4AQjuQh5rlg__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q 9. ^ Greenburg, Mark (2010). Handbook of Neurosurgery 7th Edition. New York: Thieme Publishers. pp. 1187–1188. ISBN 978-1-60406-326-4. 10. ^ Agamanolis, Dimitri P. (July 2014). "Nutritional CNS Disorders". Retrieved 13 September 2014. "Deficiency of the lipid-soluble vitamin E occurs in cases of intestinal malabsorption such as cystic fibrosis, congenital biliary atresia, intestinal resection, and abetalipoproteinemia (Bassen-Kornzweig syndrome)." 11. ^ Carmel, Ralph (2007). "The Disappearance of Cobalamin Absorption Testing: A Critical Diagnostic Loss". The Journal of Nutrition. 137 (11): 2481–2484. doi:10.1093/jn/137.11.2481. PMID 17951489. ## External links[edit] Classification D * ICD-10: G32.0, E53.8 * ICD-9-CM: 336.2, 266.2 * MeSH: D052879 * DiseasesDB: 12591 External resources * MedlinePlus: 000723 * 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 * 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 Focal lesions of the spinal cord General * Myelopathy * Myelitis * Spinal cord compression By location * Brown-Séquard syndrome * Posterior cord syndrome * Anterior cord syndrome * Central cord syndrome * Cauda equina syndrome Other * Polio * Demyelinating disease * Transverse myelitis * Tropical spastic paraparesis * Epidural abscess * Syringomyelia * Syringobulbia * Morvan's syndrome * Sensory ataxia * Tabes dorsalis * Abadie's sign * Subacute combined degeneration of spinal cord * Vascular myelopathy * Anterior spinal artery syndrome * Foix–Alajouanine 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Subacute combined degeneration of spinal cord	c0858516	28,905	wikipedia	https://en.wikipedia.org/wiki/Subacute_combined_degeneration_of_spinal_cord	2021-01-18T18:52:11	{"mesh": ["D052879"], "umls": ["C0858516"], "icd-9": ["266.2", "336.2"], "icd-10": ["E53.8", "G32.0"], "wikidata": ["Q1424137"]}
Ablepharon macrostomia syndrome Ablepharon macrostomia syndrome has an autosomal dominant mode of inheritance. Ablepharon macrostomia syndrome (AMS) is an extremely rare, autosomal dominant genetic disorder characterized by abnormal phenotypic appearances that primarily affect the head and face as well as the skull, skin, fingers and genitals. AMS generally results in abnormal ectoderm-derived structures.[1] The most prominent abnormality is the underdevelopment (microblepharon) or absence of eyelids – signifying the ablepharon aspect of the disease – and a wide, fish-like mouth – macrostomia. Infants presenting with AMS may also have malformations of the abdominal wall and nipples. Children with AMS might also experience issues with learning development, language difficulties and intellectual disabilities. AMS is caused by mutations in the TWIST2 gene, among others. It is closely related to Barber–Say syndrome in terms of phenotypic abnormalities. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 Research * 8 References * 9 External links ## Signs and symptoms[edit] AMS is generally characterized by abnormal appearances of the skin, eyes, fingers, genitals, head and face. Infants with AMS will have thin, redundantly wrinkled skin and excessive facial creases;[2] wide-set eyes with absent or severely underdeveloped eyelids and down-turned lower eyelids; and a wide, fish-like mouth that may be fused together at the corners. Other appearances of the face and head include: broad nasal bridge, wide, flared nostrils and thick and flared alae nasi (edges of the nostrils).[2] Abnormalities can also be seen in the hands and fingers, as infants with AMS will also have webbed fingers with limited ability to flex and extend the fingers.[3] Infants with AMS will also display small, rudimentary ears that are atypically low-set on the skull. Absence of the zygomatic bone is also possible. Skin may be dry and coarse, excessively wrinkled around the face and loose around the hands yet tight around the finger joints, leading to diminished use of the fingers.[1][3] Genital defects may include: ambiguous genitalia, a displaced and/or atypically small penis (micropenis), an absent scrotum around the testes and undescended testicles. Finally, alopecia and thin, sparse hair are also frequently observed. ## Causes[edit] Like Barber–Say syndrome, AMS is caused by mutations in the TWIST2 gene that affect a highly conserved residue of TWIST2 (twist-related protein 2). TWIST2 is a basic helix-loop-helix transcription factor that binds to E-box DNA motifs (5'-CANNTG-3') as a heterodimer and inhibits transcriptional activation.[4] Because TWIST2 mediates mesenchymal stem cell differentiation[5] and prevents premature or ectopic osteoblast differentiation,[6] mutations in TWIST2 that disrupt these functions by altering DNA-binding activity could explain many of the phenotypes of AMS.[7] Current research points to the substitution of the wild-type amino acid for Lysine at TWIST2 residue 75 as a significant genetic cause of AMS.[7] AMS is inherited in an autosomal dominant manner, in which an affected individual needs only one copy of the mutant allele in order to express the disease.[7][8] ## Mechanism[edit] The mesenchyme is a mesodermal embryonic tissue that can develop into a multitude of different tissues depending on the needs of the developing embryo. The mesenchyme can develop into blood, cartilage, and membranes. In a normal patient, TWIST2 is highly expressed during embryonic development, specifically in the craniofacial development and chondrogenisis. TWIST2 works to prevent the premature maturation of chondrogenic cells and osteoblasts, the cells that will form cartilage and bone respectively. The dominant mutation in TWIST2 leads to the chondrogenic and osteoblastic cells becoming mature prematurely. This then leads to the primary craniofacial deformities seen in AMS patients.[7] ## Diagnosis[edit] Ablepharon macrostomia syndrome can be diagnosed at birth by identification of characteristic physical findings, clinical evaluation, and specialized imaging techniques such as CT scans.[9] CT scans can confirm the absence of the zygomatic arch and abnormalities in the cranial and mandibular bones. An ophthalmologist can diagnose abnormalities in the eyelids and confirm microblepharon or ablepharon. Teams of specialist will typically work together to confirm diagnosis and assess treatment options. Pediatricians, gastroenterologists, dermatologists, urologists, and other care providers can be expected to aid in the diagnosis and treatment. ## Treatment[edit] Primary treatment focuses on relief of immediate symptoms such as providing lubrication to the eyes to relieve pain and dryness; antibiotics may also be prescribed to prevent infections and inflammation. Surgical measures can be taken and a plastic surgeon can correct the lack of eyelids through reconstructive surgery.[9] Surgery to correct malformations of the mouth, ears, genitals, fingers, and skin can also be performed as necessary. Macrostomia, the wide, fish-like mouth, can be corrected by a maxillofacial surgeon. The skin can be treated by means of creams to alleviate dryness and coarseness; in certain cases, botulinum toxin and skin grafts were used to improve the overall appearance. It is highly recommended that patients are able to seek the help of pediatric psychologists throughout the entire treatment process.[10] ## Prognosis[edit] While there is no cure for AMS, treatment plans provided by doctors can help improve development,[11] overall quality of life, and physical appearance. Physical appearance cannot be corrected to the "norm" but the life expectancy of patients diagnosed with AMS is normal.[12] ## Research[edit] Current research into AMS focuses on both underlying causes of the disease and surgical methods for treatment. Currently, a study in Tokyo, Japan is focusing on the role of other TWIST genes in AMS development, specifically the role of TWIST1 and the amino acid substitution that must occur to mutate the gene. TWIST1 mutations are believed to lead to craniosynostosis and ablepharon.[13] Clinical research focuses on the different surgical techniques used to treat the ablepharon aspect of AMS. The primary goal of such research is to determine which methods are most effective for the patient without being unnecessarily complex. According to a study conducted by the departments of ophthalmology in Sao Paulo and Lima, Peru, full thickness skin grafts have been shown to effectively treat microblepharon in patients with AMS without needing complicated surgeries.[14] ## References[edit] 1. ^ a b Ciriaco P, Carretta A, Negri G (August 2019). "Laryngo-tracheal stenosis in a woman with ablepharon macrostomia syndrome". BMC Pulmonary Medicine. 19 (1): 163. doi:10.1186/s12890-019-0921-8. PMC 6712709. PMID 31462237. 2. ^ a b De Maria B, Mazzanti L, Roche N, Hennekam RC (August 2016). "Barber-Say syndrome and Ablepharon-Macrostomia syndrome: An overview". American Journal of Medical Genetics. Part A. 170 (8): 1989–2001. doi:10.1002/ajmg.a.37757. PMID 27196381. 3. ^ a b "Ablepharon-Macrostomia Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2019-11-07. 4. ^ "TWIST2 - Twist-related protein 2 - Homo sapiens (Human) - TWIST2 gene & protein". www.uniprot.org. Retrieved 2019-01-25. 5. ^ Isenmann S, Arthur A, Zannettino AC, Turner JL, Shi S, Glackin CA, Gronthos S (October 2009). "TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment". Stem Cells. 27 (10): 2457–68. doi:10.1002/stem.181. PMID 19609939. 6. ^ Lee MS, Lowe G, Flanagan S, Kuchler K, Glackin CA (November 2000). "Human Dermo-1 has attributes similar to twist in early bone development". Bone. 27 (5): 591–602. doi:10.1016/S8756-3282(00)00380-X. PMID 11062344. 7. ^ a b c d Marchegiani S, Davis T, Tessadori F, van Haaften G, Brancati F, Hoischen A, et al. (July 2015). "Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes". American Journal of Human Genetics. 97 (1): 99–110. doi:10.1016/j.ajhg.2015.05.017. PMC 4572501. PMID 26119818. 8. ^ Rohena L, Kuehn D, Marchegiani S, Higginson JD (April 2011). "Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome". American Journal of Medical Genetics. Part A. 155A (4): 850–4. doi:10.1002/ajmg.a.33900. PMID 21595001. 9. ^ a b "Ablepharon-Macrostomia Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2019-04-19. 10. ^ Larumbe J, Villalta P, Velez I (2011). "Clinical variant of ablepharon macrostomia syndrome". Case Reports in Dermatological Medicine. 2011: 593045. doi:10.1155/2011/593045. PMC 3504267. PMID 23198177. 11. ^ "Ablepharon macrostomia syndrome". Global Genes. Retrieved 2019-12-13. 12. ^ "Ablepharon-Macrostomia Syndrome \| Hereditary Ocular Diseases". disorders.eyes.arizona.edu. Retrieved 2019-12-13. 13. ^ Takenouchi T, Sakamoto Y, Sato H, Suzuki H, Uehara T, Ohsone Y, Kosaki K (December 2018). "Ablepharon and craniosynostosis in a patient with a localized TWIST1 basic domain substitution". American Journal of Medical Genetics. Part A. 176 (12): 2777–2780. doi:10.1002/ajmg.a.40525. PMID 30450715. 14. ^ Cruz AA, Quiroz D, Boza T, Wambier SP, Akaishi PS (2020). "Long-Term Results of the Surgical Management of the Upper Eyelids in "Ablepharon"-Macrostomia Syndrome". Ophthalmic Plastic and Reconstructive Surgery. 36 (1): 21–25. doi:10.1097/IOP.0000000000001442. PMID 31373987. ## External links[edit] Classification D * ICD-10: GroupMajor.minor * OMIM: 200110 * MeSH: C535557 C535557, C535557 * DiseasesDB: 33818 * 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Ablepharon macrostomia syndrome	c1860224	28,906	wikipedia	https://en.wikipedia.org/wiki/Ablepharon_macrostomia_syndrome	2021-01-18T18:28:49	{"gard": ["3"], "mesh": ["C535557"], "umls": ["C1860224"], "orphanet": ["920"], "wikidata": ["Q3508585"]}
A rare, genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency in IFN-gammaR2, leading to impaired response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM). ## Epidemiology The prevalence is unknown. It was recently discovered in two patients. ## Clinical description The first reported patient with this deficiency presented with moderate mycobacterial infections secondary to BCG vaccination. She developed no other severe infections. The father of this patient was a heterozygous carrier of the mutation, but remained healthy. ## Etiology AD MSMD due to partial IFN-gammaR2 deficiency is caused by a heterozygous mutation in the IFNGR2 gene on chromosome 21q22.1-22.2 that encodes the IFN-gamma receptor ligand binding chain 2. The 186delC mutation corresponds to the first mutation conferring an AD partial IFN-gammaR2 deficiency. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency	None	28,907	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319589	2021-01-23T17:05:13	{"icd-10": ["D84.8"], "synonyms": ["Autosomal dominant MSMD due to partial IFNgammaR2 deficiency", "Autosomal dominant MSMD due to partial interferon gamma receptor 2 deficiency", "Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial interferon gamma receptor 2 deficiency"]}
A rare genetic connective tissue disorder typically characterized by the association of unexpected organ fragility (arterial/bowel/gravid uterine rupture) with inconstant physical features as thin, translucent skin, easy bruising and acrogeric traits. ## Epidemiology The true prevalence of vascular Ehlers-Danlos syndrome (vEDS) is unknown, due to underdiagnosis of both symptomatic and milder forms of the disease. Prevalence estimates range between 1/50 000 and 1/200 000. ## Clinical description Typical physical signs associated with vEDS are predominantly cutaneous, as easy bruising unrelated to trauma, thin translucent skin predominantly on the upper torso and abdomen, with abnormally visible veins. Wound healing may be delayed and may result in widened, papyraceous scars, particularly over prominent bony pressure points (knee). Extremities, particularly hands may appear prematurely aged (acrogeria). Characteristic facial features are prominent eyes, thin lips, sunken cheeks and a pinched nose. Hair loss, particularly notable in women may also be present. Clinical complications of vEDS typically start to occur in the late teenage years, more rarely during childhood, and may repeat at unpredictable time intervals through the entire adult life. Most common complications are arterial accidents involving medium size arteries, including dissections, aneurysms, arterial rupture and arteriovenous fistulas. Spontaneous carotid-cavernous fistula is almost pathognomic of vEDS. Digestive complications are dominated by spontaneous perforations of the sigmoid colon. Solid organ rupture as liver or spleen, may also occur. Other complications are gravid uterine rupture or arterial rupture in the peripartum period. Spontaneous, often recurrent hemo/pneumothoraces are not uncommon. Varicose veins are also commonly present in vEDS patients at a young age. ## Etiology The disorder is caused by mutations in the COL3A1 gene (2q32.2), which encodes for the pro-alpha1-chains of type III procollagen. ## Diagnostic methods Diagnosis is suspected on the base of physical signs and clinical complications in probands, and requires the identification of a pathogenic variant within the COL3A1 gene by molecular genetic testing (single gene testing or multigene panel including COL3A1). ## Differential diagnosis Main differential diagnosis are other forms of Ehlers-Danlos syndromes, notably classical EDS (including COL1A1 variants leading to substitutions of arginine to cysteine residues in the triple helical domain), kyphoscoliotic EDS and periodontal EDS. Other rare connective tissue disorders are: Loeys-Dietz syndromes, polycystic kidney disease, and Marfan syndrome. In children with marked bruising, coagulation disorders and child abuse are sometimes considered. ## Antenatal diagnosis Preimplantation and prenatal genetic diagnosis can be considered in families where the mutation is known. ## Genetic counseling Half of vEDS patients have inherited the pathogenic variant from an affected parent. The other half of patients have a de novo pathogenic variant, except for rare cases of parental COL3A1 somatic mosaicism. The pattern of inheritance is typically autosomal dominant, and thus there is a 50% risk of transmitting the disease to offspring. Rare cases of biallelic mutations have been reported. Therefore, genetic counseling should be offered to affected families. ## Management and treatment Patient management requires a multidisciplinary care team, ideally in dedicated centers for vEDS patients. These centers coordinate follow-up of clinically silent patients and implement prophylactic measures. Acute onset, unexplained pain require emergency imaging by appropriate means to exclude arterial rupture. Acute arterial complications commonly require hospitalization with a conservative approach in most cases. Life-saving procedures (arterial rupture, bowel perforation, etc.) may require interventional radiology, vascular or bowel surgery. Medical management includes optimal blood pressure control to minimize arterial stress. Betablockers may be of interest in reducing arterial complications, but only one has been investigated in that indication (celiprolol). Angiotensin receptor blockers might also be beneficial and are currently being investigated. ## Prognosis Prognosis is variable and depends in part on the type of pathogenic COL3A1 variant. There is also an important intra- and interfamilial heterogeneity in the age of onset of complications and life expectancy for the same variant. Overall, patients with vEDS are exposed to recurrent organ complications, estimated at a rate of 1.6 events/5 years, 1.3 events/5 years for arterial complications. Overall life-expectancy is reduced to a median 51 years of age, but with an important range in age of survival for individual patients. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Vascular Ehlers-Danlos syndrome	c0268338	28,908	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=286	2021-01-23T18:57:23	{"gard": ["2082"], "mesh": ["D004535"], "omim": ["130050"], "umls": ["C0268338"], "icd-10": ["Q79.6"], "synonyms": ["Arterial-ecchymotic EDS", "EDS IV", "Ehlers-Danlos syndrome type 4", "Sack-Barabas syndrome", "vEDS"]}
A rare pituitary deficiency characterized by herniation of the subarachnoid space into the sella turcica, resulting in flattening of the pituitary gland and endocrine dysfunction. Most common endocrine abnormalities are hyperprolactinemia and growth hormone deficit. Clinical symptoms are highly variable and include headaches, irregular menstruation, galactorrhea, obesity, and visual disturbances, among others. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Pituitary deficiency due to empty sella turcica syndrome	c4275064	28,909	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91354	2021-01-23T17:12:39	{"icd-10": ["E23.0"], "synonyms": ["Hypopituitarism due to empty sella turcica syndrome"]}
Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma is a rare form of primary cutaneous T-cell lymphoma characterized by rapidly progressing, localized or disseminated nodules, tumors or eczematous skin lesions. It has a particularly aggressive clinical course with a high tendency to spread, in advanced stages, to extracutaneous locations (the central nervous system, lung, testes). Lymph nodes are often spared. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma	c4518232	28,910	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178528	2021-01-23T18:57:16	{"icd-10": ["C84.5"], "synonyms": ["Berti lymphoma", "Primary cutaneous epidermotropic cytotoxic CD8+ T-cell lymphoma"]}
A number sign (#) is used with this entry because of evidence that mandibulofacial dysostosis with alopecia (MFDA) is caused by heterozygous mutation in the EDNRA gene (131243) on chromosome 4q31. Clinical Features Cushman et al. (2005) described a 4-year-old Caucasian girl who presented at 27 months of age for evaluation of significant scalp alopecia and malformed ears. Examination at age 3 showed mild facial asymmetry and horizontal palpebral fissures with broad dimples at the lateral aspect of the eyes, small thin lashes, laterally displaced lacrimal punctae, and mild left eyelid coloboma. Her ears were low set and significantly malformed with crumpled helices and bilateral preauricular tags, with a pit anterior to the tag on the right; the ear canals appeared normal. Her mouth was slightly asymmetric, with normal teeth and intact palate. She also had significant alopecia, especially on the top of the head, with normal-appearing hair around the sides. External genitalia were normal, as were fingernails and toenails. Cushman et al. (2005) noted that this patient exhibited many of the features of Johnson-McMillin syndrome (147770) as well as features not previously reported in that phenotype, including preauricular pits and tags, broad depression at the lateral aspects of the eyes, and abnormal left lower eyelid. Zechi-Ceide et al. (2010) reported a 2-year-old boy who was noted at birth to have cleft palate and abnormal lower eyelids. Examination at 4 months of age showed sparse eyebrows and eyelashes, wide coloboma of the lower eyelid bilaterally, zygomatic hypoplasia, and bilateral mark on the cheek just below the lower lid coloboma. His lacrimal punctae were normal. He had a broad nasal bridge and tip, micrognathia, and cleft palate. Ears were small and prominent, showing lumps of extra tissue on the superior region of the helices as well as uptilted lobules; the external auditory canals were normal. Reevaluation at 2 years of age showed alopecia, slightly asymmetric mouth, delayed primary dentition, and hearing loss. External genitalia, skin pigmentation, and nails were normal. Zechi-Ceide et al. (2010) concluded that the facial phenotype of this patient was consistent with mandibulofacial dysostosis, and suggested that it could represent a severe form of Johnson-McMillin syndrome. Gordon et al. (2015) studied 3 patients with highly similar facial dysmorphism, including the boy previously reported by Zechi-Ceide et al. (2010), as well as a more mildly affected girl originally described by Cushman et al. (2005). Features included scalp alopecia, scant eyebrows and eyelashes, severe hypoplasia or aplasia of eyelids, lateral depression below eyes, small cupped dysplastic ears with ectopic tissue at the attachment of the helix to the scalp, conductive hearing loss, short nose with squared tip, cleft palate, dental anomalies, micrognathia, and limited jaw mobility. Craniofacial 3-dimensional CT scan in 3 patients revealed maxillary dysmorphism with dysplastic zygomatic arch and hypoplastic mandible in all. Gordon et al. (2015) designated the phenotype of the 4 patients mandibulofacial dysostosis with alopecia (MFDA). Molecular Genetics By whole-exome sequencing, Gordon et al. (2015) identified a de novo heterozygous missense mutation in the EDNRA gene (Y129F; 131243.0002) in a patient with mandibulofacial dysostosis and alopecia. Sanger sequencing confirmed that the mutation was present in the patient and absent in his parents. Sequencing of EDNRA in 2 more MFDA patients, including a boy previously reported by Zechi-Ceide et al. (2010), revealed de novo heterozygosity for the same missense mutation, for which 1 of the patients was somatic mosaic. Whole-exome sequencing of a more mildly affected girl who was originally described by Cushman et al. (2005) revealed somatic mosaicism for a different de novo missense mutation in the EDNRA gene (E303K; 131243.0003). INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Thin or absent scalp hair Face \- Facial asymmetry, mild \- Maxillary hypoplasia \- Zygomatic arch dysplasia \- Mandibular dysplasia \- Limited jaw mobility Ears \- Low-set ears \- Prominent ears \- Cupped ears \- Crumpled helices \- Ectopic tissue at attachment of helix to scalp \- Preauricular tags (in some patients) \- Preauricular pits (in some patients) \- Conductive hearing loss Eyes \- Sparse eyebrows \- Sparse eyelashes \- Horizontal palpebral fissures \- Hypoplasia or aplasia of eyelids \- Coloboma of lower eyelid (in some patients) \- Broad depression at inferolateral aspect of eyes \- Laterally displaced lacrimal punctae (rare) Nose \- Broad nasal bridge \- Square nasal tip Mouth \- Slightly asymmetric mouth \- Everted lower lip \- Cleft palate \- Glossoptosis (rare) Teeth \- Delayed eruption of primary teeth \- Irregular placement of primary teeth \- Agenesis of multiple permanent teeth \- Dental crowding CARDIOVASCULAR Heart \- Bicuspid aortic valve (rare) RESPIRATORY Nasopharynx \- Upper airway obstruction requiring tracheostomy (in some patients) GENITOURINARY Ureters \- Megaureter (rare) SKELETAL Skull \- Anterior displacement of coronal suture \- Zygomatic arch dysplasia \- Absent zygomatic process of temporal bone \- Maxillary dysmorphism \- Malar thickening \- Ventral orbital margins grossly dysplastic \- Lateral orbital margins hypoplastic or absent \- Mandibular hypoplasia \- Absent temporomandibular joints \- Broad flat condyles \- Deviation of nasal cavities \- Narrow external auditory canals \- Underpneumatized mastoids \- Small middle ear cavities \- Hypoplastic ossicular chains \- Retropositioned dental arcade (in some patients) \- Hypoplastic sphenoid wings (in some patients) \- Absent maxillary sinuses (in some patients) \- Hypoplastic pterygoid processes (in some patients) SKIN, NAILS, & HAIR Hair \- Scalp alopecia, near-complete \- Sparse eyebrows \- Sparse eyelashes \- Scant body hair MISCELLANEOUS \- De novo mutation \- Somatic mosaicism has been observed in some patients MOLECULAR BASIS \- Caused by mutation in the endothelin receptor type A gene (EDNRA, 131243.0002 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	MANDIBULOFACIAL DYSOSTOSIS WITH ALOPECIA	c4225349	28,911	omim	https://www.omim.org/entry/616367	2019-09-22T15:49:08	{"doid": ["0060365"], "omim": ["616367"], "orphanet": ["443995"], "synonyms": ["MFDA"]}
A number sign (#) is used with this entry because susceptibility to basal cell carcinoma (BCC7) is influenced by variation in the TP53 gene (191170) on chromosome 17p13.1. For a general phenotypic description and a discussion of genetic heterogeneity of basal cell carcinoma, see BCC1 (605462). Molecular Genetics To identify risk variants for cutaneous basal cell carcinoma, Stacey et al. (2011) performed a genomewide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. They imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222C (191170.0041) (odds ratio (OR) = 2.36, p = 5.2 x 10(-17)), which has a frequency of 0.0192 in the Icelandic population. Stacey et al. (2011) then confirmed this association in non-Icelandic samples (OR = 1.75, p = 0.0060; overall OR = 2.16, p = 2.2 x 10(-20)). rs78378222 is in the 3-prime untranslated region of TP53 (191170) and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3-prime-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (see 176807) (OR = 1.44, p = 2.4 x 10(-6)), glioma (OR = 2.35, p = 1.0 x 10(-5)), and colorectal adenoma (see 608812) (OR = 1.39, p = 1.6 x 10(-4)). There was no observed effect for breast cancer (see 114480). INHERITANCE \- Autosomal dominant NEOPLASIA \- Basal cell carcinoma, cutaneous MOLECULAR BASIS \- Susceptibility conferred by mutation in the tumor protein p53 gene (TP53, 191170.0041 ) ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	BASAL CELL CARCINOMA, SUSCEPTIBILITY TO, 7	c3553606	28,912	omim	https://www.omim.org/entry/614740	2019-09-22T15:54:21	{"omim": ["614740"]}
A rare subtype of acute myeloid leukemia characterized by clonal proliferation of poorly differentiated myeloid blasts in the bone marrow, blood or other tissues. It usually presents with anemia, thrombocytopenia and other nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Low remission rates are reported. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Acute myeloid leukemia with minimal differentiation	c0522631	28,913	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98832	2021-01-23T18:32:58	{"umls": ["C0522631"], "icd-10": ["C92.0"], "synonyms": ["AML M0", "Minimally differentiated acute myeloblastic leukemia"]}
Congenital unguarded mitral orifice is a rare, congenital, mitral valve malformation characterized by complete absence of mitral valve leaflets and tensor apparatus at the mitral annulus, which can present clinically with cyanosis, heart murmur, electrocardiogram abnormalities, mild cardiomegaly, or congestive heart failure. Association with heterotaxy, discordant atrioventricular connections, double-outlet right ventricle, pulmonary atresia or stenosis, thin left ventricular wall, and hypoplastic left heart syndrome has been reported. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Congenital unguarded mitral orifice	None	28,914	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99060	2021-01-23T16:59:00	{"icd-10": ["Q23.3"]}
A rare myeloproliferative neoplasm characterized by a clonal proliferation of eosinophilic precursors with persistent increase of eosinophils in peripheral blood and bone marrow, accompanied by increased blasts (<20%) or clonal cytogenetic or molecular genetic abnormalities. Cases with BCR-ABL1, PCM1-JAK2, ETV6-JAK2, or BCR-JAK2 fusion, or rearrangement of PDGFRA, PDGFRB, or FGFR1, are not included in this entity. Infiltration of the liver and spleen, as well as a variety of other organs, is typical. Patients may present with constitutional symptoms and signs and symptoms of organ involvement, such as endomyocardial fibrosis, peripheral neuropathy, central nervous system manifestations, respiratory symptoms, or rheumatological findings. Acute transformation is common. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Chronic eosinophilic leukemia	c0346421	28,915	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168940	2021-01-23T17:51:49	{"mesh": ["C580364"], "umls": ["C0346421"], "icd-10": ["D47.5"]}
A number sign (#) is used with this entry because of evidence that anterior segment dysgenesis-7 (ASGD7) is caused by homozygous or compound heterozygous mutation in the PXDN gene (605158) on chromosome 2p25. Description Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). In sclerocornea there is congenital, nonprogressive corneal opacification that may be peripheral, sectoral, or central in location. Visual prognosis is related to the central corneal involvement. The cornea has a flat curvature. The majority of cases are bilateral (summary by Smith and Traboulsi, 2012). Isolated sclerocornea is caused by displacement of the limbal arcades and may be associated with cornea plana; in this condition, the anterior chamber is visible and the eye is not microphthalmic. In complex sclerocornea, however, corneal opacification is associated with microphthalmia, cataract, and/or infantile glaucoma. The central cornea is usually relatively clear, but the thickness is normal or increased, never reduced (summary by Nischal, 2007). Clinical Features Khan et al. (2011) studied a consanguineous Pakistani family (family MEP60) segregating autosomal recessive cataract, microcornea, and corneal opacity, which the authors designated CCMCO. The 3 affected family members exhibited corneas that were 7 to 8 mm in diameter, and anterior segment examination showed that the peripherally located corneal opacity appeared to be due to the sclera encroaching on the cornea. Peripheral iridocorneal adhesion was also present. Vision was reduced to counting fingers in all 3 patients. The family history suggested that the changes were not progressive. Khan et al. (2011) reported a large consanguineous Pakistani family (family MEP59) in which 4 sibs and 2 cousins had corneal opacification as well as cataract and microcornea. The lens was of normal size and shape, and the fundus was normal by indirect ophthalmoscopy. Khan et al. (2011) also described a consanguineous Cambodian family (family CA2) with 4 affected sibs who had severe corneal opacification, 3 of whom also had bilateral buphthalmos and exhibited severe vascularization of the cornea. Elevated intraocular pressures were present in 3 of the sibs, including the patient without buphthalmos. The extent of corneal opacification prevented visualization of the anterior chamber or fundus, and the presence or absence of cataract could not be determined. Choi et al. (2015) reported 3 children from 2 families with mutations in the PXDN gene. In 1 family, a brother and sister both had sclerocornea, microphthalmia, and anterior segment dysgenesis. The brother had bilateral sclerocornea and microphthalmia with iridocorneal dysgenesis and glaucoma. The right eye was more severely affected than the left. His younger sister had bilateral sclerocornea, right microphthalmia, and anterior segment dysgenesis. In addition, both sibs had hypotonia and motor delays. Choi et al. (2015) also reported an unrelated boy who had a bilateral cataract that was smaller on the right side than the left, as well as bilateral anterior segment dysgenesis and left microphthalmia. He had normal psychomotor development at age 3.3 years; brain MRI was unremarkable. Inheritance Bloch (1965) reviewed familial reports of sclerocornea. Segregation analysis showed satisfactory agreement with a recessive hypothesis. Several instances of parental consanguinity were reported. From a review of the literature, Elliott et al. (1985) suggested that an autosomal dominant form of sclerocornea (187100) is mild, whereas an autosomal recessive form is severe. In both forms, sclerocornea is often associated with cornea plana (121400, 217300). Mapping In a consanguineous Pakistani family (MEP60) segregating autosomal recessive corneal opacity with cataract and microcornea, Khan et al. (2011) identified linkage to chromosomes 2ptel and 20p, with maximum lod scores of 1.94 and 3.09 for markers D2S281 and D20S473, respectively. In a consanguineous Pakistani family (MEP59) segregating autosomal recessive corneal opacification with cataract and microcornea, Khan et al. (2011) performed microsatellite genotyping of chromosomes 2p and 20p and observed a region of homozygosity on chromosome 2p in all 4 affected individuals; a maximum multipoint lod score of 2.31 was calculated at D2S323. In a consanguineous Cambodian family with severe corneal opacification and developmental glaucoma resulting in buphthalmos, Khan et al. (2011) performed homozygosity mapping and found that each of 4 affected sibs had a single region in common on chromosome 2pter, between the telomere and SNP rs1821797. Molecular Genetics In a consanguineous Pakistani family (MEP60) segregating autosomal recessive corneal opacity with cataract and microcornea, Khan et al. (2011) analyzed all coding exons and 20-bp flanking regions within the critical intervals on chromosomes 2 and 20, and identified homozygosity for a 1-bp deletion in the PXDN gene (605158.0001). The mutation, which segregated with disease in the family, was not found in 170 ethnically matched controls. In a similarly affected consanguineous Pakistani family (MEP59) with linkage to 2p, direct sequencing of PXDN revealed a homozygous missense mutation (R880C; 605158.0002) that segregated with disease and was not present in controls. In a consanguineous Cambodian family with severe corneal opacification and buphthalmos mapping to chromosome 2pter, affected individuals were homozygous for a nonsense mutation in PXDN (R341X; 605158.0003). In a brother and sister with sclerocornea, microphthalmia, and anterior segment dysgenesis, Choi et al. (2015) performed exome sequencing and identified compound heterozygosity for mutations in the PXDN gene: a maternally inherited nonsense mutation (R341X), and a paternally inherited 23-bp deletion (605158.0004). Analysis of existing exome data for 20 other families with developmental eye defects revealed a boy with microphthalmia, cataract, and anterior segment dysgenesis who was compound heterozygous for both a missense and a frameshift mutation in PXDN. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Corneal opacification, partial or total \- Sclerocornea \- Cataract \- Microcornea \- Iridocorneal dysgenesis \- Iridocorneal adhesion \- Increased intraocular pressure \- Buphthalmos \- Microphthalmia \- Anterior segment dysgenesis MISCELLANEOUS \- Variable features may be present MOLECULAR BASIS \- Caused by mutation in the peroxidasin gene (PXDN, 605158.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	ANTERIOR SEGMENT DYSGENESIS 7	c3151617	28,916	omim	https://www.omim.org/entry/269400	2019-09-22T16:22:28	{"omim": ["269400"], "orphanet": ["289499"], "synonyms": ["SCLEROCORNEA WITH OTHER OCULAR ANOMALIES", "Alternative titles", "CORNEAL OPACIFICATION WITH OTHER OCULAR ANOMALIES", "CCMCO"]}
A severe form of lysosomal acid lipase deficiency characterized by rapidly progressive lipid accumulation in organs and tissues that presents in the neonatal or infantile period with massive hepatosplenomegaly, liver failure, diarrhea/steatorrhea and vomiting. ## Epidemiology Approximately 50 cases have been reported in the literature. ## Clinical description The disease can sometimes present in the fetus (hepatomegaly, ascitis, calcified adrenal glands), but onset more typically occurs in the first weeks of life with abdominal distension and major or even massive hepatosplenomegaly (which can occur in the neonatal period) and sometimes ascites. The presence of calcified adrenal glands (as revealed by radiography), is a common and very characteristic sign. . Children present with significant digestive disorders (such as vomiting and diarrhoea with steatorrhoea), which can lead to a sudden arrest of ponderal growth and progressive psychomotor degradation in the absence of specific neurological signs. Later, severe anemia and cachexia become apparent. ## Etiology The enzymatic deficiency results from severe mutations of the acid lipase gene (LIPAor LAL), localised to 10q24-q25. ## Diagnostic methods The diagnosis can be rapidly confirmed by measuring enzymatic activity in leucocytes or dried blood spots , revealing an almost total deficiency. ## Differential diagnosis Differential diagnosis includes familial hemophagocytic histiocytosis and other phagocytic syndromes, Gaucher disease type II, Niemann-Pick disease type A, and malignancies such as leukemia or neuroblastoma. ## Antenatal diagnosis Prenatal diagnosis can be performed by measuring enzymatic activity or by mutational analysis of chorionic villi or amniocytes. ## Genetic counseling The disease follows an autosomal recessive pattern of inheritance. ## Management and treatment Enzyme replacement therapy with sebelipase lipase is available in the US and the European union and has been shown to prolong survival. Very early bone marrow or cord blood transplant has also been used and has provided some benefit in a limited number of cases. ## Prognosis In the absence of definitive therapy, few children survive beyond one year of age. Enzyme replacement therapy, if started in a timely fashion, may prolong survival but the long term impact remains unknown. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Wolman disease	c0043208	28,917	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75233	2021-01-23T19:11:02	{"gard": ["7899"], "mesh": ["D015223"], "omim": ["278000"], "umls": ["C0043208"], "icd-10": ["E75.5"]}
Isodicentric 15 Other namesNon-telomeric tetrasomy 15q[1] An example of Isodicentric 15. The steps between 4x, 3x and 2x can be seen. Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15), is a chromosome abnormality in which a child is born with extra genetic material from chromosome 15. People with idic(15) are typically born with 47 chromosomes in their body cells, instead of the normal 46. The extra chromosome is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). Individuals with idic(15) have a total of four copies of this chromosome 15 region instead of the usual two copies (1 copy each on the maternal and paternal chromosomes). The syndrome is also often referred to by the term Chromosome 15q11.2-q13.1 Duplication Syndrome, shortened to Dup15q syndrome. Dup15q syndrome is a privately owned term, it includes both idic(15) and interstitial 15q11.2-q13.1, another type of duplication that causes similar clinical traits. The extra chromosome is occasionally found in the mosaic state, i.e. some of the cells carry the marker chromosome. However, mostly because of the marker's instability and tendency to be lost during cell division (mitosis), some cells are completely normal with 46 chromosomes. Occasionally, cells may have more than one idic(15), resulting in 48 or 49 chromosomes in all or some of their cells. A similar clinical picture albeit to a milder degree could be expected in individuals that have the extra chromosome 15 material as an interstitial duplication (when the extra piece of chromosome 15 is included within the long arm of one of the two copies of chromosome 15, rather than as a small extra 'marker' chromosome) - often abbreviated to int dup(15); the individual thus having 46 chromosomes.[2][3] ## Contents * 1 Signs and symptoms * 2 Genetics * 2.1 Isodicentric chromosome 15 and autism * 3 Screening * 4 Diagnosis * 5 Management * 6 Epidemiology * 7 Research * 8 References * 9 External links ## Signs and symptoms[edit] The severity of symptoms of idic(15) vary greatly between individuals. Individuals with idic(15) usually have delays in language development and motor skills such as walking or sitting up. Other traits may include low muscle tone (hypotonia), seizures (>50%), short stature, and intellectual disability. Distinctive facial features associated with idic(15) - where present at all - are usually very subtle but may include epicanthal folds (skin folds at the inner corners of one or both eyes), downward slanting palpebral fissures, broad forehead, a flattened nasal bridge, button nose, and a high arched palate (roof of the mouth). Some individuals show other signs that can often be associated with chromosomal conditions, such as pectus excavatum, or a unilateral or bilateral single transverse palmar crease. Many individuals with idic(15) display features of autism, such as problems with communication and social interactions, obsessional interests (often with interactive mechanisms like wheels, doors or switches), unpredictable sleep cycles (and a reduced need for sleep), and repetitive and stereotyped behaviors (e.g., lining up toys, playing with a toy in the same manner over and over again, hand flapping, rocking back and forth). Sensory processing is often affected, especially the vestibular system. A high pain threshold is often observed.[4] If speech develops, it is often echolalic but some individuals do grasp some language. With a severely affected person there may be an inability to walk or talk.[citation needed] ## Genetics[edit] Generally, idic(15) is not inherited; it is said to appear de novo, in one member of the family, by chance. In most cases, the abnormal chromosome is generated in the mother's germ cells: the oocytes. This finding is due to ascertainment bias; cases with maternally derived idic(15) usually have clinical findings and attract attention, but those with paternally derived idic(15) usually do not. Thus, diagnosed cases are usually patients where the duplicated material is derived from the mother's egg cell rather than the father's sperm cell.[5] People with idic(15) have extra genetic material that has developed from chromosome 15. The material usually exists as a little extra chromosome 15; sometimes called a marker chromosome or an extra structurally abnormal chromosome (ESAC). The marker usually exists as an isodicentric chromosome; i.e. 2 copies of a specific part of the long arm of chromosome 15q11.2-q13.1 that is mirrored and doubled, with 2 centromeres and 2 DNA satellites. The smallest markers appear to be harmless and they may go undetected. However, if they are large enough to contain a number of important genes, they may result in "idic(15) syndrome" which is characterized by learning disabilities, autism and other neurological symptoms.[6] One of the regions responsible for the symptoms of idic(15) syndrome is the critical PWS/AS-region named after the Prader-Willi and/or Angelman syndromes.[citation needed] ### Isodicentric chromosome 15 and autism[edit] For more than 12 years, scientists have noticed that some individuals with autism also have idic(15). In fact, idic(15) is the most frequently identified chromosome problem in individuals with autism. (A chromosome anomaly involves extra or missing chromosomal material, not changes within the genes such as Fragile X syndrome). It is suggested that the co-occurrence of autism and idic(15) is not by chance. There may be a gene or genes in the 15q11-q13 region that is/are related to the development of autism in some individuals.[citation needed] Genetic research studies of individuals without chromosome anomalies also support this idea that an autism-related gene may be present in 15q11.2-q13.1 Specifically, research studies found that certain DNA markers from the (15q1.2-q13.1) region were found more often in individuals with autism than in individuals without autism. Although these DNA markers are too small to be genes, they suggest that researchers may be getting close to finding an autism gene in this region.[7] A recent study reported the introduction of two extra copies of just a single gene present in the 15q11.2-q13.1 region, Ube3a, into mice to model the gene copy number expressed in the brain in idic(15).[8] These mice displayed autism-related behavioral deficits including impaired social interaction, reduced ultrasonic vocal communication, and increased repetitive behavior (self-grooming).[9] ## Screening[edit] In general, idic(15) occurs de novo but the parents must be karyotyped to make sure it is not inherited, mostly because this will affect the course of genetic counseling given to the family. If the abnormality is found prenatally and one of the parents harbour the marker, the child has a chance of not carrying the mutation. Further tests should however be done to prove the marker has not been rearranged while being inherited. This information is also necessary for counseling of future pregnancies. Each family is unique and should therefore be handled individually.[6] ## Diagnosis[edit] The extra chromosome in people with idic(15) can be easily detected through chromosome analysis (karyotyping). Additional tests are usually required. FISH (Fluorescent in situ hybridization) is used to confirm the diagnosis by distinguishing idic(15) from other supernumerary marker chromosomes. Array CGH can be used to determine the gene content and magnitude of copy number variation so that the clinical picture can be foreseen.[10] Interstitial duplications of chromosome 15 can be more difficult to detect on a routine chromosome analysis but are clearly identifiable using a 15q FISH study. Families should always discuss the results of chromosome and FISH studies with a genetic counselor or other genetics professionals to ensure accurate interpretation.[citation needed] ## Management[edit] At the present time, there is no specific treatment that can undo any chromosomal abnormality, nor the genetic pattern seen in people with idic(15). The extra chromosomal material in those affected was present at or shortly after conception, and its effects on brain development began taking place long before the child was born. Therapies are available to help address many of the symptoms associated with idic(15). Physical, occupational, and speech therapies along with special education techniques can stimulate children with idic(15) to develop to their full potential. In terms of medical management of the symptoms associated with Chromosome 15q11.2-q13.1 Duplication Syndrome, families should be aware that individuals with chromosome 15 duplications may tolerate medications differently and may be more sensitive to side effects for some classes of medications, such as the serotonin reuptake inhibitor type medications (SSRI).[11] Thus, these should be used with caution and any new medication should be instituted in a controlled setting, with slow titration of levels and with a clear endpoint as to what the expected outcome for treatment is. There is an increased risk of sudden, unexpected death among children and adults with this syndrome. The full cause is not yet understood but it is generally attributed to SUDEP (Sudden Unexplained Death in Epilepsy).[12] ## Epidemiology[edit] About half of all 'marker' chromosomes are idic(15) but idic(15) in itself is one of the rare chromosome abnormalities. Incidence at birth appears to be 1 in 30,000[13] with a sex ratio of almost 1:1; however, since dysmorphic features are absent or subtle and major malformations are rare, chromosome analysis may not be thought to be indicated, and some individuals, particularly in the older age groups, probably remain undiagnosed.[13] There are organizations for families with idic(15) children that offer extensive information and support.[3] ## Research[edit] Spontaneous EEG recordings (right) from a 28-month-old child with idic(15) show diffuse beta frequency oscillations that represent an EEG signature of idic(15) and Dup15q.[14] Patients with idic(15) and int dup(15) often feature a distinctive electroencephalography (EEG) signature or biomarker in the form of high amplitude spontaneous beta frequency (12–30 Hz) oscillations. This EEG signature was first noted as a qualitative pattern in clinical EEG readings and was later described quantitatively by researchers at the University of California, Los Angeles and their collaborators within the network of national Dup15q clinics.[14] This group of researchers found that beta activity in children with Dup15q syndrome is significantly greater than that observed in (1) healthy, typically developing children of the same age and (2) children of the same age and IQ with autism not caused by a known genetic disorder (i.e., nonsyndromic ASD). The EEG signature appears almost identical to beta oscillations induced by benzodiazepine drugs that modulate GABAA receptors, suggesting that the signature is driven by overexpression of duplicated GABAA receptor genes GABRA5, GABRB3, and GABRG3 found on 15q11.2-q13.1. Treatment monitoring and identification of molecular disease mechanisms may be facilitated by this biomarker.[citation needed] ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Duplication/inversion 15q11". www.orpha.net. Retrieved 22 May 2019. 2. ^ Hogart, Amber; Wu, David; Lasalle, Janine M.; Schanen, N. Carolyn (2008). "The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13.1". Neurobiology of Disease. 38 (2): 181–191. doi:10.1016/j.nbd.2008.08.011. PMC 2884398. PMID 18840528. 3. ^ a b IDEAS - Isodicentric 15 \| Welcome to IDEAS: IsoDicentric 15 Exchange Advocacy and Support \| Support and Advocacy for duplication 15q syndrome: IDIC15, IDIC(15), Interstitial d... Archived 2008-06-04 at the Wayback Machine 4. ^ Luchsinger, Kadi; Lau, Heather; Hedlund, Julie L; Friedman, Daniel; Krushel, Kara; Devinsky, Orrin (2016). "Parental-reported pain insensitivity in Dup15q". Epilepsy & Behavior. 55: 124–7. doi:10.1016/j.yebeh.2015.10.007. PMID 26773682. 5. ^ Cook E.H. Jr; Lindgren V.; Leventhal B.L.; Courchesne R.; Lincoln A.; Shulman C.; Lord C.; Courchesne E. (1997). "Autism or atypical autism in maternally but not paternally derived proximal 15q duplication". Am. J. Hum. Genet. 60 (4): 928–934. PMC 1712464. PMID 9106540. 6. ^ a b RJ McKinlay Gardner, Grant R. Sutherland. Chromosome Abnormalities and Genetic Counseling, 3rd Ed, Oxford University Press, New York 2004. ISBN 0-19-514960-2 7. ^ http://www.exploringautism.org/autism/iso_chr15.htm 8. ^ Smith, S. E. P.; Zhou, Y.-D.; Zhang, G.; Jin, Z.; Stoppel, D. C.; Anderson, M. P. (2011). "Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice". Science Translational Medicine. 3 (103): 103ra97. doi:10.1126/scitranslmed.3002627. PMC 3356696. PMID 21974935. 9. ^ "Science Translational Medicine: Making Mice with Autistic Behavior". 10. ^ Wang N.J.; Liu D.; Parokonny A.S.; Schanen N.C. (2004). "High-resolution molecular characterization of 15q11–q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage". Am. J. Hum. Genet. 75 (2): 267–281. doi:10.1086/422854. PMC 1216061. PMID 15197683. 11. ^ Schanen, C: Research update on chromosome 15 duplications – idic(15) and interstitial duplications: The duplication 15q syndrome. Presentation at 2005 International Conference on Isodicentric 15 and Related Disorders. 12. ^ "Physician Advisory - Dup15q". 13. ^ a b Battaglia A (2008). "The inv dup (15) or idic (15) syndrome (Tetrasomy 15q)". Orphanet J Rare Dis. 3: 30. doi:10.1186/1750-1172-3-30. PMC 2613132. PMID 19019226. 14. ^ a b Frohlich J., Senturk D., Saravanapandian V., Golshani P., Reiter L.T., Sankar R., Thibert R.L., DiStefano C., Huberty S., Cook E.H., Jeste S.S. (2016). "A Quantitative Electrophysiological Biomarker of Duplication 15q11. 2-q13. 1 Syndrome". PLOS ONE. 11 (12): e0167179. Bibcode:2016PLoSO..1167179F. doi:10.1371/journal.pone.0167179. PMC 5157977. PMID 27977700.CS1 maint: multiple names: authors list (link) ## External links[edit] Classification D * ICD-10: Q99.8 * MeSH: C580205 External resources * Orphanet: 3306 [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Isodicentric 15	c3711376	28,918	wikipedia	https://en.wikipedia.org/wiki/Isodicentric_15	2021-01-18T18:34:53	{"gard": ["5153"], "mesh": ["C580205"], "umls": ["C0795859", "C3711376"], "orphanet": ["3306"], "wikidata": ["Q2703116"]}
Laurence-Moon syndrome is a rare condition that affects many different parts of the body. Signs and symptoms vary but may include cerebellar ataxia; eye abnormalities (primarily affecting the choroid and retina); peripheral neuropathy; spastic paraplegia (progressive weakness and stiffness of the legs); intellectual disability; congenital (from birth) or childhood hypopituitarism; and short stature. Laurence-Moon syndrome is caused by changes (mutations) in the PNPLA6 gene and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person. Until recently, Laurence-Moon syndrome has been associated with Bardet-Biedl syndrome but newer research determined that they are separate 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Laurence-Moon syndrome	c0023138	28,919	gard	https://rarediseases.info.nih.gov/diseases/12635/laurence-moon-syndrome	2021-01-18T17:59:30	{"mesh": ["D007849"], "omim": ["245800"], "orphanet": ["2377"], "synonyms": ["LNMS"]}
Paraquat poisoning is a rare intoxication with paraquat (a non-selective bipyridilium herbicide that has been banned in Europe), usually occurring through ingestion of the poison, and that presents with caustic injury of the oral cavity and pharynx, as well as nausea, vomiting, epigastric pain, lethargy, loss of consciousness and fever. Patients may develop potentially life-threatening complications such as hepatic dysfunction, acute tubular necrosis and renal insufficiency, and respiratory failure (due to pulmonary fibrosis) due to its inherent toxicity and lack of effective treatment. Intoxication via inhalation, injection and dermal or mucus contact have also been reported. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Paraquat poisoning	c0238343	28,920	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=31827	2021-01-23T17:55:07	{"icd-10": ["T60.3"]}
A number sign (#) is used with this entry because of evidence that mitochondrial complex V deficiency nuclear type 4 (MC5DN4) is caused by mutation in the ATP5A1 gene (ATP5F1A; 164360) on chromosome 18q. One such family has been reported. Mutation in the ATP5A1 gene can also cause COXPD22 (616045), which shows some overlapping clinical features. For a general phenotypic description of the nuclear type of mitochondrial complex V deficiency and a discussion of genetic heterogeneity of mitochondrial complex V deficiency, see MC5DN1 (604273). Clinical Features Jonckheere et al. (2013) reported 2 sibs, born of unrelated Dutch parents, with fatal infantile encephalopathy. After birth, the infants were irritable with a high-pitched cry and showed horizontal and vertical nystagmus, abnormal primitive reflexes, and tonus dysregulation. Both died in the first weeks of life due to a severe encephalopathy characterized by intractable seizures manifest as apneic spells. Brain MRI of one of the sibs showed a progressive and severe encephalopathy characterized by hyperdense thalami and subcortical densities. Postmortem examination showed extensive cerebral damage, small cerebellum, damaged pons and brainstem, and cystic degeneration of the white matter. Other findings included hypoplastic lungs, small renal cysts, and small lipid droplets in skeletal muscle, all suggestive of a mitochondrial disease. Brain MRI of the younger sib showed progressive damage to the frontal and parietooccipital regions, the pyramidal tract, basal ganglia, cerebellum, and pons. Metabolic screening showed no abnormalities in either case. Patient fibroblasts showed decreased oxygen consumption rate, isolated complex V deficiency, and decreased complex V assembly. Inheritance The transmission pattern of MC5DN4 in the family reported by Jonckheere et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs with fatal infantile mitochondrial encephalopathy, Jonckheere et al. (2013) identified a heterozygous missense mutation in the ATP5A1 gene (R329C; 164360.0001) inherited from the unaffected father. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present in 1,200 control exomes. The sibs expressed only the mutant allele, the father expressed both the mutant and wildtype allele, and the mother expressed only the wildtype allele. Although no mutations were identified in the mother's ATP5A1 gene, there was no evidence for a splicing defect, and MLPA excluded gene rearrangements; the mother had only about 60% ATP5A1 mRNA, consistent with a gene expression defect. SNP analysis indicated that both patients inherited the same maternal allele. Complementation of patient fibroblasts with wildtype ATP5A1 completely normalized complex V amount and activity. The findings indicated that the ATP5A1 defect found in these patients was disease-causing, even though the exact nature of the mutation inherited from the mother remained unknown. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus RESPIRATORY \- Apneic episodes GENITOURINARY Kidneys \- Small renal cysts MUSCLE, SOFT TISSUES \- Lipid droplets seen on muscle biopsy NEUROLOGIC Central Nervous System \- Encephalopathy, progressive \- Irritability \- Seizures, intractable \- Abnormal primitive reflexes \- Tonus dysregulation \- Cerebral damage \- Thalamic lesions \- Subcortical lesions \- Small cerebellum \- Cystic degeneration of the white matter \- Pons damage \- Brainstem damage VOICE \- High-pitched cry LABORATORY ABNORMALITIES \- Fibroblasts show decreased mitochondrial complex V activity \- Decreased mitochondrial complex V assembly MISCELLANEOUS \- Onset at birth \- Death in first weeks of life \- Two sibs have been reported (last curated May 2013) MOLECULAR BASIS \- Caused by mutation in the ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1 (ATP5A1, 164360.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4	c3808899	28,921	omim	https://www.omim.org/entry/615228	2019-09-22T15:52:54	{"doid": ["0060333"], "omim": ["615228"], "orphanet": ["254913"], "synonyms": ["Alternative titles", "Isolated mitochondrial respiratory chain complex V deficiency", "MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, ATP5A1 TYPE"]}
An extremely rare developmental disorder characterized by bilateral, congenital and complete amputation of the distal extremities (amputation of distal epiphysis of the humerus, distal portion of the tibial diaphysis, aplasia of the radius, ulna, fibula) and aplasia of hands and feet (aplasia of carpal, metacarpal, tarsal, metatarsal and phalangeal bones). Rarely, an ectopic bone can be found at the distal end of the humerus. No other systemic manifestations have been reported and the disorder follows an autosomal recessive pattern of inheritance. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Acheiropodia	c0265559	28,922	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=931	2021-01-23T18:55:35	{"gard": ["376"], "mesh": ["C536014"], "omim": ["200500"], "umls": ["C0265559"], "icd-10": ["Q74.8"], "synonyms": ["Acheiropody"]}
Pyonephrosis SpecialtyUrology Pyonephrosis (Greek pyon "pus" + nephros "kidney") is an infection of the kidneys' collecting system. Pus collects in the renal pelvis and causes distension of the kidney. It can cause kidney failure.[1] ## Contents * 1 Causes * 2 Treatment * 3 See also * 4 References * 5 External links ## Causes[edit] Pyonephrosis is sometimes a complication of kidney stones, which can be a source of persisting infection. It may also occur spontaneously. It can occur as a complication of hydronephrosis or pyelonephritis. ## Treatment[edit] This requires drainage, best performed by ureteral stent placement or nephrostomy. ## See also[edit] * Pyelonephritis * Nephrotic syndrome ## References[edit] 1. ^ "pyonephrosis" at Dorland's Medical Dictionary ## External links[edit] Classification D * ICD-10: N13.6 * ICD-9-CM: 590.0, 590.1, 590.8 * MeSH: D053018 * SNOMED CT: 48631008 External resources * eMedicine: med/2851 * v * t * e Kidney disease Glomerular disease * See Template:Glomerular disease Tubules * Renal tubular acidosis * proximal * distal * Acute tubular necrosis * Genetic * Fanconi syndrome * Bartter syndrome * Gitelman syndrome * Liddle's syndrome Interstitium * Interstitial nephritis * Pyelonephritis * Balkan endemic nephropathy Vascular * Renal artery stenosis * Renal ischemia * Hypertensive nephropathy * Renovascular hypertension * Renal cortical necrosis General syndromes * Nephritis * Nephrosis * Renal failure * Acute renal failure * Chronic kidney disease * Uremia Other * Analgesic nephropathy * Renal osteodystrophy * Nephroptosis * Abderhalden–Kaufmann–Lignac syndrome * Diabetes insipidus * Nephrogenic * Renal papilla * Renal papillary necrosis * Major calyx/pelvis * Hydronephrosis * Pyonephrosis * Reflux nephropathy [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Pyonephrosis	c0034216	28,923	wikipedia	https://en.wikipedia.org/wiki/Pyonephrosis	2021-01-18T18:38:23	{"mesh": ["D053018"], "icd-9": ["590.1", "590.8", "590.0"], "icd-10": ["N13.6"], "wikidata": ["Q1047294"]}
Mucinous nevus Other namesNevus mucinosus SpecialtyDermatology Mucinous nevus is a rare cutaneous condition characterized by hamartoma that can be congenital or acquired.[1] ## See also[edit] * MRI burn * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. This dermatology 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Mucinous nevus	None	28,924	wikipedia	https://en.wikipedia.org/wiki/Mucinous_nevus	2021-01-18T18:48:37	{"wikidata": ["Q6931144"]}
A rare inherited inborn error of metabolism resulting in a severe zinc deficiency and characterized by acral dermatitis, alopecia, diarrhea and growth failure. ## Epidemiology The prevalence of Acrodermatitis enteropathica (AE) is unknown. It is more common in the North-West of Tunisia. ## Clinical description AE usually presents in the first 4-10 weeks of life in infants that are not breast-fed and at around the time of weaning in breast-fed infants, as cow's milk contains more zinc-binding phytates that impede zinc absorption. AE is characterized by eczematous pink scaly plaques that can become pustular, vesiculobullous, psoriasisform or crusted. Lesions usually involve the acral, periorificial and typically the anogenital areas. Skin lesions may evolve into erosions without treatment and are susceptible to secondary staphylococcal and candidal infections. Diarrhea, generalized alopecia and Beau-Reil lines on the nails are frequent manifestations. Paronychia, conjunctivitis, blepharitis and erythematous oral mucous membranes are also sometimes observed. Other features associated with severe and chronic zinc deficiency include failure to thrive, mental slowness, photophobia, hypogeusia, anemia, poor wound healing, hypogonadism in males, and delayed puberty. ## Etiology AE is due to a mutation in the SLC39A4 gene (8q24.3) that encodes a zinc transporter protein (called the Zip4 transporter). Zip4 is needed for the transcellular absorption of zinc into the enterocytes of the duodenum and jejunum where the ZnT-zinc transporters (that are not affected) allow for the transport of zinc into the bloodstream. Mutations in the SLC39A4 lead to zinc malapsorption. This can only be corrected by a high dietary intake of zinc that allows for a small fraction of zinc to be absorbed paracellularly, without the aid of Zip4. ## Diagnostic methods Diagnosis is based on clinical findings (diarrhea and acral dermatitis) as well as laboratory testing. Patients have low plasma zinc concentrations and low levels of serum alkaline phosphatase. Molecular genetic testing can identify a mutation in the SLC39A4 gene, confirming diagnosis of AE. ## Differential diagnosis Differential diagnoses include impetigo contagiosa, candidiasis, psoriasis, and other pathogen-related skin diseases. Sickle cell disease and related diseases, non-genetic or acquired causes of zinc deficiency such as glucagonoma (see these terms), chronic liver and renal diseases, nutritional deficiency, chronic inflammatory bowel diseases, AIDS, burn injuries, and excessive perspiration in hot climates should also be excluded. ## Genetic counseling AE is inherited autosomal recessively. Genetic counseling is recommended to identify other affected family members before the onset of symptoms. ## Management and treatment There is no cure for AE. In the majority of cases, zinc supplementation therapy results in the disappearance of AE symptoms, but this treatment is life-long and relapses can occur. Initial dosages of 5-10 mg/kg/day of elemental zinc, followed by maintenance doses of 1-2 mg/kg/day are recommended and are taken orally. Zinc sulphate is the best tolerated preparation, in most cases, but it can also be administered as acetate, gluconate and amino acid chelates. Zinc and copper levels should be monitored regularly. Dosages need to be increased during periods of growth, such as adolescence and during pregnancy, when relapses can occur. ## Prognosis With adherence to life-long zinc substitution therapy, the prognosis is good. Only when infants are left untreated can the disease be fatal. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Acrodermatitis enteropathica	c0221036	28,925	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=37	2021-01-23T18:46:10	{"gard": ["5723"], "mesh": ["C538178"], "omim": ["201100"], "umls": ["C0221036"], "icd-10": ["E83.2"], "synonyms": ["AEZ", "Acrodermatitis enteropathica, zinc deficiency type", "Inherited zinc deficiency"]}
PMM2 deficiency Other namesCarbohydrate-deficient Glycoprotein Syndrome (CDGS) Type Ia, Congenital Disorder of Glycosylation (CDG) Type Ia,Phosphomannomutase Deficiency[1],Jaeken Syndrome, PMM2-CDG , CDG1a PMM2 protein PMM2 deficiency or PMM2-CDG is a very rare genetic disorder caused by mutations in PMM2. It is an autosomal recessive disorder. A defective copy of the PMM2 gene is the most common cause of a disease called “congenital disorders of glycosylation” or “PMM2-CDG”. PMM2-CDG is the most common of a growing family of more than 130 extremely rare inherited metabolic disorders. Only about 1000 children and adults have been reported worldwide. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 References ## Signs and symptoms[edit] * Failure to thrive (FTT) \- Failure to gain weight and grow at the expected rate.[2] * Cerebellar hypoplasia \- Small cerebellum, which is the part of the brain that coordinates movement.[3][4][5][6][7] * Liver disease \- Elevated liver function tests.[8] * Pericardial effusion \- Fluid around the heart.[9] * Peripheral neuropathy (PN) \- Impaired nerve impulse transmission to the legs. Patients do not respond well to reflex tests.[10] * Strabismus \- Crossed eyes, mainly presented as infantile Esotropia[11] * Nystagmus \- Involuntary eye movements caused by Cerebellar ataxia.[11][12] * Hypotonia \- Weak muscle tone, commonly known as floppy baby syndrome.[13] ## Diagnosis[edit] PMM2 deficiency is diagnosed through genetic sequencing. More than 115 mutations in PMM2 gene have been found to cause this disease.[13] ## Treatment[edit] There is no cure for PMM2 deficiency. Treatment involves management of the symptoms that are apparent in each individual, including Physical Therapy to improve core strength and mobility, Occupational Therapy for coordination, Speech Therapy for talking and eating.[10] ## References[edit] 1. ^ Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E (May 1997). "Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome)". Nature Genetics. 16 (1): 88–92. doi:10.1038/ng0597-88. PMID 9140401. 2. ^ Al-Maawali AA, Miller E, Schulze A, Yoon G, Blaser SI (February 2014). "Subcutaneous fat pads on body MRI--an early sign of congenital disorder of glycosylation PMM2-CDG (CDG1a)". Pediatric Radiology. 44 (2): 222–5. doi:10.1007/s00247-013-2782-2. PMID 24037084. 3. ^ Izquierdo-Serra M, Martínez-Monseny AF, López L, Carrillo-García J, Edo A, Ortigoza-Escobar JD, et al. (February 2018). "Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy". International Journal of Molecular Sciences. 19 (2): 619. doi:10.3390/ijms19020619. PMC 5855841. PMID 29470411. 4. ^ Serrano NL, De Diego V, Cuadras D, Martinez Monseny AF, Velázquez-Fragua R, López L, Felipe A, Gutiérrez-Solana LG, Macaya A, Pérez-Dueñas B, Serrano M (September 2017). "A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG)". Orphanet Journal of Rare Diseases. 12 (1): 155. doi:10.1186/s13023-017-0707-0. PMC 5602850. PMID 28915903. 5. ^ de Diego V, Martínez-Monseny AF, Muchart J, Cuadras D, Montero R, Artuch R, Pérez-Cerdá C, Pérez B, Pérez-Dueñas B, Poretti A, Serrano M (September 2017). "Erratum to: Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG)". Journal of Inherited Metabolic Disease. 40 (5): 753–754. doi:10.1007/s10545-017-0056-0. PMID 28600669. 6. ^ Serrano M, de Diego V, Muchart J, Cuadras D, Felipe A, Macaya A, et al. (October 2015). "Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment". Orphanet Journal of Rare Diseases. 10: 138. doi:10.1186/s13023-015-0358-y. PMC 4623922. PMID 26502900. 7. ^ Barone R, Fiumara A, Jaeken J (July 2014). "Congenital disorders of glycosylation with emphasis on cerebellar involvement". Seminars in Neurology. 34 (3): 357–66. doi:10.1055/s-0034-1387197. PMID 25192513. 8. ^ Marques-da-Silva D, Dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P, Jaeken J, Cassiman D (March 2017). "Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature". Journal of Inherited Metabolic Disease. 40 (2): 195–207. doi:10.1007/s10545-016-0012-4. PMID 28108845. 9. ^ Footitt EJ, Karimova A, Burch M, Yayeh T, Dupré T, Vuillaumier-Barrot S, Chantret I, Moore SE, Seta N, Grunewald S (December 2009). "Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review". Journal of Inherited Metabolic Disease. 32 Suppl 1: S313-9. doi:10.1007/s10545-009-1262-1. PMID 19757145. 10. ^ a b Sparks SE, Krasnewich DM (1993). "PMM2-CDG (CDG-Ia)". In Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). GeneReviews®. Seattle (WA): University of Washington, Seattle. PMID 20301289. 11. ^ a b Messenger WB, Yang P, Pennesi ME (April 2014). "Ophthalmic findings in an infant with phosphomannomutase deficiency". Documenta Ophthalmologica. Advances in Ophthalmology. 128 (2): 149–53. doi:10.1007/s10633-014-9427-0. PMC 3990245. PMID 24493206. 12. ^ Coorg R, Lotze TE (October 2012). "Child Neurology: a case of PMM2-CDG (CDG 1a) presenting with unusual eye movements". Neurology. 79 (15): e131-3. doi:10.1212/WNL.0b013e31826e2617. PMID 23045520. 13. ^ a b "PMM2 gene". Genetics Home Reference. Retrieved 2018-03-12. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	PMM2 deficiency	c0349653	28,926	wikipedia	https://en.wikipedia.org/wiki/PMM2_deficiency	2021-01-18T18:57:30	{"gard": ["9826"], "mesh": ["C535739"], "orphanet": ["79318"], "wikidata": ["Q3508654"]}
STAC3 disorder (formerly known as Native American myopathy) is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with STAC3 disorder have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body that typically begins at birth. Muscle weakness underlies many of the characteristic features of STAC3 disorder. Affected individuals may have feeding and swallowing difficulties in infancy. They usually have delayed development of motor skills such as sitting, crawling, standing, and walking. Many have facial features described as "myopathic facies", which include drooping eyelids (ptosis), sunken cheeks, and a mouth often held in an open position and with the corners turned downward. Other distinctive facial features in people with STAC3 disorder can include a small lower jaw (micrognathia), an opening in the roof of the mouth (cleft palate), low-set ears that slant backward, eye openings that are shorter than average or that point downward (short or downslanting palpebral fissures), or an increased distance between the inner corners of the eyes (ocular telecanthus). Individuals with STAC3 disorder may also be born with joint deformities that restrict movement (contractures) or develop an abnormal side-to-side or back-to-front curvature of the spine (scoliosis or kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family. People with STAC3 disorder also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic drugs, which are used to block the sensation of pain, either given alone or in combination with a particular type of muscle relaxant. If given these drugs, people at risk of malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever (hyperthermia), increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless the drugs are stopped and the symptoms are treated promptly. ## Frequency STAC3 disorder was first found in individuals from the Lumbee Native American Tribe in North Carolina. The condition affects an estimated 1 in 5,000 people in this population. STAC3 disorder has since been found in other populations worldwide, though its prevalence is not known. ## Causes STAC3 disorder is caused by mutations in the STAC3 gene. This gene provides instructions for making a protein that plays a role in the tensing (contraction) of skeletal muscles. Muscle contractions are triggered by changes in the concentration of certain charged atoms (ions) in muscle cells. The STAC3 protein aids in the process that triggers the release of calcium ions within muscle cells to start (initiate) muscle contraction. The STAC3 protein interacts with two structures in muscle cells that are critical for calcium ion flow, dihydropyridine receptor (DHPR) and ryanodine receptor 1 (RYR1). However, STAC3's role in this formation is unclear. RYR1 forms a channel (the RYR1 channel) through which calcium ions can flow. In response to certain signals, DHPR turns on (activates) the RYR1 channel, and the activated RYR1 channel releases calcium ions stored in structures inside muscle cells. The resulting increase in the calcium ion concentration within muscle cells stimulates muscles to contract, allowing the body to move. STAC3 gene mutations reduce the amount or impair the function of the STAC3 protein. Although the mechanism is unclear, studies show that a shortage of functioning STAC3 protein prevents the release of stored calcium ions by RYR1 channels. A disruption in calcium ion release prevents muscles from contracting normally, leading to the muscle weakness characteristic of STAC3 disorder. It is unclear how these STAC3 gene mutations lead to malignant hyperthermia in susceptible individuals. Mutations in other genes related to malignant hyperthermia activate the RYR1 channel improperly in response to certain drugs. As a result, large amounts of calcium ions are released from storage within muscle cells, causing skeletal muscles to contract abnormally. An increase in calcium ion concentration also activates processes that generate heat (leading to hyperthermia) and produce excess acid (leading to acidosis). It is unknown if STAC3 gene mutations have a similar effect on RYR1 channel activity. ### Learn more about the gene associated with STAC3 disorder * STAC3 ## 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	STAC3 disorder	c1850625	28,927	medlineplus	https://medlineplus.gov/genetics/condition/stac3-disorder/	2021-01-27T08:25:21	{"gard": ["8432"], "mesh": ["C538343"], "omim": ["255995"], "synonyms": []}
Septic arthritis Other namesInfectious arthritis, joint infection Septic arthritis as seen during arthroscopy[1] SpecialtyOrthopedic surgery SymptomsRed, hot, painful single joint[2] Usual onsetRapid[2] CausesBacteria, viruses, fungi, parasites[3] Risk factorsArtificial joint, prior arthritis, diabetes, poor immune function[2] Diagnostic methodJoint aspiration with culture[2] Differential diagnosisRheumatoid arthritis, reactive arthritis, osteoarthritis, gout[2][3] TreatmentAntibiotics, surgery[2] MedicationVancomycin, ceftriaxone, ceftazidime[2] Prognosis15% risk of death (treatment), 66% risk of death (without treatment)[2] Frequency5 per 100,000 per year[3] Septic arthritis, also known as joint infection or infectious arthritis, is the invasion of a joint by an infectious agent resulting in joint inflammation.[3] Symptoms typically include redness, heat and pain in a single joint associated with a decreased ability to move the joint.[2] Onset is usually rapid.[2] Other symptoms may include fever, weakness and headache.[2][3] Occasionally, more than one joint may be involved.[3] Causes include bacteria, viruses, fungi and parasites.[3] Risk factors include an artificial joint, prior arthritis, diabetes and poor immune function.[2] Most commonly, joints become infected via the blood but may also become infected via trauma or an infection around the joint.[2] Diagnosis is generally based on aspirating joint fluid and culturing it.[2] White blood cells of greater than 50,000 mm3 or lactate greater than 10 mmol/l in the joint fluid also makes the diagnosis likely.[2][4] Initial treatment typically includes antibiotics such as vancomycin, ceftriaxone or ceftazidime.[2] Surgery may also be done to clean out the joint.[2] Without early treatment, long-term joint problems may occur.[2] Septic arthritis occurs in about 5 people per 100,000 each year.[3] It occurs more commonly in older people.[3] With treatment, about 15% of people die, while without treatment 66% die.[2] ## Contents * 1 Signs and symptoms * 1.1 Prosthetic joint * 2 Cause * 2.1 Risk factors * 2.2 Organisms * 2.2.1 List of organisms * 3 Diagnosis * 3.1 Joint aspiration * 3.2 Blood tests * 3.3 Imaging * 3.4 Differential diagnosis * 4 Treatment * 5 Epidemiology * 6 Outcomes * 7 References * 8 External links ## Signs and symptoms[edit] Septic arthritis most commonly causes pain, swelling and warmth at the affected joint.[2][5] Therefore, those affected by septic arthritis will often refuse to use the extremity and prefer to hold the joint rigidly. Fever is also a symptom; however, it is less likely in older people.[6] On physical examination, the septic joint should be ruled out of intra-articular (from inside the joint) or periarticular (around the joint such as bursa and skin) cause. Intra-articular arthritis usually results in severe limitation of the range of movement of the joint with the joint held in extended position; the joint space will be maximal in this position. In peri-articular arthritis, pain only occurs when the joint is moved, and the lesion usually lies in one specific area around the joint.[2] The most common joint affected is the knee.[6] Hip, shoulder, wrist and elbow joints are less commonly affected.[7] Spine, sternoclavicular and sacroiliac joints can also be involved. The most common cause of arthritis in these joints is intravenous drug use.[5] Usually, only one joint is affected. More than one joint can be involved if bacteria are spread through the bloodstream.[5] ### Prosthetic joint[edit] For those with artificial joint implants, there is a chance of 0.86 to 1.1% of getting infected in a knee joint and 0.3 to 1.7% of getting infected in a hip joint. There are three phases of artificial joint infection: early, delayed and late.[2] * Early – infection occurs in less than 3 months. Usual signs and symptoms are fever and joint pain, with redness and warmth over the joint operation site. The mode of infection is during the joint implant surgery. The usual bacteria involved are Staphylococcus aureus and gram negative bacilli.[2] * Delayed – infection occurs between 3 and 24 months. There would be persistent joint pain, due to loosening of the implant. The mode of infection is during the implant surgery. Common bacteria are coagulase-negative Staphylococcus and Cutibacterium acnes.[2] * Late – more than 24 months. It is usually presented with a sudden onset of joint pain and fever. The mode of infection is through the bloodstream. The bacteria involved are the same as those in septic arthritis of a normal joint.[2] ## Cause[edit] Septic arthritis is most commonly caused by a bacterial infection.[8] Bacteria can enter the joint by: * The bloodstream from an infection elsewhere (most common) * Direct penetration into the joint (arthrocentesis, arthroscopy, trauma)[2] * A surrounding infection in the bone or tissue (uncommon, from osteomyelitis, septic bursitis, abscess).[2][7][9] Microorganisms in the blood may come from infections elsewhere in the body such as wound infections, urinary tract infections, meningitis or endocarditis.[7] Sometimes, the infection comes from an unknown location. Joints with preexisting arthritis, such as rheumatoid arthritis, are especially prone to bacterial arthritis spread through the blood.[7] In addition, some treatments for rheumatoid arthritis can also increase a person's risk by causing an immunocompromised state.[2] Intravenous drug use can cause endocarditis that spreads bacteria in the bloodstream and subsequently causes septic arthritis.[2] Bacteria can enter the joint directly from prior surgery, intraarticular injection, trauma or joint prosthesis.[5][9][10] ### Risk factors[edit] The rate of septic arthritis varies from 4 to 29 cases per 100,000 person-years, depending on the underlying medical condition and the joint characteristics. For those with a septic joint, 85% of the cases have an underlying medical condition while 59% of them had a previous joint disorder.[2] Having more than one risk factor greatly increases risk of septic arthritis.[7] * Age over 80 years[2][7] * Diabetes mellitus[2][7] * Osteoarthritis[2] * Rheumatoid arthritis.[7] Risk of septic arthritis increases with anti-tumor necrosis factor alpha treatment.[2] * Immunosuppressive medication[2] * Intravenous drug abuse[2] * Recent joint surgery[7] * Hip or knee prosthesis and skin infection[2][7] * HIV infection[2][7] * Other causes of sepsis[2] ### Organisms[edit] Most cases of septic arthritis involve only one organism; however, polymicrobial infections can occur, especially after large open injuries to the joint.[10] Septic arthritis is usually caused by bacteria, but may be caused by viral, mycobacterial, and fungal pathogens as well. It can be broadly classified into three groups: non-gonoccocal arthritis, gonococcal arthritis, and others.[2] * Non-gonoccocal arthritis – These bacteria account for over 80% of septic arthritis cases and are usually staphyloccoci or streptococci.[2] Such infections most commonly come from drug abuse, cellulitis, abscesses, endocarditis, and chronic osteomyelitis.[2] Methicillin-resistant Staphylococcus aureus (MRSA) may affect 5 to 25% of the cases while gram negative bacilli affects 14 to 19% of the septic arthritis cases. Gram negative infections are usually acquired through urinary tract infections, drug abuse, and skin infections. Old people who are immunocompromised are also prone to get gram negative infections. Common gram negative organisms are: Pseudomonas aeruginosa and Escherichia coli.[2] Both gram positive and gram negative infections are commonly spread through the blood from an infective source; but can be introduced directly into the joint or from surrounding tissue.[5] It often affects older people, and often happens suddenly, involving only one joint. Joint aspiration cultures are positive in 90% of cases, while only 50% of blood cultures yield any organisms.[2] * Gonococcal arthritis – Neisseria gonorrhoeae is a common cause of septic arthritis in people who are sexually active and under 40 years old.[2][5] The bacteria is spread through the blood to the joint following sexual transmission. Other symptoms of disseminated gonococcal infection can include migration of joint pain, tenosynovitis and dermatitis.[2][10] Synovial fluid cultures are positive in 25 to 70% of the cases while blood cultures are seldom positive.[2] Apart from blood and joint cultures, swabs from urethra, rectum, pharynx, and cervix should also be taken. Polymerase chain reaction (PCR) is another useful way of identifying gonococcal infections if diagnosis is difficult and clinical presentation is similar to reactive arthritis.[2] * Others – Fungal and mycobacterial infections are rare causes of septic arthritis and usually have a slow onset of joint symptoms. Mycobacterial joint infection most commonly affects hip and knee joints, caused by reactivation of past mycobacterial infections, with or without signs and symptoms of tuberculosis in lungs. Synovial fluid cultures will be positive in 80% of the cases. However, acid fast smears are not useful. Histology is not specific to myocobacterial infection as there are other granulomatous diseases that can show similar histology.[2] Borrelia burgdorferi, a bacteria that causes lyme disease, can affect multiple large joints such as knee. Confirmation of Lyme disease is done through enzyme-linked immunosorbent assay (ELISA) followed by confirmation using Western Blot test. It cannot be cultured from synovial fluid. However, PCR testing yields 85% positive result from synovial fluid.[2] Viruses such as rubella, parvovirus B19, chikungunya, and HIV infection can also cause septic arthritis.[5] * Prosthetic joint infection – Artificial joint infection are usually caused by coagulase negative Staphylococci, Staphylococcus aureus, and gram negative bacilli. Concurrent infections by multiple organisms is also reported in 20% of the cases. The risk factors of prosthetic joint infections are: previous fracture, seropositive rheumatoid arthritis, obesity, revision arthroplasty, and surgical site infections.[2] #### List of organisms[edit] * Staphyloccoci (40%)[2] * Staphylococcus aureus – the most common cause in most age groups. Can be caused by skin infection, previously damaged joint, prosthetic joint or intravenous drug use.[7][10] * coagulase-negative staphylococci – usually due to prosthetic joint[5] * Streptococci – the second-most common cause[2][10] (28%)[2] * Streptococcus pyogenes – a common cause in children under 5[5] * Streptococcus pneumoniae * Group B streptococci – a common cause in infants[7] * Haemophilus influenzae[11] * Neisseria gonorrhoeae – the most common cause of septic arthritis in young, sexually active adults.[12] Multiple macules or vesicles seen over the trunk are a pathognomonic feature.[13] * Neisseria meningitidis[7][10] * Escherichia coli – in the elderly, IV drug users and the seriously ill[7] * Pseudomonas aeruginosa – IV drug users or penetrating trauma through the shoe[5][10] * M. tuberculosis, Salmonella spp. and Brucella spp. – cause septic spinal arthritis[14] * Eikenella corrodens – human bites[5] * Pasteurella multocida, bartonella henselae, capnocytophaga – animal bites or scratches[5] * Fungal species – immunocompromised state[7] * Borrelia burgdorferi – ticks, causes lyme disease[7] * Spirillum minus, Streptobacillus moniliformis– rat bites ## Diagnosis[edit] Synovial fluid examination[15][16] Type WBC per mm3 % neutrophils Viscosity Appearance Normal <200 0 High Transparent Osteoarthritis <5000 <25 High Clear yellow Trauma <10,000 <50 Variable Bloody Inflammatory 2,000-50,000 50-80 Low Cloudy yellow Septic arthritis >50,000 >75 Low Cloudy yellow Gonorrhea ~10,000 60 Low Cloudy yellow Tuberculosis ~20,000 70 Low Cloudy yellow Inflammatory = gout, rheumatoid arthritis, rheumatic fever Septic arthritis should be considered whenever a person has rapid onset pain in a swollen joint, regardless of fever. One or multiple joints can be affected at the same time.[2][5][6] The diagnosis of septic arthritis is based on physical exam and prompt arthrocentesis which yields synovial fluid from within the affected joint. This fluid should be collected before the administration of antibiotics and should be sent for gram stain, culture, leukocyte count with differential, and crystal studies.[5][7] This can include NAAT testing for N. gonorrhoeae if suspected in a sexually active person.[10] Other studies such as blood cultures, white blood cell count with differential, ESR, and CRP should also be included. However, white cell count, ESR, and CRP are nonspecific and could be elevated due to infection elsewhere in the body. Serologic studies should be done if lyme disease is suspected.[5][10] Blood cultures can be positive in 25 to 50% of those with septic arthritis due to spread of infection from the blood.[2] In children, the Kocher criteria is used for diagnosis of septic arthritis.[17] ### Joint aspiration[edit] Synovial fluid from a knee with septic arthritis In the joint fluid, the typical white blood cell count in septic arthritis is over 50,000-100,000 cells per 10−6/l (50,000-100,000 cell/mm3);[18] where more than 90% are neutrophils is suggestive of septic arthritis.[2] For those with prosthetic joints, white cell count more than 1,100 per mm3 with neutrophil count greater than 64% is suggestive of septic arthritis.[2] However, septic synovial fluid can have white blood cell counts as low as a few thousand in the early stages. Therefore, differentiation of septic arthritis from other causes is not always possible based on cell counts alone.[7][18] Synovial fluid PCR analysis is useful in finding less common organisms such as Borrelia species. However, measuring protein and glucose levels in joint fluid is not useful for diagnosis.[2] The Gram stain can rule in the diagnosis of septic arthritis, however, cannot exclude it.[7] Synovial fluid cultures are positive in over 90% of nongonoccocal arthritis; however, it is possible for the culture to be negative if the person received antibiotics prior to the joint aspiration.[5][7] Cultures are usually negative in gonoccocal arthritis or if fastidious organisms are involved.[5][7] If the culture is negative or if a gonococcal cause is suspected, NAAT testing of the synovial fluid should be done.[5] Positive crystal studies do not rule out septic arthritis. Crystal-induced arthritis such as gout can occur at the same time as septic arthritis.[2] A lactate level in the synovial fluid of greater than 10 mmol/l makes the diagnosis very likely.[4] ### Blood tests[edit] Laboratory testing includes white blood cell count, ESR and CRP. These values are usually elevated in those with septic arthritis; however, these can be elevated by other infections or inflammatory conditions and are, therefore, nonspecific.[2][5] Procalcitonin may be more useful than CRP.[19] Blood cultures can be positive in up to half of people with septic arthritis.[2][7] ### Imaging[edit] Imaging such as x-ray, CT, MRI or ultrasound are nonspecific. They can help determine areas of inflammation but cannot confirm septic arthritis.[9] When septic arthritis is suspected, x-rays should generally be taken.[7] This is used to assess any problems in the surrounding structures[7] such as bone fractures, chondrocalcinosis, and inflammatory arthritis which may predispose to septic arthritis.[2] While x-rays may not be helpful early in the diagnosis/treatment, they may show subtle increase in joint space and tissue swelling.[5] Later findings include joint space narrowing due to destruction of the joint.[9] Ultrasound is effective at detecting joint effusions.[9] CT and MRI are not required for diagnosis; but if the diagnosis is unclear or the joints are hard to examine (ie.sacroiliac or hip joints); they can help to assess for inflammation/infection in or around the joint (i.e. Osteomyelitis),[7][9] bone erosions, and bone marrow oedema.[2] Both CT and MRI scans are helpful in guiding arthrocentesis of the joints.[2] ### Differential diagnosis[edit] * Crystal induced arthritis such as gout or pseudogout[7][10] * Inflammatory arthritis[7][10] * Rheumatoid arthritis * Seronegative spondyloarthropathy such as ankylosing spondylitis or reactive arthritis * Traumatic arthritis due to hemarthrosis, fracture or foreign body[7] * Osteoarthritis[7][10] ## Treatment[edit] Treatment is usually with intravenous antibiotics, analgesia and washout and/or aspiration of the joint.[5][7] Draining the pus from the joint is important and can be done either by needle (arthrocentesis) or opening the joint surgically (arthrotomy).[2] Empiric antibiotics for suspected bacteria should be started. This should be based on Gram stain of the synovial fluid as well as other clinical findings.[2][5] General guidelines are as follows: * Gram positive cocci – vancomycin[2][7] * Gram negative cocci – Ceftriaxone[2] * Gram negative bacilli – Ceftriaxone, cefotaxime, or ceftazidime[7] * Gram stain negative and immunocompetent – vancomycin[7] * Gram stain negative and immunocompromised – vancomycin \+ third generation cephalosphorin[7] * IV drug use (possible pseudomonas aeruginosa) – ceftazidime +/- an aminoglycoside[5][7] Once cultures are available, antibiotics can be changed to target the specific organism.[5][7] After a good response to intravenous antibiotics, people can be switched to oral antibiotics. The duration of oral antibiotics varies, but is generally for 1–4 weeks depending on the offending organism.[2][5][7] Repeated daily joint aspiration is useful in the treatment of septic arthritis. Every aspirate should be sent for culture, gram stain, white cell count to monitor the progress of the disease. Both open surgery and arthroscopy are helpful in the drainage of the infected joint. During surgery, lysis of the adhesions, drainage of pus, and debridement of the necrtoic tissues are done.[2] Close follow up with physical exam & labs must be done to make sure the person is no longer feverish, pain has resolved, has improved range of motion, and lab values are normalized.[2][7] In infection of a prosthetic joint, a biofilm is often created on the surface of the prosthesis which is resistant to antibiotics.[20] Surgical debridement is usually indicated in these cases.[2][21] A replacement prosthesis is usually not inserted at the time of removal to allow antibiotics to clear infection of the region.[9][21] People that cannot have surgery may try long-term antibiotic therapy in order to suppress the infection.[9] The use of prophylactic antibiotics before dental, genitourinary, gastrointestinal procedures to prevent infection of the implant is controversial.[2] Low-quality evidence suggests that the use of corticosteroids may reduce pain and the number of days of antibiotic treatment in children.[22] ## Epidemiology[edit] Septic arthritis occurs in about 5 people per 100,000 each year.[3] It occurs more commonly in older people.[3] With treatment, about 15% of people die, while without treatment 66% die.[2] ## Outcomes[edit] Risk of permanent impairment of the joint varies greatly.[7] This usually depends on how quickly treatment is started after symptoms occur as longer lasting infections cause more destruction to the joint. The involved organism, age, preexisting arthritis, and other comorbidities can also increase this risk.[9] Gonococcal arthritis generally does not cause long term impairment.[5][7][9] For those with Staphylococcus aureus septic arthritis, 46 to 50% of the joint function returns after completing antibiotic treatment. In pneumococcal septic arthritis, 95% of the joint function will return if the person survives. One-third of people are at risk of functional impairment (due to amputation, arthrodesis, prosthetic surgery, and deteriorating joint function) if they have an underlying joint disease or a synthetic joint implant.[2] Mortality rates generally range from 10-20%.[9] These rates increase depending on the offending organism, advanced age, and comorbidities such as rheumatoid arthritis.[7][9][10] ## References[edit] 1. ^ Hagino, Tetsuo; Wako, Masanori; Ochiai, Satoshi (1 October 2011). "Arthroscopic washout of the ankle for septic arthritis in a three-month-old boy". Sports Medicine, Arthroscopy, Rehabilitation, Therapy & Technology. 3 (1): 21. doi:10.1186/1758-2555-3-21. PMC 3192658. PMID 21961455. 2. ^ 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 ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bx Horowitz, DL; Katzap, E; Horowitz, S; Barilla-LaBarca, ML (15 September 2011). "Approach to septic arthritis". American Family Physician. 84 (6): 653–60. PMID 21916390. 3. ^ a b c d e f g h i j k "Arthritis, Infectious". NORD (National Organization for Rare Disorders). 2009. Archived from the original on 21 February 2017. Retrieved 19 July 2017. 4. ^ a b Carpenter, CR; Schuur, JD; Everett, WW; Pines, JM (August 2011). "Evidence-based diagnostics: adult septic arthritis". Academic Emergency Medicine. 18 (8): 781–96. doi:10.1111/j.1553-2712.2011.01121.x. PMC 3229263. PMID 21843213. 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 Kasper, Dennis L.; Fauci, Anthony S.; Hauser, Stephen L.; Longo, Dan L.; Larry Jameson, J.; Loscalzo, Joseph (2015). "Infectious Arthritis". Harrison's principles of internal medicine. Kasper, Dennis L.,, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Longo, Dan L. (Dan Louis), 1949-, Jameson, J. Larry,, Loscalzo, Joseph (19th ed.). New York. ISBN 9780071802161. OCLC 893557976. 6. ^ a b c Margaretten, Mary E.; Kohlwes, Jeffrey; Moore, Dan; Bent, Stephen (2007-04-04). "Does this adult patient have septic arthritis?". JAMA. 297 (13): 1478–1488. doi:10.1001/jama.297.13.1478. ISSN 1538-3598. PMID 17405973. 7. ^ 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 ah ai aj ak al am an ao ap Goldberg, D.L.; Sexton, D.J. (2017). "Septic arthritis in adults". UpToDate. Waltham, MA: UpToDate Inc. 8. ^ Shirtliff, Mark E.; Mader, Jon T. (October 2002). "Acute Septic Arthritis". Clinical Microbiology Reviews. 15 (4): 527–544. doi:10.1128/CMR.15.4.527-544.2002. ISSN 0893-8512. PMC 126863. PMID 12364368. 9. ^ a b c d e f g h i j k l Shirtliff, Mark E.; Mader, Jon T. (2002-10-01). "Acute Septic Arthritis". Clinical Microbiology Reviews. 15 (4): 527–544. doi:10.1128/cmr.15.4.527-544.2002. ISSN 0893-8512. PMC 126863. PMID 12364368. 10. ^ a b c d e f g h i j k l m "Osteomyelitis and Septic Arthritis". Principles and practice of hospital medicine. McKean, Sylvia C.,, Ross, John J. (John James), 1966-, Dressler, Daniel D.,, Scheurer, Danielle (Second ed.). New York: McGraw-Hill Education. 2017. ISBN 9780071843133. OCLC 950203123.CS1 maint: others (link) 11. ^ Bowerman SG, Green NE, Mencio GA (August 1997). "Decline of bone and joint infections attributable to haemophilus influenzae type b". Clin. Orthop. Relat. Res. (341): 128–33. PMID 9269165. Peltola H, Kallio MJ, Unkila-Kallio L (May 1998). "Reduced incidence of septic arthritis in children by Haemophilus influenzae type-b vaccination. Implications for treatment". J. Bone Joint Surg. Br. 80 (3): 471–3. doi:10.1302/0301-620X.80B3.8296. PMID 9619939. 12. ^ Malik S, Chiampas G, Leonard H (November 2010). "Emergent evaluation of injuries to the shoulder, clavicle, and humerus". Emerg Med Clin North Am. 28 (4): 739–63. doi:10.1016/j.emc.2010.06.006. PMID 20971390. 13. ^ Kaandorp CJ, Dinant HJ, van de Laar MA, Moens HJ, Prins AP, Dijkmans BA (August 1997). "Incidence and sources of native and prosthetic joint infection: a community based prospective survey". Ann. Rheum. Dis. 56 (8): 470–5. doi:10.1136/ard.56.8.470. PMC 1752430. PMID 9306869. Weston VC, Jones AC, Bradbury N, Fawthrop F, Doherty M (April 1999). "Clinical features and outcome of septic arthritis in a single UK Health District 1982-1991". Ann. Rheum. Dis. 58 (4): 214–9. doi:10.1136/ard.58.4.214. PMC 1752863. PMID 10364899. 14. ^ O'Callaghan C, Axford JS (2004). Medicine (2nd ed.). Oxford: Blackwell Science. ISBN 978-0-632-05162-5. 15. ^ Flynn, John A.; Choi, Michael J.; Wooster, L. Dwight (2013). Oxford American Handbook of Clinical Medicine. OUP USA. p. 400. ISBN 978-0-19-991494-4. 16. ^ Seidman, Aaron J.; Limaiem, Faten (2019), "Synovial Fluid Analysis", StatPearls, StatPearls Publishing, PMID 30725799, retrieved 2019-12-19 17. ^ Kocher, Mininder S.; Mandiga, Rahul; Murphy, Jane M.; Goldmann, Donald; Harper, Marvin; Sundel, Robert; Ecklund, Kirsten; Kasser, James R. (June 2003). "A clinical practice guideline for treatment of septic arthritis in children: efficacy in improving process of care and effect on outcome of septic arthritis of the hip". The Journal of Bone and Joint Surgery. American Volume. 85-A (6): 994–999. doi:10.2106/00004623-200306000-00002. ISSN 0021-9355. PMID 12783993. S2CID 12100117. 18. ^ a b Courtney, Philip; Doherty, Michael (2013). "Joint aspiration and injection and synovial fluid analysis". Best Practice & Research Clinical Rheumatology. 27 (2): 137–169. doi:10.1016/j.berh.2013.02.005. PMID 23731929. 19. ^ Zhao, J; Zhang, S; Zhang, L; Dong, X; Li, J; Wang, Y; Yao, Y (August 2017). "Serum procalcitonin levels as a diagnostic marker for septic arthritis: A meta-analysis". The American Journal of Emergency Medicine. 35 (8): 1166–1171. doi:10.1016/j.ajem.2017.06.014. PMID 28623003. S2CID 27912349. 20. ^ Berbari, Elie; Baddour, L. M. (2017). "Prosthetic joint infection: Epidemiology, clinical manifestations, and diagnosis". UpToDate. Waltham, MA: UpToDate Inc. 21. ^ a b Barbari, Elie; Baddour, L. M. (2017). "Prosthetic joint infection: Treatment". UpToDate. Waltham, MA: UpToDate, Inc. 22. ^ Delgado-Noguera, Mario F; Forero Delgadillo, Jessica M; Franco, Alexis A; Vazquez, Juan C; Calvache, Jose Andres (2018-11-21). "Corticosteroids for septic arthritis in children". Cochrane Database of Systematic Reviews. 11: CD012125. doi:10.1002/14651858.cd012125.pub2. ISSN 1465-1858. PMC 6517045. PMID 30480764. ## External links[edit] Classification D * ICD-10: M00-M03 * ICD-9-CM: 711.0 * MeSH: D001170 * DiseasesDB: 29523 External resources * MedlinePlus: 000430 * eMedicine: med/3394 [1] * Patient UK: Septic arthritis * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Septic arthritis	c1692886	28,928	wikipedia	https://en.wikipedia.org/wiki/Septic_arthritis	2021-01-18T18:54:14	{"gard": ["6781"], "mesh": ["D001170"], "umls": ["C1692886"], "wikidata": ["Q924421"]}
Autosomal recessive protein C deficiency is an inherited blood clotting disorder characterized by serious protein C deficiency. The disease may be very severe and associated with neonatal purpura fulminans (NPF) or intracranial thromboembolism. It may also be a milder disorder where patients present with clotting (venous thromboembolism) in childhood, adolescence, or adulthood. It is caused by having changes in the PROC gene. The inheritance pattern is autosomal recessive. Treatment depends on the severity of the disease and may involve blood thinners, clot-dissolving medicines, or blood transfusions of fresh frozen plasma or highly purified protein C concentrate. In some cases, live donor liver transplantation which cures the 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Autosomal recessive protein C deficiency	c2930896	28,929	gard	https://rarediseases.info.nih.gov/diseases/13041/autosomal-recessive-protein-c-deficiency	2021-01-18T18:01:54	{"mesh": ["C535424"], "omim": ["612304"], "orphanet": ["745"], "synonyms": ["Autosomal recessive thrombophilia due to congenital protein C deficiency", "Autosomal recessive thrombophilia due to PC deficiency", "Severe hereditary thrombophilia due to congenital protein C deficiency", "Hereditary thrombophilia due to congenital protein C deficiency", "Hereditary thrombophilia due to PC deficiency", "Autosomal recessive hereditary thrombophilia due to protein C deficiency", "Thrombophilia due to protein C deficiency, autosomal recessive"]}
Sinonasal undifferentiated carcinoma (SNUC) is a type of cancer that develops in the sinuses of the head. SNUC occurs when cells from the layer of tissue that lines the sinuses (called the epithelium) rapidly increase in number, forming a mass. The first symptoms of SNUC may include difficulty breathing though the nose or mild facial pain. As SNUC progresses, other symptoms may include nosebleeds, facial numbness, or tingling in the face. SNUC is an aggressive cancer, meaning it grows rapidly and has a tendency to spread into healthy tissues nearby and to more distant parts of the body (metastasis). The cause of SNUC is still unknown. When possible, the treatment is the complete removal of the tumor, combined with radiation therapy and chemotherapy. In cases where the tumor can't be removed completely, the treatment is with radiation and chemotherapy. The risk of the tumor coming back (relapse) is high and the probability of cure is modest. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Sinonasal undifferentiated carcinoma	c1710096	28,930	gard	https://rarediseases.info.nih.gov/diseases/9249/sinonasal-undifferentiated-carcinoma	2021-01-18T17:57:42	{"mesh": ["C537344"], "umls": ["C1710096"], "synonyms": ["SNUC", "Highly aggressive undifferentiated carcinoma of the nasal cavity and paranasal sinuses"]}
A number sign (#) is used with this entry because of evidence that complex cortical dysplasia with other brain malformations-5 (CDCBM5) is caused by heterozygous mutation in the TUBB2A gene (615101) on chromosome 6p25. For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039). Clinical Features Cushion et al. (2014) reported 2 unrelated children with a severe neurodevelopmental disorder. A male child presented with infantile spasms at age 5 months, and was found to have hypsarrhythmia on EEG. Brain MRI showed a diffuse simplified gyral pattern with reduced volume of white matter, globular basal ganglia and thalami, enlarged ventricles, thin and dysmorphic corpus callosum, mild brainstem hypoplasia with a flattened pons, mild cerebellar vermis hypoplasia, and a mildly enlarged posterior fossa. At age 8 months, he had continued seizures and global developmental delay. The second child had a less severe phenotype. She presented with hypotonia at age 4 months. EEG showed multifocal epileptiform discharges, but clinically the seizures consisted only of subtle vertical eye movements. The seizures resolved, and she was weaned off medication at age 2 years. Brain MRI showed a dysmorphic corpus callosum but normal basal ganglia, thalami, and gyral pattern. At age 3 years, she was nonverbal and nonambulatory with generalized hypotonia. Molecular Genetics In 2 unrelated children with variable severity of complex cortical dysplasia with other brain malformations, Cushion et al. (2014) identified 2 different de novo heterozygous missense mutations in the TUBB2A gene (N247K, 615101.0001 and A248V, 615101.0002). The mutations were found by whole-exome sequencing. In vitro functional expression studies in HEK293 cells showed that the N247K mutant protein was unable to coassemble with endogenous alpha-tubulin (see 602529) subunits and to integrate into microtubule polymers. The mutant protein remained unpolymerized, suggesting that the mutation prevented correct protein processing. The A248V mutant protein showed a less severe effect; it incorporated into the in vitro cytoskeleton network, but with more of the mutant protein remaining unpolymerized in the cytoplasm compared to wildtype. The less severe functional effects of the A248V mutation correlated with the less severe phenotype in the patient with this mutation. INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay, severe \- Seizures \- Hypsarrhythmia (1 patient) \- Thin corpus callosum \- Simplified gyral pattern (1 patient) \- Enlarged ventricles (1 patient) \- Globular basal ganglia (1 patient) \- Globular thalamus (1 patient) \- Brainstem hypoplasia (1 patient) MISCELLANEOUS \- Onset in early infancy \- Variable severity \- Two unrelated patients have been reported (last curated April 2014) MOLECULAR BASIS \- Caused by mutation in the tubulin, beta-2A gene (TUBB2A, 615101.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 5	c3810407	28,931	omim	https://www.omim.org/entry/615763	2019-09-22T15:51:02	{"omim": ["615763"], "genereviews": ["NBK350554"]}
Harmful use of cocaine and amphetamine-type drugs Stimulant use disorder SpecialtyPsychiatry, Clinical psychology Stimulant use disorder is a type of substance use disorder that involves the abuse of stimulants. It is defined in the DSM-5 as "the continued use of amphetamine-type substances, cocaine, or other stimulants leading to clinically significant impairment or distress, from mild to severe".[1] These psychoactive drugs, known as stimulants, are the most widely used drugs in the world today. Approximately 200 million Americans have used some type of a stimulant in the past year alone.[2] ## Contents * 1 Definition * 2 Signs and symptoms * 2.1 Short-term effects * 2.2 Long-term effects * 2.3 Symptoms of the disorder * 3 Epidemiology * 3.1 Medical * 3.2 Recreational * 4 History * 5 See also * 6 References * 7 External links ## Definition[edit] A psychoactive drug, such as a stimulant, is a chemical or substance that affects one’s behavior, mind, and body. A stimulant can be smoked, injected, snorted, taken in pill form, chewed and even ingested in the form of a drink. Synthetic stimulants are becoming increasingly popular as users attempt to alter the chemicals in drugs to create different reactions, and ultimately steer clear of jail time, legal penalties and detection in drug screening efforts.[3] If a substance is used over a long period of time and the user becomes dependent upon it, a substance abuse issue begins to appear. Substance abuse may lead to substance dependence and with time, addiction. Both mental and physiological dependence requires the development of tolerance leading to withdrawal symptoms. Stimulants come in a very large variety of subtypes and among the most common are caffeine, nicotine, cocaine, methamphetamine, amphetamines, amphetamine congeners, electronic cigarettes, diet pills, plant stimulants, energy drinks, and the ever-evolving designer stimulants such as bath salts. Caffeine and nicotine are the most popular stimulants used today, with roughly 400 million cups of coffee consumed daily[4] and 36.5 million current cigarette smokers,[5] according to a 2015 study conducted by the Centers for Disease Control and Prevention.[6] Nicotine, however, is treated separately psychiatrically under tobacco use disorder. Conversely, caffeine misuse does not qualify as an addictive disorder; thus it can not be diagnosed as a stimulant use disorder or any other substance use disorder.[7] Certain isolated conditions related to caffeine are recognized in the DSM-5’s "substance related"[8] section, however: caffeine intoxication, caffeine withdrawal and other caffeine-induced disorders (e.g., Anxiety and Sleep Disorders).[9] ## Signs and symptoms[edit] ### Short-term effects[edit] Even in small doses, stimulants cause a decrease in appetite, an increase in physical activity and alertness, convulsions, an elevated body temperature, increased respiration, irregular heart beat and increased blood pressure;[10] some of which can cause sudden death depending upon the medical history of the user, even among first time users. ### Long-term effects[edit] The long-term abuse of stimulants can ultimately cause very serious medical issues, including addiction. Stimulant addiction, similarly to other kinds of addiction, involves neurobiological changes that cause sensitization of the reward system to the stimulus in question (stimulants, in this case). Chronic stimulant users frequently experience physiological changes that can be detrimental to quality of life and require long-term treatment.[11] ### Symptoms of the disorder[edit] The symptoms of stimulant use disorder include failure to control usage and frequency of use, an intense craving for the drug, increased use over time to obtain the same effects, known as a developed tolerance, and a continued use despite negative repercussions and interference in one’s everyday life and functioning.[12] Furthermore, a disorder is noted when withdrawal symptoms occur because of a decrease in the drug amount and frequency, as well as stopping the use of the drug entirely. These withdrawal symptoms can last for days, weeks, months, and on rare occasions, years, depending on the frequency and dosages used by the individual. These symptoms include, but are not limited to, increased appetite, decreased energy, depression, loss of motivation and interest in once pleasurable activities, anxiety, insomnia, agitation and an intense craving for the drug. Unless intensive medical and psychological treatment is sought after, there is a very high likelihood of relapse among the user.[13] ## Epidemiology[edit] The use of stimulants in humans causes rapid weight loss, cardiovascular effects such as an increase in heart rate, respirations and blood pressure, emotional or mental side effects such as paranoia, anxiety, and aggression, as well as a change in the survival pathway known as the reward/reinforcement pathway in our brain. An increase in energy, a reduced appetite, increased alertness and a boost in confidence are all additional side effects of stimulant use when introduced to the body.[14] ### Medical[edit] Currently, stimulants are used medically to treat certain types of asthma, the common cold, depression, obesity and a wide variety of physical pain and ailments. Most commonly, stimulants such as Adderall, Ritalin, and Vyvanse are prescribed for both children and adults diagnosed with attention deficit hyperactivity disorder (ADHD).[15] ### Recreational[edit] Recreationally speaking, stimulants are used to change one’s state of mind and users report feeling a "rush" as the central nervous system is flooded with dopamine and epinephrine and norepinephrine. This rush is caused by the sudden change in both the electrical and chemical activity in the brain. This alteration occurs when a stimulant is introduced, as it causes a manipulation in the natural energy chemicals which are forced out and released into the body when they are not needed. In terms of recreational use, it is common for the user to smoke, inject, snort and ingest stimulants, all of which create different effects in the body.[16] ## History[edit] Certain types of stimulants are found in plants and grow naturally. The tobacco plant, the cocoa shrub, yohimbe, the betel nut and the ephedra bush are just a few of the naturally occurring stimulants. Other forms of stimulants are man-made, with no naturally occurring plant base, and are instead created using synthetic chemicals. Often, this involves using prescription or over-the-counter pharmaceutical products as precursor materials.[17] Stimulants were first introduced to the medical community with the isolation of cocaine from the coca leaf in 1855, which is not only a stimulant but also a topical anesthetic. In 1879, Vassili von Anrep of the University of Würzburg conducted an experiment in which he applied cocaine to one side of a frog’s limbs before attempting an invasive medical procedure. Cocaine proved to be extremely effective as both an anesthetic and pain reducer.[18] In World War II, soldiers were medicated using a type of stimulant called amphetamines to keep both pilots and soldiers alert, full of energy and ready to fight. Amphetamines were given in pill form to American soldiers, as well as to Japanese and German military members.[19] It is estimated that German soldiers ingested roughly 35 million doses of Pervitin® through the course of the war. Pervitin® is a brand-name for methamphetamine, a drug that belongs to the stimulant class of drugs. The use of methamphetamine was an attempt by Nazi leadership to create "super soldiers" who felt no pain and operated with extreme energy and unwavering confidence. The United States, for comparison, had dispensed roughly 200 million Benzedrine® tablets. A mixture of amphetamine salts, these pills were favored for their ability to increase wakefulness and energy levels while simultaneously suppressing appetite.[20] The United States, around the year 1960, saw large increases in amphetamines sold as diet pills, with pharmaceutical companies recognizing the appetite suppressing and energy boosting effects stimulants could provide. It was estimated that worldwide sales of diet pills containing stimulants rocketed to over 10 billion tablets sold, and that between 6% and 8% of the U.S. population were prescribed these types of medications to aid in weight loss. Within a decade, the Comprehensive Drug Abuse Prevention and Control Act of 1970 was passed, the purpose of which was to make it more difficult for individuals to obtain these drugs, with or without a prescription. The rationale for the act were the dangerous and life-threatening side effects of such drugs, which became better understood during the 1960s.[21] ## See also[edit] * Nicotine dependence * Amphetamine dependence * Cocaine dependence * Substance use disorder ## References[edit] 1. ^ American Psychiatric Association. "Substance-Related and Addictive Disorders". In American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. doi:10.1176/appi.books.9780890425596.dsm16. 20 Feb 2017. 2. ^ Inaba, Darryl, William E. Cohen, and Michael E. Holstein. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Ashland, OR: CNS Productions, 1993. Print. 3. ^ American Psychiatric Association. "Substance-Related and Addictive Disorders". In American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. doi:10.1176/appi.books.9780890425596.dsm16. 20 Feb 2017. 4. ^ The Huffington Post. “America’s Coffee Obsession: Fun Fact’s that Prove We’re Hooked.” 2015. TheHuffingtonPost.com, Inc. 21 Feb 2017. http://www.huffingtonpost.com/2011/09/29/americas-coffee-obsession_n_987885.html 5. ^ Centers for Disease Control and Prevention. “Burden of Tobacco Use in the U.S.: Current Cigarette Smoking Among Aged 18 Years and Older.” 2017. Tips from Former Smokers™. 20 Feb 2017. https://www.cdc.gov/tobacco/campaign/tips/resources/data/cigarette-smoking-in-united-states.html 6. ^ Centers for Disease Control and Prevention. “Burden of Tobacco Use in the U.S.: Current Cigarette Smoking Among Aged 18 Years and Older.” 2017. Tips from Former Smokers™. 20 Feb 2017. https://www.cdc.gov/tobacco/campaign/tips/resources/data/cigarette-smoking-in-united-states.html 7. ^ "American Psychiatric Association Substance-Related and Addictive Disorders" (PDF). www.psychiatry.org. 2013. Retrieved 2020-07-08. 8. ^ "Substance-Related and Addictive Disorders", Diagnostic and Statistical Manual of Mental Disorders, DSM Library, American Psychiatric Association, 2013-05-22, doi:10.1176/appi.books.9780890425596.dsm16, ISBN 978-0-89042-555-8, retrieved 2020-07-08 9. ^ Addicott, Merideth A. (September 2014). "Caffeine Use Disorder: A Review of the Evidence and Future Implications". Current addiction reports. 1 (3): 186–192. doi:10.1007/s40429-014-0024-9. ISSN 2196-2952. PMC 4115451. PMID 25089257. 10. ^ National Institute on Drug Abuse. “What Are the Immediate (Short-Term) Effects of Methamphetamine Abuse?” Misuse of Prescription Drugs. Advancing Addiction Science. Sept 2013. NIH. 20 Feb 2017. https://www.drugabuse.gov/publications/research-reports/methamphetamine/what-are-immediate-short-term-effects-methamphetamine-abuse 11. ^ National Institute on Drug Abuse. “What Are the Long-Term Effects of Methamphetamine Abuse?” Misuse of Prescription Drugs. Advancing Addiction Science. Sept 2013. NIH. 20 Feb 2017. https://www.drugabuse.gov/publications/research-reports/methamphetamine/what-are-long-term-effects-methamphetamine-abuse 12. ^ National Institute on Drug Abuse. “What Are the Long-Term Effects of Methamphetamine Abuse?” Misuse of Prescription Drugs. Advancing Addiction Science. Sept 2013. NIH. 20 Feb 2017. https://www.drugabuse.gov/publications/research-reports/methamphetamine/what-are-long-term-effects-methamphetamine-abuse 13. ^ Inaba, Darryl, William E. Cohen, and Michael E. Holstein. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Ashland, OR: CNS Productions, 1993. Print. 14. ^ Yentis SM, Vlassakov KV (1999). "Vassili Von Anrep: Forgotten Pioneer of Regional Anesthesia". Anesthesiology. 90 (3): 890–5. doi:10.1097/00000542-199903000-00033. PMID 10078692. 15. ^ “Stimulant ADHD Medications: Methylphenidate and Amphetamines.”Misuse of Prescription Drugs. Advancing Addiction Science. Jan 2014. NIH. 20 Feb 2017. https://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines 16. ^ Yentis SM, Vlassakov KV (1999). "Vassili Von Anrep: Forgotten Pioneer of Regional Anesthesia". Anesthesiology. 90 (3): 890–5. doi:10.1097/00000542-199903000-00033. PMID 10078692. 17. ^ Inaba, Darryl, William E. Cohen, and Michael E. Holstein. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Ashland, OR: CNS Productions, 1993. Print. 18. ^ Yentis SM, Vlassakov KV (1999). "Vassili Von Anrep: Forgotten Pioneer of Regional Anesthesia". Anesthesiology. 90 (3): 890–5. doi:10.1097/00000542-199903000-00033. PMID 10078692. 19. ^ Inaba, Darryl, William E. Cohen, and Michael E. Holstein. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Ashland, OR: CNS Productions, 1993. Print. 20. ^ Inaba, Darryl, William E. Cohen, and Michael E. Holstein. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Ashland, OR: CNS Productions, 1993. Print. 21. ^ Inaba, Darryl, William E. Cohen, and Michael E. Holstein. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Ashland, OR: CNS Productions, 1993. Print. ## External links[edit] Classification D * ICD-10: F15.9 * ICD-9-CM: 303-305, 292.0 [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Stimulant use disorder	None	28,932	wikipedia	https://en.wikipedia.org/wiki/Stimulant_use_disorder	2021-01-18T18:38:29	{"icd-10": ["F15.10", "F14.10"], "wikidata": ["Q28208977"]}
Myoclonic epilepsy with ragged red fibers (MERRF) is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Symptoms usually first appear in childhood or adolescence after normal early development. The features of MERRF vary widely from individual to individual, even within families. Other common findings include hearing loss, short stature, optic atrophy, and cardiomyopathy with Wolff-Parkinson-White (WPW) syndrome. The diagnosis is based on clinical features and a muscle biopsy finding of ragged red fibers (RRF). In over 80% of cases, MERRF is caused by mutations in the mitochondrial gene called MT-TK. Several other mitochondrial genes have also been reported to cause MERRF, but many of the individuals with mutations in these other genes have additional signs and symptoms. Seizures associated with MERRF are generally treated with conventional anticonvulsant therapy. Coenzyme Q10 and L-carnitine are often used with the hope of improving mitochondrial function. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Myoclonic epilepsy with ragged red fibers	c0162672	28,933	gard	https://rarediseases.info.nih.gov/diseases/7144/myoclonic-epilepsy-with-ragged-red-fibers	2021-01-18T17:58:51	{"mesh": ["D017243"], "omim": ["545000"], "umls": ["C0162672"], "orphanet": ["551"], "synonyms": ["Merrf syndrome", "MERRF", "Myoclonic epilepsy associated with ragged red fibers", "Fukuhara syndrome", "Myoencephalopathy ragged-red fiber disease"]}
A rare neoplastic disease characterized by multiple, and on occasion single, asymptomatic, smooth, red-brown papulonodules located on the face, neck, trunk and/or extremities which present a nonepidermotrophic histiocytic infiltrate with immunohistochemical features of both Langerhans and non-Langerhans cells (i.e. immunopositive for S100 protein and CD1a in the absence of Birbeck granules and langerin expression). [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Indeterminate cell histiocytosis	c2825741	28,934	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=158019	2021-01-23T17:54:29	{"icd-10": ["D76.3"], "synonyms": ["Indeterminate dendritic cell neoplasm", "Indeterminate dendritic cell tumor"]}
Kenny-Caffey syndrome Other namesKenny syndrome Kenny-Caffey syndrome is a rare genetic condition causing skeletal abnormalities.[1] Individuals with the condition have a shortened stature and thickened long bones. Hypocalcemia is also common.[2] KCS is autosomal dominant and caused by a mutation in FAM111A.[2] It affects males and females in equal proportion.[1] Treatment is based on symptoms.[1] ## References[edit] 1. ^ a b c "Kenny-Caffey Syndrome". 2. ^ a b "OMIM Entry - # 127000 - KENNY-CAFFEY SYNDROME, TYPE 2; KCS2". www.omim.org. Retrieved 13 March 2019. ## External links[edit] Classification D * OMIM: 127000 * MeSH: C537020 External resources * Orphanet: 93325 [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Kenny-Caffey syndrome	c0265291	28,935	wikipedia	https://en.wikipedia.org/wiki/Kenny-Caffey_syndrome	2021-01-18T18:30:42	{"mesh": ["C537020"], "umls": ["C0265291"], "orphanet": ["2333"], "wikidata": ["Q48989142"]}
A rare genetic syndromic intellectual disability characterized by congenital microcephaly, short stature, global developmental delay, moderate to severe intellectual disability, absence or severe impairment of speech, and dysmorphic facial features (such as bitemporal narrowing, deep-set eyes, high nasal root, and prominent and dysplastic ears). Additional, more variable manifestations are seizures, ocular anomalies, and minor skeletal defects, among others. Brain imaging may show small brain stem, enlarged ventricles, hypoplastic corpus callosum, white matter abnormalities, and cerebral atrophy. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	DYRK1A-related intellectual disability syndrome	c3279839	28,936	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=464306	2021-01-23T17:41:24	{"omim": ["614104"]}
Long-term disorder that causes a strong urge to move one's legs For the song "Restless Legs" by Half Man Half Biscuit, see Achtung Bono. Restless legs syndrome Other namesWillis–Ekbom disease (WED),[1] Wittmaack–Ekbom syndrome Sleep pattern of a person with restless legs syndrome (red) compared to a healthy sleep pattern (blue) SpecialtySleep medicine SymptomsUnpleasant feeling in the legs that briefly improves with moving them[2] ComplicationsDaytime sleepiness, low energy, irritability, sadness[2] Usual onsetMore common with older age[3] Risk factorsLow iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy, certain medications[2][4][5] Diagnostic methodBased on symptoms after ruling out other possible causes[6] TreatmentLifestyle changes, medication[2] MedicationLevodopa, dopamine agonists, gabapentin[4] Frequency2.5–15% (US)[4] Restless legs syndrome (RLS) is generally a long-term disorder that causes a strong urge to move one's legs.[2][7] There is often an unpleasant feeling in the legs that improves somewhat by moving them.[2] This is often described as aching, tingling, or crawling in nature.[2] Occasionally, arms may also be affected.[2] The feelings generally happen when at rest and therefore can make it hard to sleep.[2] Due to the disturbance in sleep, people with RLS may have daytime sleepiness, low energy, irritability and a depressed mood.[2] Additionally, many have limb twitching during sleep.[8] Risk factors for RLS include low iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy and coeliac disease.[2][4][9] A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers.[5] There are two main types.[2] One is early onset RLS which starts before age 45, runs in families and worsens over time.[2] The other is late onset RLS which begins after age 45, starts suddenly, and does not worsen.[2] Diagnosis is generally based on a person's symptoms after ruling out other potential causes.[6] Restless leg syndrome may resolve if the underlying problem is addressed.[10] Otherwise treatment includes lifestyle changes and medication.[2] Lifestyle changes that may help include stopping alcohol and tobacco use, and sleep hygiene.[10] Medications used include levodopa or a dopamine agonist such as pramipexole.[4] RLS affects an estimated 2.5–15% of the American population.[4] Females are more commonly affected than males, and it becomes increasingly common with age.[3][1] ## Contents * 1 Signs and symptoms * 1.1 Primary and secondary * 2 Causes * 2.1 ADHD * 2.2 Medications * 2.3 Genetics * 3 Mechanism * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 5.1 Physical measures * 5.2 Iron * 5.3 Medications * 6 Prognosis * 7 Epidemiology * 8 History * 8.1 Nomenclature * 9 Controversy * 10 Research * 11 See also * 12 References * 13 External links ## Signs and symptoms[edit] RLS sensations range from pain or an aching in the muscles, to "an itch you can't scratch", a "buzzing sensation", an unpleasant "tickle that won't stop", a "crawling" feeling, or limbs jerking while awake. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep.[11] It is a "spectrum" disease with some people experiencing only a minor annoyance and others having major disruption of sleep and impairments in quality of life.[12] The sensations—and the need to move—may return immediately after ceasing movement or at a later time. RLS may start at any age, including childhood, and is a progressive disease for some, while the symptoms may remit in others.[13] In a survey among members of the Restless Legs Syndrome Foundation,[14] it was found that up to 45% of patients had their first symptoms before the age of 20 years.[15] * "An urge to move, usually due to uncomfortable sensations that occur primarily in the legs, but occasionally in the arms or elsewhere." The sensations are unusual and unlike other common sensations. Those with RLS have a hard time describing them, using words or phrases such as uncomfortable, painful, 'antsy', electrical, creeping, itching, pins and needles, pulling, crawling, buzzing, and numbness. It is sometimes described similar to a limb 'falling asleep' or an exaggerated sense of positional awareness of the affected area. The sensation and the urge can occur in any body part; the most cited location is legs, followed by arms. Some people have little or no sensation, yet still, have a strong urge to move. * "Motor restlessness, expressed as activity, which relieves the urge to move." Movement usually brings immediate relief, although temporary and partial. Walking is most common; however, stretching, yoga, biking, or other physical activity may relieve the symptoms. Continuous, fast up-and-down movements of the leg, and/or rapidly moving the legs toward then away from each other, may keep sensations at bay without having to walk. Specific movements may be unique to each person. * "Worsening of symptoms by relaxation." Sitting or lying down (reading, plane ride, watching TV) can trigger the sensations and urge to move. Severity depends on the severity of the person's RLS, the degree of restfulness, duration of the inactivity, etc. * "Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night." Some experience RLS only at bedtime, while others experience it throughout the day and night. Most people experience the worst symptoms in the evening and the least in the morning. * "Restless legs feel similar to the urge to yawn, situated in the legs or arms." These symptoms of RLS can make sleeping difficult for many patients and a recent poll shows the presence of significant daytime difficulties resulting from this condition. These problems range from being late for work to missing work or events because of drowsiness. Patients with RLS who responded reported driving while drowsy more than patients without RLS. These daytime difficulties can translate into safety, social and economic issues for the patient and for society. Individuals with RLS have higher rates of depression and anxiety disorders.[16] ### Primary and secondary[edit] RLS is categorized as either primary or secondary. * Primary RLS is considered idiopathic or with no known cause. Primary RLS usually begins slowly, before approximately 40–45 years of age and may disappear for months or even years. It is often progressive and gets worse with age. RLS in children is often misdiagnosed as growing pains. * Secondary RLS often has a sudden onset after age 40, and may be daily from the beginning. It is most associated with specific medical conditions or the use of certain drugs (see below). ## Causes[edit] While the cause is generally unknown it is believed to be caused by changes in the nerve transmitter dopamine[17] resulting in an abnormal use of iron by the brain.[1] RLS is often due to iron deficiency (low total body iron status).[1] Other associated conditions may include end-stage kidney disease and hemodialysis, folate deficiency, magnesium deficiency, sleep apnea, diabetes, peripheral neuropathy, Parkinson's disease, and certain autoimmune diseases, such as multiple sclerosis.[18] RLS can worsen in pregnancy, possibly due to elevated estrogen levels.[1][19] Use of alcohol, nicotine products, and caffeine may be associated with RLS.[1] A 2014 study from the American Academy of Neurology also found that reduced leg oxygen levels were strongly associated with Restless Leg Syndrome symptom severity in untreated patients.[20] ### ADHD[edit] An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder.[21] Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine, and common medications for both conditions among other systems, affect dopamine levels in the brain.[22] A 2005 study suggested that up to 44% of people with ADHD had comorbid (i.e. coexisting) RLS, and up to 26% of people with RLS had confirmed ADHD or symptoms of the condition.[23] ### Medications[edit] Certain medications may cause or worsen RLS, or cause it secondarily, including:[1] * certain antiemetics (antidopaminergic ones)[24] * certain antihistamines (especially the sedating, first generation H1 antihistamines often in over-the-counter cold medications)[24] * many antidepressants (both older TCAs and newer SSRIs)[1][24] * antipsychotics and certain anticonvulsants[1] * a rebound effect of sedative-hypnotic drugs such as a benzodiazepine withdrawal syndrome from discontinuing benzodiazepine tranquilizers or sleeping pills[1] * alcohol withdrawal can also cause restless legs syndrome and other movement disorders such as akathisia and parkinsonism usually associated with antipsychotics[25] * opioid withdrawal is associated with causing and worsening RLS[26] Both primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS.[27] The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses) is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS.[28][29] ### Genetics[edit] More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.[30] Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra.[31] Iron is well understood to be an essential cofactor for the formation of L-dopa, the precursor of dopamine. Six genetic loci found by linkage are known and listed below. Other than the first one, all of the linkage loci were discovered using an autosomal dominant model of inheritance. * The first genetic locus was discovered in one large French Canadian family and maps do chromosome 12q.[32][33] This locus was discovered using an autosomal recessive inheritance model. Evidence for this locus was also found using a transmission disequilibrium test (TDT) in 12 Bavarian families.[34] * The second RLS locus maps to chromosome 14q and was discovered in one Italian family.[35] Evidence for this locus was found in one French Canadian family.[36] Also, an association study in a large sample 159 trios of European descent showed some evidence for this locus.[37] * This locus maps to chromosome 9p and was discovered in two unrelated American families.[38] Evidence for this locus was also found by the TDT in a large Bavarian family,[39] in which significant linkage to this locus was found.[40] * This locus maps to chromosome 20p and was discovered in a large French Canadian family with RLS.[41] * This locus maps to chromosome 2p and was found in three related families from population isolated in South Tyrol.[42] * The sixth locus is located on chromosome 16p12.1 and was discovered by Levchenko et al. in 2008.[43] Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to RLS.[44] Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated with RLS.[45] There is also some evidence that periodic limb movements in sleep (PLMS) are associated with BTBD9 on chromosome 6p21.2,[46][47] MEIS1, MAP2K5/SKOR1, and PTPRD.[47] The presence of a positive family history suggests that there may be a genetic involvement in the etiology of RLS. ## Mechanism[edit] Although it is only partly understood, pathophysiology of restless legs syndrome may involve dopamine and iron system anomalies.[48][49] There is also a commonly acknowledged circadian rhythm explanatory mechanism associated with it, clinically shown simply by biomarkers of circadian rhythm, such as body temperature.[50] The interactions between impaired neuronal iron uptake and the functions of the neuromelanin-containing and dopamine-producing cells have roles in RLS development, indicating that iron deficiency might affect the brain dopaminergic transmissions in different ways.[51] Medial thalamic nuclei may also have a role in RLS as part as the limbic system modulated by the dopaminergic system[52] which may affect pain perception.[53] Improvement of RLS symptoms occurs in people receiving low-dose dopamine agonists.[54] ## Diagnosis[edit] There are no specific tests for RLS, but non-specific laboratory tests are used to rule out other causes such as vitamin deficiencies. Five symptoms are used to confirm the diagnosis:[1] * A strong urge to move the limbs, usually associated with unpleasant or uncomfortable sensations. * It starts or worsens during inactivity or rest. * It improves or disappears (at least temporarily) with activity. * It worsens in the evening or night. * These symptoms are not caused by any medical or behavioral condition. These symptoms are not essential, like the ones above, but occur commonly in RLS patients:[1][55] * genetic component or family history with RLS * good response to dopaminergic therapy * periodic leg movements during day or sleep * most strongly affected are people who are middle-aged or older * other sleep disturbances are experienced * decreased iron stores can be a risk factor and should be assessed According to the International Classification of Sleep Disorders (ICSD-3), the main symptoms have to be associated with a sleep disturbance or impairment in order to support RLS diagnosis.[56] As stated by this classification, RLS symptoms should begin or worsen when being inactive, be relieved when moving, should happen exclusively or mostly in the evening and at night, not be triggered by other medical or behavioral conditions, and should impair one's quality of life.[56][57] Generally, both legs are affected, but in some cases there is an asymmetry. ### Differential diagnosis[edit] The most common conditions that should be differentiated with RLS include leg cramps, positional discomfort, local leg injury, arthritis, leg edema, venous stasis, peripheral neuropathy, radiculopathy, habitual foot tapping/leg rocking, anxiety, myalgia, and drug-induced akathisia.[58] Peripheral artery disease and arthritis can also cause leg pain but this usually gets worse with movement.[8] There are less common differential diagnostic conditions included myelopathy, myopathy, vascular or neurogenic claudication, hypotensive akathisia, orthostatic tremor, painful legs, and moving toes.[58] ## Treatment[edit] If RLS is not linked to an underlying cause, its frequency may be reduced by lifestyle modifications such as adopting improving sleep hygiene, regular exercise, and stopping smoking.[59] Medications used may include dopamine agonists or gabapentin in those with daily restless legs syndrome, and opioids for treatment of resistant cases.[1][26] Treatment of RLS should not be considered until possible medical causes are ruled out. Secondary RLS may be cured if precipitating medical conditions (anemia) are managed effectively.[1] ### Physical measures[edit] Stretching the leg muscles can bring temporary relief.[11][60] Walking and moving the legs, as the name "restless legs" implies, brings temporary relief. In fact, those with RLS often have an almost uncontrollable need to walk and therefore relieve the symptoms while they are moving. Unfortunately, the symptoms usually return immediately after the moving and walking ceases. A vibratory counter-stimulation device has been found to help some people with primary RLS to improve their sleep.[61] ### Iron[edit] There is some evidence that intravenous iron supplementation moderately improves restlessness for people with RLS.[62] ### Medications[edit] For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be useful. Evidence supports the use of dopamine agonists including: pramipexole, ropinirole, rotigotine, and cabergoline.[63][64] They reduce symptoms, improve sleep quality and quality of life.[65] Levodopa is also effective.[66] However, pergolide and cabergoline are less recommended due to their association with increased risk of valvular heart disease.[67] Ropinirole has a faster onset with shorter duration.[68] Rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout the day.[68] One review found pramipexole to be better than ropinirole.[69][needs update] There are, however, issues with the use of dopamine agonists including augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound when symptoms increase as the drug wears off. In many cases, the longer dopamine agonists have been used the higher the risk of augmentation and rebound as well as the severity of the symptoms. Also, a recent study indicated that dopamine agonists used in restless leg syndrome can lead to an increase in compulsive gambling.[70] * Gabapentin or pregabalin, a non-dopaminergic treatment for moderate to severe primary RLS[71] * Opioids are only indicated in severe cases that do not respond to other measures due to their high rate of side effects, which may include constipation, fatigue and headache.[72][26] One possible treatment for RLS is dopamine agonists, unfortunately patients can develop dopamine dysregulation syndrome, meaning that they can experience an addictive pattern of dopamine replacement therapy. Additionally, they can exhibit some behavioral disturbances such as impulse control disorders like pathologic gambling, compulsive purchasing and compulsive eating.[73] There are some indications that stopping the dopamine agonist treatment has an impact on the resolution or at least improvement of the impulse control disorder, even though some people can be particularly exposed to dopamine agonist withdrawal syndrome.[74] Benzodiazepines, such as diazepam or clonazepam, are not generally recommended,[75] and their effectiveness is unknown.[76] They however are sometimes still used as a second line,[77] as add on agents.[76] Quinine is not recommended due to its risk of serious side effects involving the blood.[78] ## Prognosis[edit] RLS symptoms may gradually worsen with age, although more slowly for those with the idiopathic form of RLS than for people who also have an associated medical condition.[79] Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some people have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear.[79] Being diagnosed with RLS does not indicate or foreshadow another neurological disease, such as Parkinson's disease.[79] RLS symptoms can worsen over time when dopamine-related drugs are used for therapy, an effect called "augmentation" which may represent symptoms occurring throughout the day and affect movements of all limbs.[79] There is no cure for RLS.[79] ## Epidemiology[edit] RLS affects an estimated 2.5–15% of the American population.[4][80] A minority (around 2.7% of the population) experience daily or severe symptoms.[81] RLS is twice as common in women as in men,[82] and Caucasians are more prone to RLS than people of African descent.[80] RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern regions, and in 1–5% of those from East Asia, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome.[80][83] RLS diagnosed at an older age runs a more severe course.[60] RLS is even more common in individuals with iron deficiency, pregnancy, or end-stage kidney disease.[84][85] The National Sleep Foundation's 1998 Sleep in America poll showed that up to 25 percent of pregnant women developed RLS during the third trimester.[86] Poor general health is also linked.[87] There are several risk factors for RLS, including old age, family history, and uremia. The prevalence of RLS tends to increase with age, as well as its severity and longer duration of symptoms. People with uremia receiving renal dialysis have a prevalence from 20% to 57%, while those having kidney transplant improve compared to those treated with dialysis.[88] RLS can occur at all ages, although it typically begins in the third or fourth decade.[57] Genome‐wide association studies have now identified 19 risk loci associated with RLS.[89] Neurological conditions linked to RLS include Parkinson's disease, spinal cerebellar atrophy, spinal stenosis,[specify] lumbosacral radiculopathy and Charcot–Marie–Tooth disease type 2.[80] ## History[edit] The first known medical description of RLS was by Sir Thomas Willis in 1672.[90] Willis emphasized the sleep disruption and limb movements experienced by people with RLS. Initially published in Latin (De Anima Brutorum, 1672) but later translated to English (The London Practice of Physick, 1685), Willis wrote: > Wherefore to some, when being abed they betake themselves to sleep, presently in the arms and legs, leapings and contractions on the tendons, and so great a restlessness and tossings of other members ensue, that the diseased are no more able to sleep, than if they were in a place of the greatest torture. The term "fidgets in the legs" has also been used as early as the early nineteenth century.[91] Subsequently, other descriptions of RLS were published, including those by Francois Boissier de Sauvages (1763), Magnus Huss (1849), Theodur Wittmaack (1861), George Miller Beard (1880), Georges Gilles de la Tourette (1898), Hermann Oppenheim (1923) and Frederick Gerard Allison (1943).[90][92] However, it was not until almost three centuries after Willis, in 1945, that Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, Restless legs: clinical study of hitherto overlooked disease.[93] Ekbom coined the term "restless legs" and continued work on this disorder throughout his career. He described the essential diagnostic symptoms, differential diagnosis from other conditions, prevalence, relation to anemia, and common occurrence during pregnancy.[94][95] Ekbom's work was largely ignored until it was rediscovered by Arthur S. Walters and Wayne A. Hening in the 1980s. Subsequent landmark publications include 1995 and 2003 papers, which revised and updated the diagnostic criteria.[11][96] Journal of Parkinsonism and RLS is the first peer-reviewed, online, open access journal dedicated to publishing research about Parkinson's disease and was founded by a Canadian neurologist Dr. Abdul Qayyum Rana. ### Nomenclature[edit] For decades the most widely used name for the disease was restless legs syndrome, and it is still the most commonly used. In 2013 the Restless Legs Syndrome Foundation renamed itself the Willis–Ekbom Disease Foundation,[97] and it encourages the use of the name Willis–Ekbom disease; its reasons are quoted as follows:[97] > The name Willis–Ekbom disease: > > * Eliminates incorrect descriptors—the condition often involves parts of the body other than legs > * Promotes cross-cultural ease of use > * Responds to trivialization of the disease and humorous treatment in the media > * Acknowledges the first known description by Sir Thomas Willis in 1672 and the first detailed clinical description by Dr. Karl Axel Ekbom in 1945.[97] > A point of confusion is that RLS and delusional parasitosis are entirely different conditions that have both been called "Ekbom syndrome", as both syndromes were described by the same person, Karl-Axel Ekbom.[98] Today, calling WED/RLS "Ekbom syndrome" is outdated usage, as the unambiguous names (WED or RLS) are preferred for clarity. ## Controversy[edit] Some doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it.[99] Others believe it is an underrecognized and undertreated disorder.[80] Further, GlaxoSmithKline ran advertisements that, while not promoting off-licence use of their drug (ropinirole) for treatment of RLS, did link to the Ekbom Support Group website. That website contained statements advocating the use of ropinirole to treat RLS. The ABPI ruled against GSK in this case.[100] ## Research[edit] Different measurements have been used to evaluate treatments in RLS. Most of them are based on subjective rating scores, such as IRLS rating scale (IRLS), Clinical Global Impression (CGI), Patient Global Impression (PGI), and Quality of life (QoL).[101] These questionnaires provide information about the severity and progress of the disease, as well as the person's quality of life and sleep.[101] Polysomnography (PSG) and actigraphy (both related to sleep parameters) are more objective resources that provide evidences of sleep disturbances associated with RLS symptoms.[101] ## See also[edit] * Periodic limb movement disorder ## References[edit] 1. ^ a b c d e f g h i j k l m n "Restless Legs Syndrome Fact Sheet \| National Institute of Neurological Disorders and Stroke". Ninds.nih.gov. 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"The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder in Adults—An Update for 2012: Practice Parameters with an Evidence-Based Systematic Review and Meta-AnalysesAn American Academy of Sleep Medicine Clinical Practice Guideline". Sleep. 35 (8): 1039–1062. doi:10.5665/sleep.1988. ISSN 0161-8105. PMC 3397811. PMID 22851801. 75. ^ Trenkwalder, C; Winkelmann, J; Inoue, Y; Paulus, W (August 2015). "Restless legs syndrome-current therapies and management of augmentation". Nature Reviews. Neurology. 11 (8): 434–45. doi:10.1038/nrneurol.2015.122. PMID 26215616. S2CID 22534190. 76. ^ a b Carlos K, Prado GF, Teixeira CD, Conti C, de Oliveira MM, Prado LB, Carvalho LB (2017). "Benzodiazepines for restless legs syndrome". Cochrane Database Syst Rev. 3: CD006939. doi:10.1002/14651858.CD006939.pub2. PMC 6464545. 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"Update to the AASM Clinical Practice Guideline: "The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder in Adults—An Update for 2012: Practice Parameters with an Evidence-Based Systematic Review and Meta-Analyses"". Sleep. 35 (8): 1037. doi:10.5665/sleep.1986. PMC 3397810. PMID 22851800. ## External links[edit] Classification D * ICD-10: G25.8 * ICD-10-CM: G25.81 * ICD-9-CM: 333.94 * OMIM: 102300 608831 * MeSH: D012148 * DiseasesDB: 29476 External resources * MedlinePlus: 000807 * eMedicine: neuro/509 * Patient UK: Restless legs syndrome Wikimedia Commons has media related to Restless leg syndrome. * Restless legs syndrome at Curlie * 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 Authority control * NDL: 01143835 [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Restless legs syndrome	c0035258	28,937	wikipedia	https://en.wikipedia.org/wiki/Restless_legs_syndrome	2021-01-18T18:45:27	{"gard": ["11926"], "mesh": ["D012148"], "umls": ["C0035258"], "icd-9": ["333.94333.94"], "icd-10": ["G25.825.8"], "wikidata": ["Q916280"]}
A rare genetic lipodystrophy characterized by loss of subcutaneous fat layers on the limbs, lipodystrophy in the face and trunk and scleroderma-like skin disorders (thickened skin on the palms and soles and skin pigment changes on the limbs and trunk). Additional clinical signs include joint contractures, reduced relative body weight, a bird-like facial appearance with a beaked nose, micrognathia and insulin-resistant diabetes mellitus. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Lipodystrophy due to peptidic growth factors deficiency	c2931279	28,938	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1979	2021-01-23T17:41:05	{"gard": ["12604"], "mesh": ["C565529"], "omim": ["233805"], "umls": ["C1856243", "C2931279"], "icd-10": ["E88.1"], "synonyms": ["Combined insulin, insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) deficiency", "Hoepffner-Dreyer-Reimers syndrome", "Werner-like syndrome due to combined growth factor deficiency"]}
A rare developmental defect during embryogenesis where some or all of the pulmonary veins drain into the right atrium or the systemic veins, with or without the presence of pulmonary venous obstruction, leading to various manifestations such as fatigue, exertional dyspnea, pulmonary arterial hypertension, cyanosis and progressive congestive heart failure. The two main subtypes are congenital partial pulmonary venous return anomaly (PAPVC; see this term), where one or a few of the pulmonary veins are anomalous, and congenital total pulmonary venous return anomaly (TAPVC, see this term), where all of the pulmonary veins are anomalous. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Congenital pulmonary venous return anomaly	c0265916	28,939	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3090	2021-01-23T17:00:25	{"gard": ["4599"], "umls": ["C0265916"], "icd-10": ["Q26.2", "Q26.3", "Q26.4"], "synonyms": ["Congenital pulmonary venous connection anomaly"]}
A disorder that is the most frequent form of posterior corneal dystrophy and is characterized by excrescences on a thickened Descemet membrane (corneal guttae), generalized corneal edema, with gradually decreased visual acuity. ## Epidemiology The exact prevalence is not known but extreme geographical variability has been reported. FECD is the most prevalent corneal dystrophy in the USA but has been found to be uncommon in Saudi Arabia and in Singaporean Chinese, and very rare in Japan. ## Clinical description The condition is more common and more severe in women (sex ratio 3-4:1). Patients with FECD are initially asymptomatic. Clinical onset is generally in the 5th or 6th decade of life. Discomfort and painful episodes of recurrent corneal erosions occur, along with gradually developing opacification leading to hazy vision. Over time, discomfort may diminish but severe impairment of visual acuity, and even blindness in elderly patients, may be observed. The clinical course often spans 10 to 20 years. The condition is often associated with cataracts. Microbial keratitis and corneal neovascularization are extremely rare complications. Stromal edema produces a blue-gray haze anterior to Descemet membrane followed by eventual thickening of the entire corneal stroma and development of a ground-glass corneal appearance. ## Etiology The etiology of FECD is unknown, but it seems to be a heterogenous complex inherited disorder caused by the interaction of genetic and environmental factors. Mutations in certain genes have been reported in some cases of FECD. Rare cases of early onset have been related to mutations in the COL8A2 gene (1p34.2-p32.3). Heterozygous mutation in the SLC4A11 gene (20p12) has been reported in some late-onset cases of FECD. Other cases have been mapped to chromosomes 13 (13pter-3q12.13) and 18 (18q21.2- q21.32)(TCF4) and to ZEB1 (10p11.22). ## Genetic counseling Although most patients with FECD lack a positive family history, blood relatives sometimes manifest corneal guttae. FECD may also affect siblings and two or more successive generations, apparently as an autosomal dominant disorder having incomplete penetrance, but a simple autosomal dominant pattern is unlikely. ## Management and treatment Most patients with FECD ultimately require a penetrating keratoplasty or a procedure for repairing the posterior surface of the cornea, such as a deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet stripping automated endothelial keratoplasty (DSAEK). Visual acuity is markedly improved after a penetrating keratoplasty, DSEK or DSAEK. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Fuchs endothelial corneal dystrophy	c0016781	28,940	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98974	2021-01-23T18:47:45	{"mesh": ["D005642"], "omim": ["136800", "610158", "613267", "613268", "613269", "613270", "613271", "615523"], "umls": ["C0016781"], "icd-10": ["H18.5"], "synonyms": ["Endoepithelial corneal dystrophy", "FECD", "Late hereditary endothelial dystrophy"]}
An extremely rare disorder of methionine cycle and sulfur amino acid metabolism characterized by increased urine excretion of beta-mercaptolactate-cysteine disulfide (due to deficiency of mercaptopyruvate sulfurtransferase activity in erythrocytes), leading to a positive cyanide nitroprusside test. Association with intellectual disability, congenital lens dislocation, and behavioral abnormalities has been reported, however the causal link remains to be established. There have been no further descriptions in the literature since 1981. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Beta-mercaptolactate cysteine disulfiduria	c0796055	28,941	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1035	2021-01-23T19:09:26	{"gard": ["654"], "mesh": ["C563085"], "omim": ["249650"], "umls": ["C0796055"], "icd-10": ["E72.1"], "synonyms": ["3-mercaptopyruvate sulfurtransferase deficiency", "Ampola syndrome", "MCDU"]}
A number sign (#) is used with this entry because of evidence that juvenile amyotrophic lateral sclerosis-16 (ALS16) is caused by homozygous mutation in the SIGMAR1 gene (601978) on chromosome 9p13. One such family has been reported. Clinical Features Al-Saif et al. (2011) reported a consanguineous Saudi Arabian family in which 6 individuals had early-childhood onset of a neurologic disorder consistent with juvenile ALS, according to the El Escorial criteria (Brooks, 1994). Lower limb spasticity with hyperreflexia and weakness were noted at the age of 1 to 2 years. By age 9 or 10, affected individuals showed weakness of the hand and forearm muscles, which progressed to paralysis of the forearm extensors and triceps. By the age of 20 years, 2 patients used wheelchairs. None of the patients had respiratory or bulbar muscle weakness, and sensory and cerebellar functions were normal. Neurophysiologic tests showed evidence of denervation and reinnervation in limb muscles; motor unit potentials were enlarged, polyphasic, and fast firing, with normal sensory nerve action potentials and somatosensory evoked potentials. Brain imaging did not reveal any abnormalities, and cognition was preserved. Mapping By homozygosity mapping of a consanguineous Saudi Arabian family with early-childhood onset of ALS, Al-Saif et al. (2011) found linkage to a 120-kb region on chromosome 9p13.3. Molecular Genetics By homozygosity mapping followed by candidate gene sequencing, Al-Saif et al. (2011) identified a homozygous pathogenic mutation in the SIGMAR1 gene (601978.0001) in affected members of a consanguineous Saudi Arabian family with early-childhood onset of ALS. INHERITANCE \- Autosomal recessive MUSCLE, SOFT TISSUES \- Limb muscle weakness, upper and lower NEUROLOGIC Central Nervous System \- Lower motor neuron signs \- Upper motor neuron signs \- Spasticity \- Hyperreflexia \- Muscle weakness, distal, upper and lower \- Neurophysiologic studies show evidence of denervation and renervation \- Enlarged motor unit action potentials \- Normal cognition MISCELLANEOUS \- Age of onset 1 to 2 years \- Onset in lower limbs \- Progresses to involve upper limbs \- Slowly progressive \- Six patients from 1 Saudi Arabian family have been reported (last curated December 2011) \- Two of 6 patients became wheelchair-bound by age 20 years MOLECULAR BASIS \- Caused by mutation in the sigma nonopioid intracellular receptor 1 gene (SIGMAR1, 601978.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	AMYOTROPHIC LATERAL SCLEROSIS 16, JUVENILE	c3280587	28,942	omim	https://www.omim.org/entry/614373	2019-09-22T15:55:31	{"doid": ["0060207"], "omim": ["614373"], "orphanet": ["300605"], "synonyms": ["JALS", "Juvenile Charcot disease", "Juvenile Lou Gehrig disease"]}
A number sign (#) is used with this entry because of evidence that Y-linked deafness-2 (DFNY2) is caused by mutation in the TBL1Y gene (400033) on chromosome Yp11. One such family has been reported. Description Y-linked deafness-2 (DFNY2) is characterized by male-limited bilateral progressive sensorineural hearing loss of variable severity, with onset in the third to fifth decades of life (Di Stazio et al., 2019). For a discussion of genetic heterogeneity of Y-linked deafness, see DFNY1 (400043). Clinical Features Di Stazio et al. (2019) reported a large 5-generation Italian family segregating male-limited deafness. Affected individuals showed bilateral symmetric hearing loss ranging from mild to severe, with onset from 20 to 40 years of age. There was no vestibular dysfunction by history or examination. Five of the affected men, ages 46 to 80 years, also exhibited benign prostatic hyperplasia, with increased ratios of free/total PSA level. Molecular Genetics In a large 5-generation Italian family with male-limited deafness, Di Stazio et al. (2019) performed whole-exome sequencing and identified a missense mutation in the TBL1Y gene (D69V; 400033.0001) that segregated fully with disease. INHERITANCE \- Y-linked HEAD & NECK Ears \- Hearing loss, sensorineural, mild (bilateral symmetric) MISCELLANEOUS \- Onset in third to fifth decades of life \- Based on report of 1 family (last curated April 2018) MOLECULAR BASIS \- Caused by mutation in the Y-linked transducin-beta-like 1 gene (TBL1Y, 400033.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	DEAFNESS, Y-LINKED 2	None	28,943	omim	https://www.omim.org/entry/400047	2019-09-22T16:17:00	{"omim": ["400047"]}
Granulomatous meningoencephalitis (GME) is an inflammatory disease of the central nervous system (CNS) of dogs and, rarely, cats. It is a form of meningoencephalitis. GME is likely second only to encephalitis caused by canine distemper virus as the most common cause of inflammatory disease of the canine CNS.[1] The disease is more common in female dogs of young and middle age. It has a rapid onset. The lesions of GME exist mainly in the white matter of the cerebrum, brainstem, cerebellum, and spinal cord.[2] The cause is only known to be noninfectious and is considered at this time to be idiopathic. Because lesions resemble those seen in allergic meningoencephalitis, GME is thought to have an immune-mediated cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent.[3] One study searched for viral DNA from canine herpesvirus, canine adenovirus, and canine parvovirus in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis (see below for the latter two conditions), but failed to find any.[4] ## Contents * 1 Types of GME * 2 Diagnosis and treatment * 3 Pug dog encephalitis * 4 Necrotizing leukoencephalitis * 5 Other types of noninfectious meningoencephalitis * 6 See also * 7 References ## Types of GME[edit] * Disseminated – This is a diffuse disease throughout the CNS. It was previously known as inflammatory reticulosis. There is an accumulation of mononuclear cells and neutrophils around the blood vessels (perivascular) of the CNS. Meningitis is seen with this form of GME and causes fever and neck pain.[5] It has an acute progression over a few weeks. Symptoms include incoordination, nystagmus, head tilt, seizures, and depression.[3] * Focal – The disease presents as a granuloma, which mimics a tumor. It usually is found in the cerebrum or cerebellopontine angle.[6] Symptoms may be acute or develop slowly over several months and depend on the location of the lesion.[5] * Ocular – This is an uncommon form of GME and is characterized by sudden blindness caused by optic neuritis. The disease is bilateral. Ocular GME is considered to be an extension of CNS disease. The blood vessels of the posterior segment of the eye and anterior uvea have the same infiltrates of inflammatory cells as the intracranial vessels. Uveitis, retinal detachment, and secondary glaucoma may be seen.[7] ## Diagnosis and treatment[edit] Cerebrospinal fluid (CSF) analysis shows a large number of white blood cells. Typically small mature lymphocytes are the majority of cells seen, with monocytes and neutrophils making up the rest.[8] Definitive diagnosis is based on histopathology, either a brain biopsy or post-mortem evaluation (necropsy). A CT scan or MRI will show patchy, diffuse, or multifocal lesions. For a number of years, the basic treatment was some type of corticosteroid in combination with one or more immunosuppressive drugs, typically cytosine arabinoside and/or cyclosporine or other medications such as azathioprine, cyclophosphamide,[6] or procarbazine, of which were usually added one at a time to the corticosteroid until a successful combination was found. There is evidence that treatment with radiation therapy for focal GME provides the longest periods of remission.[1] ## Pug dog encephalitis[edit] Pug dog encephalitis (PDE) is an idiopathic inflammatory disease primarily affecting the prosencephalon (forebrain and thalamus). It is also known as necrotizing meningoencephalitis. The disease may be inherited in Pugs and Maltese and has been diagnosed in other breeds as well (Yorkies, Chihuahuas).[6] The prevalence of PDE in pugs is about 1%.[9] It differs in pathology from GME by more tissue breakdown and increased eosinophils (white blood cells). CSF analysis is also unique among inflammatory CNS diseases in dogs in that the cells are predominantly lymphocytes, instead of a mixed population of mononuclear cells.[10] In Maltese and Pugs, there is extensive necrosis and inflammation of the gray matter of the cerebrum and subcortical white matter. The most common early symptoms are related to forebrain disease and include seizures and dementia, and later circling, head tilt, and blindness with normal pupillary light reflexes may be seen. PDE has a poor prognosis. ## Necrotizing leukoencephalitis[edit] In Yorkshire Terriers there can be severe mononuclear inflammation of the brainstem and periventricular cerebral white matter. Because the condition in this breed frequently affects only the white matter, it has been called necrotizing leukoencephalitis. Symptoms of brainstem and central vestibular disease predominate.[11] ## Other types of noninfectious meningoencephalitis[edit] * Steroid-responsive meningoencephalitis is any noninfectious meningoencephalitis that responds well to corticosteroids and usually has an excellent prognosis. This could represent mild forms of GME or PDE, but there are two separate conditions recognized also. * Steroid-responsive meningitis/arteritis, also known as necrotizing vasculitis, is seen most commonly in Beagles, Boxers, Bernese Mountain Dogs, and German Shorthaired Pointers younger than two years of age.[12] Many cases have fever, loss of appetite, and severe neck pain without other neurologic symptoms, although long-term cases may have incoordination and limb weakness or paralysis. CSF analysis shows predominantly neutrophils. In Beagles this condition is also known as Beagle pain syndrome.[3] * Eosinophilic meningoencephalomyelitis is seen mainly in Golden Retrievers.[12] CSF analysis shows predominantly eosinophils. * An acute progressive pyogranulomatous meningoencephalomyelitis is seen in mature Pointer dogs. There is monocytic and neutrophilic infiltration of the leptomeninges. Symptoms include incoordination, reluctance to move, and neck rigidity.[13] ## See also[edit] * Encephalitis * Meningitis ## References[edit] 1. ^ a b Adamo F, O'Brien R (2004). "Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs". J Am Vet Med Assoc. 225 (8): 1211–6, 1196. doi:10.2460/javma.2004.225.1211. PMID 15521442. 2. ^ Suzuki M, Uchida K, Morozumi M, Yanai T, Nakayama H, Yamaguchi R, Tateyama S (2003). "A comparative pathological study on granulomatous meningoencephalomyelitis and central malignant histiocytosis in dogs". J Vet Med Sci. 65 (12): 1319–24. doi:10.1292/jvms.65.1319. PMID 14709820. 3. ^ a b c Vite, C.H. (2005). "Inflammatory Diseases of the Central Nervous System". Braund's Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment. Retrieved 2007-02-15. 4. ^ Schatzberg S, Haley N, Barr S, de Lahunta A, Sharp N (2005). "Polymerase chain reaction screening for DNA viruses in paraffin-embedded brains from dogs with necrotizing meningoencephalitis, necrotizing leukoencephalitis, and granulomatous meningoencephalitis". J Vet Intern Med. 19 (4): 553–9. doi:10.1892/0891-6640(2005)19[553:PCRSFD]2.0.CO;2. PMID 16095173. 5. ^ a b "Idiopathic Inflammatory Diseases". The Merck Veterinary Manual. 2006. Retrieved 2007-02-15. 6. ^ a b c Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3. 7. ^ Gelatt, Kirk N. (ed.) (1999). Veterinary Ophthalmology (3rd ed.). Lippincott, Williams & Wilkins. ISBN 0-683-30076-8.CS1 maint: extra text: authors list (link) 8. ^ Vernau, William (2005). "Cerebrospinal Fluid Analysis in Dogs and Cats" (PDF). Proceedings of the 50° Congresso Nazionale Multisala SCIVAC. Retrieved 2007-02-18. 9. ^ Greer, K. A.; Wong, A. K.; Liu, H.; Famula, T. R.; Pedersen, N. C.; Ruhe, A.; Wallace, M.; Neff, M. W. (April 2010). "Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis". Tissue Antigens. 76 (2): 110–8. doi:10.1111/j.1399-0039.2010.01484.x. PMID 20403140. 10. ^ Higginbotham, Michael J.; Kent, Marc; Glass, Eric N. (August 2007). "Noninfectious Inflammatory Central Nervous System Diseases in Dogs". Compendium on Continuing Education for the Practicing Veterinarian. Veterinary Learning Systems. 29 (8): 488–497. PMID 17849703. 11. ^ Garosi, Laurent S. (2006). "CNS inflammatory (UK) problems: The neurologist's viewpoint, clinical approach and treatment" (PDF). Proceedings of the 53° Congresso Nazionale Multisala SCIVAC. Retrieved 2007-02-18. 12. ^ a b Chrisman, Cheryl; Clemmons, Roger; Mariani, Christopher; Platt, Simon (2003). Neurology for the Small Animal Practitioner (1st ed.). Teton New Media. ISBN 1-893441-82-2. 13. ^ "Meningitis and Encephalitis: Introduction". The Merck Veterinary Manual. 2006. Retrieved 2007-02-15. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Granulomatous meningoencephalitis	c0393440	28,944	wikipedia	https://en.wikipedia.org/wiki/Granulomatous_meningoencephalitis	2021-01-18T18:32:19	{"wikidata": ["Q1543252"]}
Transient bullous dermolysis of the newborn is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by generalized blistering at birth that usually regresses within the first 6 to 24 months of life. ## Epidemiology Prevalence is unknown. Less than 30 cases have been reported to date. ## Clinical description The disease usually manifests at birth. Skin blisters generally affect the whole body. Blisters can also affect the oral cavity. Healing of blisters is associated with mild, mostly atrophic, scarring and milia formation. Disease activity usually ceases within the first 6 to 24 months of life. However, nail dystrophy and some degree of skin fragility can persist in adulthood. Ultrastructurally, the presence in basal keratinocytes of peculiar cytoplasmic inclusions, known as stellate bodies, filled with unsecreted procollagen VII, is typical of the disease. ## Etiology Transient bullous dermolysis of the newborn is caused by mutations within the type VII collagen gene (COL7A1). Mutations in this gene lead to reduced amounts or an alteration in function of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis. ## Genetic counseling The condition is usually inherited in an autosomal dominant manner, but can also rarely be transmitted as an autosomal recessive trait. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Transient bullous dermolysis of the newborn	c1851573	28,945	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79411	2021-01-23T18:58:20	{"gard": ["10010"], "mesh": ["C536979"], "omim": ["131705"], "umls": ["C1851573"], "icd-10": ["Q81.2"], "synonyms": ["DEB, bullous dermolysis of the newborn", "DEB-BDN"]}
Rare genetic disorder caused by a deletion of six genes 17q21.31 microdeletion syndrome (Koolen–de Vries syndrome) Other namesKoolen–De Vries syndrome, Koolen de Vries syndrome, Koolen De Vries syndrome 17q21.31 microdeletion syndrome, also known as Koolen–de Vries syndrome (KdVS), is a rare genetic disorder caused by a deletion of a segment of chromosome 17 which contains six genes. This deletion syndrome was discovered independently in 2006 by three different research groups.[1][2][3][4][5][6][7][8][9] ## Contents * 1 Presentation * 2 Genetics * 2.1 Affected genes * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 Further reading * 8 External links ## Presentation[edit] The symptoms associated with this syndrome are variable, but common features include: low birthweight, low muscle tone at birth, poor feeding in infancy (often requiring feeding by tube for a period) and oromotor dyspraxia together with moderate developmental delays and learning disabilities but amiable behaviour. Other clinically important features include epilepsy, heart defects (atrial septal defect, ventricular septal defect) and kidney/urological anomalies. Silvery depigmentation of strands of hair have been noted in several patients. With age, there is an apparent coarsening of facial features. 17q21.3 was reported simultaneously in 2006 by three independent groups, with each group reporting several patients, and is now recognised to be one of the more common recurrent microdeletion syndromes.[1][2][3] In 2007, a patient with a small duplication in same segment of DNA was described.[10] An overview of the clinical features of the syndrome, by reviewing 22 individuals with a 17q21.31 microdeletion, estimated the disorder is present in 1 in every 16,000 people.[5] ## Genetics[edit] The recurrent deletion is between 500 and 650 kilobases (Kb) in size encompassing at least six genes, among them the microtubule-associated protein tau (MAPT). A review of five patients found the parental chromosome from which the deletion originated carried a common 900kb inversion polymorphism.[5] The orientation of low copy repeats flanking the deleted segment suggests the inversion in the parental chromosome influences the deletion in the child's chromosome via a non-allelic homologous recombination (NAHR) mechanism. ### Affected genes[edit] The deletion that causes this disease can remove up to six different genes. These include: * The uncharacterised protein C17orf69 (also known as FLJ25168). * The protein SPPL2c, putative intramembrane-protease, member of the presenilin-homologues, the SPP/SPPL-proteases * Corticotropin releasing hormone receptor 1 (CRHR1, also known as CRF-R, CRF1) * Microtubule-associated protein tau (MAPT) * The uncharacterised protein KIAA1267 (also known as DKFZP727C091, KANSL1) ## Diagnosis[edit] Diagnosis is established with a chromosome microarray analysis. The symptoms of Koolen–de Vreis syndrome can be very variable, and there is no single clinical sign required to establish the diagnosis.[11] ## Treatment[edit] Treatment centres around the symptoms in each individual and can include: early physiotherapy for feeding and motor problems, physiotherapy for strengthening the muscles, speech therapy, sign language, pictures or computer touchscreens for communication, special education, routine antiepileptic medications, orthopaedic care for scoliosis, hip dislocation and positional deformities of the feet, treatment for cardiac, renal, urologic and other medical issues and surgery for cryptorchidism if indicated.[11] ## History[edit] The syndrome is named after Dutch geneticists David A. Koolen and Bert B. A. de Vries, who helped discover the syndrome in 2006.[3] ## References[edit] 1. ^ a b Sharp AJ, Hansen S, Selzer RR, et al. (September 2006). "Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome". Nat. Genet. 38 (9): 1038–42. doi:10.1038/ng1862. PMID 16906162. 2. ^ a b Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos AC, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP (2006). "Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability". Nat Genet. 38 (9): 1032–7. doi:10.1038/ng1858. PMID 16906163. 3. ^ a b c Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, Kooy RF, Reyniers E, Romano C, Fichera M, Schinzel A, Baumer A, Anderlid BM, Schoumans J, Knoers NV, van Kessel AG, Sistermans EA, Veltman JA, Brunner HG, de Vries BB (2006). "A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism". Nat Genet. 38 (9): 999–1001. doi:10.1038/ng1853. PMID 16906164. 4. ^ Lupski JR (2006). "Genome structural variation and sporadic disease traits". Nat Genet. 38 (9): 974–6. doi:10.1038/ng0906-974. PMID 16941003. 5. ^ a b c Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, Saugier-Veber P, Pfundt R, Vissers LE, Destrée A, Grisart B, Rooms L, Van der Aa N, Field M, Hackett A, Bell K, Nowaczyk MJ, Mancini GM, Poddighe PJ, Schwartz CE, Rossi E, De Gregori M, Antonacci-Fulton LL, McLellan MD, Garrett JM, Wiechert MA, Miner TL, Crosby S, Ciccone R, Willatt L, Rauch A, Zenker M, Aradhya S, Manning MA, Strom TM, Wagenstaller J, Krepischi-Santos AC, Vianna-Morgante AM, Rosenberg C, Price SM, Stewart H, Shaw-Smith C, Brunner HG, Wilkie AO, Veltman JA, Zuffardi O, Eichler EE, de Vries BB (2008). "Clinical and molecular delineation of the 17q21.31 microdeletion syndrome". J Med Genet. 45 (11): 710–20. doi:10.1136/jmg.2008.058701. PMC 3071570. PMID 18628315. 6. ^ Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S, Kirk EP, Love D, Ronan A, Darmanian A, Slavotinek A, Hogue J, Moeschler JB, Ozmore J, Widmer R, Bruno D, Savarirayan R, Peters G (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome". J Med Genet. 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831. 7. ^ Varela MC, Krepischi-Santos AC, Paz JA, Knijnenburg J, Szuhai K, Rosenberg C, Koiffmann CP (2006). "A 17q21.31 microdeletion encompassing the MAPT gene in a mentally impaired patient". Cytogenet Genome Res. 114 (1): 89–92. doi:10.1159/000091934. PMID 16717456. 8. ^ Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW, Cardone MF, Graves TA, Kidd JM, Cheng Z, Abouelleil A, Chen L, Wallis J, Glasscock J, Wilson RK, Reily AD, Duckworth J, Ventura M, Hardy J, Warren WC, Eichler EE (2008). "Evolutionary toggling of the MAPT 17q21.31 inversion region". Nat Genet. 40 (9): 1076–83. doi:10.1038/ng.193. PMC 2684794. PMID 19165922. 9. ^ Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E, Tolmie J, Jackson AP (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype". Cytogenet Genome Res. 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647. 10. ^ Kirchhoff M, Bisgaard AM, Duno M, Hansen FJ, Schwartz M (2007). "A 17q21.31 microduplication, reciprocal to the newly described 17q21.31 microdeletion, in a girl with severe psychomotor developmental delay and dysmorphic craniofacial features". Eur J Med Genet. 50 (4): 256–63. doi:10.1016/j.ejmg.2007.05.001. PMID 17576104. 11. ^ a b "Koolen de Vries syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-03-11. ## Further reading[edit] * Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S, et al. (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome". J Med Genet. 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831. * Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E, et al. (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype". Cytogenet Genome Res. 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647. * Wright EB, Donnai D, Johnson D, Clayton-Smith J (2011). "Cutaneous features in 17q21.31 deletion syndrome: a differential diagnosis for cardio-facio-cutaneous syndrome". Clin Dysmorphol. 20 (1): 15–20. doi:10.1097/MCD.0b013e32833e8f1e. PMC 3000393. PMID 21084979. * Rao PN, Li W, Vissers LE, Veltman JA, Ophoff RA (2010). "Recurrent inversion events at 17q21.31 microdeletion locus are linked to the MAPT H2 haplotype". Cytogenet Genome Res. 129 (4): 275–9. doi:10.1159/000315901. PMC 3202913. PMID 20606400. ## External links[edit] Classification D * OMIM: 610443 External resources * GeneReviews: 17q21.31 microdeletion syndrome * Orphanet: 363958 * DECIPHER database entry for 17q21.31 microdeletion syndrome * Orphanet entry for 17q21.31 microdeletion syndrome * v * t * e Mutation Mechanisms of mutation * Insertion * Deletion * Substitution * Transversion * Transition Mutation with respect to structure Point mutation * Nonsense mutation * Missense mutation * Conservative mutation * Silent mutation * Frameshift mutation * Dynamic mutation Large-scale mutation * Chromosomal translocations * Chromosomal inversions Mutation with respect to overall fitness * Deleterious mutation * Advantageous mutation * Neutral mutation * Nearly neutral mutation * Synonymous mutation * Nonsynonymous mutation * v * t * e Chromosome abnormalities Autosomal Trisomies/Tetrasomies * Down syndrome * 21 * Edwards syndrome * 18 * Patau syndrome * 13 * Trisomy 9 * Tetrasomy 9p * Warkany syndrome 2 * 8 * Cat eye syndrome/Trisomy 22 * 22 * Trisomy 16 Monosomies/deletions * (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) * 1 * Wolf–Hirschhorn syndrome * 4 * Cri du chat syndrome/Chromosome 5q deletion syndrome * 5 * Williams syndrome * 7 * Jacobsen syndrome * 11 * Miller–Dieker syndrome/Smith–Magenis syndrome * 17 * DiGeorge syndrome * 22 * 22q11.2 distal deletion syndrome * 22 * 22q13 deletion syndrome * 22 * genomic imprinting * Angelman syndrome/Prader–Willi syndrome (15) * Distal 18q-/Proximal 18q- X/Y linked Monosomy * Turner syndrome (45,X) Trisomy/tetrasomy, other karyotypes/mosaics * Klinefelter syndrome (47,XXY) * XXYY syndrome (48,XXYY) * XXXY syndrome (48,XXXY) * 49,XXXYY * 49,XXXXY * Triple X syndrome (47,XXX) * Tetrasomy X (48,XXXX) * 49,XXXXX * Jacobs syndrome (47,XYY) * 48,XYYY * 49,XYYYY * 45,X/46,XY * 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid * Burkitt's lymphoma t(8 MYC;14 IGH) * Follicular lymphoma t(14 IGH;18 BCL2) * Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) * Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) * Acute lymphoblastic leukemia Myeloid * Philadelphia chromosome t(9 ABL; 22 BCR) * Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) * Acute promyelocytic leukemia t(15 PML,17 RARA) * Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other * Ewing's sarcoma t(11 FLI1; 22 EWS) * Synovial sarcoma t(x SYT;18 SSX) * Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) * Myxoid liposarcoma t(12 DDIT3; 16 FUS) * Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) * Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other * Fragile X syndrome * Uniparental disomy * XX male syndrome/46,XX testicular disorders of sex development * Marker chromosome * Ring chromosome * 6; 9; 14; 15; 18; 20; 21, 22 [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	17q21.31 microdeletion syndrome	c1864871	28,946	wikipedia	https://en.wikipedia.org/wiki/17q21.31_microdeletion_syndrome	2021-01-18T18:39:06	{"gard": ["10727"], "mesh": ["C566476"], "umls": ["C1864871"], "orphanet": ["96169"], "wikidata": ["Q4553565"]}
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (November 2010) (Learn how and when to remove this template message) Bitemporal hemianopsia Other namesBitemporal heteronymous hemianopsia or Bitemporal hemianopia SpecialtyOphthalmology Bitemporal hemianopsia, is the medical description of a type of partial blindness where vision is missing in the outer half of both the right and left visual field. It is usually associated with lesions of the optic chiasm, the area where the optic nerves from the right and left eyes cross near the pituitary gland.[1][2] ## Contents * 1 Causes * 2 Etymology * 3 See also * 4 References * 5 External links ## Causes[edit] In bitemporal hemianopsia, vision is missing in the outer (temporal or lateral) half of both the right and left visual fields. Information from the temporal visual field falls on the nasal (medial) retina. The nasal retina is responsible for carrying the information along the optic nerve, and crosses to the other side at the optic chiasm. When there is compression at optic chiasm, the visual impulse from both nasal retina are affected, leading to inability to view the temporal, or peripheral, vision. This phenomenon is known as bitemporal hemianopsia. Knowing the neurocircuitry of visual signal flow through the optic tract is very important in understanding bitemporal hemianopsia. Bitemporal hemianopsia most commonly occurs as a result of tumors located at the mid-optic chiasm. Since the adjacent structure is the pituitary gland, some common tumors causing compression are pituitary adenomas and craniopharyngiomas. Also, another relatively common neoplastic cause is meningiomas. A cause of vascular origin is an aneurysm of the anterior communicating artery which arise superior to the chiasm, enlarge, and compress it from above. ## Etymology[edit] The absence of vision in half of a visual field is described as hemianopsia. The visual field of each eye can be divided in two vertically, with the outer half being described as temporal, and the inner half being described as nasal. "Bitemporal hemianopsia" can be broken down as follows: * bi-: involves both left and right visual fields * temporal: involves the temporal visual field * hemi-: involves half of each visual field * anopsia: blindness (formed by a(n) no \+ opsis vision \+ ia) ## See also[edit] * Binasal hemianopsia * Homonymous hemianopsia ## References[edit] 1. ^ "Bitemporal hemianopsia". Science Daily. 2. ^ Peli, E; Satgunam, P (2014). "Bitemporal hemianopia; its unique binocular complexities and a novel remedy". Ophthalmic and Physiological Optics. 34 (2): 233–242. doi:10.1111/opo.12118. PMC 3947624. PMID 24588535. ## External links[edit] Classification D * ICD-10: H53.4 * ICD-9-CM: 368.47 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Bitemporal hemianopsia	c0221184	28,947	wikipedia	https://en.wikipedia.org/wiki/Bitemporal_hemianopsia	2021-01-18T18:33:42	{"mesh": ["D006423"], "icd-9": ["368.47"], "icd-10": ["H53.4"], "wikidata": ["Q2351027"]}
X-linked myopathy with excessive autophagy This condition is inherited in an X-linked recessive manner. SpecialtyNeurology X-linked myopathy with excessive autophagy (XMEA) is a rare childhood onset disease characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is no known cardiac or intellectual involvement. ## Contents * 1 Presentation * 2 Genetics * 3 Pathology * 4 Diagnosis * 4.1 Investigations * 4.2 Differential diagnosis * 5 Treatment * 6 History * 7 References * 8 External links ## Presentation[edit] The incidence of this disease is not precisely known but it is considered to be rare (< 1/106 population). It has been reported in 15 families to date mostly from Canada, Finland and France.[citation needed] This disease usually presents between the ages of 5 to 10 years old. The usual picture is with weakness involving the upper legs and affects activities such as running and climbing stairs. As the condition progresses, patients tend to experience weakness in their lower legs and arms. Some remain able to walk in advanced age, while others require assistance in adulthood.[citation needed] ## Genetics[edit] This disorder is inherited in a recessive X linked fashion. As a result, males are much more commonly affected than females.It is due to a mutation in VMA21 gene - the human homolog of the yeast Vma21p protein. This gene is located on the long arm of chromosome X (Xq28). It is an essential assembly chaperone of the vacuolar ATPase \- the principal mammalian proton pump complex. Mutations in this gene increase lysosomal pH. This in turn reduces lysosomal degradative ability and blocks autophagy.[citation needed] ## Pathology[edit] The muscle fibers are rarely necrotic but have evidence of excessive autophagic activity and exocytosis of the phagocytosed material. They have increased variation in size and are predominantly composed of round small and hypertrophic fibers. The vacuoles are strongly reactive for dystrophin and lysosome associated membrane protein 2 (LAMP2). Membrane bound vacuoles and balls of dense material under the basal lamina are present. Deposition of the C5b-9 complement attack complex, subsarcolemmal deposition of calcium and expression of MHC1 complex also occur.[citation needed] On electron microscopy characteristic balls of dense material are commonly seen. The vacuoles may contain remains of mitochondria, membrane whorls and calcium apatite crystals.[citation needed] ## Diagnosis[edit] The diagnosis can be established by muscle biopsy.[citation needed] ### Investigations[edit] The serum creatinine is raised.[vague] ### Differential diagnosis[edit] * Acid maltase deficiency * Danon disease ## Treatment[edit] This section is empty. You can help by adding to it. (December 2017) ## History[edit] This disorder was described in 1988 by Kalimo et al in Finland in three brothers. The same condition affected their maternal grandfather and great-uncle.[1] ## References[edit] 1. ^ Kalimo H, Savontaus ML, Lang H, Paljärvi L, Sonninen V, Dean PB, Katevuo K, Salminen A (1988) X-linked myopathy with excessive autophagy: a new hereditary muscle disease. Ann Neurol 23(3):258-265 ## External links[edit] Classification D * ICD-10: G71.8 * OMIM: 310440 * MeSH: C536522 * v * t * e Diseases of muscle, neuromuscular junction, and neuromuscular disease Neuromuscular- junction disease * autoimmune * Myasthenia gravis * Lambert–Eaton myasthenic syndrome * Neuromyotonia Myopathy Muscular dystrophy (DAPC) AD * Limb-girdle muscular dystrophy 1 * Oculopharyngeal * Facioscapulohumeral * Myotonic * Distal (most) AR * Calpainopathy * Limb-girdle muscular dystrophy 2 * Congenital * Fukuyama * Ullrich * Walker–Warburg XR * dystrophin * Becker's * Duchenne * Emery–Dreifuss Other structural * collagen disease * Bethlem myopathy * PTP disease * X-linked MTM * adaptor protein disease * BIN1-linked centronuclear myopathy * cytoskeleton disease * Nemaline myopathy * Zaspopathy Channelopathy Myotonia * Myotonia congenita * Thomsen disease * Neuromyotonia/Isaacs syndrome * Paramyotonia congenita Periodic paralysis * Hypokalemic * Thyrotoxic * Hyperkalemic Other * Central core disease Mitochondrial myopathy * MELAS * MERRF * KSS * PEO General * Inflammatory myopathy * Congenital myopathy * v * t * e Symptoms and conditions relating to muscle Pain * Myalgia * Fibromyalgia * Acute * Delayed onset Inflammation * Myositis * Pyomyositis Destruction * Muscle weakness * Rhabdomyolysis * Muscle atrophy/Amyotrophy Other * Myositis ossificans * Fibrodysplasia ossificans progressiva * Compartment syndrome * Anterior * Diastasis of muscle * Diastasis recti * Muscle spasm [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Myopathy, X-linked, with excessive autophagy	c1839615	28,948	wikipedia	https://en.wikipedia.org/wiki/Myopathy,_X-linked,_with_excessive_autophagy	2021-01-18T18:46:29	{"gard": ["3892"], "mesh": ["C564093", "C536522"], "umls": ["C1839615"], "icd-10": ["G71.8"], "orphanet": ["25980"], "wikidata": ["Q3456637"]}
A number sign (#) is used with this entry because of evidence that familial hypocalciuric hypercalcemia type III (HHC3) is caused by heterozygous mutation in the AP2S1 gene (602242) on chromosome 19q13. For a general phenotypic description and discussion of genetic heterogeneity of hypocalciuric hypercalcemia, see HCC1 (145980). Clinical Features McMurtry et al. (1992) provided clinical and metabolic characterization of familial hypocalciuric hypercalcemia in a kindred from Oklahoma. Nineteen affected members were found. Immunoreactive parathyroid hormone (iPTH) levels, determined in 3 separate immunoassays, became supranormal by about age 30 years in the group of 15 hypercalcemic subjects examined biochemically and appeared to increase further thereafter. Serum alkaline phosphatase activity and creatinine levels were normal in these individuals, but inorganic phosphate levels were lower than in unaffected members of the kindred. Three of 5 affected adults older than age 40 years who were studied radiographically had changes suggestive of osteomalacia. Biopsy of the iliac crest in one of these subjects, a 51-year-old woman, confirmed the presence of defective skeletal mineralization. Differentiation from primary hyperparathyroidism was especially difficult in this kindred because serum iPTH levels may be elevated. Furthermore, the disorder may not be totally benign. Osteomalacia, perhaps due to mild hypophosphatemia, can develop during adulthood in these patients. Nesbit et al. (2010) studied a kindred from Northern Ireland in which 16 individuals over 3 generations had hypocalciuric hypercalcemia in association with normal or elevated PTH concentrations. In addition, the 16 individuals had significantly higher serum magnesium and PTH levels than their normocalcemic relatives, and hypercalcemic individuals above the age of 30 years had a significantly lower serum phosphate concentration than those below the age of 30 years. Nesbit et al. (2010) noted that these features were all consistent with HHC3, although unlike the Oklahoma family originally described by McMurtry et al. (1992), the Northern Ireland kindred did not exhibit developmental elevations in serum PTH concentration or hypophosphatemic osteomalacia in older affected members. Clinical Management Howles et al. (2016) studied 3 unrelated patients with familial hypocalciuric hypercalcemia who each had a different mutation in the AP2S1 gene, R15C (602242.0001), R15L (602242.0002), or R15H (602242.0003). The patients reported headaches, fatigue, and generalized aches and pains, that did not resolve after parathyroidectomy. Treatment with cinacalcet, a calcium-sensing receptor (CASR; 601199) allosteric activator, resulted in more than 20% reductions in serum calcium levels and abatement of symptoms. Howles et al. (2016) concluded that cinacalcet-mediated allosteric modulation of CASR can correct the loss of function due to AP2S1 mutations, and reduce the symptoms of HHC3 associated with all 3 AP2S1 mutations. Mapping Trump et al. (1995) studied a 5-generation kindred from Oklahoma, originally reported by McMurtry et al. (1992), in which there were 19 individuals with hypocalciuric hypercalcemia and 2 obligate carriers. Trump et al. (1995) demonstrated lack of linkage to the sites of familial benign hypocalciuric hypercalcemia (HCC1) on 3q21-q24 (145980; see also 601199) and 19p13.3 (HHC2; 145981), as well as lack of linkage to 11q13 and 11p15, where the genes for multiple endocrine neoplasia type I (MEN1; 131100) and PTH (168450) have been mapped, respectively. Thus, this form of FHH, designated the Oklahoma variant, represents a distinct genetic entity. Lloyd et al. (1999) established linkage between the Oklahoma form of familial benign hypercalcemia and 8 loci in the 19q13 region, with the highest lod score, 6.67 (recombination fraction = 0.00), obtained with D19S606. Recombination events narrowed the critical region to an approximately 12-cM interval flanked by D19S908 and D19S866. In the Oklahoma kindred with hypocalciuric hypercalcemia that was originally described by McMurtry et al. (1992), Hannan et al. (2010) used 24 polymorphic loci to refine further the HHC3 locus to a 4.1-Mb region flanked by D19S112 and SNP rs245111. In a 3-generation kindred from Northern Ireland with hypocalciuric hypercalcemia, in which mutation in the CASR gene (601199) and linkage to the CASR locus had been excluded, Nesbit et al. (2010) analyzed 11 polymorphic loci on chromosome 19q13 and established linkage between HHC and 8 of the loci, obtaining the highest peak lod score of 5.98 at D19S412 (theta = 0). Haplotype analysis indicated that the Oklahoma kindred with HHC mapping to chromosome 19q13, originally studied by McMurtry et al. (1992), and the Northern Ireland kindred were not related. Recombination events in the Northern Ireland family narrowed the critical region to a 3.46-Mb interval flanked centromerically by rs1990932 and telomerically by D19S604; combining these data with those of the Oklahoma kindred defined a 2.79-Mb minimum nonrecombinant interval flanked by rs1019212 and D19S879. Molecular Genetics Using exome capture and high-throughput sequence analysis of genomic DNA from an affected individual from each of 2 unrelated kindreds with HHC mapping to chromosome 19q13, originally described by McMurtry et al. (1992) and Nesbit et al. (2010), respectively, Nesbit et al. (2013) identified a heterozygous missense mutation in the AP2S1 gene (R15C; 602242.0001). The mutation, which was confirmed by dideoxynucleotide sequencing, segregated completely with disease in each family and was not found in 55 normocalcemic controls. Analysis of the AP2S1 gene in 50 unrelated patients with HHC who were negative for mutation in the CASR gene identified 11 who were heterozygous for AP2S1 missense mutations, all of which involved the R15 residue: R15C in 4 patients, R15L (602242.0002) in 4 patients, and R15H (602242.0003) in 3 patients. ### Exclusion Studies In an affected individual from an Oklahoma kindred with hypocalciuric hypercalcemia mapping to chromosome 19q13, originally reported by McMurtry et al. (1992), Hannan et al. (2010) analyzed 12 candidate genes but found no abnormalities. INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Medullary cystic disease (rare) \- Renal failure (rare) SKELETAL \- Bone pain \- Osteomalacia \- Chondrocalcinosis \- Pseudofracture MUSCLE, SOFT TISSUES \- Muscle weakness (in some patients) \- Periarticular calcifications (in some patients) NEUROLOGIC Central Nervous System \- Headaches (in some patients) Behavioral Psychiatric Manifestations \- Depression (in some patients) \- Fatigue (in some patients) ENDOCRINE FEATURES \- Elevated serum parathyroid hormone (PTH) levels \- Parathyroid gland unremarkable on ultrasound \- Parathyroid tissue unremarkable on biopsy LABORATORY ABNORMALITIES \- Hypercalcemia \- Hypocalciuria \- Hypophosphatemia, mild \- Hypermagnesemia, mild MISCELLANEOUS \- Variable skeletal features may be present \- Hypercalcemia appears as early as 1.5 years of age \- Serum PTH increases with age and is above the normal range by age 30 years MOLECULAR BASIS \- Caused by mutation in the adaptor-related protein complex 2, sigma-1 subunit gene (AP2S1, 602242.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE III	c1809471	28,949	omim	https://www.omim.org/entry/600740	2019-09-22T16:15:57	{"doid": ["0060702"], "omim": ["600740"], "orphanet": ["405", "101050"], "synonyms": ["Alternative titles", "FAMILIAL BENIGN HYPERCALCEMIA, TYPE III", "HYPERCALCEMIA, FAMILIAL BENIGN, TYPE III", "HYPERCALCEMIA, FAMILIAL BENIGN, OKLAHOMA TYPE"]}
Renal glycosuria and hyperglycinuria without increased excretion of other amino acids were the features observed by Kaser et al. (1962) in 14 persons in 7 sibships of 3 generations of 1 kindred with probable autosomal dominant inheritance. Lab \- Renal glycosuria \- Hyperglycinuria Inheritance \- Autosomal dominant ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	GLUCOGLYCINURIA	c0268536	28,950	omim	https://www.omim.org/entry/138070	2019-09-22T16:40:40	{"mesh": ["C562670"], "omim": ["138070"]}
Not to be confused with Cryptosporidiosis. Potentially fatal fungal disease Cryptococcosis Other namesCryptococcal disease Micrograph of cryptococcosis showing the characteristically thick capsule of cryptococcus. Field stain. Pronunciation * /ˌkrɪptəkəˈkoʊsɪs, -toʊ-, -kɒ-/[1][2] SpecialtyInfectious disease, Pulmonology Cryptococcosis, sometimes informally called crypto, is a potentially fatal fungal disease caused by a few species of Cryptococcus (most often Cryptococcus neoformans or Cryptococcus gattii). Cryptococcosis is believed to be acquired by inhalation of the infectious propagule from the environment. Although the exact nature of the infectious propagule is unknown, the leading hypothesis is the basidiospore created through sexual or asexual reproduction. ## Contents * 1 Cause * 2 Diagnosis * 3 Prevention * 4 Treatment * 4.1 IRIS in those with normal immune function * 5 Other animals * 6 References * 7 Further reading * 8 External links ## Cause[edit] Cryptococcosis is a defining opportunistic infection for AIDS, and is the second-most-common AIDS-defining illness in Africa. Other conditions that pose an increased risk include certain lymphomas (e.g., Hodgkin's lymphoma), sarcoidosis, liver cirrhosis, and patients on long-term corticosteroid therapy.[citation needed] Distribution is worldwide in soil.[3] The prevalence of cryptococcosis has been increasing over the past 20 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.[citation needed] In humans, C. neoformans causes three types of infections:[citation needed] * Wound or cutaneous cryptococcosis * Pulmonary cryptococcosis * Cryptococcal meningitis. Cryptococcal meningitis (infection of the meninges, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Often there is also silent dissemination throughout the brain when meningitis is present. Cryptococcus gattii causes infections in immunocompetent people (fully functioning immune system), but C. neoformans v. grubii, and v. neoformans usually only cause clinically evident infections in persons with some form of defect in their immune systems (immunocompromised persons). People with defects in their cell-mediated immunity, for example, people with AIDS, are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, even if treated. It is estimated that the three-month case-fatality rate is 9% in high-income regions, 55% in low/middle-income regions, and 70% in sub-Saharan Africa. As of 2009 there were globally approximately 958,000 annual cases and 625,000 deaths within three months after infection.[4] Although the most common presentation of cryptococcosis is of C. neoformans infection in an immunocompromised person (such as persons living with AIDS), the C. gattii is being increasingly recognised as a pathogen in what is presumed to be immunocompetent hosts,[5] especially in Canada and Australia. This may be due to rare exposure and high pathogenicity, or to unrecognised isolated defects in immunity, specific for this organism.[citation needed] ## Diagnosis[edit] Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion.[6] Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.[citation needed] Any person who is found to have cryptococcosis at a site outside of the central nervous system (e.g., pulmonary cryptococcosis), a lumbar puncture is indicated to evaluate the cerebrospinal fluid (CSF) for evidence of cryptococcal meningitis, even if they do not have signs or symptoms of CNS disease. Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis.[7] Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis,[8] although the sensitivity is poor in early infection, and may miss 15–20% of patients with culture-positive cryptococcal meningitis.[9] Unusual morphological forms are rarely seen.[10] Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity.[11] Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011.[9][12] Polymerase chain reaction (PCR) has been used on tissue specimens. Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with Cryptococcus gattii. * * * * * * ## Prevention[edit] Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.[13][14] Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis.[15] The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL.[16] This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy.[14][17] Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.[18][19] Antifungal prophylaxis such as fluconazole and itraconazole reduces the risk of contracting cryptococcosis in those with low CD4 cell count and high risk of developing such disease in a setting of cryptococcal antigen screening tests are not available.[20] ## Treatment[edit] Treatment options in persons without HIV-infection have not been well studied. Intravenous Amphotericin B combined with flucytosine by mouth is recommended for initial treatment (induction therapy).[21] People living with AIDS often have a greater burden of disease and higher mortality (30–70% at 10-weeks), but recommended therapy is with amphotericin B and flucytosine. Where flucytosine is not available (many low and middle income countries), fluconazole should be used with amphotericin.[16] Amphotericin-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10-weeks.[7][22] Based on a systematic review of existing data, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin B coupled with high-dose fluconazole.[22] After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks used with secondary prophylaxis with fluconazole thereafter.[16] The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis.[23] A 2018 Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment.[24] ### IRIS in those with normal immune function[edit] The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by C. gattii and C. grubii. Several weeks or even months into appropriate treatment, there can be deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms. IRIS is however much more common in those with poor immune function (≈25% vs. ≈8%).Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. Radiographic appearance of cryptococcal IRIS brain lesions can mimic that of toxoplasmosis with ring enhancing lesions on head computed tomography (CT). CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.[citation needed] The increasing inflammation can cause brain injury or be fatal.[25][26][27] The mechanism behind IRIS in cryptococcal meningitis is primarily immunologic. With reversal of immunosuppression, there is paradoxical increased inflammation as the recovering immune system recognises the fungus. In severe IRIS cases, treatment with systemic corticosteroids has been utilized – although evidence-based data are lacking. ## Other animals[edit] Cryptococcosis is also seen in cats and occasionally dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses, and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with FeLV infection in cats. Cryptococcosis is most common in dogs and cats but cattle, sheep, goats, horses, wild animals, and birds can also be infected. Soil, fowl manure, and pigeon droppings are among the sources of infection.[28][29] ## References[edit] 1. ^ "Cryptococcosis". Oxford Dictionaries UK Dictionary. Oxford University Press. Retrieved 2016-01-21. 2. ^ "Cryptococcosis". Merriam-Webster Dictionary. Retrieved 2016-01-21. 3. ^ "Meningitis: cryptococcal: Overview". Medical Reference: Encyclopedia. University of Maryland Medical Center. September 2010. 4. ^ Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM (2009-02-20). "Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS". AIDS. 23 (4): 525–30. doi:10.1097/QAD.0b013e328322ffac. PMID 19182676. S2CID 5735550. 5. ^ Tripathi K, Mor V, Bairwa NK, Del Poeta M, Mohanty BK (2012). "Hydroxyurea treatment inhibits proliferation of Cryptococcus neoformans in mice". Front Microbiol. 3: 187. doi:10.3389/fmicb.2012.00187. PMC 3390589. PMID 22783238. 6. ^ Barron MA, Madinger NE (November 18, 2008). "Opportunistic Fungal Infections, Part 3: Cryptococcosis, Histoplasmosis, Coccidioidomycosis, and Emerging Mould Infections". Infections in Medicine. 7. ^ a b Rhein, J; Boulware DR (2012). "Prognosis and management of cryptococcal meningitis in patients with HIV infection". Neurobehavioral HIV Medicine. 4: 45. doi:10.2147/NBHIV.S24748. 8. ^ Zerpa, R; Huicho, L; Guillén, A (September 1996). "Modified India ink preparation for Cryptococcus neoformans in cerebrospinal fluid specimens". Journal of Clinical Microbiology. 34 (9): 2290–1. doi:10.1128/JCM.34.9.2290-2291.1996. PMC 229234. PMID 8862601. 9. ^ a b Boulware, DR; Rolfes, MA; Rajasingham, R; von Hohenberg, M; Qin, Z; Taseera, K; Schutz, C; Kwizera, R; Butler, EK; Meintjes, G; Muzoora, C; Bischof, JC; Meya, DB (Jan 2014). "Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast". Emerging Infectious Diseases. 20 (1): 45–53. doi:10.3201/eid2001.130906. PMC 3884728. PMID 24378231. 10. ^ Shashikala; Kanungo, R; Srinivasan, S; Mathew, R; Kannan, M (Jul–Sep 2004). "Unusual morphological forms of Cryptococcus neoformans in cerebrospinal fluid". Indian Journal of Medical Microbiology. 22 (3): 188–90. PMID 17642731. 11. ^ Antinori, Spinello; Radice, Anna; Galimberti, Laura; Magni, Carlo; Fasan, Marco; Parravicini, Carlo (November 2005). "The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis" (PDF). Journal of Clinical Microbiology. 43 (11): 5828–9. doi:10.1128/JCM.43.11.5828-5829.2005. PMC 1287839. PMID 16272534. 12. ^ Jarvis JN, Percival A, Bauman S, Pelfrey J, Meintjes G, Williams GN, et al. (2011). "Evaluation of a novelpoint-of-care cryptococcal antigen test on serum, plasma, and urine frompatients with HIV-associated cryptococcal meningitis". Clin Infect Dis. 53 (10): 1019–23. doi:10.1093/cid/cir613. PMC 3193830. PMID 21940419. 13. ^ "FIGURE 1. Prevalence of asymptomatic antigenemia with corresponding cost per life saved based on LFA cost of $2.50 per test". 14. ^ a b Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR (August 2010). "Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings". Clin. Infect. Dis. 51 (4): 448–55. doi:10.1086/655143. PMC 2946373. PMID 20597693. 15. ^ Rajasingham, R; Meya, DB; Boulware, DR (Apr 15, 2012). "Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care". Journal of Acquired Immune Deficiency Syndromes. 59 (5): e85–91. doi:10.1097/QAI.0b013e31824c837e. PMC 3311156. PMID 22410867. 16. ^ a b c World Health Organization. "Rapid advice: Diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents, and children". Retrieved 1 August 2012. 17. ^ Jarvis, JN; Harrison, TS; Govender, N; Lawn, SD; Longley, N; Bicanic, T; Maartens, G; Venter, F; Bekker, LG; Wood, R; Meintjes, G (2011). "Routine cryptococcal antigen screening for HIV-infected patients with low CD4+ T-lymphocyte counts—time to implement in South Africa?" (PDF). South African Medical Journal. 101 (4): 232–4. doi:10.7196/samj.4752. PMID 21786721. 18. ^ Rajasingham, R; Boulware, DR (Dec 2012). "Reconsidering cryptococcal antigen screening in the U.S. among persons with CD4 <100 cells/mcL". Clinical Infectious Diseases. 55 (12): 1742–4. doi:10.1093/cid/cis725. PMC 3501329. PMID 22918997. 19. ^ McKenney J, Smith RM, Chiller TM, Detels R, French A, Margolick J, Klausner JD (July 2014). "Prevalence and correlates of cryptococcal antigen positivity among AIDS patients—United States, 1986–2012". MMWR Morb. Mortal. Wkly. Rep. 63 (27): 585–7. PMC 4584711. PMID 25006824. 20. ^ Awotiwon, Ajibola A; Johnson, Samuel; Rutherford, George W; Meintjes, Graeme; Eshun-Wilson, Ingrid (2018-08-29). Cochrane Infectious Diseases Group (ed.). "Primary antifungal prophylaxis for cryptococcal disease in HIV-positive people". Cochrane Database of Systematic Reviews. 8: CD004773. doi:10.1002/14651858.CD004773.pub3. PMC 6513489. PMID 30156270. 21. ^ "Practice Guidelines for the Management of Cryptococcal Disease". Infectious Disease Society of America. 2010. 22. ^ a b Rajasingham, Radha; Rolfes, M.A.; Birkenkamp, K.E.; Meya, D.B.; Boulware, D.R. (2012). Farrar, Jeremy (ed.). "Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis". PLOS Medicine. 9 (9): e1001316. doi:10.1371/journal.pmed.1001316. PMC 3463510. PMID 23055838. 23. ^ Boulware, DR; Meya, DB; Muzoora, Conrad; Rolfes, MA; Huppler Hullsiek, K; Musubire, Abdu; Taseera, Kabanda; Nabeta, HW; Schutz, C; Williams, DA A.; Rajasingham, R; Rhein, J; Thienemann, F; Lo, MW; Nielsen, K; Bergemann, T L.; Kambugu, A; Manabe, YC; Janoff, EN; Bohjanen, PR; Meintjes, G (26 June 2014). "Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis". New England Journal of Medicine. 370 (26): 2487–2498. doi:10.1056/NEJMoa1312884. PMC 4127879. PMID 24963568. 24. ^ Eshun-Wilson, Ingrid; Okwen, Mbah P.; Richardson, Marty; Bicanic, Tihana (24 July 2018). "Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningitis". The Cochrane Database of Systematic Reviews. 7: CD009012. doi:10.1002/14651858.CD009012.pub3. ISSN 1469-493X. PMC 6513637. PMID 30039850. 25. ^ Lane M, McBride J, Archer J (August 2004). "Steroid responsive late deterioration in Cryptococcus neoformans variety gattii meningitis". Neurology. 63 (4): 713–4. doi:10.1212/01.WNL.0000134677.29120.62. PMID 15326249. S2CID 42308361. 26. ^ Einsiedel L, Gordon DL, Dyer JR (October 2004). "Paradoxical inflammatory reaction during treatment of Cryptococcus neoformans var. gattii meningitis in an HIV-seronegative woman". Clin. Infect. Dis. 39 (8): e78–82. doi:10.1086/424746. PMID 15486830. 27. ^ Ecevit IZ, Clancy CJ, Schmalfuss IM, Nguyen MH (May 2006). "The poor prognosis of central nervous system cryptococcosis among nonimmunosuppressed patients: a call for better disease recognition and evaluation of adjuncts to antifungal therapy". Clin. Infect. Dis. 42 (10): 1443–7. doi:10.1086/503570. PMID 16619158. 28. ^ "Deep Fungal Infections". Archived from the original on 2010-04-13. 29. ^ Akira Takeuchi, D. V. M. (July 2014). "Feline Cryptococcosis – WSAVA 2003 Congress – VIN". Vin.com. ## Further reading[edit] * Perfect JR, et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clinical Infectious Diseases. 50 (3): 291–322. doi:10.1086/649858. PMC 5826644. PMID 20047480. * Gullo FP, et al. (2013). "Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment". European Journal of Clinical Microbiology & Infectious Diseases. 32 (11): 1377–1391. doi:10.1007/s10096-013-1915-8. PMID 24141976. S2CID 11317427. * Perfect JR, et al. (2005). "Cryptococcus neoformans: a sugar-coated killer with designer genes". FEMS Immunology and Medical Microbiology. 45 (11): 395–404. doi:10.1016/j.femsim.2005.06.005. PMID 16055314. (Review) ## External links[edit] Classification D * ICD-10: B45 * ICD-9-CM: 117.5 * MeSH: D003453 * DiseasesDB: 3213 External resources * MedlinePlus: 001328 * eMedicine: med/482 * Patient UK: Cryptococcosis * Orphanet: 1546 * Medscape entry on cryptococcosis * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis * v * t * e Meningitis and other diseases of meninges Meningitis * Arachnoiditis * Bacterial * Tuberculous * Haemophilus * Pneumococcal * Viral * Herpesviral * Fungal * Cryptococcal * Aseptic * Drug-induced Other * Meningoencephalitis [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Cryptococcosis	c0010414	28,951	wikipedia	https://en.wikipedia.org/wiki/Cryptococcosis	2021-01-18T19:00:03	{"gard": ["6218"], "mesh": ["D003453"], "umls": ["C0010414"], "icd-9": ["117.5117.5"], "icd-10": ["B4545."], "orphanet": ["1546"], "wikidata": ["Q1470140"]}
A rare, X-linked, multiple congenital anomalies/dysmorphic malformation-intellectual disability syndrome characterized by developmental delay, mild to moderate intellectual disability, speech disturbance, behavioral problems (such as anxiety, hyperactivity, and aggressiveness) and mild facial dysmorphism (including facial hypotonia, thin arched eyebrows, ectropion, epicanthus, malar flatness, thick vermillion of the lips and prognathia). Additional variable manifestations include short stature, skeletal and genital anomalies, seizures, and autism spectrum disorders. Brain imaging may reveal cerebellar vermis hypoplasia, thin corpus callosum, and enlarged subarachnoid spaces. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Xq25 microduplication syndrome	c4311049	28,952	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=521258	2021-01-23T17:45:29	{"omim": ["300979"], "synonyms": ["Dup(X)(q25)", "Xq25 microtriplication"]}
A number sign (#) is used with this entry because of evidence that sedoheptulokinase deficiency (SHPKD) is caused by homozygous mutation in the SHPK gene (605060) on chromosome 17p13. Description SHPK deficiency is an autosomal recessive inborn error of metabolism characterized by increased urinary erythritol and sedoheptulose. Additional phenotypic consequences of this deficiency are unclear (summary by Wamelink et al., 2015). Clinical Features Wamelink et al. (2015) reported 2 unrelated children with isolated SHPK deficiency identified by a metabolic screening that showed increased levels of erythritol and sedoheptulose. Patient 1 was a 3-year-old boy born of Caucasian parents with suspected consanguinity; patient 2 was a 2-year-old girl born of consanguineous Turkish parents. There were some common features between the 2 children: both had perinatal asphyxia and variable dysmorphic features, including high forehead with large fontanels, hypotelorism, small orbits, and abnormally thin abdominal skin in patient 1, and round asymmetrical eyes, ptosis, Bell palsy, small mouth, high nasal bridge, dysplastic low-set ears, adducted thumbs, congenital arthrogryposis, hip dysplasia, and small feet in patient 2. Both also had delayed development and intellectual disability; patient 1 had sensorineural deafness. Otherwise, the patients had different disease courses. Patient 1 had chronic diarrhea with steatorrhea and severe growth retardation with short stature, cholestatic hepatitis, transient renal failure, short-fasting hypoglycemic episodes, and postprandial hyperglycemia. He required exocrine pancreatic yeast supplementation and blood transfusions due to chronic microcytic hypochromic anemia. He had recurrent infections, but immunodeficiency was excluded. Brain imaging showed enlarged ventricles, subcortical atrophy, hyperintense periventricular lesions, hypomyelinization, and Chiari malformation type 1. Patient 2 had feeding difficulties, but normal growth and no evidence of immune dysfunction; brain imaging was normal in this child. TALDO deficiency (606003) was ruled out in both patients, and there was no clinical overlap with cystinosis (219800). Wamelink et al. (2015) noted that it was unclear whether the clinical features in these patients were related to the SHPK deficiency, and that the presence of other recessive disorders in these consanguineous families could not be excluded. Clarification requires the identification of additional individuals with SHPK deficiency. Inheritance The transmission pattern of SHPK deficiency in the family reported by Wamelink et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 unrelated children with biochemical evidence of SHPK deficiency, Wamelink et al. (2015) identified homozygous truncating mutations in the SHPK gene (R119X, 605060.0001 and E71X, 605060.0002). INHERITANCE \- Autosomal recessive LABORATORY ABNORMALITIES \- Increased urinary erythritol \- Increased urinary sedoheptulose MISCELLANEOUS \- Two unrelated patients, both born of consanguineous parents, have been reported (last curated November 2016) \- The patients had different multisystem manifestations, including delayed psychomotor development and dysmorphic features, but the relationship of these features to the SHPK deficiency is unclear MOLECULAR BASIS \- Caused by mutation in the sedoheptulokinase gene (SHPK, 605060.0001 ) ▲ 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	SEDOHEPTULOKINASE DEFICIENCY	c1291373	28,953	omim	https://www.omim.org/entry/617213	2019-09-22T15:46:37	{"omim": ["617213"], "orphanet": ["440713"], "synonyms": ["Isolated SHPK deficiency"]}
Monomelic amyotrophy (MMA) is a rare disease that causes muscle weakness in the upper extremities. MMA affects the lower motor neurons. Lower motor neurons are cells that help communicate information from the brain to the muscles that are involved in movement (skeletal muscles). Specifically, monomelic amyotrophy causes weakness and loss of muscle mass in the arms and fingers. Symptoms of the disease typically begin between the ages of 14-25 years-old. The disease is most common in Asia, especially in Japan and India. Males are more likely to develop the disease than females. The exact cause of monomelic amyotrophy is unknown. It is possible that the disease is caused by movement of the sac that surrounds the spinal cord due to repeated downward movement (flexion) of the neck. Monomelic amyotrophy can sometimes run in families, but it is not thought to be caused by a specific genetic change. Diagnosis of the disease is based on imaging studies and electromyography (EMG) consistent with the disease. Treatment options may include muscle strengthening exercises and neck bracing. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Monomelic amyotrophy	c1865384	28,954	gard	https://rarediseases.info.nih.gov/diseases/9697/monomelic-amyotrophy	2021-01-18T17:58:59	{"mesh": ["C538253"], "omim": ["602440"], "umls": ["C1865384"], "orphanet": ["65684"], "synonyms": ["Hirayama disease", "Spinal muscular atrophy juvenile nonprogressive", "Benign focal amyotrophy", "Juvenile muscular atrophy of distal upper extremity (JMADUE)", "Juvenile muscular atrophy of distal upper limb"]}
A rare form of multicystic dysplastic kidney (MCDK), a congenital anomaly of the kidney and urinary tract (CAKUT), in which one kidney is large, distended by multiple cysts, and non-functional. ## Epidemiology Unilateral MCDK is the most common form of MCDK with a birth prevalence estimated at 1/4,300 live births. ## Clinical description Unilateral MCDK frequently presents antenatally at routine ultrasound scans, with the majority detected around the 20th week of gestation. The large majority of patients are asymptomatic but unilateral MCDK may occasionally present with abdominal obstructive signs (abdominal distention, feeding difficulties, respiratory distress) when the cysts become too large. Patients may also develop hypertension, proteinuria, and renal failure in the long run. The contralateral renal tract has an increased incidence of additional CAKUT such as vesicoureteral reflux and pelvi-ureteric junction obstruction (PUJO). Hypertrophy of the contralateral kidney may occur in 24-46% cases before birth, and in up to 80% in the years after birth. ## Etiology Unilateral MCDK results from disrupted nephrogenesis but the exact pathogenic mechanism is still unknown. Disturbed formation of nephrons could result from impaired fetal urine flow early in development. Mutations in the HNF1B gene (17q12), coding for hepatocyte nuclear transcription factor 1beta, associated with renal cysts and diabetes syndrome, have been detected in cases of unilateral MCDK. MCDK is also linked to gestational diabetes and to the use of some medications during pregnancy, such as anti-epileptic drugs. ## Diagnostic methods Diagnosis is mainly based on prenatal ultrasound showing large hypoechogenic non-communicating cysts within an irregularly outlined kidney with no visible renal pelvis. A tiny remnant kidney can be observed if the cysts have involuted. Complete prenatal involution has been described in 5% of MCDK, with complete involution in 50% during the first decade of life. Histologic examination shows that cysts are surrounded by undifferentiated and metaplastic cells with occasional residual functional renal tissue with recognizable glomeruli and proximal tubules. Renography with technetium-99m-labeled dimercaptosuccinic acid may show little or no renal uptake. As this has no clinical consequences, renography is not routinely indicated. ## Differential diagnosis Differential diagnoses include PUJO, in which the largely dilated calices may appear to be cysts, or in case of involuting MCKD, renal hypoplasia or renal agenesis. ## Antenatal diagnosis Ultrasonographic screening can detect unilateral MCDKs from midway through gestation. ## Genetic counseling Both sporadic and familial cases have been observed. In familial cases, transmission is autosomal dominant with a recurrence risk of 50%. ## Management and treatment Partially based on the supposed increased risk of hypertension and malignancy of which no evidence is found, nephrectomy was performed routinely until recently, whereas nowadays most cases of unilateral MCDK are left in situ and followed with serial ultrasound. However, nephrectomy may be indicated in case of abdominal obstructive complaints when the cysts become too large. Due to an increased risk of hypertension and/or proteinuria, as a sign of glomerular hyperfiltration or renal dysplasia in the solitary functioning kidney, individuals with unilateral MCDK deserve long-term follow-up. Up to 30% of unilateral cases of MCDK may lead to renal failure at the age of 30 years, at which stage renal replacement therapy is indicated. ## Prognosis The prognosis is influenced by the presence of abnormalities in the contralateral kidney. * European Reference Network [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Unilateral multicystic dysplastic kidney	c1567426	28,955	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97363	2021-01-23T17:42:15	{"mesh": ["D021782"], "umls": ["C1567426"], "icd-10": ["Q61.4"], "synonyms": ["Unilateral MCDK", "Unilateral multicystic renal dysplasia"]}
A number sign (#) is used with this entry because of evidence that X-linked selective tooth agenesis-1 (STHAGX1) is caused by mutation in the gene encoding ectodysplasin A (EDA; 300451) on chromosome Xq13. Mutations in the same gene can cause hypohidrotic ectodermal dysplasia (305100). For a discussion of genetic heterogeneity of selective tooth agenesis, see 106600. Clinical Features Erpenstein and Pfeiffer (1967) described transmission of oligodontia or hypodontia through 4 generations of a family. Males had oligodontia; females had hypodontia. No male-to-male transmission was observed. However, only 2 affected males had children (4 unaffected sons, 1 daughter with hypodontia). X-linked inheritance seemed likely. In at least 18 persons in 4 generations Dahlberg (1937) noted absence of at least 6 anterior teeth in both dentitions. He suggested X-linked dominant inheritance, but against this was 1 unaffected daughter of the 1 affected male with children in the kindred. Tao et al. (2006) reported a Mongolian family in which several members had congenital absence of teeth inherited in an X-linked recessive pattern. No member of the family had any other feature of hypohidrotic ectodermal dysplasia. The manifestation of hypodontia was not uniform in the family, indicating incomplete penetrance or variable expressivity. Affected members commonly had 2 pairs of permanent first molars. All of those affected had congenital absence of lower incisors and lower lateral incisors. Tarpey et al. (2007) reported an Indian family in which almost all affected males had absence of all mandibular incisors and maxillary lateral incisors in both the primary and permanent dentition, with maxillary central incisors also missing in some cases. The absence of at least 1 incisor, typically of the maxillary lateral incisors, was also observed in affected females; at least 1 female had as severe a dental phenotype as the affected males. Inheritance was consistent with an X-linked dominant mechanism. No individuals reported abnormal sweating or heat intolerance. Tarpey et al. (2007) noted that the hypodontia in the family reported by Tao et al. (2006) was more severe and involved all classes of teeth. Mapping In a family segregating X-linked congenital hypodontia, Tao et al. (2006) found linkage of the disorder with marker loci DXS1111, DXS1689, and DXS8101 (maximum 2-point lod score of 3.55). Haplotype analysis confined the locus to a less than 6.48-cM interval between DXS1124 and DXS1213 at Xq12-q13.1. Molecular Genetics In a family segregating X-linked congenital hypodontia, Tao et al. (2006) identified a missense mutation in the EDA gene (R65G; 300451.0014) in all affected males and carrier females. Three of the 9 female carriers (33%) had a skewed X-chromosome inactivation pattern. In affected members of an Indian family with X-linked incisor hypodontia, Tarpey et al. (2007) identified a mutation in the EDA gene (Q358E; 300451.0015). In 4 affected males and 1 affected female carrier from a Chinese family with congenital hypodontia, Han et al. (2008) identified a mutation in the EDA gene (T338M; 300451.0018). The 7-year-old male proband had several deciduous teeth missing, but the shape of the residual teeth was normal. All 16 of the participating family members reported normal levels of sweating and of lachrymal and salivary secretions. Facial features, skin, hair, and nails appeared normal, and none had malformed teeth. In 15 unrelated Chinese men with selective tooth agenesis, Song et al. (2009) sequenced the EDA gene and identified 4 patients with missense mutations: A259E (300451.0020) in 2 of the patients, and R289C (300451.0021) and R334H (300451.0022) in 1 each. The authors observed that all 4 patients had extensively distributed missing teeth in both upper and lower dentitions, including central and/or lateral incisors, but the shape and size of residual teeth were normal. Hair, skin, and nails were normal, and the patients reported normal sweating with no history of dry mouth, heat intolerance, or susceptibility to respiratory tract infections. Genotype/Phenotype Correlations Han et al. (2008) analyzed 24 patients with defined mutations in the EDA gene and known patterns of tooth agenesis in their permanent dentition. Teeth with the highest probability of absence were the maxillary and mandibular lateral incisors (92%) and the mandibular central incisors (83%). Comparative analysis of the pattern of tooth agenesis between patients with EDA mutations and patients with hypodontia or tooth agenesis due to mutations in the MSX1 (142983) or PAX9 (167416) genes revealed several statistically significant differences (p less than 0.001): patients with EDA mutations were more likely to be missing maxillary and mandibular central incisors, lateral incisors, and canines, but maxillary and mandibular first permanent molars were more likely to be present. INHERITANCE \- X-linked dominant HEAD & NECK Teeth \- Oligodontia \- Hypodontia MOLECULAR BASIS \- Caused by mutation in the ectodysplasin A gene (EDA, 300451.0014 ) ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	TOOTH AGENESIS, SELECTIVE, X-LINKED, 1	c1970757	28,956	omim	https://www.omim.org/entry/313500	2019-09-22T16:17:13	{"doid": ["0050591"], "mesh": ["C567060"], "omim": ["313500"], "orphanet": ["99798"], "synonyms": ["Alternative titles", "Selective tooth agenesis", "HYPODONTIA/OLIGODONTIA, X-LINKED, 1"]}
Uveal melanoma (155720) is the most common primary intraocular malignancy. Monosomy 3, which is an unusual finding in most tumors, is present in approximately 50% of uveal melanomas and is significantly correlated with metastatic disease. To obtain positional information on putative tumor suppressor genes on chromosome 3, Tschentscher et al. (2001) investigated tumors from 333 patients by comparative genomic hybridization, microsatellite analysis, or conventional karyotype analysis. A partial deletion of the long arm was found in 8 tumors, and the smallest region of deletion overlap (SRO) spanned 3q24-q26. They found 6 tumors with a partial deletion of the short arm and defined a second SRO of about 2.5 Mb in 3p25. This SRO did not overlap with the von Hippel-Lindau disease gene (608537). Tschentscher et al. (2001) interpreted their findings as suggesting a role for 2 tumor suppressor genes in metastasizing uveal melanoma: one on 3q, here designated UVM1 (606660), and a second on 3p25, here designated UVM2. The involvement of 2 tumor suppressor genes may explain the loss of an entire chromosome 3 in metastatic uveal melanomas. Parrella et al. (2003) mapped both arms of chromosome 3 in 21 uveal melanomas that did not show monosomy 3 in previous allelotype studies. DNA was isolated from microdissected paraffin sections of posterior uveal melanoma treated by enucleation from 1993 to 1998 and archived by the Eye Pathology Laboratory of the Wilmer Ophthalmologic Institute, Johns Hopkins. In an initial screening, 14 microsatellite markers on 3p and 13 on 3q were used. Loss of heterozygosity for at least 1 marker was found in 9 of 21 tumors (43%) on 3p and 8 of 21 tumors (38%) on 3q. Two common regions of allelic loss on 3p were further mapped with an additional 14 microsatellite markers. A 1.4-Mb minimal region of allelic loss was identified between microsatellite markers D3S3610 and D3S1554 on 3p25.2-p25.1. Ten tumors had allelic loss in this region; 2 of these tumors had corresponding putative homozygous deletions. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	MELANOMA, UVEAL, SUSCEPTIBILITY TO, 2	c0346388	28,957	omim	https://www.omim.org/entry/606661	2019-09-22T16:10:16	{"doid": ["6039"], "omim": ["606661"], "orphanet": ["39044"], "synonyms": ["Alternative titles", "UVM2"]}
A rare condition characterized by the presence of juvenile hamartomatous polyps in the gastrointestinal (GI) tract. ## Epidemiology Annual incidence is estimated at between 1/100,000 and 1/15,000. ## Clinical description Polyps may develop at any age from infancy through to adulthood, with most affected individuals presenting polyps by adolescence/early adulthood. A diagnosis of JIP is made on the basis of one or several of the following findings: the presence of more than five juvenile polyps in the colon and/or rectum; the presence of juvenile polyposis throughout the digestive tract, including the stomach; the presence of any number of juvenile polyps in association with a family history of JIP. Several types of JIP have been described, including three forms that differ on the basis of the location of the polyps (generalized juvenile polyposis of the upper and lower GI tract, juvenile polyposis coli and juvenile polyposis of the stomach) and a more severe infantile form, juvenile polyposis of infancy (see this term). Regardless of the subtype, the clinical signs of JIP are isolated rectal bleeding, anemia, abdominal pain, intussusceptions and diarrhea. Rectal prolapse and spontaneous anal elimination of polyps have been noted in juvenile polyposis coli and generalized juvenile polyposis. Other associated signs may include growth delay and edema. ## Etiology JIP is transmitted in an autosomal dominant manner and mutations in the SMAD4 (18q21.1) and BMPR1A (10q22.3) genes have been associated with the disease. However, no genetic anomalies have been identified so far in around 60% of the cases. A few genotype-phenotype correlations have been established: the frequency of gastric polyposis is higher in SMAD4 carriers than in BMPR1A carriers and the association of JPS with hereditary hemorrhagic telangiectasia (juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome) is observed in just under a quarter of SMAD4 mutation carriers. ## Diagnostic methods Diagnosis is based on the clinical findings, family history, endoscopic findings and histological analysis of the polyps. Molecular genetic testing may also be useful for confirming the diagnosis in carriers of SMAD4 and BMPR1A gene mutations. ## Differential diagnosis The differential diagnosis should include other syndromes associated with polyposis including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, familial adenomatous polyposis and Peutz-Jeghers syndrome (see these terms). ## Management and treatment Management should involve routine colonoscopy and if the number of polyps remains low endoscopic polypectomy is the gold standard for treatment. Due to the risk of cancer and polyposis extension, surgical colectomy associated with protectomy and ileoanal anastomosis may also be proposed. ## Prognosis The prognosis of JIP is based on the risk of developing GI or pancreatic cancer after 20 years of age. The cumulative risk for developing cancer in patients with JIP is 20% at the age of 35 years and 68% after the age of 60 years. The risk of cancer is higher among individuals with generalized juvenile polyposis. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Juvenile polyposis syndrome	c0345893	28,958	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2929	2021-01-23T18:29:05	{"gard": ["3065"], "mesh": ["C537702"], "omim": ["174900", "175050", "612242"], "umls": ["C0345893"], "icd-10": ["D12.6"], "synonyms": ["JIP", "JPS", "Juvenile gastrointestinal polyposis", "Juvenile intestinal polyposis"]}
Not to be confused with anarchy or anarchism. Anorchia Other namesCongenital absence of testes SpecialtyMedical genetics Anorchia (also called anorchidism or anorchism) is a disorder of sex development in which a person with XY karyotype, which usually corresponds to male sex, is born without testes. Within a few weeks of fertilization, the embryo develops rudimentary gonads (testes), which produce hormones responsible for the development of the reproductive system. If the testes fail to develop within eight weeks, the baby will develop female genitalia (see Swyer syndrome). If the testes begin to develop but are lost or cease to function between eight and 10 weeks, the baby will have ambiguous genitalia when it is born. However, if the testes are lost after 14 weeks, the baby will have partial male genitalia with the notable absence of gonads. Tests include observable lack of testes, low testosterone levels (typical female levels), elevated follicle stimulating hormone and luteinizing hormone levels, XY karyotype, ultrasound or magnetic resonance imaging showing absent gonadal tissue, low bone density, low anti-Müllerian hormone levels, and surgical exploration for evidence of male gonadal tissue. ## Contents * 1 Cause * 2 Treatment * 3 Terminology * 4 See also * 5 References * 6 External links ## Cause[edit] This section is empty. You can help by adding to it. (August 2017) ## Treatment[edit] Treatment includes androgen (testosterone) supplementation to artificially initiate puberty, testicular prosthetic implantation, and psychological support. Gender Dysphoria may result in anorchic individuals who are assigned male at birth and raised as male despite lacking the necessary masculinizing hormones during prenatal, childhood, and adolescent development. Anorchic individuals who have a female identity may be administered estrogen alone in place of testosterone as no androgen blockers are necessary due to the lack of gonads. ## Terminology[edit] Other names for anorchia include * congenital anorchia * vanishing testes syndrome * vanishing testes * empty scrotum * testicular regression syndrome (TRS) ## See also[edit] * Cryptorchidism * Monorchism * Polyorchidism * 46 XX ## References[edit] * "Anorchia". University of Maryland Medical Center. Archived from the original on 6 February 2006. Retrieved January 25, 2006. ## External links[edit] Classification D * ICD-10: Q55.0 * ICD-9-CM: 752.89 * OMIM: 273250 * DiseasesDB: 29633 External resources * MedlinePlus: 001185 * Orphanet: 325124 * v * t * e Male congenital anomalies of the genitalia, including Intersex and DSD Internal Testicle * Cryptorchidism * Polyorchidism * Monorchism * Anorchia * Sertoli cell-only syndrome * True hermaphroditism * Mixed gonadal dysgenesis * Swyer syndrome Vas deferens * Congenital absence of the vas deferens Other * Persistent Müllerian duct syndrome External Penis * Hypospadias * Epispadias * Chordee * Micropenis * Penile agenesis * Diphallia * Penoscrotal transposition Other * Pseudohermaphroditism [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Anorchia	c1261504	28,959	wikipedia	https://en.wikipedia.org/wiki/Anorchia	2021-01-18T18:47:51	{"gard": ["5819"], "mesh": ["C537770"], "icd-9": ["752.89"], "icd-10": ["Q55.0\|"], "orphanet": ["325124"], "synonyms": ["Bilateral anorchia"], "wikidata": ["Q567694"]}
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: "CHARGE syndrome" – news · newspapers · books · scholar · JSTOR (July 2008) (Learn how and when to remove this template message) CHARGE syndrome "Lop ear" phenotype characteristic of a person with CHARGE syndrome, along with her cochlear implant. SpecialtyMedical genetics CHARGE syndrome (formerly known as CHARGE association) is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness.[1] These features are no longer used in making a diagnosis of CHARGE syndrome, but the name remains. About two thirds of cases are due to a CHD7 mutation. CHARGE syndrome occurs only in 0.1–1.2 per 10,000 live births; as of 2009 it was the leading cause of congenital deafblindness in the US.[2] ## Contents * 1 Genetics * 2 Diagnosis * 2.1 Signs * 2.2 Genetic testing * 2.3 Screening other organ systems * 3 Therapy * 3.1 Education * 4 Epidemiology * 5 History * 6 References * 7 External links ## Genetics[edit] CHARGE syndrome was formerly referred to as CHARGE association, which indicates a non-random pattern of congenital anomalies that occurs together more frequently than one would expect on the basis of chance. Very few people with CHARGE will have 100% of its known features. In 2004, mutations on the CHD7 gene (located on Chromosome 8) were found in 10 of 17 patients in the Netherlands, making CHARGE an official syndrome.[3] A 2006 US study of 110 individuals with CHARGE syndrome showed that 60% of those tested had a mutation of the CHD7 gene.[4] In 2010, a review of 379 clinically diagnosed cases of CHARGE syndrome, in which CHD7 mutation testing was undertaken found that 67% of cases were due to a CHD7 mutation.[5] CHD7 is a member of the chromodomain helicase DNA-binding (CHD) protein family that plays a role in transcription regulation by chromatin remodeling.[6] ## Diagnosis[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (July 2016) (Learn how and when to remove this template message) The diagnosis of CHARGE syndrome is often difficult, because it is rare. The syndrome spans many disciplines, and as such, can be diagnosed by a pediatrician, family medicine physician, oral and maxillofacial surgeon, ENT specialist, ophthalmologist, endocrinologist, cardiologist, urologist, developmental specialist, radiologist, geneticist, physiotherapist, occupational therapist, speech therapist, or orthopedic specialist.[citation needed] ### Signs[edit] Although genetic testing positively identifies nearly two thirds of children with CHARGE syndrome, diagnosis is still largely clinical.[citation needed] The following signs were originally identified in children with this syndrome, but are no longer used in to make the diagnosis alone. * C – Coloboma of the eye, central nervous system anomalies * H – Heart defects * A – Atresia of the choanae * R – Lack of growth and/or development * G – Genital and/or urinary defects (hypogonadism, undescended testicles, besides hypospadias) * E – Ear anomalies and/or deafness and abnormally bowl-shaped and concave ears, known as "lop ears". ### Genetic testing[edit] Genetic testing for CHARGE syndrome involves specific genetic testing for the CHD7 gene. The test is available[when?] at most major genetic testing laboratories. Insurance companies sometimes do not pay for such genetic tests, though this is changing rapidly as genetic testing is becoming standard across all aspects of medicine. CHARGE syndrome is a clinical diagnosis, which means genetic testing is not required in order to make the diagnosis. Rather, the diagnosis can be made based on clinical features alone. ### Screening other organ systems[edit] Once the diagnosis is made based on clinical signs, it is important to investigate other body systems that may be involved. For example, if the diagnosis is made based on the abnormal appearance of the ears and developmental delay, it is important to check the child's hearing, vision, heart, nose, and urogenital system. Ideally, every child newly diagnosed with CHARGE syndrome should have a complete evaluation by an ENT specialist, audiologist, ophthalmologist, pediatric cardiologist, developmental therapist, and pediatric urologist. ## Therapy[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (July 2016) (Learn how and when to remove this template message) Children with CHARGE syndrome may have a number of life-threatening medical conditions; with advances in medical care, these children can survive and can thrive with the support of a multidisciplinary team of medical professionals. Therapies and education must take into consideration hearing impairment, vision problems, and any others. Early intervention, such as occupational, speech-language, and physical therapy, to improve static posture, ambulation, and self-care skills is important. The intelligence of children with multiple health impairments, such as combined deafblindness, can be underestimated in the absence of early intervention. ### Education[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (July 2016) (Learn how and when to remove this template message) Children with CHARGE syndrome will vary greatly in their abilities in the classroom: some may need little support, while some may require full-time support and individualized programs. Taking each of the various affected body systems into account is vital to the success of the child in the educational setting. An important step in dealing with abnormal behavior is understanding why it is occurring and helping the child learn more appropriate methods of communicating. ## Epidemiology[edit] The incidence is estimated to range from 0.1–1.2 per 10,000 live births, though the true incidence is unknown.[7] As of 2005, the highest prevalence was found in Canada and estimated at 1 in 8,500 live births.[8] ## History[edit] B.D. Hall first described the CHARGE association in a 1979 journal paper of about 17 children who had been born with choanal atresia.[9] During the same year, H.M. Hittner described 10 children who had choanal atresia as well as coloboma, congenital heart defect, and hearing loss.[10] Using both coloboma or choanal atresia and some of the other related characteristic malformations, R. A. Pagon first coined the acronym CHARGE in 1981 to emphasize that this cluster of associated malformations occurred together.[1] It came to be recognised[when?] as a syndrome within the umbrella of the CHARGE association, a set of apparently random signs occurring together. Since the signs seen in CHARGE are caused by a genetic anomaly, its name was eventually[when?] changed to 'CHARGE syndrome'.[citation needed] ## References[edit] 1. ^ a b Pagon RA, Graham JM, Zonana J, Yong SL (1981). "Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association". J. Pediatr. 99 (2): 223–7. doi:10.1016/S0022-3476(81)80454-4. PMID 6166737. 2. ^ The 2008 National Child Count of Children and Youth who are Deaf-Blind Archived 2012-03-15 at the Wayback Machine, The National Consortium on Deaf-Blindness, 2009\|pages=30\|page= 3. ^ Vissers, L. E.; van Ravenswaaij, C. M.; Admiraal, R.; Hurst, J. A.; de Vries, B. B.; Janssen, I. M.; et al. (2004). "Mutations in a new member of the chromodomain gene family cause CHARGE syndrome". Nature Genetics. 36 (9): 955–957. doi:10.1038/ng1407. PMID 15300250. 4. ^ Lalani SR, Safiullah AM, Fernbach SD, et al. (2006). "Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation". Am. J. Hum. Genet. 78 (2): 303–14. doi:10.1086/500273. PMC 1380237. PMID 16400610. 5. ^ Zentner GE, Layman WS, Martin DM, Scacheri PC (2010). "Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome". Am J Med Genet A. 152 (3): 674–686. doi:10.1002/ajmg.a.33323. PMC 2918278. PMID 20186815. 6. ^ Janssen, N; Bergman, JE; Swertz, MA; Tranebjaerg, L; Lodahl, M; Schoots, J; Hofstra, RM; van Ravenswaaij-Arts, CM; Hoefsloot, LH (August 2012). "Mutation update on the CHD7 gene involved in CHARGE syndrome". Human Mutation. 33 (8): 1149–1160. doi:10.1002/humu.22086. PMID 22461308. 7. ^ Blake, KD; Prasad, C (Sep 7, 2006). "CHARGE syndrome". Orphanet Journal of Rare Diseases. 1: 34. doi:10.1186/1750-1172-1-34. PMC 1586184. PMID 16959034. 8. ^ Issekutz, KA; Graham JM Jr; Prasad, C; Smith, IM; Blake, KD (Mar 15, 2005). "An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study". American Journal of Medical Genetics Part A. 133A (3): 309–17. doi:10.1002/ajmg.a.30560. PMID 15637722. 9. ^ Hall BD (1979). "Choanal atresia and associated multiple anomalies". J. Pediatr. 95 (3): 395–8. doi:10.1016/S0022-3476(79)80513-2. PMID 469662. 10. ^ Hittner HM, Hirsch NJ, Kreh GM, Rudolph AJ (1979). "Colobomatous microphthalmia, heart disease, hearing loss, and mental retardation--a syndrome". Journal of Pediatric Ophthalmology and Strabismus. 16 (2): 122–8. PMID 458518. ## External links[edit] Classification D * ICD-10: Q87.8 * ICD-9-CM: 759.89 * OMIM: 214800 * MeSH: D058747 * DiseasesDB: 32233 External resources * eMedicine: ped/367 * v * t * e Disorders of transcription and post transcriptional modification Chromatin remodeling * CHD7 (CHARGE syndrome) Polyadenylation * PABPN1 (Oculopharyngeal muscular dystrophy) RNA splicing * PRPF31 (Retinitis pigmentosa 11) * PRPF8 (Retinitis pigmentosa 13) * 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	CHARGE syndrome	c0265354	28,960	wikipedia	https://en.wikipedia.org/wiki/CHARGE_syndrome	2021-01-18T18:54:42	{"gard": ["29"], "mesh": ["D058747"], "umls": ["C0265354", "C2936502"], "icd-10": ["Q89.8"], "orphanet": ["138"], "wikidata": ["Q1023604"]}
## Clinical Features Golden et al. (1977) described a male with severe short stature who had a brother and maternal uncle who had died at ages 16 and 21 years, respectively, of respiratory failure. Mild facial and bony abnormalities were described in the mother, a maternal aunt, and the maternal grandmother. The proband had coarse facies due to hypertelorism, flat wide nasal bridge, and anteverted nostrils. Strabismus and searching nystagmus were present. Other features were marked contractures of the knees and hips, hyperextensible fingers, severe kyphosis with mild thoracolumbar scoliosis, pectus carinatum, and enlarged joints. Neurologic signs attributed to 'subluxation of the dens' (projection on the second cervical vertebra) were also described. Psychomotor development was mildly retarded with disproportionate speech impairment. Radiographic features included flat vertebral bodies, lacy ossification of the metaphyses of long bones and iliac crests, and marked sclerosis of the base of the skull. The proximal femora were normal, and the vertebral changes differentiated the disorder from parastremmatic dwarfism. Jackson (1981) reported the same disorder in 2 male first cousins once removed (related through females). Mental retardation was associated with the spondylometaepiphyseal dysplasia. The fingers were stubby but tapering, and the fingernails foreshortened. In his observations, heterozygous females showed strong facial resemblance to the affected boys, had less marked but characteristic radiologic changes, and had an abnormal waddling gait as though the pelvic and hip changes were partially symptomatic. Jackson (1989) stated that the older boy died at age 12 of cardiorespiratory failure. Mamunes (1990) confirmed that the radiologic features in the patients studied by Jackson (1981) were identical to those in the family reported by Golden et al. (1977). INHERITANCE \- X-linked dominant GROWTH Height \- Short stature, severe HEAD & NECK Face \- Coarse facies Eyes \- Hypertelorism \- Strabismus \- Searching nystagmus Nose \- Flat nasal bridge \- Broad nasal bridge \- Anteverted nostrils RESPIRATORY \- Respiratory failure CHEST Ribs Sternum Clavicles & Scapulae \- Pectus carinatum SKELETAL Skull \- Marked sclerosis of skull base Spine \- Kyphosis, severe \- Thoracolumbar scoliosis, mild \- Flat vertebral bodies \- Subluxation of C2 Pelvis \- Marked contractures of hip \- Lacy ossification of iliac crest Limbs \- Joint enlargement \- Marked contractures of knees \- Lacy ossification of long bone metaphyses Hands \- Stubby fingers \- Tapered fingers \- Hyperextensible fingers SKIN, NAILS, & HAIR Nails \- Short fingernails NEUROLOGIC Central Nervous System \- Psychomotor retardation, mild \- Speech impairment MISCELLANEOUS \- Mild facial and skeletal features in heterozygous females ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	SPONDYLOMETAPHYSEAL DYSPLASIA, X-LINKED	c0796172	28,961	omim	https://www.omim.org/entry/313420	2019-09-22T16:17:12	{"mesh": ["C563124"], "omim": ["313420"], "orphanet": ["168544"], "synonyms": ["Alternative titles", "SPONDYLOMETAPHYSEAL DYSPLASIA, RICHMOND TYPE"]}
Bowel dysfunction that is characterized by infrequent or difficult evacuation of feces Constipation Other namesCostiveness,[1] dyschezia[2] Constipation in a young child seen on X-ray. Circles represent areas of fecal matter (stool is white surrounded by black bowel gas). SpecialtyGastroenterology SymptomsInfrequent or hard to pass bowel movements, abdominal pain, bloating[2][3] ComplicationsHemorrhoids, anal fissure, fecal impaction[4] CausesSlow movement of stool within the colon, irritable bowel syndrome, celiac disease, non-celiac gluten sensitivity, pelvic floor disorders[4][5][6] Risk factorsHypothyroidism, diabetes, Parkinson's disease, gluten-related disorders, colon cancer, diverticulitis, inflammatory bowel disease, certain medications[4][5][6] TreatmentDrinking enough fluids, eating more fiber, exercise[4] MedicationLaxatives of the bulk forming agent, osmotic agent, stool softener, or lubricant type[4] Frequency2–30%[7] Constipation refers to bowel movements that are infrequent or hard to pass.[2] The stool is often hard and dry.[4] Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement.[3] Complications from constipation may include hemorrhoids, anal fissure or fecal impaction.[4] The normal frequency of bowel movements in adults is between three per day and three per week.[4] Babies often have three to four bowel movements per day while young children typically have two to three per day.[8] Constipation has many causes.[4] Common causes include slow movement of stool within the colon, irritable bowel syndrome, and pelvic floor disorders.[4] Underlying associated diseases include hypothyroidism, diabetes, Parkinson's disease, celiac disease, non-celiac gluten sensitivity, colon cancer, diverticulitis, and inflammatory bowel disease.[4][5][6][9] Medications associated with constipation include opioids, certain antacids, calcium channel blockers, and anticholinergics.[4] Of those taking opioids about 90% develop constipation.[10] Constipation is more concerning when there is weight loss or anemia, blood is present in the stool, there is a history of inflammatory bowel disease or colon cancer in a person's family, or it is of new onset in someone who is older.[11] Treatment of constipation depends on the underlying cause and the duration that it has been present.[4] Measures that may help include drinking enough fluids, eating more fiber, and exercise.[4] If this is not effective, laxatives of the bulk forming agent, osmotic agent, stool softener, or lubricant type may be recommended.[4] Stimulant laxatives are generally reserved for when other types are not effective.[4] Other treatments may include biofeedback or in rare cases surgery.[4] In the general population rates of constipation are 2–30 percent.[7] Among elderly people living in a care home the rate of constipation is 50–75 percent.[10] People spend, in the United States, more than US$250 million on medications for constipation a year.[12] ## Contents * 1 Definition * 2 Causes * 2.1 Diet * 2.2 Medications * 2.3 Medical conditions * 2.4 Psychological * 2.5 Congenital * 3 Pathothysiology * 4 Diagnostic approach * 4.1 Description * 4.2 Examination * 4.3 Diagnostic tests * 4.4 Criteria * 5 Prevention * 6 Treatment * 6.1 Fiber supplements * 6.2 Laxatives * 6.3 Enemas * 6.4 Physical intervention * 6.5 Surgical intervention * 7 Prognosis * 8 Epidemiology * 9 History * 10 Special populations * 10.1 Children * 10.2 Postpartum women * 11 See also * 12 References * 13 External links ## Definition Bristol stool chart Constipation is a symptom, not a disease. Most commonly, constipation is thought of as infrequent bowel movements, usually less than 3 stools per week.[13][14] However, people may have other complaints as well including:[3][15] * Straining with bowel movements * Excessive time needed to pass a bowel movement * Hard stools * Pain with bowel movements secondary to straining * Abdominal pain * Abdominal bloating. * the sensation of incomplete bowel evacuation. The Rome III Criteria are a set of symptoms that help standardize the diagnosis of constipation in various age groups. These criteria help physicians to better define constipation in a standardized manner. ## Causes The causes of constipation can be divided into congenital, primary, and secondary.[2] The most common kind is primary and not life-threatening.[16] It can also be divided by the age group affected such as children and adults. Primary or functional constipation is defined by ongoing symptoms for greater than six months not due to an underlying cause such as medication side effects or an underlying medical condition.[2][17] It is not associated with abdominal pain, thus distinguishing it from irritable bowel syndrome.[2] It is the most common kind of constipation, and is often multifactorial.[16][18] In adults, such primary causes include: dietary choices such as insufficient dietary fiber or fluid intake, or behavioral causes such as decreased physical activity. In the elderly, common causes have been attributed to insufficient dietary fiber intake, inadequate fluid intake, decreased physical activity, side effects of medications, hypothyroidism, and obstruction by colorectal cancer.[19] Evidence to support these factors however is poor.[19] Secondary causes include side effects of medications such as opiates, endocrine and metabolic disorders such as hypothyroidism, and obstruction such as from colorectal cancer.[18] Celiac disease and non-celiac gluten sensitivity may also present with constipation.[5][20][6] Cystocele can develop as a result of chronic constipation.[21] ### Diet Constipation can be caused or exacerbated by a low-fiber diet, low liquid intake, or dieting.[15][22] Dietary fiber helps to decrease colonic transport time, increases stool bulk but simultaneously softens stool. Therefore, diets low in fiber can lead to primary constipation.[18] ### Medications Many medications have constipation as a side effect. Some include (but are not limited to) opioids, diuretics, antidepressants, antihistamines, antispasmodics, anticonvulsants, tricyclic antidepressants, antiarrythmics, beta-adrenoceptor antagonists, anti-diarrheals, 5-HT3 receptor antagonists such as ondansetron, and aluminum antacids.[15][23] Certain calcium channel blockers such as nifedipine and verapamil can cause severe constipation due to dysfunction of motility in the rectosigmoid colon.[24] Supplements such as calcium and iron supplements can also have constipation as a notable side effect.[citation needed] ### Medical conditions Metabolic and endocrine problems which may lead to constipation include: hypercalcemia, hypothyroidism, hyperparathyroidism, porphyria, chronic kidney disease, pan-hypopituitarism, diabetes mellitus, and cystic fibrosis.[15][16] Constipation is also common in individuals with muscular and myotonic dystrophy.[15] Systemic diseases that may present with constipation include celiac disease and systemic sclerosis.[5][20][25] Constipation has a number of structural (mechanical, morphological, anatomical) causes, namely through creating space-occupying lesions within the colon that stop the passage of stool, such as colorectal cancer, strictures, rectocoles, anal sphincter damage or malformation and post-surgical changes. Extra-intestinal masses such as other malignancies can also lead to constipation from external compression.[26] Constipation also has neurological causes, including anismus, descending perineum syndrome, and Hirschsprung's disease.[7] In infants, Hirschsprung's disease is the most common medical disorder associated with constipation. Anismus occurs in a small minority of persons with chronic constipation or obstructed defecation.[27] Spinal cord lesions and neurological disorders such as Parkinson's disease and pelvic floor dysfunction[16] can also lead to constipation. ### Psychological Voluntary withholding of the stool is a common cause of constipation.[15] The choice to withhold can be due to factors such as fear of pain, fear of public restrooms, or laziness.[15] When a child holds in the stool a combination of encouragement, fluids, fiber, and laxatives may be useful to overcome the problem.[28] Early intervention with withholding is important as this can lead to anal fissures.[29] ### Congenital A number of diseases present at birth can result in constipation in children. They are as a group uncommon with Hirschsprung's disease (HD) being the most common.[30] There are also congenital structural anomalies that can lead to constipation, including anterior displacement of the anus, imperforate anus, strictures, and small left colon syndrome.[31] ## Pathothysiology This section is empty. You can help by adding to it. (July 2019) ## Diagnostic approach Significant constipation in the plain X-ray of an 8-year-old The diagnosis is typically made based on a person's description of the symptoms. Bowel movements that are difficult to pass, very firm, or made up of small hard pellets (like those excreted by rabbits) qualify as constipation, even if they occur every day. Constipation is traditionally defined as three or fewer bowel movements per week.[13] Other symptoms related to constipation can include bloating, distension, abdominal pain, headaches, a feeling of fatigue and nervous exhaustion, or a sense of incomplete emptying.[32] Although constipation may be a diagnosis, it is typically viewed as a symptom that requires evaluation to discern a cause. ### Description Distinguish between acute (days to weeks) or chronic (months to years) onset of constipation because this information changes the differential diagnosis. This in the context of accompanied symptoms helps physicians discover the cause of constipation. People often describe their constipation as bowel movements that are difficult to pass, firm stool with lumpy or hard consistency, and excessive straining during bowel movements. Bloating, abdominal distension, and abdominal pain often accompany constipation.[33] Chronic constipation (symptoms present at least three days per month for more than three months) associated with abdominal discomfort is often diagnosed as irritable bowel syndrome (IBS) when no obvious cause is found.[34] Poor dietary habits, previous abdominal surgeries, and certain medical conditions can contribute to constipation. Diseases associated with constipation include hypothyroidism, certain types of cancer, and irritable bowel syndrome. Low fiber intake, inadequate amounts of fluids, poor ambulation or immobility, or medications can contribute to constipation.[15][22] Once the presence of constipation is identified based on a culmination of the symptoms described above, then the cause of the constipation should be figured out. Separating non-life-threatening from serious causes may be partly based on symptoms. For example, colon cancer may be suspected if a person has a family history of colon cancer, fever, weight loss, and rectal bleeding.[13] Other alarming signs and symptoms include family or personal history of inflammatory bowel disease, age of onset over 50, change in stool caliber, nausea, vomiting, and neurological symptoms like weakness, numbness and difficulty urinating.[33] ### Examination A physical examination should involve at least an abdominal exam and rectal exam. Abdominal exam may reveal an abdominal mass if there is significant stool burden and may reveal abdominal discomfort. Rectal examination gives an impression of the anal sphincter tone and whether the lower rectum contains any feces or not. Rectal examination also gives information on the consistency of the stool, the presence of hemorrhoids, blood and whether any perineal irregularities are present including skin tags, fissures, anal warts.[22][15][13] Physical examination is done manually by a physician and is used to guide which diagnostic tests to order. ### Diagnostic tests Functional constipation is common and does not warrant diagnostic testing. Imaging and laboratory tests are typically recommended for those with alarm signs or symptoms.[13] The laboratory tests performed depends on the suspected underlying cause of the constipation. Tests may include CBC (complete blood count), thyroid function tests, serum calcium, serum potassium, etc.[15][13] Abdominal X-rays are generally only performed if bowel obstruction is suspected, may reveal extensive impacted fecal matter in the colon, and may confirm or rule out other causes of similar symptoms.[22][15] Colonoscopy may be performed if an abnormality in the colon like a tumor is suspected.[13] Other tests rarely ordered include anorectal manometry, anal sphincter electromyography, and defecography.[15] Colonic propagating pressure wave sequences (PSs) are responsible for discrete movements of the bowel contents and are vital for normal defecation. Deficiencies in PS frequency, amplitude, and extent of propagation are all implicated in severe defecatory dysfunction (SDD). Mechanisms that can normalize these aberrant motor patterns may help rectify the problem. Recently the novel therapy of sacral nerve stimulation (SNS) has been utilized for the treatment of severe constipation.[35] ### Criteria The Rome III Criteria for functional constipation must include two or more of the following and present for the past three months, with symptoms starting for at least 6 months prior to diagnosis.[13] * Straining during defecation for at least 25% of bowel movements * Lumpy or hard stools in at least 25% of defecations * Sensation of incomplete evacuation for at least 25% of defecations * Sensation of anorectal obstruction/blockage for at least 25% of defecations * Manual maneuvers to facilitate at least 25% of defecations * Fewer than 3 defecations per week * Loose stools are rarely present without the use of laxatives * There are insufficient criteria for irritable bowel syndrome ## Prevention Constipation is usually easier to prevent than to treat. Following the relief of constipation, maintenance with adequate exercise, fluid intake, and high-fiber diet is recommended.[15] ## Treatment A limited number of causes require urgent medical intervention or will result in severe consequences.[3] The treatment of constipation should focus on the underlying cause if known. The National Institute of Health and Care Excellence (NICE) break constipation in adults into two categories - chronic constipation of unknown cause and constipation due to opiates.[36] In chronic constipation of unknown cause, the main treatment involves the increased intake of water and fiber (either dietary or as supplements).[16] The routine use of laxatives or enemas is discouraged, as having bowel movements may come to be dependent upon their use.[citation needed] ### Fiber supplements Soluble fiber supplements such as psyllium are generally considered first-line treatment for chronic constipation, compared to insoluble fibers such as wheat bran. Side effects of fiber supplements include bloating, flatulence, diarrhea, and possible malabsorption of iron, calcium, and some medications. However, patients with opiate-induced constipation will likely not benefit from fiber supplements.[29] ### Laxatives If laxatives are used, milk of magnesia or polyethylene glycol are recommended as first-line agents due to their low cost and safety.[3] Stimulants should only be used if this is not effective.[16] In cases of chronic constipation, polyethylene glycol appears superior to lactulose.[37] Prokinetics may be used to improve gastrointestinal motility. A number of new agents have shown positive outcomes in chronic constipation; these include prucalopride[38] and lubiprostone.[39] Cisapride is widely available in third world countries, but has been withdrawn in most of the west. It has not been shown to have a benefit on constipation, while potentially causing cardiac arrhythmias and deaths.[40] ### Enemas Enemas can be used to provide a form of mechanical stimulation. A large volume or high enema[41] can be given to cleanse as much of the colon as possible of feces,[42][43] and the solution administered commonly contains castile soap which irritates the colon's lining resulting in increased urgency to defecate.[44] However, a low enema is generally useful only for stool in the rectum, not in the intestinal tract.[45] ### Physical intervention Constipation that resists the above measures may require physical intervention such as manual disimpaction (the physical removal of impacted stool using the hands; see fecal impaction). Regular exercise can help improve chronic constipation.[46] ### Surgical intervention In refractory cases, procedures can be performed to help relieve constipation. Sacral nerve stimulation has been demonstrated to be effective in a minority of cases. Colectomy with ileorectal anastomosis is another intervention performed only in patients known to have a slow colonic transit time and in whom a defecation disorder has either been treated or is not present.[3] Because this is a major operation, side effects can include considerable abdominal pain, small bowel obstruction, and post-surgical infections. Furthermore, it has a very variable rate of success and is very case dependent.[29] ## Prognosis Complications that can arise from constipation include hemorrhoids, anal fissures, rectal prolapse, and fecal impaction.[15][22][47][48] Straining to pass stool may lead to hemorrhoids. In later stages of constipation, the abdomen may become distended, hard and diffusely tender. Severe cases ("fecal impaction" or malignant constipation) may exhibit symptoms of bowel obstruction (nausea, vomiting, tender abdomen) and encopresis, where soft stool from the small intestine bypasses the mass of impacted fecal matter in the colon. ## Epidemiology Constipation is the most common chronic gastrointestinal disorder in adults. Depending on the definition employed, it occurs in 2% to 20% of the population.[16][49] It is more common in women, the elderly and children.[49] Specifically constipation with no known cause affects females more often affected than males.[50] The reasons it occurs more frequently in the elderly is felt to be due to an increasing number of health problems as humans age and decreased physical activity.[17] * 12% of the population worldwide reports having constipation.[51] * Chronic constipation accounts for 3% of all visits annually to pediatric outpatient clinics.[15] * Constipation-related health care costs total $6.9 billion in the US annually.[16] * More than four million Americans have frequent constipation, accounting for 2.5 million physician visits a year.[48] * Around $725 million is spent on laxative products each year in America.[48] ## History 19th century satirical cartoon of a monkey rejecting an old style clyster for a new design, filled with marshmallow and opium Since ancient times different societies have published medical opinions about how health care providers should respond to constipation in patients.[52] In various times and places, doctors have made claims that constipation has all sorts of medical or social causes.[52] Doctors in history have treated constipation in reasonable and unreasonable ways, including use of a spatula mundani.[52] After the advent of the germ theory of disease then the idea of "auto-intoxication" entered popular Western thought in a fresh way.[52] Enema as a scientific medical treatment and colon cleansing as alternative medical treatment became more common in medical practice.[52] Since the 1700s in the West there has been some popular thought that people with constipation have some moral failing with gluttony or laziness.[53] ## Special populations ### Children Main article: Constipation in children Approximately 3% of children have constipation, with girls and boys being equally affected.[31] With constipation accounting for approximately 5% of general pediatrician visits and 25% of pediatric gastroenterologist visits, the symptom carries a significant financial impact upon the healthcare system.[8] While it is difficult to assess an exact age at which constipation most commonly arises, children frequently suffer from constipation in conjunction with life-changes. Examples include: toilet training, starting or transferring to a new school, and changes in diet.[8] Especially in infants, changes in formula or transitioning from breast milk to formula can cause constipation. The majority of constipation cases are not tied to a medical disease, and treatment can be focused on simply relieving the symptoms.[31] ### Postpartum women The six-week period after pregnancy is called the postpartum stage.[54] During this time, women are at increased risk of being constipated. Multiple studies estimate the prevalence of constipation to be around 25% during the first 3 months.[55] Constipation can cause discomfort for women, as they are still recovering from the delivery process especially if they have had a perineal tear or underwent an episiotomy.[56] Risk factors that increase the risk of constipation in this population include:[56] * Damage to the levator ani muscles (pelvic floor muscles) during childbirth * Forceps-assisted delivery * Lengthy second stage of labor * Delivering a large child * Hemorrhoids Hemorrhoids are common in pregnancy and also may get exacerbated when constipated. Anything that can cause pain with stooling (hemorrhoids, perineal tear, episiotomy) can lead to constipation because patients may withhold from having a bowel movement so as to avoid pain.[56] The pelvic floor muscles play an important role in helping pass a bowel movement. Injury to those muscles by some of the above risk factors (examples- delivering a large child, lengthy second stage of labor, forceps delivery) can result in constipation.[56] Enemas may be administered during labor and these can also alter bowel movements in the days after giving birth.[54] However, there is insufficient evidence to make conclusions about the effectiveness and safety of laxatives in this group of people.[56] ## See also * Obstructed defecation * Rectal tenesmus ## References 1. ^ "Costiveness – Definition and More from the Free Merriam-Webster Dictionary". Archived from the original on 11 April 2010. 2. ^ a b c d e f Chatoor D, Emmnauel A (2009). "Constipation and evacuation disorders". Best Pract Res Clin Gastroenterol. 23 (4): 517–30. doi:10.1016/j.bpg.2009.05.001. PMID 19647687. 3. ^ a b c d e f American Gastroenterological Association; Bharucha, AE; Dorn, SD; Lembo, A; Pressman, A (January 2013). 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PMID 32761813. ## External links Classification D * ICD-10: K59.0 * ICD-9-CM: 564.0 * MeSH: D003248 * DiseasesDB: 3080 External resources * MedlinePlus: 003125 * eMedicine: med/2833 * 09-129b. at Merck Manual of Diagnosis and Therapy Home Edition * Constipation - Introduction (UK NHS site) * MedlinePlus Overview constipation * Constipation Guideline \- the World Gastroenterology Organisation (WGO) * 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 Authority control * GND: 4132815-2 * NDL: 00560602 [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Constipation	c0009806	28,962	wikipedia	https://en.wikipedia.org/wiki/Constipation	2021-01-18T18:48:40	{"mesh": ["D003248"], "umls": ["C0009806", "C0237326"], "wikidata": ["Q178436"]}
Lymphangitis Other namesInflamed lymph vessels[1] Forearm lymphangitis due to cellulitis of the hand SpecialtyAngiology For discussion of the condition in horses, see Equine lymphangitis. Lymphangitis is an inflammation or an infection of the lymphatic channels[2] that occurs as a result of infection at a site distal to the channel. The most common cause of lymphangitis in humans is Streptococcus pyogenes (Group A strep), hemolythic streptococci, and in some cases, mononucleosis, cytomegalovirus, tuberculosis, syphilis, and the fungus Sporothrix schenckii.[3] Lymphangitis is sometimes mistakenly called "blood poisoning". In reality, "blood poisoning" is synonymous with sepsis. Lymphatic vessels are smaller than capillaries and tiny venules and are ubiquitous in the body. These vessels are fitted with valves to direct flow in only one direction. Fluid diffusing through the thin walled small capillaries should be collected and the lymphatic system does just that: a fluid rich in protein, minerals, nutrients, and other substances useful for tissue growth. As well as essential nutrients, the lymphatic system can also transport or carry cancer cells, defective or damaged cells, and pathogens such as bacteria and viruses, as well as foreign bodies and organisms. The lymph nodes are found in close proximity to unique white blood cells that engulf or metabolize pathogens (bacteria and viruses) and defective or cancerous cells, preventing infections and malignant cancer cells from spreading. [4]Infection spreads out of the wound site to enter the lymphatic system. The wound may be small or it may be an abscess constantly feeding bacteria into the lymphatic system. After infection, lymph nodes enlarge. Ear, skin, nose, and eye infections can spread into the lymphatic system. Red streak in the skin along the direction of regional lymph nodes indicates lymphatic involvement. Infection may spread within hours and can cause septicemia and death. ## Contents * 1 Symptoms * 2 Disease that Resemble Lymphangitis * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Symptoms[edit] [5]Warm skin over site of infection. The person may also have chills and a high fever - between 38 and 40 degrees Celsius - along with moderate throbbing pain and swelling. The red streaks can be clearly outlined and demarcated or just barely visible, particularly in dark-skinned patients. Malaise, anorxia, tenderness at the site of infection, skin ulcers (rare symptom of lymphangitis), rapid pulse, and enlarged, swollen, and tender lymph nodes. If these symptoms are absent, it is suggestive of other underlying disorders such as tuberculosis, lymphoma, or Hodgkin’s disease. A person with lymphangitis should be hospitalized and closely monitored by medical professionals.[6]When the inferior limbs are affected, the redness of the skin runs over the great saphenous vein location and can be confused for thrombophlebitis. Lymphangitis resulting from bed bug bites Chronic lymphangitis is a cutaneous condition that is the result of recurrent bouts of acute bacterial lymphangitis.[7]:261 ## Disease that Resemble Lymphangitis[edit] [8]Infectious lymphangitis should be differentiated from other conditions such as superficial thrombophlebitis (swelling is local to the affected vein), cat scratch (swellings feels hard to the touch), acute streptococcal hemolytic gangrene and necrotizing fasciitis (infected area crackles to the touch and the patient looks very ill). ## Diagnosis[edit] [9]To detect and identify infectious agents such as streptococci and staphylococci bacterial strains blood tests and bacteria cultures can be used. Bacteria culture is suitable for identifying infectious agents in cases of severe lymphangitis that do not respond well to treatment. ## Treatment[edit] Both drug and non-drug based treatment options are available to treat with lymphanginitis. The wound should be treated properly, dead tissues should be removed from the wound site, and pus drained. Applying heat to the affected lymph node using hot, moist compresses, or heating pads. Immobilizing and elevating the affected limb whenever it is possible, and administering analgesics to control pain. [10]If a local infection is invasive, immediate antibiotic drug therapy is required. Streptococci strains are the most common infectious agents and respond well to cephalosporins – cephalexin at a dose of 0.5 mg for between 7 and 10 days – or extended-spectrum penicillin. Methiciline-resistant staphylococcus aureus is common in communities and hence the need to use improved antibiotic drugs such as trimethoprim-sulfamethoxazole for 7 to 10 days. Naficillin, oxacillin, and dicloxacillin are also effective against infections of the lymphatic system. ## See also[edit] * Chronic lymphangitis * Lymphadenopathy * Lymphangitis carcinomatosa ## References[edit] 1. ^ "Lymphangitis : MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 4 June 2019. 2. ^ "Lymphangitis" at Dorland's Medical Dictionary 3. ^ Sporothrix spp. Archived 2013-04-14 at Archive.today Doctor Fungus 4. ^ "Medically Sound: Awash with Protein-rich Fluid, the Lymphatic System Invites for a Direct Invasion by Microbes". Medically Sound. 2020-11-02. Retrieved 2020-11-07. 5. ^ "Medically Sound: Awash with Protein-rich Fluid, the Lymphatic System Invites for a Direct Invasion by Microbes". Medically Sound. 2020-11-02. Retrieved 2020-11-07. 6. ^ Prentice, Arnheim's Principles of Athletic Training, 12th edition, pg. 988. 7. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 8. ^ "Medically Sound: Awash with Protein-rich Fluid, the Lymphatic System Invites for a Direct Invasion by Microbes". Medically Sound. 2020-11-02. Retrieved 2020-11-07. 9. ^ "Medically Sound: Awash with Protein-rich Fluid, the Lymphatic System Invites for a Direct Invasion by Microbes". Medically Sound. 2020-11-02. Retrieved 2020-11-07. 10. ^ "Medically Sound: Awash with Protein-rich Fluid, the Lymphatic System Invites for a Direct Invasion by Microbes". Medically Sound. 2020-11-02. Retrieved 2020-11-07. ## External links[edit] Classification D * ICD-10: I89.1 * ICD-9-CM: 457.2 * MeSH: D008205 * DiseasesDB: 29093 External resources * MedlinePlus: 007296 * eMedicine: ped/1336 * 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 * t * e Lymphatic disease: organ and vessel diseases Thymus * Abscess * Hyperplasia * Hypoplasia * DiGeorge syndrome * Ectopic thymus * Thymoma * Thymic carcinoma Spleen * Asplenia * Asplenia with cardiovascular anomalies * Accessory spleen * Polysplenia * Wandering spleen * Splenomegaly * Banti's syndrome * Splenic infarction * Splenic tumor Lymph node * Lymphadenopathy * Generalized lymphadenopathy * Castleman's disease * Intranodal palisaded myofibroblastoma * Kikuchi disease * Tonsils * see Template:Respiratory pathology Lymphatic vessels * Lymphangitis * Lymphangiectasia * Lymphedema * Primary lymphedema * Congenital lymphedema * Lymphedema praecox * Lymphedema tarda * Lymphedema–distichiasis syndrome * Milroy's disease * Secondary lymphedema * Bullous lymphedema * Factitial lymphedema * Postinflammatory lymphedema * Postmastectomy lymphangiosarcoma * Waldmann 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Lymphangitis	c0024225	28,963	wikipedia	https://en.wikipedia.org/wiki/Lymphangitis	2021-01-18T18:32:20	{"mesh": ["D008205"], "umls": ["C0024225"], "wikidata": ["Q1476027"]}
Amaurotic nystagmus Other namesVisual Deprivation Nystagmus SpecialtyOphthalmology, Neurology Amaurotic nystagmus is defined as the nystagmus associated with blindness or the central vision defects.[1][2] It is characterized by the pendular or jerky movements of the eyes in the patients who have visual impairement for a long period of time.[3] ## References[edit] 1. ^ Miller, Maurice H.; Schein, Jerome Daniel (2008). Hearing Disorders Handbook. Plural Publishing. ISBN 9781597568388. 2. ^ "amaurotic nystagmus". Academic Dictionaries and Encyclopedias. Retrieved 2017-12-16. 3. ^ Agarwal, Amar (2015-05-10). Manual of Neuro-ophthalmology. JP Medical Ltd. ISBN 9789351527824. ## External links[edit] Classification D * ICD-10: H55.03 * ICD-9-CM: 379.53 This article about an ophthalmic disease 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Amaurotic nystagmus	c0271384	28,964	wikipedia	https://en.wikipedia.org/wiki/Amaurotic_nystagmus	2021-01-18T18:33:43	{"mesh": ["D009759"], "umls": ["C0271384"], "wikidata": ["Q47166292"]}
A rare ophthalmic disorder with cranial nerve involvement characterized by partial or complete ptosis and ophthalmoplegia with impaired ability to elevate, depress, or adduct the eyeball, causing strabismus and amblyopia. The pupils can also be dilated. The condition is typically unilateral and may present with or without aberrant regeneration. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Congenital oculomotor nerve palsy	None	28,965	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=440221	2021-01-23T17:09:01	{"icd-10": ["Q07.8"], "synonyms": ["Congenital CNIII lesion", "Congenital third cranial nerve palsy"]}
Acinar adenocarcinoma is a histological subtype of gland-forming cancer that is diagnosed when cuboidal and/or columnar shaped malignant cells in the neoplastic tissue form acini and tubules.[1] It is a common form of cancer occurring in the lung and prostate gland. ## Contents * 1 Acinar adenocarcinoma of the lung * 2 Acinar adenocarcinoma of the prostate * 3 References * 4 External links ## Acinar adenocarcinoma of the lung[edit] Adenocarcinoma ("adeno" = "gland", "carcinoma" = cancer of epithelium) is the most common type of lung cancer in the U.S., Japan, and most of Western Europe, although it is the second most common form in Eastern parts of Europe (after squamous cell carcinoma).[2] Adenocarcinomas are exceptionally heterogeneous neoplasms, occurring in four major tissue architectures (acinar, papillary, bronchioloalveolar, and solid), and several rarer variants. Most commonly, however, these lesions show a mixture of two or more subtypes or variants, and are subclassified as "adenocarcinoma with mixed subtypes".[1][2] In China, which has the largest number of smokers and lung cancer cases in the world, the acinar tissue architectural pattern is by far the most common histological subtype of adenocarcinoma, comprising about 40% of all adenocarcinomas,[3] and its incidence has increased significantly in recent decades.[4] In Europe, acinar adenocarcinoma may comprise the dominant architectural pattern in as many as 50–60% of all adenocarcinomas.[5] Acinar adenocarcinoma of the lung is a highly lethal disease. Overall five-year survival rates approximate 16% to 22%. Generally, survival is better in all stages for patients with the acinar (or papillary) pattern than it is in patients with the solid pattern, but considerably worse than those with the bronchioloalveolar pattern.[5][6] Survival is significantly better in patients whose tumors are well differentiated (i.e. the glands and/or tubules are more completely developed) than when poorly differentiated (i.e. with rudimentary glands).[7] Some studies suggest that the oncogenes H-ras and fes are important drivers of oncogenesis in many acinar-type lung cancers.[8] ## Acinar adenocarcinoma of the prostate[edit] Acinar adenocarcinomas are the most common form of prostate gland malignancy.[9] ## References[edit] 1. ^ a b Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; Harris, Curtis C, 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 2009-08-23. Retrieved 2012-04-13. 2. ^ a b Riquet M, Foucault C, Berna P, Assouad J, Dujon A, Danel C (June 2006). "Prognostic value of histology in resected lung cancer with emphasis on the relevance of the adenocarcinoma subtyping". Ann. Thorac. Surg. 81 (6): 1988–95. doi:10.1016/j.athoracsur.2006.01.021. PMID 16731118. 3. ^ Huang ZY (July 1988). "[Pathologic analysis of 302 primary bronchogenic adenocarcinomas]". Zhonghua Zhong Liu Za Zhi (in Chinese). 10 (4): 280–3. PMID 3248485. 4. ^ Jia X, He A, Zhang D, Wang E, Song J (October 2001). "[Comparison and analysis of clinicopathology of lung cancer between 1980s and 1990s in the Shenyang area (1,224 cases)]". Zhonghua Bing Li Xue Za Zhi (in Chinese). 30 (5): 332–5. PMID 11769727. 5. ^ a b Sørensen JB, Hirsch FR, Olsen J (July 1988). "The prognostic implication of histopathologic subtyping of pulmonary adenocarcinoma according to the classification of the World Health Organization. An analysis of 259 consecutive patients with advanced disease". Cancer. 62 (2): 361–7. doi:10.1002/1097-0142(19880715)62:2<361::AID-CNCR2820620222>3.0.CO;2-M. PMID 3383137. 6. ^ Sørensen JB, Olsen JE (February 1989). "Prognostic implications of histopathologic subtyping in patients with surgically treated stage I or II adenocarcinoma of the lung". J. Thorac. Cardiovasc. Surg. 97 (2): 245–51. doi:10.1016/S0022-5223(19)35331-0. PMID 2915561. 7. ^ Chapelier A, Fadel E, Macchiarini P, et al. (November 2000). "Factors affecting long-term survival after en-bloc resection of lung cancer invading the chest wall". Eur J Cardiothorac Surg. 18 (5): 513–8. doi:10.1016/S1010-7940(00)00537-6. PMID 11053809. 8. ^ Nishio H, Nakamura S, Horai T, Ikegami H, Matsuda M (March 1992). "Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer". Cancer. 69 (5): 1130–6. doi:10.1002/cncr.2820690512. PMID 1310887. S2CID 9846338. 9. ^ Randolph TL, Amin MB, Ro JY, Ayala AG (June 1997). "Histologic variants of adenocarcinoma and other carcinomas of prostate: pathologic criteria and clinical significance". Mod. Pathol. 10 (6): 612–29. PMID 9195581. ## External links[edit] * "Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart". World Health Organization Classification of Tumours. Archived from the original on 2015-11-15. Retrieved 2010-05-29. (download page) * "Lung cancer page". National Cancer Institute. * 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]: 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Acinar adenocarcinoma	c0206685	28,966	wikipedia	https://en.wikipedia.org/wiki/Acinar_adenocarcinoma	2021-01-18T18:57:02	{"mesh": ["D018267"], "wikidata": ["Q4674156"]}
A rare, late adult-onset myofibrillar myopathy characterized by progressive distal muscle weakness associated with peripheral neuropathy and hyporeflexia. Ambulation may be lost within a few years. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Distal myotilinopathy	c3714934	28,967	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98911	2021-01-23T18:03:23	{"mesh": ["C563775"], "omim": ["609200"], "icd-10": ["G71.8"]}
## Clinical Features Zechi-Ceide et al. (2007) reported 3 sibs, born to consanguineous parents, with occipital atretic cephalocele, hypoplastic cerebellar vermis, Dandy-Walker variant, mental retardation, prominent forehead, short narrow palpebral fissures, midface hypoplasia, broad nose and nasal root, grooved nasal tip and columella, hypoplastic alae nasi with small nares, cleft lip, cleft palate, narrow ears with abnormal helices, antihelices and lobules, narrow auditory canals, oligodontia, large wide feet with a gap between the 1st and 2nd toes, hypoplastic nails, and short metatarsals and distal phalanges. The phenotype was variable in the 3 patients. Inheritance Zechi-Ceide et al. (2007) noted that 3 affected sibs of a consanguineous union strongly suggests autosomal recessive inheritance for this disorder. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Prominent forehead Face \- Midface hypoplasia Ears \- Narrow ears \- Narrow auditory canals \- Abnormal helices, antihelices and lobules Eyes \- Short palpebral fissures \- Narrow palpebral fissures Nose \- Broad nose \- Broad nasal root \- Hypoplastic alae nasi \- Small nares \- Grooved nasal tip Mouth \- Cleft lip \- Cleft palate \- Grooved columella Teeth \- Oligodontia SKELETAL Feet \- Large wide feet \- Gap between the 1st and 2nd toes (sandal gap) \- Short metatarsals \- Short distal phalanges SKIN, NAILS, & HAIR Nails \- Hypoplastic nails NEUROLOGIC Central Nervous System \- Occipital atretic cephalocele \- Hypoplastic cerebellar vermis \- Dandy-Walker variant \- Mental retardation ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	ZECHI-CEIDE SYNDROME	c2752047	28,968	omim	https://www.omim.org/entry/612916	2019-09-22T16:00:21	{"mesh": ["C567865"], "omim": ["612916"], "orphanet": ["217017"], "synonyms": ["Alternative titles", "OCCIPITAL ATRETIC CEPHALOCELE, UNUSUAL FACIES, AND LARGE FEET"]}
Form of agnosia Main article: Agnosia Autotopagnosia from the Greek a and gnosis, meaning "without knowledge", topos meaning "place", and auto meaning "oneself", autotopagnosia virtually translates to the "lack of knowledge about one's own space," and is clinically described as such.[1] Autotopagnosia is a form of agnosia, characterized by an inability to localize and orient different parts of the body.[2] The psychoneurological disorder has also been referred to as "body-image agnosia" or "somatotopagnosia." Somatotopagnosia has been argued to be a better suited term to describe the condition. While autotopagnosia emphasizes the deficiencies in localizing only one's own body parts and orientation, somatotopagnosia also considers the inability to orient and recognize the body parts of others or representations of the body (e.g., manikins, diagrams).[3] Typically, the cause of autotopagnosia is a lesion found in the parietal lobe of the left hemisphere of the brain.[3] However, it as also been noted that patients with generalized brain damage present with similar symptoms of autotopagnosia.[4] As a concept, autotopagnosia has been criticized as nonspecific; some claim that this is a manifestation of a greater symptomatic complex of anomia, marked by an inability to name things in general—not just parts of the human body.[5] ## Contents * 1 Causes * 1.1 Brain Lesions * 1.2 Mental Representations of Body Schema * 2 Symptoms * 3 Diagnosis * 4 Treatment * 5 Case studies * 5.1 Ennio De Renzi * 5.2 G. Denes et. al * 5.3 J. Schwoebel et. al * 5.4 Carlo Semenza * 5.5 Cecilia Guariglia * 6 History * 7 See also * 8 References * 9 External links ## Causes[edit] Due to the subjective nature of autotopagnosia, there are many hypotheses presented as to the underlying causation. Since the condition by definition is an inability to recognize the human body and its parts, the disorder could stem from a language deficit specific to body parts. On the other hand, the patient could suffer from a disrupted body image or a variation of the inability to separate parts from whole. It is also believed that autotopagnosia has multiple underlying causes that cannot be categorized as either language-specific or body-image-specific. The rarity of autotopagnosia, frequently combined with the manifestation of other psychoneurological disorders, makes the prime cause extremely difficult to study. In many cases, one of these accompanying conditions—often aphasia—could be masking the patient's autotopagnosia altogether.[4] ### Brain Lesions[edit] Animation. Parietal lobe of the left cerebral hemisphere. Although it is still unclear what precise deficits in brain function cause the symptoms of autotopagnosia, the location of brain damage is not as ambiguous. Autotopagnosia is most often attributed to lesions in the parietal lobe of the left hemisphere of the brain. However, it is also believed that the disorder can be caused by general brain damage as well.[4] Many different types of brain lesions can cause autotopagnosia; however, neoplastic lesions seem to be the most common. “Pure” autotopagnosia is often seen with smaller lesions, as larger lesions tend to create other unseen deficits that can confuse or mask the appearance of the symptoms of autotopagnosia—such as aphasia, as discussed above.[6] The parietal lobe is involved in the integration of sensory information and visuospatial processing. The left parietal lobe, specifically, is important to the understanding of language and mathematics, and has a more prominent role for right handed people. ### Mental Representations of Body Schema[edit] Lesions in the left parietal lobe are thought to disrupt one or more of four putative mental representations of body schema. The deficiencies associated with the disease seem to arise from a dysfunction in the mental representation of the body; however, the human psyche interprets its body schema and orientation in space through various sources of representation systems. According to Felician et al. (2003),[7] the notion of body schema can be categorized into four tiers of mental representation: Level Type Description 1 Lexical and Semantic Representations of the Body At the first level, the mind anchors its body image to refer to body-related conceptual knowledge, associated with speech and language recognition. For instance, the identification of body parts are attributed to fundamental knowledge of the names and titles, rather than the physical locations and relationships of body parts.[7] 2 Category-specific Visuospatial Representations of the Body On the second tier, unlike semantic representation, the visuospatial schema specifies the structural position of parts over the body surface. In particular, it relates to the local relationship between body parts and the boundaries between them.[7] 3 Classical Notion of Postural Schema On a third level, the classical notion of postural schema emerges, which draws from various sources of sensory afferences. Information from proprioceptive, tactile, visual, auditory, and vestibular systems is consolidated to construct an on-line, three-dimensional and dynamic representation of the body in space, a “somatosensory representation.” [7] 4 Motor Representations Finally, the skeletal-muscular system provides motor representations that participate in the formation and preservation of the somatosensory representations.[7] ## Symptoms[edit] Patients with autotopagnosia exhibit an inability to locate parts of their own body, the body of an examiner's, or the parts of a representation of a human body. Deficiencies can be in localizing parts of a certain area of the body, or the entire body. Contiguity errors, the most common errors made by patients with autotopagnosia, refer to errors made when the patient is asked to locate a certain body part and points to the surrounding body parts, but not the part they’ve been asked to locate. Semantic errors refer to errors made when patients point to body parts in the same category as that which they’ve been asked to locate, but cannot locate the correct body part. An example of a semantic error would be a patient pointing to an elbow when asked to locate a knee. Semantic errors are much less common than contiguity errors.[3] Some patients demonstrating the symptoms of autotopagnosia have a decreased ability to locate parts of other multipart object. Patients are considered to suffer from “pure” autotopagnosia, however, if their deficiency is specific to body part localization.[3] Patients suffering from “pure” autotopagnosia often have no problems carrying out tasks involved in everyday life that require body part awareness. Patients have difficulty locating body parts when directly asked, but can carry out activities such as putting on pants without difficulty. Patients can describe the function and appearance of body parts, yet they are still unable to locate them.[3] Damage to the left parietal lobe can result in what is called Gerstmann syndrome. It can include right-left confusion, a difficulty with writing Agraphia[4] and a difficulty with mathematics Acalculia.[8] In addition, it can also produce language deficiencies Aphasia[9] and an inability to recognize objects normally Agnosia. Other related disorders include: * Apraxia: an inability to perform skilled movements despite understanding of the movements and intact sensory and motor systems.[4] * Finger agnosia: An inability to name the fingers, move a specific finger upon being asked, and/or recognize which finger has been touched when an examiner touches one.[4] ## Diagnosis[edit] The nature of the alleged mental representations that underlie the act of pointing to target body parts have been a controversial issue. Originally, it was diagnosed as the effects of general mental deterioration or of aphasia on the task of pointing to body parts on verbal command. However, contemporary neuropsychological therapy seeks to establish the independence of autotopagnosia from other disorders.[10] With such a general definition, a patient that presents with a dysfunction of or failure in accessing one of four mental representation systems suffers from autotopagnosia. Through observational testing, the type of mental misrepresentation of the body can be deduced: whether semantic, visuospatial, somatosensory, or motor misrepresentations. Neuropsychological tests can provide a proper diagnosis in regards to the specificity of patient's agnosic condition.[7] 1) Test 1: Body Part Localization: Free vision and no vision conditions This exploratory approach assesses the patient's ability to localize one's body parts and those of the examiner in several different conditions. The examiner and subjects are seated facing one another at a one-meter distance. At the start of each trial, the examiner ensures that the subject's hands are at rest on the arms of the chair and legs uncrossed. In addition, errors are categorized as (1) left-right reversal: response to correct part on incorrect side; (2) spatial: response to area contiguous with target; (3) functional/semantic: response to area non-contiguous with target, but sharing function or a part of a larger unit; (4) unrelated to examiner's request.[11] Test 1 Specifications Description A Verbal Command: Point to Self Examiner names a body part, and the subjects are instructed to point to that part on themselves. B Verbal Command: Point to Examiner Examiner names a body part, and subjects are instructed to point to that named part on the examiner. C Visual Cue: Point to Self Examiner points to body parts on himself, and subjects are required to point to the homologous part on themselves. D Visual Cue: Point to Examiner Examiner points to a body part on the subjects, and they are required to point to the homologous part on the examiner. E Blindfold Post-Visual Cue: Point to Self Same as Study 1c., except subjects are blindfolded after examiner points to himself, prior to response execution.[11] 2) Test 2: On-line positioning of body vis-à-vis objects If deficits in body part localization are due to impairments in body schema, then patients should be deficient in reaching and grasping objects. This test evaluates the specificity of the patient's insufficiency, in regards to the specific positioning of body parts with respect to objects.[11] 3) Test 3: Localization of objects on the body surface Patients were asked to point to small objects mounted on the body, acting as a body reference system (body schema). The investigation is to determine whether localization of the same points on the body surfaces assessed in Test 1 might be improved when these points correspond to external objects.[11] 4) Test 4: Body part semantic knowledge Patient is shown photographs of 10 items of clothing and 7 grooming tools, 1 per trial, and asked to point to the part of his own body associated with each item.[11] 5) Test 5: Matching body parts: Effect of viewing angle Assessment of whether the patient's deficit in body part representation extends to individual body parts, and whether visual attributes of the body and its parts, such as viewing angle, affect their recognition.[11] ## Treatment[edit] A CT scanner As autotopagnosia arises from neurological and irreversible damage, options regarding symptom reversal or control are limited. As of April 2010, there are no known specific treatments for autotopagnosia.[12] No medications or pharmaceutical remedies have been approved by the U.S. Food and Drug Administration to treat or cure autotopagnosia. There have been cases in which extensive rehabilitation has been beneficial following restitution, repetitive training to correct the impaired function, and compensation of other skills to make up for the deficit. Rehabilitation is not a definitive treatment and only shows signs of slight improvement in a small percentage of autotopagnosia patients.[13] The condition of the disease can be monitored with continued neurological examination and using a CT scan to note the progression of the parietal lesion. ## Case studies[edit] As autotopagnosia is not a life-threatening condition it is not on the forefront of medical research. Rather, more research is conducted regarding treatments and therapies to alleviate the lesions and traumas that can cause autotopagnosia. Of all the agnosias, visual agnosia is the most common subject of investigation because it is easiest to assess and has the most promise for potential treatments. Most autotopagnosia studies are centered on a few test subjects as part of a group of unaffected or “controlled” participants, or a simple case study. Case studies surrounding a single patient are most common due to the vague nature of the disease. Autotopagnosia studies frequently investigate several areas of patient examination: indication, verification, construction and drawing, structural and functional information and spatial and functional vicinity. The studies most often probe a patient to correctly verbally identify certain body parts on themselves, others, and an artificial model. Indication seeks to employ both verbal and non-verbal stimuli, and to differentiate the patient from themselves and others. Most patients fail the indication section however pass the verification exam, which confirms the patients knowledge of what a certain body part or object truly is. Most patients were able to draw the object or body part, yet are unable to construct its location on a working model. The structural and functional information verifies the patient's competency in deterring the specific body parts function and spatial relation to other body parts. Spatial and functional vicinity tests probe a patient to physically locate the various body parts in relation to others and by function; however these tests are usually failed. ### Ennio De Renzi[edit] Ennio De Renzi worked extensively with a variety of agnosias in 1963 and 1970. He explored, on two patients with autotopagnosia in particular, the difficulties of mentally recognizing the physical division of a whole object into sections. For example, he found his patients could not describe the position or parts of a bike, and were unable to focus on a part of the whole. De Renzi's studies gave way to countless others to give insight as to the complicated and varied mechanisms behind autotopagnosia. ### G. Denes et. al[edit] G. Denes et al. (2000) conducted a series of tests on two patients suffering from autotopagnosia in order to verify how the body schema uses body representation to determine one's spatial arrangement. The two subjects, each suffering from a condition which affected their parietal lobe, presented with similar degrees of agnosia according to neurological testing, yet did not suffer from any language, behavior or memory limitations. G. Denes performed a series of tests to challenge the subjects, consisting of body related tasks, non-body localizing tasks and reaction to stimuli. The subjects were asked to name body parts and identify objects singled out by the examiner on themselves and in a picture. In addition, the objects and body parts were presented from different perspectives. The subjects were asked both on paper and via verbal command, to locate body parts on themselves, others, and mannequins. On paper there was no difference between the test and control patients however neither autotopagnosia subject was able to locate the correct body parts on command on either themselves or a mannequin, although could partially identify the objects. Most of the errors in this experiment were considered functional errors, that is, the patient touched body parts similar in function to the ones being prompted. These deficits could not be attributed to mental deterioration or visual deficiencies.[12] ### J. Schwoebel et. al[edit] J. Schwoebel et al. (2001) studied an elderly woman suffering from autotopagnosia following a car accident which damaged her lateral occipital, left posterior temporal and posterior parietal lobe. They performed a similar series of tests, examining her ability to identify and locate body parts on a drawn figure and herself, upon verbal command. They expanded the study, repeating the verbal command tests in areas of unfamiliarity and with a series of objects rather than body parts. Schwoebel found that the subject was able to identify objects with more ease than body parts and that location familiarity was not relevant. Schwoebel stressed the difference between function and spatial vicinity tests however the subject failed both tests. Overall, the subject was unable to locate the correct parts of her body or that of another, thereby presented the classic signs of autotopagnosia.[14] ### Carlo Semenza[edit] Carlo Semenza (1988) analyzed the deficits associated with patients presenting with autotopagnosia compared with the test results of non-afflicted patients. He found the majority of testing errors for patients with autotopagnosia were either spatial (contiguity) or functional (conceptual), and there were few examples of random error. Similar to other studies, Semenza used both verbal and non-verbal commands and applied tests of verification, construction and description to his patients,[15] at a complex and body specific representational system, stored in the left parietal lobe, is responsible for mediating simple body location tasks. He theorized that the spatial and functional errors were due to the concept that one's knowledge of one's body is stored apart from other knowledge. This knowledge is then organized into a set of ideas, which represent a single body part, and parts of similar functionality are closely related despite actual spatial distances on the body. Semenza (2003) investigated Pick's original work surrounding the discovery of autotopagnosia. ### Cecilia Guariglia[edit] Guariglia and coll. (2002) described a case (EC) of pure autotopagnosia following a left subcortical vascular accident.[16] EC did not suffer of any other neuropsychological deficit, including language disorder or general mental deterioration. An in-depth analysis of the deficit in localizing body parts and parts of objects or animals revealed a clear-cut dissociation between defective performances in body representation tests and normal performances on tests involving other types of stimuli. EC's performances were particularly defective on tests relying on visuo-spatial body representation, but her semantic and linguistic knowledge about body and body parts were spared. Being the first observation of a subject not affected by any cognitive impairment other than autotopoagnosia, EC represents a demonstration of the existence of a system specifically devoted to body representation. ## History[edit] German Physiologist Hermann Munk (1839–1912) was the first to investigate the representation of our body's orientation. He discussed how multisensory imagery of our sensations allows for a vivid representation of the body in space, and how small legions on the sensorimotor cortex would lead to a loss of images for a specific part of the body. Accredited with finding Wernicke's Area, German neuro-pathologist Carl Wernicke (1848–1905) challenged Munk's theories, arguing that signals sent from different body parts are different from each other. The cortex was then thought to create a stable image of each body part in space by combining all of the varying incoming signals. The “master” signal integration was said to create an image of the overall body, known as “body consciousness”. Gaston Bonnier (1853–1922) was the first to recognize disorders of the bodies spatial schema as physiological rather than psychiatric. However his work has been consistently criticized due to several experimental discrepancies regarding his patients association of their body parts to their actual position. Colleagues Sir Gordon Holmes (1876–1965) and Henry Head (1861–1940)[15] considered the image of the body as a specific representation, and noted this body schema as a model which postural changes were measured against. The two neurobiologists integrated the sensations from different sensors into a dynamic model of our actual posture, and studied patients lacking this postural schema. Head and Holme's studies (1911) were developed alongside those of Arnold Pick (1851–1924), who was the first to describe autotopagnosia (1908) as the inability to locate body parts on command on a whole body structure. Pick noted those afflicted with autotopagnosia as having a dissociation between the capacity to recognize and name their own body part (as commanded by an examiner) and the inability to find the same body part on command. In a series of studies, Pick focused on patients who were unable to point to their own body parts and those of the examiner. His patients could however comprehend the body part terminology as well as locate them on a painted visual; however none had a clear demonstration of body specificity. Pick concluded a disturbance of “visual” body image and body awareness. Pick's studies introduced autotopagnosia and other category specific agnosias, such as visual and tactile agnosia. Josef Gerstmann (1887–1969) first developed the term somatotopagnosia, meaning the lack of knowledge about the body space. Gerstmann studied patients whose deficits were in the body schema and thus lacked the ability to recognize, identify or name the fingers on either hand, a phenomenon known as finger agnosia.[15] This particular ailment, known as Gerstmann syndrome, is often seen in patients with a lesion on their left angular gyrus, which is known to be frequently anatomically correlated with autotopagnosia. Until the 1980s, there had been no scientifically accredited cases of autotopagnosia, rather agnosias that have been secondary to other neurological deficits such as dementia.[15] In fact the term autotopagnosia does not appear until Pick's studies in 1908 and 1922.[17] More recently, Carlos Semenza (2003) has expanded on Pick's theories. As of April, 2010, the active areas of research surrounding autotopagnosia are focused on more individual case studies, and are aimed at developing possible treatment options as well as eradicating any concerns regarding the disease's legitimacy. ## See also[edit] * Allochiria ## References[edit] 1. ^ 9\. “Autotopagnosia.” Mosby’s Medical Dictionary, 2009. Volume 8. Last updated 2009. Accessed February 22, 2011. http://medical-dictionary.thefreedictionary.com/autotopagnosia 2. ^ Dorlands Medical Dictionary 3. ^ a b c d e Goldenberg, G (2000). "9. Disorders of Body Perception". In Farah, Martha J; Feinberg, Todd E (eds.). Patient-based approaches to cognitive neuroscience. Cambridge, Mass: MIT Press. pp. 110–111. ISBN 0-262-56123-9. OCLC 41712668. 4. ^ a b c d e f Ogden, Jenni A. (2005). Fractured minds: a case-study approach to clinical neuropsychology. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-517136-5. OCLC 488457821. 5. ^ Gainotti G, Caltagirone C, Carecchi A, Ibba A (1976). "[An experimental study of autotopagnosia (author's transl)]". Riv Patol Nerv Ment (in Italian). 97 (2): 94–114. PMID 195331. 6. ^ G. Denes; Luigi Pizzamiglio (1999). Handbook of Clinical and Experimental Neuropsychology. Psychology Press. p. 192. ISBN 978-0-86377-542-0. 7. ^ a b c d e f Felician O, Ceccaldi M, Didic M, Thinus-Blanc C, Poncet M (2003). "Pointing to body parts: a double dissociation study". Neuropsychologia. 41 (10): 1307–16. doi:10.1016/S0028-3932(03)00046-0. PMID 12757904. 8. ^ Levin, Harvey S. et al. "Chapter 5: Acalculia." Clinical Neuropsychology. Ed. Kenneth M. Heilman and Edward Valenstein. New York: Oxford University Press, 1993. Print. 9. ^ Benson, Frank. "Chapter 2: Aphasia." Clinical Neuropsychology. Ed. Kenneth M. Heilman and Edward Valenstein. New York: Oxford University Press, 1993. Print. 10. ^ Farah, Martha J. and Feinberg, Todd E. 'Patient-Based Approaches to Cognitive Neuroscience', 2nd Ed. The MIT Press, (c) 2005. 151-155. 11. ^ a b c d e f Buxbaum LJ, Coslett HB (June 2001). "Specialised structural descriptions for human body parts: Evidence from autotopagnosia". Cogn Neuropsychol. 18 (4): 289–306. doi:10.1080/02643290126172. PMID 20945217. 12. ^ a b Denes G, Cappelletti JY, Zilli T, Dalla Porta F, Gallana A (2000). "A category-specific deficit of spatial representation: the case of autotopagnosia". Neuropsychologia. 38 (4): 345–50. doi:10.1016/s0028-3932(99)00101-3. PMID 10683386. 13. ^ Ghadiali, Eric. “Agnosia”. ACNR, 4(5), November/December, 2004: 18-20. The Walton Centre for Neurology and Neurosurgery, Liverpool. http://www.acnr.co.uk/pdfs/volume4issue5/v4i5cognitive.pdf 14. ^ Schwoebel J, Coslett HB, Buxbaum LJ (June 2001). "Compensatory coding of body part location in autotopagnosia: Evidence for extrinsic egocentric coding". Cogn Neuropsychol. 18 (4): 363–81. doi:10.1080/02643290126218. PMID 20945221. 15. ^ a b c d Semenza C (September 1988). "Impairment in localization of body parts following brain damage". Cortex. 24 (3): 443–9. doi:10.1016/s0010-9452(88)80007-8. ISSN 0010-9452. PMID 3191727. 16. ^ Guariglia C, Piccardi L, Puglisi Allegtra MC, Traballesi M (2002). "Is autotopoagnosia real? EC says yes. A case study". Neuropsychologia. 40 (10): 1774–8. doi:10.1016/S0028-3932(02)00013-1. PMID 11992662. 17. ^ De Renzi, E.; Scotti, G. (1970). "Autotopagnosia: Fiction or Reality? Report of a Case". Archives of Neurology. 23 (3): 221–227. doi:10.1001/archneur.1970.00480270031005. ISSN 0003-9942. ## External links[edit] * Agnosia pdfreference 2002 * Body Representation Workshop pdfreference 2007 * Carlos Semenza pdfreference * Somatosensation pdfreference [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Autotopagnosia	c0234511	28,969	wikipedia	https://en.wikipedia.org/wiki/Autotopagnosia	2021-01-18T18:51:38	{"mesh": ["D000377"], "icd-10": ["R48.1"], "wikidata": ["Q4827018"]}
A number sign (#) is used with this entry because of evidence that multiple epiphyseal dysplasia-1 (EDM1) is caused by heterozygous mutation in the gene encoding cartilage oligomeric matrix protein (COMP; 600310) on chromosome 19p13. Mutation in the COMP gene can also cause the more severe disorder pseudoachondroplasia (PSACH; 177170). Description Multiple epiphyseal dysplasia is a skeletal disorder characterized by short stature and early-onset osteoarthrosis (Briggs et al., 1995). ### Genetic Heterogeneity of Multiple Epiphyseal Dysplasia Multiple epiphyseal dysplasia is a genetically heterogeneous disorder. See also EDM2 (600204), caused by mutation in the COL9A2 gene (120260); EDM3 (600969), caused by mutation in the COL9A3 gene (120270); EDM4 (226900), caused by mutation in the DTDST gene (606718); EDM5 (607078), caused by mutation in the MATN3 gene (602109); EDM6 (614135), caused by mutation in the COL9A1 gene (120210); and EDM7 (617719), caused by mutation in the CANT1 gene (613165). Clinical Features Severe osteoarthritis of the hips develops in early adulthood. The diagnosis in the adult is aided by the changes in the distal tibia (Leeds, 1960). A deficiency in the lateral part of the distal tibial ossification center seen in children results in a sloping end of the tibia in adulthood. Short stature and brachydactyly are features. Considerable heterogeneity undoubtedly exists within this category. Chondrodystrophia calcificans congenita is a congenital form of multiple epiphyseal dysplasia (215100). Bachman and Norman (1967) described a 47-year-old woman, height 61.5 inches, with marked hyperextensibility of fingers and precocious osteoarthritis of the hips. A son and a daughter had very flexible fingers and, by hand x-ray, delay in carpal ossification, proximal pseudoepiphyses of metacarpals 2-5, cone-cup epiphyses-metaphyses, and widened joint spaces. Other joints showed extensive changes with widening of joint spaces and irregular epiphyses. The mother's mother, aunt, uncle, and cousin had hyperextensibility of the fingers and premature osteoarthritis. These authors referred to the condition as peripheral dysostosis but it seems different from the peripheral dysostosis (170700) described by Singleton et al. (1960); the term 'peripheral' seems inappropriate, and the description suggests what others would call Fairbank multiple epiphyseal dysplasia. (See 105835 for another interpretation of the family reported by Bachman and Norman (1967).) Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank (Fairbank, 1945) and milder Ribbing (Ribbing, 1937) types. Fairbank multiple epiphyseal dysplasia is probably the same as that described as enchondral dysostosis by Odman (1959). Hulvey and Keats (1969) commented on the variability in the extent of spinal involvement and presented a family in which many members had severe peripheral involvement with no spinal involvement. The dividing line between multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia tarda (see 313400) can be indistinct, as evidenced by the family reported by Diamond (1970)--see 184100. Wynne-Davies et al. (1985) stated that the wrists and hands are often normal in the mild, or Ribbing, type, whereas they are short and stubby in the severe Fairbank type. Villarreal et al. (1992) described a form of epiphyseal dysplasia in a mother and 5 of her 10 children. A distinctive feature was unusually short hands and feet and particularly a short fourth metatarsal bone. Round face was also described. Curiously, the height of the affected individuals was not given. Stanescu et al. (1993) performed morphologic and biochemical studies on the upper tibial cartilage from a case of multiple epiphyseal dysplasia of the Fairbank type. They concluded that the changes are similar to those described in pseudoachondroplasia (e.g., 177170) by Stanescu et al. (1982, 1984). However, the inclusions were smaller and the growth cartilage much less disorganized in MED. The similarities between the 2 disorders suggested that they have a similar pathogenesis. Diagnosis Genetic diagnosis of the COMP-related skeletal dysplasias pseudoachondroplasia and multiple epiphyseal dysplasia is difficult because COMP mutations are scattered throughout the gene and 5 additional disease genes for multiple epiphyseal dysplasia exist. Mabuchi et al. (2004) presented evidence that plasma COMP levels are significantly decreased in patients with COMP mutations compared with controls (p less than 0.0001). In addition, plasma COMP levels were significantly decreased in MED patients carrying mutations in COMP relative to those who lacked COMP mutations (p = 0.001). These results indicated that measuring the level of circulating COMP may be an easier, more rapid, and cost-efficient method for diagnosing PSACH and particularly for diagnosing MED. Mapping By demonstrating discordant inheritance of restriction fragment length polymorphisms (RFLPs) and MED in an extensively affected kindred, Weaver et al. (1993) excluded the gene for type II (120140) collagen and the genes for the 3 chains of type VI (120220, 120240, 120250) collagen as the site of the mutation. By linkage studies, Oehlmann et al. (1993) also excluded the COL9A1 gene (120210), which maps to 6q13, and the CRTL1 gene (HAPLN1; 115435), which maps to 5q13. However, linkage to DNA markers suggested location of the gene close to the centromere of chromosome 19. The highest lod score was observed for D19S199; maximum lod = 4.67 at theta = 0.09. Oehlmann et al. (1994) later reported a maximum lod score of 6.37 at theta = 0.05 for linkage with D19S215. Multipoint linkage analysis indicated that MED was located between D19S212 and D19S215, a map interval of 1.7 cM. The gene for pseudoachondroplastic dysplasia (177170) has been mapped to the pericentric region of chromosome 19; this finding, combined with the morphologic similarity between pseudoachondroplasia and MED, mentioned earlier, again raised the possibility of allelism of the 2 disorders. Deere et al. (1995) confirmed the linkage of autosomal dominant multiple epiphyseal dysplasia to D19S212; maximum lod = 3.22 at theta = 0.00. In a family in which 3 of 7 sibs were affected and the parents were unaffected, they excluded linkage to chromosome 19 (using both autosomal recessive and autosomal dominant models, with either reduced penetrance or germline mosaicism considered). Linkage to candidate genes COL9A1, COL9A2 (120260), and COL11A2 (120290) was tested and excluded for both genetic models in the latter family. COL11A1 (120280) was also excluded under a recessive model. The EDM1/PSACH locus had been found to be flanked by D19S212 and D19S215. These 2 markers had been localized in the chromosome 19 physical map consisting of cosmid contigs ordered by high-resolution fluorescence in situ hybridization. These 2 markers defined an interval of approximately 3.1 Mb at the 19p13.1-p12 boundary. With as many as 5 informative crossovers in 1 family with EDM1 and 1 family with a mild form of PSACH, Knowlton et al. (1995) did recombination mapping at greater resolution. From cosmid contigs physically mapped within the D19S12/D19S215 interval, they found 4 new dinucleotide repeat polymorphisms. Analysis of recombinant haplotypes in the 2 families narrowed the possible location of the EDM1/PSACH gene to an interval of approximately 600 kb. Molecular Genetics As outlined by Hecht et al. (1995) and by Briggs et al. (1995), it is generally agreed that the EDM1 and PSACH loci are in the centromeric region of 19p, 19p13.1-p12. Furthermore, the gene for cartilage oligomeric matrix protein (COMP; 600310) maps to the same region. Both Hecht et al. (1995) and Briggs et al. (1995) demonstrated mutations in the COMP gene in pseudoachondroplasia (e.g., 600310.0001) and Briggs et al. (1995) demonstrated a mutation in the COMP gene in a patient with multiple epiphyseal dysplasia (see 600310.0005). Jakkula et al. (2003) found a heterozygous mutation in the COMP gene (600310.0017) in patients with muscle weakness, moderate creatine kinase elevation, and MED beginning with the knee joints, uncovering a clinical and radiologic overlap with MED caused by mutation in the collagen IX genes (see 600204 and 600969). Ballo et al. (1997) studied mild MED in a South African kindred and demonstrated heterozygosity for an asn523-to-lys amino acid substitution in the COMP protein (600310.0008). ### Reviews Jackson et al. (2012) conducted a 7-year study (2003-2007) of 130 patients with pseudoachondroplasia or suspected multiple epiphyseal dysplasia and provided a detailed review of the clinical diagnoses and molecular findings in these patients compared to previously reported patients. The authors noted that whereas PSACH was relatively straightforward to diagnose based on clinical and radiographic information, the more subtle and variable radiographic signs of MED make that diagnosis more difficult. In contrast to previous studies suggesting that mutations in the known genes are not the major cause of MED, Jackson et al. (2012) concluded that mutations in COMP, MATN3, and type IX collagen genes account for the vast majority of classic autosomal dominant MED. Heterogeneity In 29 consecutive MED patients, Jakkula et al. (2005) found a DTDST mutation in 4 (14%), a COMP mutation in 3 (10%), and an MATN3 mutation in 3 (10%). Disease-causing mutations were identified in only 10 patients (34%). Jakkula et al. (2005) concluded that mutations in the known genes are not the major cause of MED and are responsible for less than half of the cases. Jakkula et al. (2005) described 2 distinct phenotypic entities in patients with MED but no observed mutations. Severe early-onset dysplasia of the proximal femurs with almost complete absence of the secondary ossification centers and abnormal development of the femoral necks was found in 3 patients (609324). Two patients had strikingly small secondary ossification centers ('mini-epiphyses') in all joints, resulting in severe dysplasia of the proximal femoral heads (609325). Animal Model PSACH and EDM1 patients often have a mild myopathy characterized by mildly increased plasma creatine kinase levels, a variation in myofiber size and/or small atrophic fibers. Pirog et al. (2010) studied skeletal muscle, tendon, and ligament in a mouse model of mild PSACH harboring a T585M mutation. T585M-mutant mice exhibited a progressive muscle weakness associated with an increased number of muscle fibers with central nuclei at the perimysium and at the myotendinous junction. Collagen fibril diameters in the mutant tendons and ligaments were thicker, and tendons became more lax in cyclic strain tests. Pirog et al. (2010) hypothesized that the myopathy in PSACH-MED may originate from underlying tendon and ligament pathology that may be a direct result of abnormalities in collagen fibril architecture. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature, mild to moderate \- Dwarfism, mild short-limb \- Final adult height 145-170cm SKELETAL \- Generalized joint laxity Spine \- Ovoid vertebral bodies \- Mild irregularity of vertebral endplates Pelvis \- Avascular necrosis of femoral head \- Limited hip movement \- Broad, short femoral neck \- Hip osteoarthritis (early-onset) Limbs \- Late ossifying epiphyses \- Small, irregular epiphyses \- Genua valga Hands \- Short metacarpals \- Short phalanges MISCELLANEOUS \- Genetic heterogeneity (see EDM2 600204 , EDM3 600969 , EDM4 226900 , EDM5 607078 ) \- Allelic to pseudoachondroplasia ( 177170 ) \- Hip joint replacement often necessary \- Symptoms usually manifest in childhood including waddling gait and painful, stiff joints MOLECULAR BASIS \- Caused by mutation in cartilage oligomeric matrix protein (COMP, 600310.0005 ) ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	EPIPHYSEAL DYSPLASIA, MULTIPLE, 1	c1838280	28,970	omim	https://www.omim.org/entry/132400	2019-09-22T16:41:30	{"doid": ["0070303"], "mesh": ["C535501"], "omim": ["132400"], "orphanet": ["93308"], "synonyms": ["Alternative titles", "MULTIPLE EPIPHYSEAL DYSPLASIA, COMP-RELATED"], "genereviews": ["NBK1123"]}
Epidermolysis bullosa simplex (EBS) is one of the major forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. EBS is classified into two groups of subtypes by the layer of skin at which the peeling originates. The basal subtypes cause skin peeling at the lower layers of the epidermis. The most common basal subtypes include EBS localized, Dowling Meara EBS, Generalized other EBS and EBS with muscular dystrophy. More rarely seen basal subtypes include EBS with mottled pigmentation, EBS with pyloic atreseia, EBS Ogna, and EBS circinate migratory.The suprabasal subtypes cause skin peeling at the upper layers of the epidermis and include the rare forms known as Lethal acantolythic EB, Plakophilin deficiency, and EBS superficialis (EBSS). Symptoms of EBS range from mild in the Weber-Cockayne type to severe with blistering that is present at birth or after. Milder phenotypes of EBS have blistering confined to the limbs, whereas in the most severe Dowling Meara type, blisters may also form in the mouth. All of the types are typically caused by mutations in the KRT5 and KRT14 genes. They are usually inherited in an autosomal dominant pattern, but autosomal recessive inheritance has occurred in rare cases.[2913] Treatment plans differ depending on severity but typically focus on preventing formation of blisters, caring for blistered skin, and treating infection. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Epidermolysis bullosa simplex	c0079298	28,971	gard	https://rarediseases.info.nih.gov/diseases/10752/epidermolysis-bullosa-simplex	2021-01-18T18:00:42	{"mesh": ["D016110"], "omim": ["131800", "131900", "131760", "131960", "601001"], "orphanet": ["304"], "synonyms": ["Epidermolysis bullosa intraepidermic"]}
## Summary ### Clinical characteristics. Spinocerebellar ataxia type 2 (SCA2) is characterized by progressive cerebellar ataxia, including nystagmus, slow saccadic eye movements, and in some individuals, ophthalmoparesis or parkinsonism. Pyramidal findings are present; deep tendon reflexes are brisk early on and absent later in the course. Age of onset is typically in the fourth decade with a ten- to 15-year disease duration. ### Diagnosis/testing. The diagnosis of SCA2 rests on the use of molecular genetic testing to detect an abnormal CAG trinucleotide repeat expansion in ATXN2. Affected individuals have alleles with 33 or more CAG trinucleotide repeats. ### Management. Treatment of manifestations: Management is supportive. Affected individuals should maintain activity. Canes and walkers help prevent falls; grab bars, raised toilet seats, and ramps to accommodate motorized chairs may be necessary. Speech therapy and communication devices such as writing pads and computer-based devices may benefit those with dysarthria. Weighted eating utensils and dressing hooks help maintain a sense of independence. When dysphagia becomes troublesome, video swallowing studies can identify the consistency of food least likely to trigger aspiration. Prevention of secondary complications: Vitamin supplements are recommended; weight control helps minimize difficulties with ambulation and mobility. Surveillance: Annual examination by a physician experienced in movement disorders and ataxia. Agents/circumstances to avoid: Alcohol and medications known to affect cerebellar function. ### Genetic counseling. SCA2 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the causative CAG trinucleotide repeat expansion. The repeat may expand significantly, especially when transmitted by the father. Prenatal testing for pregnancies at increased risk is possible if the diagnosis has been established by molecular genetic testing in an affected family member. ## Diagnosis ### Suggestive Findings Spinocerebellar ataxia type 2 (SCA2) should be suspected in individuals with the following: * Slowly progressive ataxia and dysarthria * Nystagmus and slow saccadic eye movements * Family history consistent with autosomal dominant inheritance ### Establishing the Diagnosis The diagnosis of SCA2 is established in a proband with a heterozygous pathogenic variant in ATXN2 (see Table 1). The clinical features of SCA2 do not allow diagnosis with certainty; thus, diagnosis depends on molecular genetic testing. Allele sizes * Alleles not causing SCA2. Alleles with 31 or fewer CAG repeats * Alleles of uncertain clinical significance. Alleles with 32 repeats are uncommon; correlation with clinical findings and family history may be helpful. * Alleles predisposed to meiotic instability (longer normal alleles) have a CAG length-dependent increased instability [Almaguer-Mederos et al 2018]. Precise risk estimates based on large numbers of affected individuals from different ethnic groups are not available. In a small number of observations, presence of an uninterrupted (pure CAG) repeat structure increases risk of expansion and conversely, CAA interruptions appear to stabilize the repeat in transmissions. * Amyotrophic lateral sclerosis-risk alleles. Alleles with 30, 31, or 32 repeats [Neuenschwander et al 2014] * Recessive SCA2-causing alleles. Homozygous 31/31 repeat alleles [Tojima et al 2018] * Dominant SCA2-causing alleles. Alleles with 33 or more CAG repeats (see Note) [Pulst et al 1996, Charles et al 2007]. Persons who have an SCA2-causing allele are considered at risk of developing SCA2 in their lifetime. SCA2-causing alleles are further classified as follows: * Reduced-penetrance SCA2-causing alleles. 33-34 CAG trinucleotide repeats. An individual with an allele in this range is at risk for SCA2 but may not develop symptoms. Alleles of 33 CAG repeats are considered "late onset" (age >50 years). An older asymptomatic individual with 34 CAG repeats has been reported [Riess et al 1997]. * Full-penetrance SCA2-causing alleles. The most common disease-causing alleles have 37 to 39 repeats. Extreme CAG repeat expansion (>200) has been reported [Babovic-Vuksanovic et al 1998] (see Anticipation). Note: Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size because both CAG and CAA code for glutamine [Costanzi-Porrini et al 2000]; however, the interruption may enhance the meiotic stability of the repeat [Choudhry et al 2001]. Conversely, the lack of CAA interruption in some expanded alleles may increase the instability of the expansion and therefore increase the risk of transmission of a larger expansion to offspring, who may become symptomatic. Molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Targeted analysis for a homozygous or heterozygous ATXN2 allele with >31 CAG repeats should be performed first. * A multigene panel that includes ATXN2 CAG-repeat analysis and other genes of interest (see Differential Diagnosis) may also be considered. 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. ### Table 1. Molecular Genetic Testing Used in SCA2 View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ATXN2Targeted analysis for pathogenic variants 3~100% 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\. Detects abnormal number of CAG trinucleotide repeats. PCR amplification detects smaller CAG trinucleotide repeat expansions up to ~100 repeats. Southern blotting is required to detect highly expanded CAG trinucleotide repeat expansions (>100 repeats) and may be indicated in symptomatic infants and children [Mao et al 2002]. Note: Testing individuals with a positive family history of ataxia has a much higher yield than testing individuals with ataxia without an obvious family history. * In the series reported by Riess et al [1997] only two of 842 affected individuals without a family history of ataxia were heterozygous for an ATXN2 expansion in the pathogenic allele size range. * In the series reported by Cancel et al [1997] only two of 90 individuals with olivopontocerebellar atrophy without a known family history were heterozygous for an ATXN2 expansion in the pathogenic allele size range. ## Clinical Characteristics ### Clinical Description Spinocerebellar ataxia type 2 (SCA2) is characterized by slowly progressive ataxia and dysarthria associated with the ocular findings of nystagmus, slow saccadic eye movements, and in some individuals, ophthalmoparesis. Tendon reflexes are brisk during the first years of life, but absent later. Mean age of onset is typically in the fourth decade with a ten- to 15-year disease duration. The disease is more rapidly progressive when onset occurs before age 20 years. In the original study from Cuba, the earliest symptoms included gait ataxia often accompanied by leg cramps [Orozco Diaz et al 1990]. More than 50% of affected individuals developed a kinetic or postural tremor, decreased muscle tone, decreased tendon reflexes, and abnormal eye movements with slowed saccades progressing to supranuclear ophthalmoplegia. Detailed analyses of the eye movement abnormalities have been reported [Engel et al 2004, Velázquez-Pérez et al 2004]. In individuals with molecularly confirmed ATXN2, Geschwind et al [1997b] found almost universal presence of cerebellar ataxia and slow saccadic eye movements in affected individuals, as well as a relatively high incidence of dystonia or chorea (38%) and dementia (37%). Mild, primarily cerebellar symptoms appeared to segregate in some families, whereas others had an early onset with dementia and chorea. Luo et al [2017] described the initial manifestations in SCA2 and other ataxias. Similar findings were also reported by Cancel et al [1997] in a series of 111 individuals from 32 families of diverse origins. Slow eye movements were seen in 56%, fasciculations in 25%, and dystonia in 9%. The authors also correlated these findings with disease duration and increasing CAG repeat length. An SCA2 phenotype that includes L-dopa-responsive parkinsonism has been reported [Furtado et al 2002, Payami et al 2003, Charles et al 2007]. In one Alberta family, the phenotype was consistent with autosomal dominant Parkinson disease, with PET scan showing reduced striatal fluorodopa uptake and normal raclopride binding in two affected members [Furtado et al 2002]. Charles et al [2007] proposed that an interrupted repeat structure may lead to differential binding with RNA-binding proteins and thus result in a parkinsonian rather than a cerebellar phenotype. Neuropathology. Seven postmortem examinations have been reported in the Holguin population of Cuba [Orozco et al 1989]. A marked reduction in the number of cerebellar Purkinje cells was observed. In silver preparations, Purkinje cell dendrites had poor arborization and torpedo-like formation of their axons as they passed through the granular layer. Parallel fibers were scant and granule cells were decreased in number, whereas Golgi and basket cells were well preserved, as were neurons in the dentate and other cerebellar nuclei. In the brain stem, marked neuronal loss in the inferior olive and pontocerebellar nuclei was observed. Six of seven brains also had marked loss in the substantia nigra. In five spinal cords that were available for analysis, marked demyelination was present in the posterior columns and to a lesser degree in the spinocerebellar tracts. Motor neurons and neurons in Clarke's column were reduced in size and number. In the lumbar and sacral segments, anterior and posterior roots were partially demyelinated. Degeneration in the thalamus and reticulotegmental nucleus of the pons has also been reported [Rüb et al 2003, Rüb et al 2004, Rüb et al 2005]. In addition, Orozco et al [1989] noted severe gyral atrophy, most prominent in the frontotemporal lobes. The cerebral cortex was thinned, but without neuronal rarefaction. The cerebral white matter was atrophic and gliotic. Degeneration in the pallidonigroluysian system mainly involved the substantia nigra. One brain showed patchy loss in parts of the third-nerve nuclei. Adams et al [1997] reported similar findings in one individual. Seidel et al [2017] studied the distribution of polyQ aggregates in brain stem sections of individuals with SCA2 and found that cytoplasmic aggregates correlated with disease severity. An affected individual with white matter pathology has been described [Armstrong et al 2005]. Nerve biopsy has shown moderate loss of large myelinated fibers [Filla et al 1995]. ### Genotype-Phenotype Correlations Probands. In general, a clear inverse correlation exists between age of onset and CAG repeat length. However, repeat length cannot predict age of onset or disease severity in an individual. About 50% of age-of-onset variance is not explained by CAG repeat length [Figueroa et al 2017]. * The widest range of age of onset is observed among individuals with fewer than 40 CAG repeats. Some individuals with alleles of 33 and 34 repeats have had onset after age 60 years. In one study, the presence of 37 repeats was associated with ages of onset ranging from 20 to 60 years [Pulst et al 1996]. * For larger repeat sizes, the variability in age of onset is less; repeat sizes greater than 45 are almost always associated with disease onset before age 20 years [Imbert et al 1996, Pulst et al 1996, Sanpei et al 1996, Cancel et al 1997, Geschwind et al 1997b, Riess et al 1997, Moretti et al 2004]. Homozygosity for expanded ATXN2 alleles (2 alleles in the pathogenic range) does not appear to influence age of onset [Sanpei et al 1996]. At-risk individuals. The age of onset, severity, specific symptoms, and progression of the disease are variable and cannot be predicted by the family history or by molecular genetic (DNA) testing. ### Penetrance See Establishing the Diagnosis, Allele sizes and Genotype-Phenotype Correlations. ### Anticipation Anticipation (i.e., an increase in the severity of the phenotype and earlier age of onset in later generations) has been observed in SCA2. The tendency of the ATXN2 CAG repeat to expand as it is transmitted provides a biologic explanation for the earlier age of onset in subsequent generations. Paternal transmission of alleles with full penetrance or reduced penetrance is most likely to demonstrate meiotic instability and result in anticipation, although large expansions can also be seen in maternally inherited alleles [Figueroa et al 2017]. In one case report, a man who had 43 repeats and onset of symptoms at age 22 years had an infant with apnea, hypotonia, and dysphagia and an allele of 202 CAG repeats [Babovic-Vuksanovic et al 1998]. Mao et al [2002] identified large expansions in four individuals using a Southern blot assay. ### Nomenclature Terms used in the past for SCA2 and other hereditary ataxias include Marie's ataxia, OPCA, and forme fruste of Friedreich ataxia. These terms are no longer in use. ### Prevalence Geschwind et al [1997b] found that in an ethnically varied population in the University of California Los Angeles ataxia clinic, SCA2 accounted for 13% of the autosomal dominant cerebellar ataxias (ADCAs) compared with 6% for SCA1 and 23% for SCA3. A similar percentage (15%) was reported by Cancel et al [1997] in 184 families from an ethnically and geographically diverse population. In the Baylor College of Medicine ataxia clinic, SCA2 was the most common ADCA (18%) [Lorenzetti et al 1997]. Moseley et al [1998] reported that SCA2 was common in individuals presenting to an ataxia clinic at an academic medical center, representing 15% of persons from families with autosomal dominant inheritance and 2% of simplex cases (i.e., a single occurrence in a family) [Moseley et al 1998]. In a large series from several ataxia clinics in Germany, SCA2 represented 14% of ADCA pedigrees [Riess et al 1997]. SCA2 is the most common type of ADCA in Korea [Lee et al 2003]. (See also Hereditary Ataxia Overview.) ## Differential Diagnosis It is difficult and often impossible to distinguish spinocerebellar ataxia type 2 (SCA2) from the other hereditary ataxias (see Hereditary Ataxia Overview). The differential diagnosis should also include Parkinson disease and acquired causes of cerebellar ataxia. SCA2-related ATXN2 pathogenic variants should be in the differential diagnosis of adult-onset sporadic progressive ataxia, multiple system atrophy (MSA, Shy-Drager syndrome; OMIM 146500), L-dopa-responsive parkinsonism, atypical Friedreich ataxia [Abele et al 2002], and amyotrophic lateral sclerosis [Neuenschwander et al 2014]. ### Table 2. Proportion of Individuals with SCA2 Manifesting Phenotypic Features Compared with Individuals with SCA1, SCA3, and SCA6 View in own window Phenotypic FeatureSCA2SCA1SCA3SCA6 Cerebellar dysfunction100%100%100%100% Reduced saccadic velocity71%-92%50%10%0%-6% Myoclonus0%-40%0%4%0% Dystonia or chorea0%-38%20%8%0%-25% Pyramidal involvement29%-31%70%70%33%-44% Peripheral neuropathy44%-94%100%80%16%-44% Intellectual impairment31%-37%20%5%0% Percentages modified from Geschwind et al [1997a], Geschwind et al [1997b], Schöls et al [1997a], and Schöls et al [1997b] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with spinocerebellar ataxia type 2 (SCA2), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Neurologic examination * Ophthalmologic examination * Baseline assessment of cognition * Neuroimaging * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Management of individuals remains supportive as no known therapy to delay or halt the progression of the disease exists. Although neither exercise nor physical therapy has been shown to stem the progression of incoordination or muscle weakness, individuals should maintain activity. Canes and walkers help prevent falls. Modification of the home with such conveniences as grab bars, raised toilet seats, and ramps to accommodate motorized chairs may be necessary. Speech therapy and communication devices such as writing pads and computer-based devices may benefit those with dysarthria. Weighted eating utensils and dressing hooks help maintain a sense of independence. When dysphagia becomes troublesome, video esophagrams can identify the consistency of food least likely to trigger aspiration. Improvement of severe tremor with thalamic stimulation has been reported in one individual [Pirker et al 2003]. Another individual showed improvement with stimulation of the subthalamic nucleus [Freund et al 2007]. The American Academy of Neurology has developed guidelines for the treatment of motor dysfunction in patients with ataxia [Zesiewicz et al 2018]. ### Prevention of Secondary Complications No dietary factor has been shown to curtail symptoms; however, vitamin supplements are recommended, particularly if caloric intake is reduced. Weight control is important because obesity can exacerbate difficulties with ambulation and mobility. ### Surveillance Affected individuals should be examined at least annually by a physician experienced in movement disorders and ataxia. ### Agents/Circumstances to Avoid Alcohol and medications known to affect cerebellar function should be avoided. ### 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. ### Other Tremor-controlling drugs do not work well for cerebellar tremors. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Spinocerebellar Ataxia Type 2	c0752121	28,972	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1275/	2021-01-18T20:55:44	{"mesh": ["D020754"], "synonyms": ["SCA2"]}
Ribosomopathies are diseases caused by abnormalities in the structure or function of ribosomal component proteins or rRNA genes, or other genes whose products are involved in ribosome biogenesis.[1][2][3] ## Contents * 1 Ribosomes * 2 Diseases * 2.1 Diamond–Blackfan anemia * 2.2 Dyskeratosis congenita * 2.3 Shwachman–Diamond syndrome * 2.4 5q- myelodysplastic syndrome * 2.5 Treacher Collins syndrome * 2.6 Cartilage–hair hypoplasia * 2.7 North American Indian childhood cirrhosis * 2.8 Isolated congenital asplenia * 2.9 Bowen–Conradi syndrome * 2.10 Other * 2.10.1 Familial colorectal cancer type X * 3 p53 * 4 Cancer * 5 References ## Ribosomes[edit] Ribosomes are essential for protein synthesis in all living organisms. Prokaryotic and eukaryotic ribosomes both contain a scaffold of ribosomal RNA (rRNA) on which are arrayed an extensive variety of ribosomal proteins (RP).[4] Ribosomopathies can arise from abnormalities of either rRNA or the various RPs. The nomenclature of rRNA subunits is derived from each component's Svedberg unit, which is an ultracentrifuge sedimentation coefficient, that is affected by mass and also shape. These S units of the rRNA subunits cannot simply be added because they represent measures of sedimentation rate rather than of mass. Eukaryotic ribosomes are somewhat larger and more complex than prokaryotic ribosomes. The overall 80S eukaryotic rRNA structure is composed of a large 60S subunit (LSU) and a small 40S subunit (SSU).[5] In humans, a single transcription unit separated by 2 internally transcribed spacers encodes a precursor, 45S. The precursor 45S rDNA is organized into 5 clusters (each has 30-40 repeats) on chromosomes 13, 14, 15, 21, and 22. These are transcribed in the nucleolus by RNA polymerase I. 45S is processed in the nucleus via 32S rRNA to 28S[6] and 5.8S,[7] and via 30S to 18S,[8] as shown in the diagram. 18S is a component of the ribosomal 40S subunit. 28S, 5.8S and 5S,[9] which is transcribed independently, are components of 60S. The 5S DNA occurs in tandem arrays (~200-300 true 5S genes and many dispersed pseudogenes); the largest is on chromosome 1q41-42. 5S rRNA is transcribed by RNA polymerase III.[5] It is not fully clear why rRNA is processed in this way rather than being directly transcribed as mature rRNA, but the sequential steps may have a role in the proper folding of rRNA or in subsequent RP assembly. The products of this processing within the cell nucleus are the four principal types of cytoplasmic rRNA: 28S, 5.8S, 18S, and 5S subunits.[10]:291 and (cite)(cite) (Mammalian cells also have 2 types of mitochondrial rRNA molecules, 12S and 16S.) In humans, as in most eukaryotes, the 18S rRNA is a component of 40S ribosomal subunit, and the 60S large subunit contains three rRNA species (the 5S, 5.8S and 28S in mammals, 25S in plants). 60S rRNA acts as a ribozyme, catalyzing peptide bond formation, while 40S monitors the complementarity between tRNA anticodon and mRNA. ## Diseases[edit] Abnormal ribosome biogenesis is linked to several human genetic diseases. Ribosomopathy has been linked to skeletal muscle atrophy,[11] and underpins most Diamond–Blackfan anemia (DBA),[2] the X-linked subtype of dyskeratosis congenita (DKCX),[12][13] Treacher Collins syndrome (TCS),[2][14] Shwachman–Diamond syndrome (SDS)[15] and 5q- myelodysplastic syndrome.(5q- MDS),(cite)(cite) North American Indian childhood cirrhosis (NAIC),[16] isolated congenital asplenia (ICAS),[16][17][18][19] and Bowen–Conradi syndrome (BWCNS), CHARGE syndrome[20][21][22][23] and ANE syndrome (ANES).[24] The associated chromosome, OMIM genotype, phenotype, and possible disruption points are shown: Ribosomopathies name chromosome genotype[25] phenotype protein disruption(cite)(cite) DBA1[25] 19q13.2 603474 105650 RPS19 30S to 18S[10]:291(cite) DBA2 8p23-p22 unknown 606129 DBA3 10q22-q23 602412 610629 RPS24[26] 30S to 18S[10]:291(cite) DBA4 15q 180472 612527 RPS17[27] 30S to 18S[10]:291 DBA5 3q29-qter 180468 612528 RPL35A[28] 32S to 5.8S/28S[10]:291(cite) DBA6 1p22.1 603634 612561 RPL5[29] 32S to 5.8S/28S[10]:291 DBA7 1p36.1-p35 604175 612562 RPL11[29] 32S to 5.8S/28S[10]:291 DBA8 2p25 603658 612563 RPS7[29] 30S to 18S[10]:291 DBA9 6p 603632 613308 RPS10[25] 30S to 18S[30] DBA10 12q 603701 613309 RPS26 30S to 18S[31] DBA11 17p13 603704 614900 RPS26 30S to 18S[31] DBA12 3p24 604174 615550 RPL15 45S to 32S[32] DBA13 14q 603633 615909 RPS29 DKCX Xq28 300126 305000 dyskerin associated with both H/ACA small nucleolar RNA (snoRNA) and with the RNA component of TERC[33] TCS 5q- 5q33.1 130620 153550 RPS14 30S to 18S[10]:291 SDS 7q11.21 607444 260400 SBDS 60S to 80S[10]:291 CHH 9p13.3 157660 250250 RMRP mitochondrial RNA processing NAIC 16q22.1 607456 604901 cirhin partial loss of interaction between cirhin and NOL11[34] ICAS 3p22.1 150370 271400 RPSA BWCNS 12p13.31 611531 211180 EMG1 18S to 40S CHARGE 8q12.1-q12.2; also 7q21.11 608892 214800 CHD7; also SEMA3E ACES xxx xxx RBM28 Several ribosomopathies share features such as inherited bone marrow failure, which is characterized a reduced number of blood cells and by a predisposition to cancer.[5] Other features can include skeletal abnormalities and growth retardation.[16] However, clinically these diseases are distinct, and do not show a consistent set of features.[16] ### Diamond–Blackfan anemia[edit] With the exception of rare GATA1 genotypes,(cite) Diamond–Blackfan anemia (DBA) arises from a variety of mutations that cause ribosomopathies.[35] ### Dyskeratosis congenita[edit] The X-linked subtype of dyskeratosis congenita (DKCX) ### Shwachman–Diamond syndrome[edit] Shwachman–Diamond syndrome (SDS) is caused by bi-allelic mutations in the SBDS protein that affects its ability to couple GTP hydrolysis by the GTPase EFL1 to the release of eIF6 from the 60S subunit.[36] Clinically, SDS affects multiple systems, causing bony abnormalities, and pancreatic and neurocognitive dysfunction.[37] SBDS associates with the 60S subunit in human cells and has a role in subunit joining and translational activation in yeast models. ### 5q- myelodysplastic syndrome[edit] 5q- myelodysplastic syndrome (MDS)[37] is associated with acquired haplo-insufficiency of RPS14,[38] a component of the eukaryotic small ribosomal subunit (40S).[5] RPS14 is critical for 40S assembly, and depletion of RPS14 in human CD34(+) cells is sufficient to recapitulate the 5q- defect of erythropoiesis with sparing of megakaryocytes.[5] ### Treacher Collins syndrome[edit] Treacher Collins syndrome (TCS) ### Cartilage–hair hypoplasia[edit] Cartilage–hair hypoplasia (CHH) - some sources list confidently as ribosomopathy, others question[citation needed] ### North American Indian childhood cirrhosis[edit] Main article: North American Indian childhood cirrhosis NAIC is an autosomal recessive abnormality of the CIRH1A gene, which codes for cirhin. Neonatal jaundice advances over time to biliary cirrhosis with severe liver fibrosis. ### Isolated congenital asplenia[edit] Main article: Isolated congenital asplenia ### Bowen–Conradi syndrome[edit] Main article: Bowen–Conradi syndrome Bowen–Conradi syndrome (BCS[39] or BWCNS[40]) is an autosomal recessive abnormality of the EMG1 gene, which plays a role in small ribosomal subunit (SSU) assembly.[39][41][42] Most affected children have been from North American Hutterite families, but BWCNS can affect other population groups.[40][43] Skeletal dysmorphology is seen[40][43] and severe prenatal and postnatal growth failure usually leads to death by one year of age.[44] ### Other[edit] #### Familial colorectal cancer type X[edit] Unlike the mutations of the 5 genes associated with DNA mismatch repair, which are associated with Lynch syndrome with hereditary nonpolyposis colorectal cancer (HNPCC) due to microsatellite instability, familial colorectal cancer (CRC) type X (FCCX) gives rise to HNPCC despite microsatellite stability.[45] FCCX is most likely etiologically heterogeneous but RPS20 may be implicated in some cases.[45] ## p53[edit] The p53 pathway is central to the ribosomopathy phenotype.[46] Ribosomal stress triggers activation of the p53 signaling pathway.[47][48] ## Cancer[edit] Cancer cells have irregularly shaped, large nucleoli, which may correspond ribosomal gene transcription up-regulation, and hence high cell proliferation. Oncogenes, like c-Myc, can upregulate rDNA transcription in a direct and indirect fashion. Tumor suppressors like Rb and p53, on the other hand, can suppress ribosome biogenesis. Additionally, the nucleolus is an important cellular sensor for stress and plays a key role in the activation of p53. Ribosomopathy has been linked to the pathology of various malignancies.[46] Several ribosomopathies are associated with an increased rate of cancer. For example, both SDS and 5q- syndrome lead to impaired hematopoiesis and a predisposition to leukemia.[37] Additionally, acquired defects in ribosomal proteins that have not been implicated in congenital ribosomopathies have been found in T-lymphoblastic leukemia/lymphoma, stomach cancer and ovarian cancer.[3] New cancer therapies might therefore target ribosome biogenesis specifically. As of 2014, two experimental agents inhibit RNA polymerase I by disrupting the rDNA promoter complex: CX-5461 activates p53 via nuclear stress and induces apoptosis of leukemia and lymphoma cells while leaving normal cells unharmed; BMH-21, inhibits rDNA transcription and induces nucleolar capping or nucleolar reorganization. This nucleolar stress eventually causes decreased cell proliferation and death. It also activates p-53 but p-53 activation was not required for the drug to be effective. The promise of these drugs is that they leave healthy cell DNA unharmed and specifically target the fact that cancer cells rely heavily on ribosome biogenesis. It has been said that ribosome biogenesis is the “Achilles heel in cancer cells.” [49] ## References[edit] 1. ^ Nakhoul H, Ke J, Zhou X, et al. (2014). "Ribosomopathies: Mechanisms of disease". Clinical Medicine Insights: Blood Disorders. 7: 7–16. doi:10.4137/CMBD.S16952. PMC 4251057. PMID 25512719. 2. ^ a b c Narla A, Ebert B. L. (2010). 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[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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Ribosomopathy	None	28,973	wikipedia	https://en.wikipedia.org/wiki/Ribosomopathy	2021-01-18T18:48:47	{"wikidata": ["Q23807991"]}
Paroxysmal kinesigenic dyskinesia (PKD) is a form of paroxysmal dyskinesia (see this term), characterized by recurrent brief involuntary hyperkinesias, such as choreoathetosis, ballism, athetosis or dystonia, triggered by sudden movements. ## Epidemiology The prevalence is estimated to be 1/150,000 worldwide. PKD is the most common form of paroxysmal dyskinesia. Males are more commonly affected than females (sex ratio of 3 or 4 to 1) in the sporadic form. ## Clinical description The age of disease onset is typically in childhood or adolescence with a peak in puberty. PKD is triggered by a sudden movement from rest (such as rising from a chair or starting to walk, or by exercise) and is characterized by brief attacks of dystonia, chorea or athetosis movements preceded by aura (that usually last less than 1 min), without alteration of consciousness. Attacks are often unilateral, but can alternate or be bilateral, and their frequency is variable. Some patients have additional neurologic disorders such as benign familial infantile epilepsy (BFIE) (see this term). Infantile convulsion and choreoathetosis (ICCA; see this term) is considered to be a variable form of PKD. ## Etiology The exact etiology of PKD is still unknown but the PRRT2 (proline-rich transmembrane protein 2) gene (16p11.2) is believed to be the major causative gene. The PRRT2 gene encodes a protein that is hypothesized to interact with the SNAP25 protein which plays a role in presynaptic neurotransmitter release. It has been postulated that mutations in PRRT2 lead to a reduction of SNAP25 resulting in the dysregulation of neurotransmitter release, thus causing the symptoms seen in PKD. ## Diagnostic methods The clinical diagnosis of PKD relies on the following proposed criteria: (1) identification of kinesigenic trigger of the attacks; (2) short duration of attacks (<1min); (3) no loss of consciousness or pain during attacks; (4) exclusion of other organic diseases and normal neurologic examination in the case of primary PKD; (5) control of attacks with phenytoin or carbamazepine, if attempted; and (6) age of onset between 1 year and 20 years, if no family history of PKD. Moreover, molecular genetic screening of the PRRT2 gene may help to confirm the diagnosis. ## Differential diagnosis The differential diagnosis of PKD includes paroxysmal non-kinesigenic dyskinesia, juvenile myoclonic epilepsy, hyperekplexia, episodic ataxia, autosomal dominant nocturnal frontal lobe epilepsy, encephalopathy due to GLUT1 deficiency (see these terms) and shuddering attacks. ## Genetic counseling More than 60% of the patients with PKD have a family history of a similar disorder. PKD is mainly a familial disorder with autosomal dominant inheritance and incomplete penetrance, but sporadic cases occur. Individuals with onset before 20 years of age, and having a positive family history, should be screened for PRRT2 mutations. ## Management and treatment Attacks are suppressed or dramatically reduced by low-dose anticonvulsant medication such as carbamazepine or phenytoin. Moreover, treatment based on caffeine citrate, that may help to reduce the severity and frequency of attacks, has been described in a single case report. ## Prognosis The prognosis of PKD is usually favorable, with improvement of the attacks and even remission in adulthood. A gender difference in prognosis is also observed, with woman having a better prognosis and a higher chance of complete remission. An improvement of attacks can also be observed during pregnancy. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Paroxysmal kinesigenic dyskinesia	c1868682	28,974	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98809	2021-01-23T18:45:20	{"gard": ["8721"], "omim": ["128200", "611031"], "umls": ["C1868682"], "icd-10": ["G24.8"], "synonyms": ["Familial PKD", "Familial paroxysmal kinesigenic dyskinesia", "Paroxysmal kinesigenic choreathetosis"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant vitreoretinochoroidopathy (VRCP) is caused by heterozygous mutation in the bestrophin-1 gene (BEST1; 607854) on chromosome 11q12. Clinical Features Under the designation autosomal dominant vitreoretinochoroidopathy (ADVIRC), Kaufman et al. (1982) described a seemingly 'new' fundus dystrophy characterized by chorioretinal hypopigmentation and hyperpigmentation, usually lying between the vortex veins and the ora serrata for 360 degrees. In this zone, a discrete posterior boundary, preretinal punctate white opacities, retinal arteriolar narrowing and occlusion, and, in some cases, choroidal atrophy are found. Most affected persons in the 1 kindred observed by Kaufman et al. (1982) had diffuse retinal vascular incompetence, cystoid macular edema, and presenile cataracts. Fibrillar condensation and a moderate pleocytosis characterized the vitreous. Progression was very slow. Electroretinogram was normal in younger affected persons and only moderately abnormal in older ones. Preretinal neovascularization was progressive in the proband. No systemic or skeletal abnormalities, high myopia, optically empty vitreous lattice degeneration, areas of white-without-pressure, retinal breaks or retinal detachment were found in any to point to a previously delineated entity. Blair et al. (1984) described a second family with this disorder. Affected persons in 3 generations and male-to-male transmission confirmed autosomal dominant inheritance (although the authors pointed out that the changes were minimal in the father and paternal grandmother and 'possibly could be nonspecific'). Traboulsi and Payne (1993) described a third family with ADVIRC in which 13 members of 5 generations were affected. Visual acuity was 20/25 or better in all but 1 patient. All affected individuals had vitreous liquefaction with or without peripheral vitreal condensations. Peripheral pigmentary changes and choroidal atrophy were characteristic. Cataracts developed in 6 patients in their early forties and required extraction. One patient had glaucoma, 1 developed a retinal detachment, and 1 had a spontaneous vitreous hemorrhage. One instance of male-to-male transmission was observed. In a 70-year-old affected member of the pedigree described by Traboulsi and Payne (1993), Oh and Vallar (2006) found evidence of central cone dysfunction. The patient had normal full-field electroretinography (ERG) but focally reduced macular multifocal ERG. Ocular coherence tomography showed thinning of the fovea and perifoveal region of both eyes. Hermann (1958) reported a French family with microphthalmia in 13 members of 4 generations. Six of the affected individuals also had pigmentary retinopathy, 5 had cataract (peripheral opacities as well as sutural and posterior polar), and 4 had glaucoma. The author noted that several individuals had dyschromatopsia, and nystagmus and strabismus were also observed in this family. No extraocular abnormalities were mentioned. Francois et al. (1993) examined 28 members of the family originally described by Hermann (1958), in which the 4 major features of microcornea, vitreoretinochoroidopathy, glaucoma, and cataract segregated in an autosomal dominant fashion. Francois et al. (1993) provided a detailed description of an affected woman, her 2 daughters, and the 2 affected children of 1 of the daughters: all 5 patients had bilateral microcornea and circumferential peripheral retinopathy involving pigmentary clumping and whitish dots, with atrophy around the optic disc extending to the macula; the 3 youngest patients had a whitish equatorial demarcation line bordering the retinopathy. The 2 oldest patients also had bilateral cataract and glaucoma, and the 65-year-old mother had bilateral microphthalmia and posterior staphyloma. Lafaut et al. (2001) examined 12 affected and 4 unaffected members of a 3-generation Belgian family segregating autosomal dominant vitreoretinochoroidopathy. Characteristic annular peripheral pigmentary changes were present in all affected members, as well as chorioretinal atrophy varying from a tigroid appearance to marked atrophy. Seven patients had a fibrillary vitreous, although vitreal cells were seen in only 3 patients. Six patients developed premature cataracts. Four patients had microcornea and shallow anterior chamber without microphthalmia (although the reported axial length of the right eye of 1 of those 4 patients was 21.0 mm, and the axial lengths of 3 eyes in 2 other affected family members measured 21.2 mm, 21.9 mm, and 21.5 mm). Two patients developed acute angle-closure glaucoma at ages 64 and 45 years, and another developed subacute angle-closure glaucoma at age 35 years. Visual fields tended to constrict concentrically with age. Electrooculography was abnormal in the 10 affected family members tested and normal in 4 unaffected family members. ERG findings were variable: low-normal to normal rod and cone responses were found in 6 younger patients, whereas 3 older patients had mild to moderate reduction of cone and rod responses with near-normal latencies. Two patients, aged 37 and 61 years, had severely reduced rod and cone responses with moderately increased latencies; they were also the only patients who had extensive midperipheral and macular chorioretinal atrophy. Lafaut et al. (2001) concluded that the presentation of VRCP is variable and may be associated with microcornea, shallow anterior chamber, and angle-closure glaucoma. Reddy et al. (2003) described 6 patients from a 3-generation English family with a complex developmental disorder of the eye, typically involving night blindness during the second decade of life and poor vision due to cataracts before age 30 years, with cataract surgery required in the second or third decade. Older individuals had poor vision (ranging from no light perception to 20/400) while younger individuals retained good visual acuities (20/30). All individuals had small corneas, and 2 older individuals had chronic angle closure glaucoma. Younger individuals had pulverulent-like cataracts and moderate myopia; the older patients were aphakic due to previous cataract surgery. All affected members had retinal abnormalities consisting of peripheral retinal pigment epithelium atrophy and retinal pigmentation. In addition, there was evidence of a posterior staphyloma in 9 of 12 eyes; in younger individuals, there was a clear-cut demarcation line possibly related to the boundary of the staphyloma, anterior to which there was retinal pigmentation. Although clinical examination showed some features consistent with a diagnosis of nanophthalmos, patients did not have consistently reduced axial lengths: ultrasonography revealed eye sizes within the normal range except in the 3 eyes without staphyloma, which had axial lengths of 18.73 mm, 16.63 mm, and 16.44 mm. The ERG was extinguished in 2 older family members, and subnormal photopic and scotopic responses were demonstrated in a mother and her 2 children, 1 of whom had reduced scotopic responses compared to the photopic responses. No systemic disease or abnormality was identified as segregating with the retinal disease. Reddy et al. (2003) designated the phenotype in this family 'MRCS,' for microcornea, rod-cone dystrophy, cataract, and posterior staphyloma. Michaelides et al. (2006) described a 12-year-old boy with MRCS who had high myopia, astigmatism, poor visual acuity (20/200 in his left eye and detecting only hand movements with his right eye), and pulverulent-like cataracts bilaterally. Direct questioning elicited a history of problems with night vision. Examination showed bilateral microcornea, peripheral retinal atrophy, and hyperpigmentation of the retinal pigment epithelium. ERG testing revealed generalized retinal dysfunction, with rods and cones approximately equally affected. Ultrasonography showed bilateral posterior staphyloma nasal to the optic nerve head. Both parents had a normal ocular examination and there was no family history of eye disease. In an affected sister and brother from a family with genetically confirmed ADVIRC, Burgess et al. (2009) described the proband with the typical phenotype involving a developmental anomaly of the anterior segment predisposing to angle closure glaucoma, early adult-onset cataract, and the typical fundus appearance of a broad post-oral circumferential band of atrophy and pigmentation. Her brother had a milder phenotype but also had the typical peripheral retinal abnormality. Mapping In a 3-generation English family with microcornea, rod-cone dystrophy, cataract, and posterior staphyloma, Reddy et al. (2003) performed PCR-based microsatellite marker genotyping using a positional candidate gene approach; they excluded linkage to other candidate microphthalmia loci and found suggestive linkage, with a maximum lod score of 2.01, to a region on 11q13 within the nanophthalmos-1 (NNO1; 600165) genetic interval. In the then 4-generation Belgian family with a combined vitreous and retinal phenotype, originally reported by Lafaut et al. (2001), Yardley et al. (2004) found linkage to chromosome 11, with a maximum lod score of 3.26 at markers D11S4152 and D11S4200. Haplotype analysis using microsatellite markers narrowed the critical region to a 38-cM to 73-cM interval between D11S4152 and D11S4139, overlapping the putative loci for NNO1 and the MRCS phenotype. Molecular Genetics Yardley et al. (2004) noted that both the Belgian family reported by Lafaut et al. (2001) and the English family reported by Reddy et al. (2003) had pathologically low electrooculograms, a clinical finding also seen in vitelliform macular dystrophy (VMD; 153700) caused by mutation in the BEST1 gene (607854), which lies within the critical region of linkage for both families. Yardley et al. (2004) therefore sequenced the BEST1 gene in those 2 families and 3 others that also had autosomal dominant developmental eye abnormalities associated with retinal dystrophy, including a 6-generation French family with vitreoretinochoroidopathy, microcornea, glaucoma, and cataract originally reported by Hermann (1958), and identified 3 different heterozygous mutations, respectively (607854.0019-607854.0021). In an affected sister and brother from a family with ADVIRC, Burgess et al. (2009) identified heterozygosity for a missense mutation in the BEST1 gene (607854.0026). Heterogeneity In a 12-year-old boy with microcornea, retinal dystrophy, cataract, and posterior staphyloma, Michaelides et al. (2006) failed to identify disease-causing sequence variants in the BEST1 gene, suggesting genetic heterogeneity. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Night blindness onset during teen years \- Cataracts, pulverulent \- Microphthalmia (some) \- Dyschromatopsia (some) \- Vitreoretinochoroidopathy \- Punctate white opacities in the retina \- Vitreous fibrillar condensation \- Breakdown of the blood retinal barrier with retinal neovascularization \- Fundus dystrophy \- Peripheral retinal pigment epithelium atrophy \- Retinal pigmentation anterior to boundary of the staphyloma in younger patients \- Pigmentary retinopathy throughout the posterior pole and into the staphyloma in older individuals \- Posterior staphyloma in most eyes \- Reduced axial length (nanophthalmos) if no staphyloma \- Microcornea \- Glaucoma, chronic angle-closure, in older patients LABORATORY ABNORMALITIES \- Reduced electroretinogram (scotopic > photopic) becoming extinguished in older patients MOLECULAR BASIS \- Caused by mutation in the bestrophin 1 gene (BEST1, 607854.0020 ) ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	VITREORETINOCHOROIDOPATHY	c2674009	28,975	omim	https://www.omim.org/entry/193220	2019-09-22T16:31:57	{"mesh": ["C536352"], "omim": ["193220"], "orphanet": ["263347", "3086"], "synonyms": ["Alternative titles", "VITREORETINOCHOROIDOPATHY, AUTOSOMAL DOMINANT", "VITREORETINOCHOROIDOPATHY WITH MICROCORNEA, GLAUCOMA, AND CATARACT", "VITREORETINOCHOROIDOPATHY, AUTOSOMAL DOMINANT, WITH NANOPHTHALMOS"]}
proposed neurological condition Misophonia Other namesselective sound sensitivity syndrome,[1] select sound sensitivity syndrome, sound-rage[2][3] SpecialtyPsychiatry Misophonia, meaning "hatred of sound", is a proposed neurological condition in which certain sounds trigger emotional or physiological responses others may deem unreasonable.[4] Reactions to trigger sounds range from anger and annoyance to activating a fight-or-flight response. The condition is sometimes called selective sound sensitivity syndrome. Common triggers include oral sounds (e.g., loud breathing, chewing, swallowing), clicking sounds (e.g., keyboard tapping, finger tapping, windshield wipers), and sounds associated with movement (e.g., fidgeting). Oftentimes, hated sounds are repetitive in nature. Although the condition was first proposed in 2000, it has yet to be considered a diagnosable condition. Misophonia is not classified as an auditory or psychiatric condition, and so is different from phonophobia (fear of sound); there are no standard diagnostic criteria, and there is little research on how common it is or the treatment. Proponents suggest misophonia can adversely affect the ability to achieve life goals and to enjoy social situations. As of 2019 there were no evidence-based methods to manage the condition. ## Contents * 1 Signs and symptoms * 2 Mechanism * 3 Diagnosis * 3.1 Classification * 4 Management * 5 Epidemiology * 6 Etymology * 7 Comparisons and associations with other phenomena * 8 Society and culture * 8.1 Notable cases * 9 See also * 10 References ## Signs and symptoms[edit] As of 2016[update] the literature on misophonia was limited.[2] Some small studies show that people with misophonia generally have strong negative feelings, thoughts, and physical reactions to specific sounds, which the literature calls "trigger sounds". These sounds usually appear quiet to others, but can seem loud to the person with misophonia, as if they can't hear anything except the sound. One study found that around 80% of the sounds were related to the mouth (e.g., eating, slurping, chewing or popping gum, whispering, whistling) and around 60% were repetitive. A visual trigger may develop related to the trigger sound,[2][5] and a misophonic reaction can occur in the absence of an actual sound.[2] More girls and women tend to have misophonia than boys and men.[4] Reactions to triggers can range from mild (anxiety, discomfort, and/or disgust) to severe (rage, anger, hatred, panic, fear, and/or emotional distress).[4] Reactions to the triggers can include aggression toward the origin of the sound, leaving, remaining in its presence but suffering, trying to block it or trying to mimic the sound.[5] The first misophonic reaction may occur when a person is young, often between the ages of 9 and 13,[4] and can originate from someone in a close relationship, or a pet.[5] Particularly severe cases of misophonia may result in violent impulses toward the source of the sound. One such case described in the journal Psychiatry and Clinical Psychopharmacology detailed 'involuntary violence' exhibited by a sufferer in response to a trigger in the form of another person eating loudly.[6] People with misophonia are aware they experience it and some consider it abnormal; the disruption it causes in their lives ranges from mild to severe.[5] Avoidance and other behaviors can make it harder for people with this condition to achieve their goals and enjoy interpersonal interactions.[3] ## Mechanism[edit] Misophonia's mechanism is not known, but it appears that, like hyperacusis, it may be caused by a dysfunction of the central auditory system in the brain and not of the ears.[2] The perceived origin and context of the sound appears to be essential to trigger a reaction.[2] A 2017 study found that the anterior insular cortex (which plays a role both in emotions like anger and in integrating outside input, such as sound, with input from organs such as the heart and lungs) causes more activity in other parts of the brain in response to triggers, particularly in the parts responsible for long-term memories, fear, and other emotions. It also found that people with misophonia have higher amounts of myelin (a fatty substance that wraps around nerve cells in the brain to provide electrical insulation). It is not clear whether myelin is a cause or an effect of misophonia and its triggering of other brain areas.[7][8] ## Diagnosis[edit] There are no standard diagnostic criteria,[5] and many doctors are unaware of this condition.[4] Misophonia is distinguished from hyperacusis, which is not specific to a given sound and does not involve a similar strong reaction, and from phonophobia, which is a fear of loud sounds,[5] but it may occur with either.[9] It is not clear whether people with misophonia usually have comorbid conditions, nor whether there is a genetic component.[5] It appears that misophonia can occur on its own or along with other health, developmental and psychiatric problems.[4] When attempting to diagnose a patient with misophonia, doctors sometimes mistake its symptoms for an anxiety disorder, bipolar disorder or obsessive-compulsive disorder.[4] ### Classification[edit] The diagnosis of misophonia is not recognized in the DSM-IV or the ICD 10, and it is not classified as a hearing or psychiatric disorder.[5] It may be a form of sound–emotion synesthesia, and has parallels with some anxiety disorders.[2] As of 2018 it was not clear whether misophonia should be classified as a symptom or as a condition.[3] ## Management[edit] Cognitive behavioral therapy As of 2018 there are no evidence-based treatments for the condition and no randomized clinical trial has been published; health care providers generally try to help people cope with misophonia by recognizing what the person is experiencing and working on coping strategies.[2][5] Some small studies have been published on the use of sound therapy similar to tinnitus retraining therapy and on cognitive behavioral therapy and particularly exposure therapy, to help people become less aware of the trigger sound.[2][3] None of these approaches has been sufficiently studied to determine its effectiveness.[3][10] ## Epidemiology[edit] The prevalence is not yet known; it is not known whether males or females, or older or younger people, are more likely to have misophonia.[2][5] The existence of several online support groups with thousands of members has been cited as possibly indicative of its prevalence.[11] ## Etymology[edit] "Misophonia" comes from the Greek words μίσος (IPA: /'misɔs/), meaning "hate", and φωνή (IPA: /fɔˈni/), meaning "voice", loosely translating to "hate of sound", and was coined by audiologists Pawel and Margaret Jastreboff in 2000 to differentiate the condition from other forms of decreased sound tolerance such as hyperacusis (hypersensitivity to certain frequencies and volume ranges) and phonophobia (fear of sounds).[3][10][12] ## Comparisons and associations with other phenomena[edit] Some people have sought to relate misophonia to ASMR (autonomous sensory meridian response, or auto-sensory meridian response), a pleasant form of paresthesia, a tingling sensation that typically begins on the scalp and moves down the back of the neck and upper spine. ASMR is described as the opposite of what can be observed in reactions to specific audio stimuli in misophonia.[citation needed] There are plentiful anecdotal reports of people who claim to have both misophonia and ASMR. Common to these reports is the experience of ASMR in response to some sounds, and misophonia in response to others.[13][14] ## Society and culture[edit] People who experience misophonia have formed online support groups.[15][11] In 2016, Quiet Please, a documentary about misophonia, was released.[16][17] In 2020, a team of misophonia researchers[18] received the Ig Nobel Prize in Medicine "for diagnosing a long-unrecognized medical condition: Misophonia, the distress at hearing other people make chewing sounds".[19] ### Notable cases[edit] * Barron Lerner[20] * Kelly Ripa[21] * Melanie Lynskey[22] * Kelly Osbourne[23] * Pat McAfee[24] ## See also[edit] * Stimulus control ## References[edit] 1. ^ Sanchez, TG (2017). "Familial misophonia or selective sound sensitivity syndrome : evidence for autosomal dominant inheritance?". Brazilian Journal of Otorhinolaryngology. 84 (5): 553–559. doi:10.1016/j.bjorl.2017.06.014. PMID 28823694. 2. ^ a b c d e f g h i j Bruxner, G (2016). "'Mastication rage': a review of misophonia—an under-recognised symptom of psychiatric relevance?". Australasian Psychiatry. 24 (2): 195–197. doi:10.1177/1039856215613010. PMID 26508801. S2CID 7106232. 3. ^ a b c d e f Cavanna AE, Seri S (August 2015). "Misophonia: current perspectives". Neuropsychiatr Dis Treat. 11: 2117–23. doi:10.2147/NDT.S81438. PMC 4547634. PMID 26316758. 4. ^ a b c d e f g "What Is Misophonia?". WebMD. Retrieved 1 September 2020. 5. ^ a b c d e f g h i j Duddy DF, Oeding KA (2014). "Misophonia: An Overview". Semin Hear. 35 (2): 084–091. doi:10.1055/s-0034-1372525. 6. ^ Tunç, Serhat (2017). "An extreme physical reaction in misophonia: stop smacking your mouth!". Psychiatry and Clinical Psychopharmacology. 27 (4): 416–418. doi:10.1080/24750573.2017.1354656. 7. ^ PhD, James Cartreine (21 April 2017). "Misophonia: When sounds really do make you "crazy"". Harvard Health Blog. 8. ^ Kumar, Sukhbinder; Tansley-Hancock, Olana; Sedley, William; Winston, Joel S.; Callaghan, Martina F.; Allen, Micah; Cope, Thomas E.; Gander, Phillip E.; Bamiou, Doris-Eva; Griffiths, Timothy D. (20 February 2017). "The Brain Basis for Misophonia". Current Biology. 27 (4): 527–533. doi:10.1016/j.cub.2016.12.048. ISSN 0960-9822. PMC 5321671. PMID 28162895. 9. ^ Jastreboff PJ, Jastreboff MM (2015). Decreased sound tolerance: hyperacusis, misophonia, diplacousis, and polyacousis. Handb Clin Neurol. Handbook of Clinical Neurology. 129. pp. 375–87. doi:10.1016/B978-0-444-62630-1.00021-4. ISBN 9780444626301. PMID 25726280. 10. ^ a b Cavanna, Andrea E. (1 April 2014). "What is misophonia and how can we treat it?". Expert Review of Neurotherapeutics. 14 (4): 357–359. doi:10.1586/14737175.2014.892418. ISSN 1744-8360. PMID 24552574. S2CID 36026220. 11. ^ a b Denys, Damiaan; Vulink, Nienke; Schröder, Arjan (23 January 2013). "Misophonia: Diagnostic Criteria for a New Psychiatric Disorder". PLOS ONE. 8 (1): e54706. Bibcode:2013PLoSO...854706S. doi:10.1371/journal.pone.0054706. ISSN 1932-6203. PMC 3553052. PMID 23372758. 12. ^ Jastreboff, Margaret M.; Jastreboff, Pawel J. (2001). "Components of decreased sound tolerance : hyperacusis, misophonia, phonophobia" (PDF). 13. ^ "ASMR and Misophonia: Sounds-Crazy!". Science in our world: certainty and controversy. Pennsylvania State University. 16 September 2015. 14. ^ Higa, Kerin (11 June 2015). "Technicalities of the Tingles: The science of sounds that feel good. #ASMR". Neuwrite. Retrieved 20 January 2016. 15. ^ Cohen, Joyce (5 September 2011). "When a Chomp or a Slurp is a Trigger for Outrage". The New York Times. Retrieved 5 February 2012. 16. ^ Jeffries, Adrianne (17 June 2016). "There's a New Film About Misophonia, Where People Get Enraged by Certain Sounds". Motherboard. Retrieved 18 September 2020. 17. ^ Garcy, Pamela D. (27 January 2016). "What Jeffrey S. Gould Can Teach Us about Misophonia". Psychology Today. 18. ^ Schröder A, Vulink N, Denys D (2013) Misophonia: Diagnostic Criteria for a New Psychiatric Disorder. PLoS ONE 8(1): e54706. https://doi.org/10.1371/journal.pone.0054706 19. ^ 2020 Ig Nobel Prizes 20. ^ Lerner, Barron H. (2 March 2015). "Please Stop Making That Noise". Well. New York Times. Retrieved 18 October 2016. 21. ^ Misophonia: Kelly Ripa Has Rare Disorder. 20/20. ABC News. 18 May 2012. Retrieved 18 October 2016. 22. ^ Bisley, Interview by Alexander (10 March 2015). "Melanie Lynskey on Togetherness, realism and 'radical' nudity". The Guardian. ISSN 0261-3077. Retrieved 30 June 2017. 23. ^ "Kelly Osbourne Has Misophonia". www.mirror.co.uk. 24. ^ "Pat McAFLEET on Twitter: "I have this thing called Misophonia where I can't listen to people chew. It's a real thing, I have to leave the room #PatMcAfeeShowLIVE"". twitter.com. 19 November 2020. 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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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Misophonia	c4324623	28,976	wikipedia	https://en.wikipedia.org/wiki/Misophonia	2021-01-18T19:05:40	{"gard": ["12058"], "wikidata": ["Q2054837"]}
Yim–Ebbin syndrome Other namesAmelia cleft lip palate hydrocephalus iris coloboma Yim–Ebbin syndrome is a congenital disorder characterized by the absence of arms, a cleft lip and palate, hydrocephalus, and an iris coloboma.[1] It was first described by Yim and Ebbin in 1982,[2] and later by Thomas and Donnai in 1994.[3] In 1996, a third case was reported by Froster et al. who suggested that the three cases were related and represented a distinct syndrome.[4] In 2000, a similar case was reported by Pierri et al.[5] It is also known as "amelia cleft lip palate hydrocephalus iris coloboma".[1] ## References[edit] 1. ^ a b "MeSH Supplementary Concept Data". MeSH. Retrieved 2011-11-05. 2. ^ A. J., D. K. C.; Ebbin (1982). "Bilateral brachial amelia with cleft lip and palate and hydrocephaly: case report 82". Syndrome Identification. 8: 3–5. 3. ^ Thomas, M.; Donnai, D. (1994). "Bilateral brachial amelia with facial clefts and holoprosencephaly". Clinical Dysmorphology. 3 (3): 266–269. doi:10.1097/00019605-199407000-00015. PMID 7981864. 4. ^ Froster, U. G.; Briner, J.; Zimmerman, R.; Huch, R.; Huch, A. (1996). "Bilateral brachial amelia, facial clefts, encephalocele, orbital cyst and omphalocele: a recurrent fetal malformation pattern coming into focus". Clinical Dysmorphology. 5 (2): 171–174. doi:10.1097/00019605-199604000-00010. PMID 8723568. 5. ^ Pierri, N. B.; Lecora, M.; Passariello, A.; Scala, I.; Andria, G. (2000). "New case of bilateral upper limb amelia, facial clefts, and renal hypoplasia". American Journal of Medical Genetics. 91 (2): 123–125. doi:10.1002/(SICI)1096-8628(20000313)91:2<123::AID-AJMG8>3.0.CO;2-N. PMID 10748410. ## External links[edit] * Yim–Ebbin syndrome at Online Mendelian Inheritance in Man Classification D * ICD-10: none * ICD-9-CM: none * OMIM: 601357 * MeSH: C536713 This genetic disorder 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Yim–Ebbin syndrome	c1832434	28,977	wikipedia	https://en.wikipedia.org/wiki/Yim%E2%80%93Ebbin_syndrome	2021-01-18T18:48:46	{"gard": ["388", "641"], "mesh": ["C536713"], "umls": ["C1832434"], "wikidata": ["Q17133302"]}
Simple (monoclonal) cryoglobulinemia or type I cryoglobulinemia refers to the presence in the serum of one isotype or subclass of immunoglobulin (Ig) that precipitates reversibly below 37°C. ## Epidemiology The prevalence is unknown. ## Clinical description This serological disorder is almost invariably associated with well-known hematological disorders, usually B-cell dyscrasias (multiple myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia; see these terms). Type I cryoglobulinemia is frequently asymptomatic per se but patients may develop acrocyanosis, retinal hemorrhage, Raynaud's phenomenon, and arterial thrombosis. These symptoms may be the expression of hyperviscosity syndrome due to high levels of monoclonal cryoglobulins. The cryoprecipitate in type I cryoglobulinemia is usually composed of IgG or IgM, but infrequent cases with IgA and very rarely monoclonal light-chain protein cryoprecipitation have been reported. Type I cryoglobulins lack rheumatoid factor activity (RF) and do not easily activate complement. ## Etiology The pathogenetic processes in simple cryoglobulinemia generally appear to be related to those of the underlying lymphoproliferative diseases. The mechanisms of cryoprecipitation are poorly understood but may be partially related to the structure of the component immunoglobulin heavy and light chains. ## Diagnostic methods Diagnosis is based on detection of cryoglobulins through blood sampling, clotting, and serum separation (carried out at 37°C), and cryoglobulin isolation and cryocrit determination (carried out at 4°C). Ig composition is commonly evaluated by simple diffusion on agarose gels or by immunoelectrophoresis (performed at 37°C to avoid precipitation and loss of cryoglobulins during the procedures). ## Differential diagnosis The principle differential diagnosis is mixed cryoglobulinemia (MC type II-III; see these terms). Type I cryoglobulinemia and MC type II-III are two distinct clinico-serological entities. In contrast to type I cryoglobulinemia, the cryoprecipitate in MC type II-III is composed ofimmune complexes containing polyclonal IgGs and mono- (type II) or polyclonal (type III) IgMs. Patients with simple cryoglobulinemia lack the typical vasculitic manifestations and serological findings (RF positivity and low complement C4) that characterize MC patients. Clinical course, treatment, and prognosis of type I cryoglobulinemia largely depend on the underlying disorder. Patients with a benign monoclonal gammopathy of undetermined significance are generally asymptomatic or present with a mild disorder. ## Management and treatment Plasma exchange treatment, with/without steroids and/or immunosuppressors, is beneficial for simple cryoglobulinemia patients presenting with clinically overt hyperviscosity syndrome. In patients with malignant B-cell neoplasias, the chemotherapy may lead to resolution of this serological manifestation. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Simple cryoglobulinemia	c4510006	28,978	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91139	2021-01-23T17:06:26	{"icd-10": ["D89.1"], "synonyms": ["Cryoglobulinemia type 1"]}
Southeast Asian ovalocytosis SpecialtyHematology Southeast Asian ovalocytosis is a blood disorder that is similar to, but distinct from hereditary elliptocytosis.[1] It is common in some communities in Malaysia and Papua New Guinea, as it confers some resistance to cerebral Falciparum Malaria.[2] ## Contents * 1 Pathophysiology * 1.1 Southeast Asian ovalocytosis * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Pathophysiology[edit] ### Southeast Asian ovalocytosis[edit] It is hereditary haemolytic anaemia in which the red blood cell is oval-shaped. The primary defect in SAO differs significantly from other forms of elliptocytosis in that it is a defect in the gene coding for a protein that is not directly involved in the cytoskeleton scaffolding of the cell. Rather, the defect lies in a protein known as the band 3 protein, which lies in the cell membrane itself. The band 3 protein normally binds to another membrane-bound protein called ankyrin, but in SAO this bond is stronger than normal. Other abnormalities include tighter tethering of the band 3 protein to the cell membrane, increased tyrosine phosphorylation of the band 3 protein, reduced sulfate anion transport through the cell membrane, and more rapid ATP consumption. These (and probably other) consequences of the SAO mutations lead to the following erythrocyte abnormalities:[3] * A greater robustness of cells to a variety of external forces, including: * Reduction in cellular sensitivity to osmotic pressures * Reduction in fragility related to temperature change * greater general rigidity of the cell membrane * Loss of sensitivity to substances that cause spiculation of cells * Reduced anion exchange Figure 3 - A representation of the steps involved in the entry of Plasmodium falciparum into an erythrocyte. * Partial intracellular depletion of ATP * A reduction in expression of multiple antigens These changes are thought to give rise to the scientifically and clinically interesting phenomenon that those with SAO exhibit: a marked in vivo resistance to infection by the causative pathogen of malaria, Plasmodium falciparum. Unlike those with the Leach phenotype of common hereditary elliptocytosis (see above), there is a clinically significant reduction in both disease severity and prevalence of malaria in those with SAO. Because of this, the 35% incidence rate of SAO along the north coast of Madang Province in Papua New Guinea, where malaria in endemic, is a good example of natural selection.[4] The reasons behind the resistance to malaria become clear when given an explanation the way in which Plasmodium falciparum invades its host. This parasite is an obligate intracellular parasite, which must enter the cells of the host it is invading. The band 3 proteins aggregate on the cell membrane at the site of entry, forming a circular orifice that the parasite squeezes through. These band 3 proteins act as receptors for the parasite. Normally a process much like endocytosis occurs, and the parasite is able to isolate itself from the intracellular proteins that are toxic to it while still being inside an erythrocyte (see figure 2). The increased rigidity of the erythrocyte membrane in SAO is thought to reduce the capacity of the band 3 proteins to cluster together, thereby making it more difficult for the malaria parasite to properly attach to and enter the cell. The reduced free ATP within the cell has been postulated as a further mechanism behind which SAO creates a hostile environment for Plasmodium falciparum. ## Diagnosis[edit] This section is empty. You can help by adding to it. (November 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (November 2017) ## See also[edit] * Hereditary elliptocytosis * Sickle-cell disease * List of hematologic conditions ## References[edit] 1. ^ Wrong, O; Bruce, LJ; Unwin, RJ; Toye, AM; Tanner, MJA (July 2002). "Band 3 mutations, distal renal tubular acidosis, and Southeast Asian ovalocytosis". Kidney International. 62 (1): 10–19. doi:10.1046/j.1523-1755.2002.00417.x. PMID 12081559. 2. ^ Allen, S. J.; Clegg, J. B.; Alpers, M. P.; Mgone, C. S.; Peto, T. E.; O'Donnell, A.; Weatherall, D. J.; Alexander, N. D. (1999). "Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3 -- Allen et al. 60 (6): 1056 -- American Journal of Tropical Medicine and Hygiene". The American Journal of Tropical Medicine and Hygiene. 60 (6): 1056–1060. doi:10.4269/ajtmh.1999.60.1056. PMID 10403343. 3. ^ Liu, S.C.; Palek, J; Nichols, PE; Derick, LH; Chiou, SS; Amato, D; Corbett, JD; Golan, DE (1 July 1995). "Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton". Blood. 86 (1): 349–58. doi:10.1182/blood.V86.1.349.bloodjournal861349. PMID 7795244. 4. ^ Mgone, Cs; Koki, G; Paniu, Mm; Kono, J; Bhatia, Kk; Genton, B; Alexander, Nd; Alpers, Mp (May 1996). "Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria endemicity in Papua New Guinea". Transactions of the Royal Society of Tropical Medicine and Hygiene. 90 (3): 228–31. doi:10.1016/S0035-9203(96)90223-0. ISSN 0035-9203. PMID 8758056. ## External links[edit] Classification D * ICD-10: D58.1 * ICD-9-CM: 282.1 * OMIM: 109270 * MeSH: C566230 * DiseasesDB: 9416 * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Southeast Asian ovalocytosis	c1862322	28,979	wikipedia	https://en.wikipedia.org/wiki/Southeast_Asian_ovalocytosis	2021-01-18T18:38:41	{"mesh": ["C566230"], "omim": ["166900"], "icd-9": ["282.1"], "icd-10": ["D58.1"], "orphanet": ["98868"], "synonyms": ["Hereditary ovalocytosis", "Melanesian elliptocytosis", "Melanesian ovalocytosis", "SAO", "Stomatocytic elliptocytosis"], "wikidata": ["Q3358864"]}
Pontocerebellar hypoplasia type 9 is a rare, genetic, subtype of non-syndromic pontocerebellar hypoplasia characterized by progressive cerebellum and brainstem atrophy, corpus callosum hypo-/aplasia and progressive post-natal microcephaly. Patients typically present profound global developmental delay, spastic tetraparesis, seizures, cortical visual impairment and, on neuroimaging, abnormal brain morphology that includes pontocerebellar hypoplasia, ''figure of 8'' midbrain appearance, and, more variably, interhemispheric cysts, ventriculomegaly and cerebral dysmyelination. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Pontocerebellar hypoplasia type 9	c4014354	28,980	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=369920	2021-01-23T17:19:48	{"omim": ["615809"], "icd-10": ["Q04.3"], "synonyms": ["PCH9"]}
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: "Perfume intolerance" – news · newspapers · books · scholar · JSTOR (February 2015) (Learn how and when to remove this template message) Perfume intolerance or perfume allergy is a condition wherein people exhibit sensitivity or allergic reactions to ingredients in some perfumes and some other fragrances. It is a form of multiple chemical sensitivity, a more general phenomenon for this diagnosis.[1] ## Symptoms[edit] Symptoms depend on each person's allergies and each perfume's or fragrance's ingredients. Symptoms may include allergic contact dermatitis, asthma attacks, headaches, and others.[2] The most common allergic reactions to perfume or fragrances added to products is contact dermatitis,[3][4] though other symptoms may occur, including allergic conjunctivitis.[5] Patch test The diagnosis of the causal allergen is made by patch testing with a mixture of fragrance ingredients, the fragrance mix. This gives a positive patch-test reaction in about 10% of tested patients with eczema, and the most recent estimates show that 1.7–4.1% of the general population are sensitized to ingredients of the fragrance mix. Two studies show that inhalant-like allergies and sensitivity/intolerances are experienced by a subset of the US population, in the form of asthma and chemical sensitivities. Results aggregated from both surveys found that 30.5% of the general population[6] reported scented products on others irritating, 19% reported adverse health effects from air fresheners, and 10.9% reported irritation by scented laundry products vented outside. Household products, such as soaps and detergents, perfume products, cosmetics, and other consumer goods, are estimated to use 2,500 different fragrance ingredients. Of those, approximately 100 different substances are known to elicit responses in at least some individuals. An estimated 1.7–4.1% of the general population shows a contact allergic response to a mix of common perfume ingredients.[7] The diagnosis is made by patch testing with a mixture of fragrance ingredients, the fragrance mix. This gives a positive patch-test reaction in about 10% of tested patients with eczema, and the most recent estimates show that 1.7–4.1% of the general population are sensitized to ingredients of the fragrance mix.[citation needed] Although products can be labeled "fragrance-free", many still contain lesser-known fragrance chemicals that consumers may not recognize.[8] Cinnamaldehyde (cinnamic aldehyde) is a common fragrance allergen.[3][9] ## References[edit] 1. ^ Sorg, Barbara A. (1999). "Multiple Chemical Sensitivity: Potential Role for Neural Sensitization". Critical Reviews in Neurobiology. 13 (3): 283–316. doi:10.1615/CritRevNeurobiol.v13.i3.30. PMID 10803638. 2. ^ Dodson, Robin E.; Nishioka, Marcia; Standley, Laurel J.; Perovich, Laura J.; Brody, Julia Green; Rudel, Ruthann A. (2012). "Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products". Environmental Health Perspectives. 120 (7): 935–943. doi:10.1289/ehp.1104052. PMC 3404651. PMID 22398195. 3. ^ a b Saiyasombati, Penpan (1995). Mathematical model for predicting percutaneous absorption of fragrance raw materials (PDF) (B.S. in Pharmacy). Chulalongkorn University. Archived from the original on July 20, 2011. 4. ^ Anne C. Steinemann. "Exposure Assessment: Answers to Frequently Asked Questions". University of Washington. Archived from the original on October 29, 2010. Retrieved July 13, 2016. 5. ^ "Allergies: Nothing to Sneeze At". McKinley Health Center. Archived from the original on June 28, 2016. Retrieved July 13, 2016. 6. ^ Caress S. M., Steinemann A. C. (2009). "Prevalence of fragrance sensitivity in the American population". J. Environ. Health. 71 (7): 46–50. PMID 19326669.CS1 maint: uses authors parameter (link) 7. ^ Johansen, Jeanne D (2003). "Fragrance Contact Allergy". American Journal of Clinical Dermatology. 4 (11): 789–798. doi:10.2165/00128071-200304110-00006. PMID 14572300. 8. ^ Scheinman, P (December 2001). "Exposing covert fragrance chemicals". American Journal of Contact Dermatitis. 12 (4): 225–228. doi:10.1053/ajcd.2001.28697. PMID 11753900. 9. ^ "trans-Cinnamaldehyde". fscimage.fishersci.com. 1998-02-10. Archived from the original on 2020-03-01. Retrieved 2020-03-01. ## Further reading[edit] * Elberling, J.; Linneberg, A.; Dirksen, A.; Johansen, J. D.; Frolund, L.; Madsen, F.; Nielsen, N. H.; Mosbech, H. (January 2005). "Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity". Clinical & Experimental Allergy. 35 (1): 75–81. doi:10.1111/j.1365-2222.2005.02138.x. PMID 15649270. * Kumar, P; Caradonna-Graham, VM; Gupta, S; Cai, X; Rao, PN; Thompson, J (November 1995). "Inhalation challenge effects of perfume scent strips in patients with asthma". Annals of Allergy, Asthma & Immunology. 75 (5): 429–33. PMID 7583865. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Perfume intolerance	c0577618	28,981	wikipedia	https://en.wikipedia.org/wiki/Perfume_intolerance	2021-01-18T18:39:28	{"umls": ["C0577618"], "wikidata": ["Q7168310"]}
## Clinical Features In a large Mennonite kindred in Alberta, Canada, Smith et al. (1994) described a seemingly 'new' familial enteropathy manifested by recurrent acute, life-threatening secretory diarrhea associated with distinctive jejunal histologic changes and IgG2 subclass deficiency. Symptoms began abruptly with anorexia and vomiting, and progressed within hours to massive secretory diarrhea and shock with profound neutropenia and hypoproteinemia, including hypoalbuminemia and hypogammaglobulinemia. Affected survivors recovered quickly and thereafter grew and developed normally. Biopsy specimens obtained during remission from 3 adults and 11 children showed club-shaped jejunal villi broadened by edema and histiocytes with imbibed fluid; the overlying intestinal epithelium and brush border appeared normal, but the basement membrane was interrupted in some areas. No characteristic microorganisms had been identified in association with the syndrome. Clinical manifestations ceased in the second decade, but the abnormal jejunal histologic pattern persisted into adult life. Female and male patients were equally affected, although all fatal cases had been in female subjects. Affected individuals had a reduced serum concentration of IgG2. The pedigree published by Smith et al. (1994) showed 31 affected members. Four sibships were affected in the first of the 2 generations and 8 sibships in the second. Inheritance Smith et al. (1994) suggested that the disorder in the family they reported was autosomal dominant with incomplete penetrance. There were numerous examples of male-to-male transmission. One family member without a history of diarrhea had characteristic biopsy findings and another appeared to be an obligate carrier with normal biopsy findings. Mapping In the Mennonite kindred with a familial form of enteropathy reported by Smith et al. (1994), Johannes et al. (2007) found linkage of the disorder to chromosome 11q23 with a lod score of 6.2 at theta = zero. A higher-density microsatellite marker array refined the critical region to a 2-Mb interval between D11S4142 and D11S1364. Molecular Genetics By sequencing the open reading frames of 9 genes located within the critical region of chromosome 11q23 linked to the enteropathy in the Mennonite family reported by Smith et al. (1994), Johannes et al. (2007) identified a 198-bp in-frame duplication in the APOA4 gene (107690) that segregated with the disorder in the family. The mutation was not detected in 200 unrelated controls. Immunology \- IgG2 subclass deficiency \- Anorexia and vomiting Inheritance \- Autosomal dominant with incomplete penetrance Misc \- Remission of clinical manifestations in second decade Lab \- Neutropenia \- Hypoproteinemia \- Hypoalbuminemia \- Hypogammaglobulinemia \- Jejunal biopsy shows club-shaped jejunal villi broadened by edema and histiocytes with imbibed fluid with normal overlying intestinal epithelium and brush border Vascular \- Shock GI \- Familial enteropathy \- Recurrent acute, secretory diarrhea ▲ 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	ENTEROPATHY, FAMILIAL, WITH VILLOUS EDEMA AND IMMUNOGLOBULIN G2 DEFICIENCY	c1838238	28,982	omim	https://www.omim.org/entry/600351	2019-09-22T16:16:14	{"mesh": ["C563949"], "omim": ["600351"]}
STING-associated vasculopathy with onset in infancy (SAVI) is a disorder involving abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs. Inflammation normally occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and help with tissue repair. Excessive inflammation damages the body's own cells and tissues. Disorders such as SAVI that result from abnormally increased inflammation are known as autoinflammatory diseases. The signs and symptoms of SAVI begin in the first few months of life, and most are related to problems with blood vessels (vasculopathy) and damage to the tissues that rely on these vessels for their blood supply. Affected infants develop areas of severely damaged skin (lesions), particularly on the face, ears, nose, fingers, and toes. These lesions begin as rashes and can progress to become wounds (ulcers) and dead tissue (necrosis). The skin problems, which worsen in cold weather, can lead to complications such as scarred ears, a hole in the tissue that separates the two nostrils (nasal septum perforation), or fingers or toes that require amputation. Individuals with SAVI also have a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. Affected individuals may also experience episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. In addition to problems affecting the skin, people with SAVI have recurrent low-grade fevers and swollen lymph nodes. They may also develop widespread lung damage (interstitial lung disease) that can lead to the formation of scar tissue in the lungs (pulmonary fibrosis) and difficulty breathing; these respiratory complications can become life-threatening. Rarely, muscle inflammation (myositis) and joint stiffness also occur. ## Frequency The prevalence of this condition is unknown. Only a few affected individuals have been described in the medical literature. ## Causes SAVI is caused by mutations in the STING1 gene. This gene provides instructions for making a protein called STING, which is involved in immune system function. STING helps produce beta-interferon, a member of a class of proteins called cytokines that promote inflammation. The STING1 gene mutations that cause SAVI are described as "gain-of-function" mutations because they enhance the activity of the STING protein, leading to overproduction of beta-interferon. Abnormally high beta-interferon levels cause excessive inflammation that results in tissue damage, leading to the signs and symptoms of SAVI. ### Learn more about the gene associated with STING-associated vasculopathy with onset in infancy * STING1 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, this condition likely results from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	STING-associated vasculopathy with onset in infancy	c4014722	28,983	medlineplus	https://medlineplus.gov/genetics/condition/sting-associated-vasculopathy-with-onset-in-infancy/	2021-01-27T08:24:38	{"gard": ["12357"], "omim": ["615934"], "synonyms": []}
Shapero et al. (1994) noted that the expression of many liver-specific genes is extinguished when cultured hepatoma cells are fused with fibroblasts. Extinguished liver genes can be reexpressed in hybrid segregants that have lost chromosomes from the fibroblast parent, suggesting that extinction is an active process mediated by trans-acting regulatory factors. Two extinguisher loci had been reported previously: one, TSE1, on human chromosome 17 (188830), and a second, TSE2, on human chromosome 2 (601136). Shapero et al. (1994) transferred human chromosomes with a selectable marker into rat hepatoma cells by microcell fusion and studied the expression of liver-specific mRNAs in nearly 200 human/rat microcell hybrid clones, using the transcript from rat PEPCK (614168) as a detectable molecular marker. PEPCK mRNA synthesis was extinguished in 12 of these hybrid clones. The authors noted that some of these hybrids contained human TSE1, but others contained a novel extinguishing function that mapped to human chromosome 14. The identity and mechanism of the locus, designated TSE3 by them, remained to be defined. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	TISSUE-SPECIFIC EXTINGUISHER 3	None	28,984	omim	https://www.omim.org/entry/601221	2019-09-22T16:15:12	{"omim": ["601221"], "synonyms": ["Alternative titles", "TSE3"]}
Fundus albipunctatus is a rare, genetic retinal dystrophy disorder characterized by the presence of numerous small, round, yellowish-white retinal lesions that are distributed throughout the retina but spare the fovea. Patients present in childhood with non-progressive night blindness with prolonged cone and rod adaptation times. The macula may or may not be involved, which may result in a decrease of central visual acuity with age. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Fundus albipunctatus	c0311338	28,985	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=227796	2021-01-23T17:55:44	{"mesh": ["C562733"], "omim": ["136880"], "umls": ["C0311338"], "icd-10": ["H35.5"]}
Inflammatory arthritis is a group of diseases which includes: rheumatoid arthritis, psoriatic arthropathy, inflammatory bowel disease, adult-onset Still's disease, scleroderma, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE).[1] ## Contents * 1 Signs and symptoms * 2 Management * 3 Prognosis * 4 Epidemiology * 5 References ## Signs and symptoms[edit] Symptoms of inflammatory arthritis include stiffness, pain, and swelling of the joints, restricted motions, and reduced physical strength. Other symptoms may include systemic complaints including fatigue.[2] ## Management[edit] Treatments for inflammatory arthritis vary by subtype, though they may include drugs like DMARDs (disease-modifying anti-rheumatic drugs) and tumor necrosis factor inhibitors.[2] ## Prognosis[edit] Inflammatory arthritis can be disabling to the point where people with the diseases can lose their jobs, which can cause psychological distress. Because it is typically progressive, those who lose their jobs are unlikely to re-enter the workforce after leaving due to their diagnosis. Programs now aim to retain those with inflammatory arthritis by preventing work-related injuries and by making necessary accommodations in the workplace. A 2014 Cochrane review found low-quality evidence that work focused interventions, including counseling, education, advocacy, and occupational medicine consultations, were effective in retaining workers with inflammatory arthritis.[2] ## Epidemiology[edit] The worldwide prevalence of inflammatory arthritis is approximately 3%. Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and undifferentiated spondyloarthritis are the most common subtypes of inflammatory arthritis. The diseases occur most commonly in the 30-40 age group.[2] ## References[edit] 1. ^ Greenstein, Ben Greenstein, Adam (2007). Concise clinical pharmacology. London: Pharmaceutical Press. p. 102. ISBN 978-0853695769. 2. ^ a b c d Hoving JL, Lacaille D, Urquhart DM, Hannu TJ, Sluiter JK, Frings-Dresen MH (2014). "Non-pharmacological interventions for preventing job loss in workers with inflammatory arthritis". The Cochrane Database of Systematic Reviews. 11 (11): CD010208. doi:10.1002/14651858.CD010208.pub2. PMID 25375291. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Inflammatory arthritis	c1562028	28,986	wikipedia	https://en.wikipedia.org/wiki/Inflammatory_arthritis	2021-01-18T19:08:29	{"umls": ["C1562028"], "wikidata": ["Q16965166"]}
Roitman et al. (1980) described an obese, slightly mentally retarded 4-year-old boy with large testes. The only endocrine disorder found was absence of an increase in plasma prolactin after stimulation. No information relevant to a possible genetic basis was available. Endocrine \- Absent increase in plasma prolactin after stimulation GU \- Large testes Growth \- Obesity Neuro \- Slight mental retardation 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	PROLACTIN DEFICIENCY WITH OBESITY AND ENLARGED TESTES	c1849698	28,987	omim	https://www.omim.org/entry/264120	2019-09-22T16:23:11	{"mesh": ["C564870"], "omim": ["264120"], "synonyms": ["Alternative titles", "PRL DEFICIENCY WITH OBESITY AND ENLARGED TESTES"]}
Chordoid glioma is an extremely rare glial neoplasm occurring in the region of the anterior third ventricle or hypothalamus, which is non-infiltrative and well-circumscribed and presents most frequently in middle-aged women with symptoms of memory loss and headaches and, because of its location, has a poor prognosis due to surgical morbidity. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Chordoid glioma	c1322252	28,988	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251674	2021-01-23T17:56:37	{"icd-10": ["C71.9"]}
Postaxial polydactyly-dental and vertebral anomalies syndrome is a rare, genetic, developmental defect during embryogenesis syndrome characterized by postaxial polydactyly and other abnormalities of the hands and feet (e.g. brachydactyly, broad toes), hypoplasia and fusion of the vertebral bodies, as well as dental abnormalities (fused teeth, macrodontia, hypodontia, short roots). There have been no further descriptions in the literature since 1977. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Postaxial polydactyly-dental and vertebral anomalies syndrome	c1849732	28,989	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2916	2021-01-23T17:02:28	{"mesh": ["C564880"], "omim": ["263540"], "umls": ["C1849732"], "icd-10": ["Q87.2"]}
Grinker myelinopathy Other namesDelayed post-hypoxic Encephalopathy, Delayed post-hypoxic Leukoencephalopathy (DPHL),[1] Delayed post-anoxic leukoencephalopathy,[1] Delayed post-anoxic encephalopathy,[1] Delayed post-hypoxic encephalopathy,[1] Delayed neurologic sequelae[1] SpecialtyNeurology Grinker's myelinopathy, also known as anoxic leukoencephalopathy,[2] is a rare disease of the central nervous system. The disease is characterized by a delayed leukoencephalopathy after a hypoxic episode.[2] It is typically, though not necessarily, related to carbon monoxide poisoning or heroin overdose. It occurs in roughly 2.8% of those who experience an acute hypoxic/anoxic episode.[3] Because of the wide range of symptoms and the delay in onset, it is often misdiagnosed as other neuropathologies. Grinker's myelinopathy was originally characterized by Roy R. Grinker in 1925[4][5] or 1926,[3] depending on the source. ## Contents * 1 Categorization * 2 Symptoms * 2.1 Onset * 3 Causes * 3.1 Carbon monoxide toxicity * 3.2 Cerebral edema * 3.3 Disruption of myelin-creating pathways * 4 Diagnosis * 4.1 Neuroimaging * 5 Treatment * 6 Prognosis * 7 References ## Categorization[edit] Following an apparent rehabilitation from a severe episode of prolonged cerebral oxygen deprivation, patients with Grinker's myelinopathy begin to experience massive white matter death that leads to a wide range of neurological dysfunctions ranging from confusion and apathy to Parkinson-like symptoms.[3] ## Symptoms[edit] The symptoms have been known to include apathy, dementia, Parkinsonism, agitation, urinary incontinence, and pseudobulbar palsy, among many other neuropsychiatric symptoms. Microscopically, extensive hemispheric demyelination and the degeneration of basal ganglia are observed.[1] ### Onset[edit] The onset of the symptoms usually occurs several weeks after the initial hypoxic episode. The hypoxic episode is necessarily severe, usually with an arterial oxygen partial pressure less than 40mmHg.[3] Following the severe hypoxia, the patient typically falls unconscious or into a coma, with the exception of cases of carbon monoxide poisoning.[2][1] If the patient recovers from this unconscious state, usually within 24 hours, it is typically followed by a successful recovery over a few days (generally 4 to 5). After the short recovery, a lucid period is observed, lasting anywhere from 1 to 4 weeks, in which the patient exhibits no symptoms related to the anoxic episode. It is after this period that the degenerative symptoms begin to appear and rapidly grow in severity.[6] ## Causes[edit] The main cause of the neurological disorders is believed to be demyelination of the cerebral hemispheres, though there is currently no widely accepted consensus on why. The most commonly accepted theories for the cause of demyelination include hypoxia and cerebral edema due to carbon monoxide toxicity, drug overdose, or cerebral blood vessel damage, and a disruption of myelin-producing pathways. ### Carbon monoxide toxicity[edit] Because carbon monoxide binds to hemoglobin more efficiently than oxygen and lower systemic blood pressure brought upon by an acute anoxic episode in conjunction with carbon monoxide poisoning often leads to cerebral ischemia, a condition where the brain does not receive enough oxygen to satisfy its needs. This results in lesions to a great deal of subcortical cerebral white matter but leaves axons, U-fibers, and perivascular myelin mostly untouched. Support against this theory stems from the ability to replicate these lesions by using nitrogen-induced hypoxia and hypotension in cats[7] and the onset of this disease in individuals who experienced acute hypoxia without carbon monoxide poisoning[1] ### Cerebral edema[edit] Cerebral edema, or unusual swelling of the brain, is commonly caused by anoxic episodes. If it is severe enough, it is known to cause preferential damage to cerebral white matter due to excessive swelling of glial cells while leaving many other tissues unharmed.[6] This theory suggests that hypoxia and carbon monoxide induce a form of edema resulting in white matter necrosis. Evidence for this theory comes from the observation of pathological lesions mimicking those of carbon monoxide poisoning where hypoxia and dehydration along with too-rapid rehydration have taken place without carbon monoxide present. ### Disruption of myelin-creating pathways[edit] The anoxic event is likely to cause damage to cytoplasmic ATP-dependent enzymes in oligodendrocytes. Because many of these enzymes play essential roles in myelin turnover, damage to these enzymes is thought to adversely affect the ability of the body to sustain myelin in white matter, leading to the demyelination of those areas of the brain. The inability to regenerate and remove myelin on certain cells is thought to be responsible for the delay in onset of the disease and for the specificity of the white matter death.[1][8] ## Diagnosis[edit] Grinker's myelinopathy is diagnosed by establishing a clinical history of carbon monoxide poisoning, narcotic overdose, myocardial infarction, or other global cerebral hypoxic events. This diagnosis can then be supported by neuroimaging confirmation of broadcast cerebral hemisphere demyelination sparing cerebellar and brainstem tracts. The neuroimaging evidence can also be used to diagnose Grinker's myelinopathy through an elevation in the concentrations of a myelin basic protein in the cerebrospinal fluid .[1] Because this disease shares many of the symptoms with various forms of dementia or hysteria, these possibilities must be eliminated before a diagnosis for Grinker's myelinopathy can be made. ### Neuroimaging[edit] While there are no standard criteria for the diagnosis of Grinker's myelinopathy, neuroimaging can be an important diagnostic tool in ruling out other diagnoses. Magnetic resonance imaging (MRI) or computed tomography (CT) scans can be used to demonstrate a decrease in white matter density in the patient's cerebral hemispheres, with the typical exception of overlying cortices. Unexplained, uniform demyelination of white matter can indicate acute onset Grinker's myelinopathy.[1] ## Treatment[edit] Treatment Grinker's myelinopathy is still in the experimental stages and is very individualized. Some suggested treatments are early supportive care, rehabilitation therapies, oxygen treatments, and bed rest. Some episodes of Grinker's myelinopathy that progress to comas have no known treatment to reverse the course. Early supportive care is the anchor of treatment during the first two weeks. Rehabilitation is an important part of the care process and it is important to start the rehabilitation as soon as the patient is able to participate in therapy. Types of therapy include: physical therapy, occupational therapy, speech therapy, and respiratory therapy. This therapies are used to assess the patient's functional status and to develop treatment goals. Each goal is individualized to target the specific neurological impairments to improve the patient's functional abilities. One way to prevent the likelihood of Grinker's myelinopathy occurring is standard or hyperbaric oxygen after carbon monoxide poisoning. The hyperbaric oxygen treatment eliminates carbon dioxide from the brain, while the standard oxygen treatment normalizes carboxyhemoglobin levels. Another preventative measure one can take is to be on bed rest and abstain from stressful and strenuous procedures for the first 10 days after an extended hypoxic event. Expectation and recognition will also lead to an earlier and more accurate and appropriate use of health care services.[1] ## Prognosis[edit] Those patients who survive initial hospitalization are likely to recover from Grinker's Myelinopathy, but may take up to a year or longer. Age seems to be a factor in the time for recovery, as one study indicated that the mean age of patients who recovered within one year was 10 years younger than that of patients who did not. For most patients, a recovery time of 3–6 months is typical. Even after recovering, however, some symptoms may persist, including cognitive deficits or Parkinsonian symptoms that can be treated separately.[1] ## References[edit] 1. ^ a b c d e f g h i j k l m Schprecher, David; Mehta, Lahar (January 2010). "The syndrome of delayed post-hypoxic leukoencephalopathy". NeuroRehabilitation. 26 (1): 65–72. doi:10.3233/NRE-2010-0536. PMC 2835522. PMID 20166270. 2. ^ a b c Pantoni MD, Leonardo; Garcia MD; Julio H (1997). "Pathogenesis of Leukoaraiosis". Stroke. 28 (3): 652–659. doi:10.1161/01.STR.28.3.652. hdl:2434/579412. PMID 9056627. 3. ^ a b c d Custodio, Christian M; Basford, Jeffrey R (March 2004). "Delayed postanoxic encephalopathy: a case report and literature review". Archives of Physical Medicine and Rehabilitation. 85 (3): 502–505. doi:10.1016/S0003-9993(03)00471-4. PMID 15031841. 4. ^ H. Bour, Iain McAllan Ledingham, Iain McA. Ledingham (1967) Carbon Monoxide Poisoning. p.73 5. ^ Hideo H. Itabashi, MD, John M. Andrews, MD, Uwamie Tomiyasu, MD (2007) Forensic Neuropathology: A Practical Review of the Fundamentals. p.295 6. ^ a b PLUM, FRED (July 1962). "Delayed Neurological Deterioration After Anoxia". Archives of Internal Medicine. 110 (1): 18–25. doi:10.1001/archinte.1962.03620190020003. PMID 14487254. 7. ^ Okeda R, Song S.-Y., Funta N, Higashino F (1983). "An experimental study of the pathogenesis of Grinker's myelinopathy in carbon monoxide intoxication". Acta Neuropathologica. 59 (3): 200–2006. doi:10.1007/BF00703204. PMID 6845982. 8. ^ Sprecher, David; Flanigan, K.; Smith, G.A.; Smith, S.; Schenkenberg, T.; Steffens, J. (September 2008). "Clinical and Diagnostic Features of Delayed Hypoxic Leukoencephalopathy". The Journal of Neuropsychiatry and Clinical Neurosciences. 20 (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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Grinker myelinopathy	None	28,990	wikipedia	https://en.wikipedia.org/wiki/Grinker_myelinopathy	2021-01-18T18:44:47	{"wikidata": ["Q5609501"]}
A rare acute myeloid leukemia with recurrent genetic anomaly disorder characterized by a t(8;21)(q22;q22) balanced translocation cytogenetic abnormality, forming a RUNX1-RUNX1T1 fusion gene, presenting with morphological characteristics which include myeloblasts with indented nuclei, basophilic cytoplasm with a prominent paranuclear hof that may contain a few azurophilic granules, prominent and possibly large promyelocytes, myelocytes and metamyelocytes, easily identifiable Auer rods and, more variably, bone marrow eosinophilia. Myeloid sarcoma is frequently present at diagnosis. Detection of the t(8;21)(q22;22) translocation is sufficient for diagnosis irrespective of blast count. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Acute myeloid leukemia with t(8;21)(q22;q22) translocation	None	28,991	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=102724	2021-01-23T18:33:00	{"icd-10": ["C92.0"], "synonyms": ["AML with t(8;21)(q22;q22) translocation"]}
Human disease Paracetamol poisoning Other namesAcetaminophen toxicity, paracetamol toxicity, acetaminophen poisoning, paracetamol overdose, acetaminophen overdose, Tylenol toxicity Paracetamol SpecialtyToxicology SymptomsEarly: Non specific, feeling tired, abdominal pain, nausea[citation needed] Later: Yellowish skin, blood clotting problems, confusion[citation needed] ComplicationsLiver failure, kidney failure, pancreatitis, low blood sugar, lactic acidosis.[citation needed] Usual onsetAfter 24 hours (toxicity)[1] CausesParacetamol (acetaminophen) usually > 7 g[2][1] Risk factorsAlcoholism, malnutrition, certain other medications[1] Diagnostic methodBlood levels at specific times following use[1] Differential diagnosisAlcoholism, viral hepatitis, gastroenteritis[1] TreatmentActivated charcoal, acetylcysteine, liver transplant[1][citation needed] PrognosisDeath occurs in ~0.1%[1] Frequency>100,000 per year (US)[1] Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen).[2] Most people have few or non-specific symptoms in the first 24 hours following overdose. These include feeling tired, abdominal pain, or nausea. This is typically followed by a couple of days without any symptoms, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks.[3][4] Without treatment, death from toxicity occurs 4 to 18 days later.[5] Paracetamol poisoning can occur accidentally or as an attempt to end one's life. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other medications.[1] Liver damage results not from paracetamol itself, but from one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI).[6] NAPQI decreases the liver's glutathione and directly damages cells in the liver.[7] Diagnosis is based on the blood level of paracetamol at specific times after the medication was taken.[1] These values are often plotted on the Rumack-Matthew nomogram to determine level of concern.[1] Treatment may include activated charcoal if the person seeks medical help soon after the overdose.[1] Attempting to force the person to vomit is not recommended.[6] If there is a potential for toxicity, the antidote acetylcysteine is recommended.[1] The medication is generally given for at least 24 hours.[6] Psychiatric care may be required following recovery.[1] A liver transplant may be required if damage to the liver becomes severe.[citation needed] The need for transplant is often based on low blood pH, high blood lactate, poor blood clotting, or significant hepatic encephalopathy.[citation needed] With early treatment liver failure is rare.[6] Death occurs in about 0.1% of cases.[1] Paracetamol poisoning was first described in the 1960s.[6] Rates of poisoning vary significantly between regions of the world.[8] In the United States more than 100,000 cases occur a year.[1] In the United Kingdom it is the medication responsible for the greatest number of overdoses.[7] Young children are most commonly affected.[1] In the United States and the United Kingdom, paracetamol is the most common cause of acute liver failure.[9][1] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Risk factors * 3 Pathophysiology * 4 Diagnosis * 4.1 Detection in body fluids * 5 Prevention * 5.1 Limitation of availability * 5.2 Combination with other agents * 5.3 Paracetamol replacements * 6 Treatment * 6.1 Gastric decontamination * 6.2 Acetylcysteine * 6.3 Liver transplant * 7 Prognosis * 8 Epidemiology * 9 References * 10 External links ## Signs and symptoms[edit] The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, a pale appearance, and sweating.[10] However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.[11][12] The second phase occurs between 24 h and 72 h following overdose and consists of signs of increasing liver damage. In general, damage occurs in liver cells as they metabolize the paracetamol. The individual may experience right upper quadrant abdominal pain. The increasing liver damage also changes biochemical markers of liver function; International normalized ratio (INR) and the liver transaminases ALT and AST rise to abnormal levels.[13] Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.[14] The third phase follows at 3 to 5 days, and is marked by complications of massive liver necrosis leading to fulminant liver failure with complications of coagulation defects, low blood sugar, kidney failure, hepatic encephalopathy, brain swelling, sepsis, multiple organ failure, and death.[10] If the third phase is survived, the liver necrosis runs its course, and liver and kidney function typically return to normal in a few weeks.[15] The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received. ## Cause[edit] The toxic dose of paracetamol is highly variable. In general the recommended maximum daily dose for healthy adults is 4 grams.[16][17] Higher doses lead to increasing risk of toxicity. In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity.[18][19] Toxicity can also occur when multiple smaller doses within 24 hours exceed these levels.[19] Following a dose of 1 gram of paracetamol four times a day for two weeks, patients can expect an increase in alanine transaminase in their liver to typically about three times the normal value.[20] It is unlikely that this dose would lead to liver failure.[21] Studies have shown significant hepatotoxicity is uncommon in patients who have taken greater than normal doses over 3 to 4 days.[22] In adults, a dose of 6 grams a day over the preceding 48 hours could potentially lead to toxicity,[19] while in children acute doses above 200 mg/kg could potentially cause toxicity.[23] Acute paracetamol overdose in children rarely causes illness or death, and it is very uncommon for children to have levels that require treatment, with chronic larger-than-normal doses being the major cause of toxicity in children.[19] Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity.[24] In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.[25] In rare individuals, paracetamol toxicity can result from normal use.[26] This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the metabolic pathways that handle paracetamol (see paracetamol's metabolism). ### Risk factors[edit] A number of factors can potentially increase the risk of developing paracetamol toxicity. Chronic excessive alcohol consumption can induce CYP2E1, thus increasing the potential toxicity of paracetamol. In one study of patients with liver injury, 64% reported alcohol intakes of greater than 80 grams a day, while 35% took 60 grams a day or less.[27] Whether chronic alcoholism should be considered a risk factor has been debated by some clinical toxicologists.[28][29] For chronic alcohol users, acute alcohol ingestion at the time of a paracetamol overdose may have a protective effect.[28][30] For non-chronic alcohol users, acute alcohol consumption had no protective effect. Fasting is a risk factor, possibly because of depletion of liver glutathione reserves.[19] The concomitant use of the CYP2E1 inducer isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is related to the hepatotoxicity in this case is unclear.[31][32] Concomitant use of other drugs that induce CYP enzymes, such as antiepileptics including carbamazepine, phenytoin, and barbiturates, have also been reported as risk factors.[33] ## Pathophysiology[edit] Main pathways of paracetamol metabolism (click to enlarge). The pathway leading to NAPQI is shown in red. When taken in normal therapeutic doses, paracetamol has been shown to be safe.[13] Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system.[34] Cytochromes P450 2E1 and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzoquinone imine (NAPQI).[34][13][35][36][37] Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.[34][38] In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration.[38] NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis.[34][39] In animal studies, the liver's stores of glutathione must be depleted to less than 70% of normal levels before liver toxicity occurs.[35] ## Diagnosis[edit] Rumack Matthew Nomogram with treatment line added at 150 A person's history of taking paracetamol is somewhat accurate for the diagnosis.[40] The most effective way to diagnose poisoning is by obtaining a blood paracetamol level. A drug nomogram developed in 1975, called the Rumack-Matthew nomogram, estimates the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion.[10] To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the nomogram. Use of a timed serum paracetamol level plotted on the nomogram appears to be the best marker indicating the potential for liver injury.[19] A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Therefore, a serum level taken before 4 hours is not recommended.[18] Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours.[41] Right-upper-quadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of liver necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time.[42] After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed.[41] In some cases, the AST and ALT levels can exceed 10,000 IU/L.[43] ### Detection in body fluids[edit] Paracetamol may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. The concentration in serum after a typical dose of paracetamol usually peaks below 30 mg/l, which equals 200 µmol/L.[44] Levels of 30–300 mg/L (200–2000 µmol/L) are often observed in overdose patients. Postmortem blood levels have ranged from 50–400 mg/L in persons dying due to acute overdosage. Automated colorimetric techniques, gas chromatography and liquid chromatography are currently in use for the laboratory analysis of the drug in physiological specimens.[45][46] ## Prevention[edit] ### Limitation of availability[edit] Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacist's discretion.[47][48] In Ireland, the limits are 24 and 12 tablets, respectively.[49] Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.[50] One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people.[51] In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use.[52] ### Combination with other agents[edit] One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic[51] or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine,[53] an amino acid formerly[19] used in the treatment of paracetamol overdose. There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.[54] Calcitriol, the active metabolite of vitamin D3, appears to be a catalyst for glutathione production.[55] Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration.[56] It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes. ### Paracetamol replacements[edit] Paracetamol ester prodrug with L-pyroglutamic acid (PCA), a biosynthetic precursor of glutathione, has been synthesized to reduce paracetamol hepatotoxicity and improve bioavailability. The toxicological studies of different paracetamol esters show that L-5-oxo-pyrrolidine-2-paracetamol carboxylate reduces toxicity after administration of an overdose of paracetamol to mice. The liver glutathione values in mice induced by intraperitoneal injection of the ester are superimposable with the GSH levels recorded in untreated mice control group. The mice group treated with an equivalent dose of paracetamol showed a significative decrease of glutathione of 35% (p<0.01 vs untreated control group). The oral LD50 was found to be greater than 2000 mg kg-1, whereas the intraperitoneal LD50 was 1900 mg kg-1. These results taken together with the good hydrolysis and bioavailability data show that this ester is a potential candidate as a prodrug of paracetamol.[57] ## Treatment[edit] ### Gastric decontamination[edit] In adults, the initial treatment for paracetamol overdose is gastrointestinal decontamination. Paracetamol absorption from the gastrointestinal tract is complete within two hours under normal circumstances, so decontamination is most helpful if performed within this timeframe. Gastric lavage, better known as stomach pumping, may be considered if the amount ingested is potentially life-threatening and the procedure can be performed within 60 minutes of ingestion.[58] Activated charcoal is the most common gastrointestinal decontamination procedure as it adsorbs paracetamol, reducing its gastrointestinal absorption.[59][60] Administering activated charcoal also poses less risk of aspiration than gastric lavage.[61] It appears that the most benefit from activated charcoal is gained if it is given within 30 minutes to two hours of ingestion.[62][63] Administering activated charcoal later than 2 hours can be considered in patients that may have delayed gastric emptying due to co-ingested drugs or following ingestion of sustained- or delayed-release paracetamol preparations. Activated charcoal should also be administered if co-ingested drugs warrant decontamination.[41] There was reluctance to give activated charcoal in paracetamol overdose, because of the concern that it may also absorb the oral antidote acetylcysteine.[64] Studies have shown that 39% less acetylcysteine is absorbed into the body when they are administered together.[65] There are conflicting recommendations regarding whether to change the dosing of oral acetylcysteine after the administration of activated charcoal, and even whether the dosing of acetylcysteine needs to be altered at all.[65][66] Intravenous acetylcystine has no interaction with activated charcoal. Inducing vomiting with syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated charcoal and oral acetylcysteine.[18] Liver injury is extremely rare after acute accidental ingestion in children under 6 years of age. Children with accidental exposures do not require gastrointestinal decontamination with either gastric lavage, activated charcoal, or syrup of ipecac.[19] ### Acetylcysteine[edit] Acetylcysteine is the antidote for paracetamol toxicity Acetylcysteine, also called N-acetylcysteine or NAC, works to reduce paracetamol toxicity by replenishing body stores of the antioxidant glutathione. Glutathione reacts with the toxic NAPQI metabolite so that it does not damage cells and can be safely excreted.[67] NAC was usually given following a treatment nomogram (one for patients with risk factors, and one for those without) but the use of the nomogram is no longer recommended as the evidence base to support the use of risk factors was poor and inconsistent and many of the risk factors are imprecise and difficult to determine with sufficient certainty in clinical practice.[68] Cysteamine and methionine have also been used to prevent hepatotoxicity,[69] although studies show that both are associated with more adverse effects than acetylcysteine.[19] Additionally, acetylcysteine has been shown to be a more effective antidote, particularly in patients presenting greater than 8 hours post-ingestion[70] and for those who present with liver failure symptoms.[60] If the person presents less than eight hours after paracetamol overdose, then acetylcysteine significantly reduces the risk of serious hepatotoxicity and guarantees survival.[19] If acetylcysteine is started more than 8 hours after ingestion, there is a sharp decline in its effectiveness because the cascade of toxic events in the liver has already begun, and the risk of acute liver necrosis and death increases dramatically. Although acetylcysteine is most effective if given early, it still has beneficial effects if given as late as 48 hours after ingestion.[71][needs update] If the person presents more than eight hours after the paracetamol overdose, then activated charcoal is not useful, and acetylcysteine is started immediately. In earlier presentations, charcoal can be given when the patient arrives and acetylcysteine is initiated while waiting for the paracetamol level results to return from the laboratory.[19] In United States practice, intravenous (IV) and oral administration are considered to be equally effective and safe if given within 8 hours of ingestion.[72][73] However, IV is the only recommended route in Australasian and British practice.[19][74] Oral acetylcysteine is given as a 140 mg/kg loading dose followed by 70 mg/kg every four hours for 17 more doses, and if the patient vomits within 1 hour of dose, the dose must be repeated.[75][76] Oral acetylcysteine may be poorly tolerated due to its unpleasant taste, odor, and its tendency to cause nausea and vomiting.[72] If repeated doses of charcoal are indicated because of another ingested drug, then subsequent doses of charcoal and acetylcysteine should be staggered.[41] Intravenous acetylcysteine is given as a continuous infusion over 20 hours for a total dose 300 mg/kg. Recommended administration involves infusion of a 150 mg/kg loading dose over 15 to 60 minutes, followed by a 50 mg/kg infusion over four hours; the last 100 mg/kg are infused over the remaining 16 hours of the protocol.[19] Intravenous acetylcysteine has the advantage of shortening hospital stay, increasing both doctor and patient convenience, and allowing administration of activated charcoal to reduce absorption of both the paracetamol and any co-ingested drugs without concerns about interference with oral acetylcysteine.[77][needs update] Intravenous dosing varies with weight, specifically in children. For patients less than 20 kg, the loading dose is 150 mg/kg in 3 mL/kg diluent, administered over 60 minutes; the second dose is 50 mg/kg in 7 mL/kg diluent over 4 hours; and the third and final dose is 100 mg/kg in 14 mL/kg diluent over 16 hours.[76] The most common adverse effect to acetylcysteine treatment is an anaphylactoid reaction, usually manifested by rash, wheeze, or mild hypotension. Adverse reactions are more common in people treated with IV acetylcysteine, occurring in up to 20% of patients.[78][79] Anaphylactoid reactions are more likely to occur with the first infusion (the loading dose).[78] Rarely, severe life-threatening reactions may occur in predisposed individuals, such as patients with asthma or atopic dermatitis, and may be characterized by respiratory distress, facial swelling, and even death.[78][80][81] If an anaphylactoid reaction occurs the acetylcysteine is temporarily halted or slowed and antihistamines and other supportive care is administered.[78][82][83] For example, a nebulised beta-agonist like salbutamol may be indicated in the event of significant bronchospasm (or prophylactically in patients with a history of bronchospasm secondary to acetylcysteine). It is also important to closely monitor fluids and electrolytes.[78] ### Liver transplant[edit] In people who develop acute liver failure or who are otherwise expected to die from liver failure, the mainstay of management is liver transplantation.[51] Liver transplants are performed in specialist centers. The most commonly used criteria for liver transplant were developed by physicians at King's College Hospital in London. Patients are recommended for transplant if they have an arterial blood pH less than 7.3 after fluid resuscitation or if a patient has Grade III or IV encephalopathy, a prothrombin time greater than 100 seconds, and a serum creatinine greater than 300 mmol/L In a 24-hour period.[84] Other forms of liver support have been used including partial liver transplants. These techniques have the advantage of supporting the patient while their own liver regenerates. Once liver function returns immunosuppressive drugs are commenced and they have to take immunosuppressive medication for the rest of their lives.[85][86] ## Prognosis[edit] The mortality rate from paracetamol overdose increases two days after the ingestion, reaches a maximum on day four, and then gradually decreases. Acidosis is the most important single indicator of probable mortality and the need for transplantation. A mortality rate of 95% without transplant was reported in patients who had a documented pH less than 7.30. Other indicators of poor prognosis include chronic kidney disease (stage 3 or worse), hepatic encephalopathy, a markedly elevated prothrombin time, or an elevated blood lactic acid level (lactic acidosis).[84][87] One study has shown that a factor V level less than 10% of normal indicated a poor prognosis (91% mortality), whereas a ratio of factor VIII to factor V of less than 30 indicated a good prognosis (100% survival).[88] Patients with a poor prognosis are usually identified for likely liver transplantation.[84] Patients that do not die are expected to fully recover and have a normal life expectancy and quality of life.[89] ## Epidemiology[edit] See also: Chicago Tylenol murders Many over-the-counter and prescription-only medications contain paracetamol. Because of its wide availability paired with comparably high toxicity, (compared to ibuprofen and aspirin) there is a much higher potential for overdose.[90] Paracetamol toxicity is one of the most common causes of poisoning worldwide.[24] In the United States, the United Kingdom, Australia, and New Zealand, paracetamol is the most common cause of drug overdoses.[19][91][92] Additionally, in both the United States and the United Kingdom it is the most common cause of acute liver failure.[93][9] In England and Wales an estimated 41,200 cases of paracetamol poisoning occurred in 1989 to 1990, with a mortality of 0.40%. It is estimated that 150 to 200 deaths and 15 to 20 liver transplants occur as a result of poisoning each year in England and Wales.[79] Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance, accounting for more than 100,000 calls, as well as 56,000 emergency room visits, 2,600 hospitalizations, and 458 deaths due to acute liver failure per year.[94] A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the USA found that paracetamol was the cause of 41% of all cases in adults, and 25% of cases in children.[95] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 11. ISBN 9780323448383. Archived from the original on September 10, 2017. Retrieved July 6, 2017. 2. ^ a b Woolley, David; Woolley, Adam (2017). 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"Early indicators of prognosis in fulminant hepatic failure". Gastroenterology. 97 (2): 439–45. doi:10.1016/0016-5085(89)90081-4. PMID 2490426. 85. ^ Jaeck D, Boudjema K, Audet M, Chenard-Neu MP, Simeoni U, Meyer C, Nakano H, Wolf P (2002). "Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure". Journal of Gastroenterology. 37 Suppl 13: 88–91. doi:10.1007/BF02990107. PMID 12109674. S2CID 21768850. 86. ^ Lodge JP, Dasgupta D, Prasad KR, Attia M, Toogood GJ, Davies M, Millson C, Breslin N, Wyatt J, Robinson PJ, Bellamy MC, Snook N, Pollard SG (February 2008). "Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success". Annals of Surgery. 247 (2): 238–49. doi:10.1097/SLA.0b013e31816401ec. PMID 18216528. S2CID 9408710. 87. ^ Bernal W, Donaldson N, Wyncoll D, Wendon J (February 2002). "Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study". Lancet. 359 (9306): 558–63. doi:10.1016/S0140-6736(02)07743-7. PMID 11867109. S2CID 10651412. 88. ^ Pereira LM, Langley PG, Hayllar KM, Tredger JM, Williams R (1992). "Coagulation factor V and VIII/V ratio as predictors of outcome in paracetamol induced fulminant hepatic failure: relation to other prognostic indicators". Gut. 33 (1): 98–102. doi:10.1136/gut.33.1.98. PMC 1373872. PMID 1740285. 89. ^ Ding GK, Buckley NA (September 2008). "Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity". QJM : Monthly Journal of the Association of Physicians. 101 (9): 723–9. doi:10.1093/qjmed/hcn077. PMID 18606611. 90. ^ Sheen C, Dillon J, Bateman D, Simpson K, Macdonald T (2002). "Paracetamol toxicity: epidemiology, prevention and costs to the health-care system". QJM : Monthly Journal of the Association of Physicians. 95 (9): 609–19. doi:10.1093/qjmed/95.9.609. PMID 12205339. Archived from the original on January 29, 2009. 91. ^ Hawkins LC, Edwards JN, Dargan PI (2007). "Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature". Drug Safety. 30 (6): 465–79. doi:10.2165/00002018-200730060-00002. PMID 17536874. S2CID 36435353. 92. ^ Khashab M, Tector AJ, Kwo PY (March 2007). "Epidemiology of acute liver failure". Current Gastroenterology Reports. 9 (1): 66–73. doi:10.1007/s11894-008-0023-x. PMID 17335680. S2CID 30068892. 93. ^ Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiødt FV, Ostapowicz G, Shakil AO, Lee WM; Acute Liver Failure Study Group. (December 2005). "Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study". Hepatology. 42 (6): 1364–72. doi:10.1002/hep.20948. PMID 16317692. S2CID 24758491.CS1 maint: multiple names: authors list (link) 94. ^ Lee WM (July 2004). "Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure". Hepatology. 40 (1): 6–9. doi:10.1002/hep.20293. PMID 15239078. S2CID 15485538.[dead link] 95. ^ Bower WA, Johns M, Margolis HS, Williams IT, Bell BP (November 2007). "Population-based surveillance for acute liver failure". The American Journal of Gastroenterology. 102 (11): 2459–63. PMID 17608778. ## External links[edit] Classification D * ICD-10: T39.1 * ICD-9-CM: 965.4 External resources * MedlinePlus: 002598 * eMedicine: ped/7 * Gerth, Jeff; T. Christian Miller (September 20, 2013). "Use Only as Directed". ProPublica. 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[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 [FSH]: Follicle-stimulating hormone	Paracetamol poisoning	c0237963	28,992	wikipedia	https://en.wikipedia.org/wiki/Paracetamol_poisoning	2021-01-18T18:46:41	{"icd-9": ["965.4"], "icd-10": ["T39.1"], "orphanet": ["464458"], "synonyms": ["Acetaminophen poisoning"], "wikidata": ["Q2572879"]}
## Summary ### Clinical characteristics. The 16p11.2 recurrent microdeletion phenotype is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder (ASD). Developmental delays are related to diminished language, cognitive function, and motor impairments. While IQ scores range from mild intellectual disability to normal, those with IQ scores in the average range typically have other developmental issues such as language delay or ASD. Expressive language appears to be more affected than receptive language. Seizures are observed in approximately 20% of individuals with the recurrent microdeletion. Macrocephaly is common, usually becoming apparent by age two years. Chiari malformations/cerebellar ectopia are the most frequently observed structural brain abnormalities. In individuals with the 16p11.2 recurrent microdeletion the frequency of birth defects of all types is slightly increased, with vertebral anomalies appearing to be most frequent. ### Diagnosis/testing. The 16p11.2 microdeletion is defined as the recurrent ~593-kb heterozygous deletion at the approximate position of 29.6-30.2 Mb in the reference genome (GRCh37/hg19). The microdeletion is identified by genomic testing that determines copy number of sequences, such as chromosomal microarray (CMA). This deletion cannot be detected by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques. While FISH analysis is not appropriate for identification of the deletion in a proband, it may be used to test relatives of a proband who is known to have the deletion. ### Management. Treatment of manifestations: Treatment should be targeted to the specific deficits identified. Full developmental assessment, including neuropsychological testing by a clinical psychologist, is strongly suggested to establish neurodevelopmental needs and treatment recommendations. Refer to a neurologist if seizures are suspected. Because of the high risk of obesity beginning in adolescence, encourage healthy eating habits with attention to portion size and an active lifestyle from a young age. Routine management of vertebral anomalies. Surveillance: Routine surveillance, screening, and management based on American Academy of Pediatrics published guidelines on developmental delays and ASD. Maintain a low index of suspicion for possible seizures (which may manifest as, e.g., abnormal movements, staring spells). Obtain brain MRI if manifestations of Chiari I malformation appear. Periodic reevaluation by a medical geneticist to apprise the family of new developments and/or recommendations and facilitate long-term monitoring for emerging medical and/or mental health concerns. ### Genetic counseling. 16p11.2 microdeletion is inherited in an autosomal dominant manner. The proband often has a de novo deletion; however, the deletion can also be transmitted from a parent to a child. Prenatal diagnosis for at-risk pregnancies requires prior identification of the deletion in an affected family member. Interpretation of results from prenatal testing is challenging given the inherent difficulty in accurately predicting the phenotype. ## Diagnosis ### Suggestive Findings The 16p11.2 recurrent microdeletion should be suspected in individuals with the following clinical findings: * Delayed language development (with expressive language typically more affected than receptive language) and abnormal speech articulation * Learning difficulties/intellectual disability * Social impairments with or without a diagnosis of autism spectrum disorder (ASD) * Macrocephaly * Chiari I/cerebellar tonsillar ectopia * Seizures/epilepsy * Vertebral anomalies * Obesity starting in adolescence, and in the setting of developmental delay ### Establishing the Diagnosis The diagnosis of the 16p11.2 recurrent microdeletion is established by demonstration of deletion of the ~593-kb critical region at the approximate position of 29.6-30.2 Mb in the reference genome (GRCh37/hg19) (see Table 1 and Molecular Genetics). Of note, an adjacent (distal) recurrent 16p11.2 microdeletion (GRCh37/hg19 chr16:28.8-29.0 Mb) which is also associated with variable features is not discussed further as this GeneReview addresses the 29.6-30.2-Mb recurrent deletion only. Molecular methods that determine the copy number of sequences can include chromosomal microarray (CMA) or targeted deletion analysis by fluorescence in situ hybridization (FISH). Note: The 16p11.2 microdeletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques. * Chromosomal microarray (CMA) using oligonucleotide arrays or SNP genotyping arrays can detect the recurrent deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 16p11.2 region. Note: (1) Most individuals with 16p11.2 recurrent microdeletion are identified by CMA performed in the context of evaluation of developmental delay, intellectual disability, or ASD. (2) Prior to 2008 many CMA platforms did not include coverage for this region and thus may not have detected this deletion. * Targeted deletion analysis. FISH analysis, quantitative PCR (qPCR), multiplex ligation-dependent probe amplification (MLPA), or other targeted quantitative methods may be used to test relatives of a proband known to have the 16p11.2 recurrent microdeletion. Note: (1) Targeted deletion testing is not appropriate for an individual in whom the 16p11.2 recurrent microdeletion was not detected by CMA designed to target this region. (2) It is not possible to size the deletion routinely by use of targeted methods. ### Table 1. Genomic Testing Used for the 16p11.2 Recurrent Microdeletion View in own window Deletion 1ISCA ID 2Region Location 3, 4MethodSensitivity ProbandAt-risk family members ~593-kb heterozygous deletion at 16p11.2ISCA-37400GRCh37/hg19 chr16: 29,606,852-30,199,855Chromosomal microarray 5100%100% Targeted deletion analysis 6Not applicable 6100% 6 1\. See Molecular Genetics for details of the deletion. 2\. Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays (ISCA) Consortium) 3\. Genomic coordinates represent the minimum deletion size associated with the recurrent 16p11.2 deletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Please note that the size of the deletion as calculated from these genomic positions may differ from the expected deletion size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the recurrent 16p11.2 deletion (see Genetically Related Disorders). 4\. See Molecular Genetics, Genes typically included in this region. 5\. Chromosome microarray analysis (CMA) using oligonucleotide arrays or SNP genotyping arrays. CMA designs in current clinical use target the 16p11.2 region. Note: The 16p11.2 recurrent microdeletion may not have been detectable by older oligonucleotide or BAC platforms. 6\. Targeted deletion analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods. Targeted deletion analysis is not appropriate for an individual in whom the 16q11.2 recurrent microdeletion was not detected by CMA designed to target this region. Evaluating at-risk relatives. FISH, qPCR, or other quantitative methods of targeted deletion analysis can be used to identify the 16q11.2 recurrent microdeletion in at-risk relatives of the proband. Testing parental samples is important in determining recurrence risk (see Genetic Counseling). ## Clinical Characteristics ### Clinical Description The 16p11.2 recurrent microdeletion was first reported in individuals with autism spectrum disorder (ASD) [Kumar et al 2008, Marshall et al 2008, Weiss et al 2008]. Prior to that, this 16p11.2 recurrent microdeletion was reported as a de novo copy number variant in an individual with Asperger disorder [Sebat et al 2007] and in two monozygotic twins with seizures, mild intellectual disability, and aortic valve abnormalities [Ghebranious et al 2007]. Clinical follow-up data from adults suggests that the greatest medical challenges are obesity and related comorbidities that can be exacerbated by medications used to treat behavioral and psychiatric problems. Males and females are equally affected. Cognitive impairment. On average, the IQ of individuals with the 16p11.2 recurrent microdeletion is approximately 2 SD lower than other family members without the deletion. Average IQ was 82.7, representing a 26.8-point (1.8 SD) shift downward compared to the full scale IQ average of 109.5 of familial controls [Hanson et al 2015]. Other developmental delay. Most, if not all, individuals with the 16p11.2 recurrent microdeletion experience some degree of developmental delay, although the severity varies. Developmental coordination (motor) disorder was one of the most common diagnoses in individuals with the 16p11.2 recurrent microdeletion, followed by phonologic processing disorder, language disorders, and ASD [Hanson et al 2015]. In the authors' clinical experience, most individuals with the 16p11.2 recurrent microdeletion have been ascertained through genetic testing performed in the evaluation of developmental delay, intellectual disability, or ASD. Although developmental delays in this population are more related to diminished language and cognitive function, they can also involve problems with gross and fine motor skills. Language delay. About 70% of individuals with 16p11.2 recurrent microdeletion have one or more speech/language-related diagnoses. Overall, expressive language appears to be more affected than receptive language and phonologic (articulation) issues are the most common diagnosis given [Hanson et al 2015]. Children do acquire verbal skills but have significant issues with verbal communication including apraxia for the first five years of life. It is speculated that these delays in speech and language development may contribute to behavior problems. Autistic features. Individuals with the 16p11.2 recurrent microdeletion identified in the earliest reported research studies were ascertained primarily through cohorts of individuals with an ASD. Although not all individuals with the 16p11.2 recurrent microdeletion meet diagnostic criteria for ASD, almost all have some behavioral traits shared with ASD including insistence on sameness, reduced scope of interest, repetitive behaviors, and problems with social communication [Zufferey et al 2012, Hanson et al 2015, Moreno-De-Luca et al 2015]. Based on current literature reports, ASD is diagnosed in approximately 20% of individuals with the 16p11.2 microdeletion (i.e, with much greater frequency than in the general population, in which ASD is diagnosed in ~1:68 children). In a study by Hanson et al [2010], 11 individuals with the 16p11.2 recurrent microdeletion were evaluated for ASD using detailed measures including the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview: three of the 11 met full criteria for ASD (i.e., cutoffs on both measures); six had findings of ASD but did not meet full criteria; and two did not meet criteria for ASD. In addition, all 11 had some level of restricted or repetitive behavior patterns or interests either currently or in the past [Gault et al 2003]. More recently Hanson et al [2015] assessed 85 individuals with the 16p11.2 recurrent microdeletion with the detailed measures reported above and found that 24% had ASD. The majority of individuals with the deletion who did not meet full criteria for ASD had significantly higher rates of autism-related characteristics (e.g., social and behavioral difficulties and repetitive and stereotyped behaviors) when compared to family members who did not have the deletion. Psychiatric disease and behavioral issues. Hanson et al [2015] reported that 93% of individuals with the 16p11.2 microdeletion had at least one psychiatric diagnosis, compared to 21% of familial controls. The mean number of diagnoses in family members who did not have the deletion was 0.3; individuals with the deletion had an average of 2.9 diagnoses. These differences persisted after controlling for having ASD. Individuals with 16p11.2 microdeletion were found to have significantly higher levels and numbers of behavioral issues than familial controls [Hanson et al 2015]. Hanson et al [2010] did not find a link to ADHD although affective problems, somatic issues, and anxiety were commonly reported. Neurologic issues * Seizures are seen in about 20% of individuals with the 16p11.2 recurrent microdeletion. In a case report, one affected individual had EEG abnormalities without overt seizures [Rosenfeld et al 2010]. Heterozygous loss-of-function PRRT2 pathogenic variants (which cause paroxysmal kinesigenic dyskinesia; see following) also cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome [Heron et al 2012], both of which have been reported in a number of individuals with the 16p11.2 recurrent microdeletion. * Paroxysmal kinesigenic dyskinesia has been observed in a number of individuals with the 16p11.2 recurrent deletion [Termsarasab et al 2014]. Onset of movement-induced choreoathetosis and/or dystonia begins between ages six and 15 years with increasing frequency of paroxysms with age. Of note, loss-of-function heterozygous pathogenic variants in PRRT2, located at 16p11.2, have been identified as a cause of autosomal dominant paroxysmal kinesigenic dyskinesia [Chen et al 2011, Wang et al 2011, Lee et al 2012, Li et al 2012]. * Handedness. Of 75 of individuals with the 16p11.2 microdeletion, 19% had left hand dominance and 29% had mixed dominance compared to 3% and 11%, respectively, of family members without the deletion [Hanson et al 2015]. * Neuroimaging findings are mostly nonrecurrent abnormalities such as arachnoid cyst [Bijlsma et al 2009], prominent extra-axial CSF spaces and ventricles [Shinawi et al 2010], mega cisterna magna, and cavernous malformation [Rosenfeld et al 2010]. The most common recurrent structural brain abnormalities are posterior fossa and/or craniocervical junction-related abnormalities (e.g., Chiari I malformation, cerebellar tonsillar ectopia, platybasia) [Zufferey et al 2012]. In one case report, two persons with 16p11.2 microdeletion were reported to have syringomyelia (accompanied by a Chiari I malformation in one) [Schaaf et al 2011]. Quantitative structural MRI analysis has shown a pervasive increase in volume throughout the brain, with white matter and thalami being the most dramatically affected [Qureshi et al 2014]. Obesity. The 16p11.2 recurrent microdeletion is a predisposing factor for overweight (defined as sex-specific BMI for age 85-95th centile) and obesity (defined as sex-specific BMI for age >95th centile). Overall, several studies show that obesity is a feature of 16p11.2 microdeletion and that the prevalence of overweight and obesity in individuals with 16p11.2 microdeletion is higher than in the general population [Ghebranious et al 2007, Bijlsma et al 2009, Bochukova et al 2010, Fernandez et al 2010, Shinawi et al 2010, Walters et al 2010, Jacquemont et al 2011, Gill et al 2014]. Longitudinal studies show that the weight increase starts about age nine years and becomes increasingly problematic into adulthood, especially with use of certain medications used to treat problematic behaviors. Cardiac malformations and disease associations. Most individuals in whom the diagnosis of 16p11.2 microdeletion is confirmed have not had diagnostic cardiac imaging; however, limited clinical reports suggest that the incidence of cardiac malformations is slightly increased. Congenital heart disease was identified in 6% of 233 individuals with the 16p11.2 recurrent microdeletion [Zufferey et al 2012]. Other medical issues. Although consistent patterns of other medical problems are not observed, the following have been reported in individuals with the 16p11.2 recurrent microdeletion: * Height is slightly below average for individuals who are not overweight and may be average for individuals who are overweight. * Vertebral anomalies (often associated with scoliosis) were observed in 21% of 233 individuals with the microdeletion [Zufferey et al 2012]. * Macrocephaly is frequently observed, usually becomes apparent by age two years, and is usually not secondary to hydrocephalus. * Craniosynostosis was observed in 2% of 233 individuals [Zufferey et al 2012]. * Hearing impairment (sensorineural and conductive hearing loss) is seen in up to 11% of individuals. * A characteristic pattern of dysmorphic features that would facilitate a clinical diagnosis is not observed in individuals with the16p11.2 recurrent microdeletion. However, several studies have reported on various dysmorphic features [Bijlsma et al 2009, Rosenfeld et al 2010, Shinawi et al 2010]. * Severe combined immunodeficiency (SCID) was reported in one individual with 16p11.2 microdeletion on one chromosome 16 and a single-nucleotide variant in CORO1A on the other chromosome 16 [Shiow et al 2009]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been observed. ### Prevalence Estimates of prevalence vary. In one population of 299 individuals with autism and 18,834 control samples, three individuals in each category had 16p11.2 microdeletion, giving a population prevalence of approximately 3:10,000 [Weiss et al 2008]. That number is supported by more recent data showing 16p11.2 deletion in approximately 3.5 of 10,000 individuals from a larger, but overlapping, cohort of more than 76,000 Icelandic individuals [Stefansson et al 2014]. It should be noted that "controls" in that study may have had other diagnoses besides autism. Thus, some degree of neurodevelopmental disability in those individuals cannot be ruled out. 16p11.2 recurrent microdeletion was identified in seven of 1,105 children (0.7%) with unexplained intellectual disability but no history of autism [Mefford et al 2009]. Similar genetic testing of 4,284 individuals with intellectual disability or multiple congenital anomalies detected 22 (14 index cases and 8 family members) with the recurrent microdeletion of 16p11.2 [Bijlsma et al 2009]. Individuals identified in these reports did not have a recognizable clinical phenotype. Data drawing on the large ClinGen database of more than 15,000 cases tested in clinical labs demonstrates that the 16p11.2 deletion is the second most commonly identified microdeletion, occurring in one of every 235 cases tested [Kaminsky et al 2011]. ## Differential Diagnosis The differential diagnosis is broad, including any cause of developmental delay and/or autism spectrum disorder without obvious distinguishing clinical features. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with the 16p11.2 recurrent microdeletion, the following are recommended: * Routine clinical examination, including dysmorphology examination and broad review of all organ systems * Measurement of height and weight * Evaluate for hypertension and diabetes in patients who are overweight or obese * Developmental assessment with cognitive and behavioral testing, including neuropsychological testing by a clinical psychologist * Consultation with a neurologist (with possible EEG and MRI) if history suggests possible seizures * Consideration of brain MRI for headache (especially occipital), neck pain, oropharyngeal dysfunction, or other manifestations of brain stem dysfunction * Diagnostic radiograph of the spine to evaluate for vertebral anomalies/scoliosis * Consideration of evaluation and echocardiogram by a cardiologist if a heart murmur is detected * Audiologic testing * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Manifestations of the 16p11.2 recurrent microdeletion are variable, and treatment should be targeted to the specific findings identified. Early diagnosis and provision of therapies facilitate the best outcome. Referral to other appropriate medical specialists (e.g., a developmental/behavioral pediatrician, pediatric neurologist, and/or clinical geneticist) is recommended based on specific symptoms or signs. Neurodevelopmental disabilities including autism spectrum disorder (ASD). Interventions may include speech and language therapy, occupational therapy, and physical therapy. Because of the high incidence of expressive language delays, speech therapy and augmentative and assistive means of communication should be considered early. Guidelines for management of individuals with ASD are available from the American Academy of Pediatrics [Myers et al 2007] (full text). Seizures. Choice of antiepileptic medication is guided by patient age, seizure type, EEG and imaging findings, side effect profiles, and response to treatment. No specific antiepileptic medications have been identified to be most effective. Paroxysmal kinesigenic dyskinesia is responsive to low doses of carbamazepine and phenytoin. Obesity and overweight. It is important to initiate weight management and nutrition counseling in young children before excessive weight gain begins. Control food intake with normal portion sizes and limitation of food intake between meals. Maintain an active lifestyle. Increased calories are specifically ingested in the absence of hunger and suggest that close supervision of portion size and meal times can be beneficial. Chiari I malformation or syringomyelia. Brain and spine MRI are indicated for new or progressive symptoms suggestive of a Chiari I malformation or syringomyelia, including sleep apnea, dysarthria, dysphagia, gait disturbance, and scoliosis. ### Surveillance Routine developmental surveillance and screening are recommended because of the increased incidence of developmental delay, intellectual disability, and autism. See the American Academy of Pediatrics guidelines on surveillance and screening to identify patients with developmental disorders in general [Council on Children with Disabilities 2006] and autism in particular [Johnson et al 2007] and recommendations for management of children with ASD [Myers et al 2007] (Published Guidelines / Consensus Statements). Surveillance should include the following: * Monitoring of height, weight, and BMI * Monitoring for abnormal movements, staring spells, or other events of concern for possible seizures * Monitoring for headache (especially occipital), neck pain, and other symptoms of brain stem or spinal cord dysfunction that could indicate Chiari malformations/cerebellar ectopia, and neurologic consultation and brain MRI if indicated * Clinical screening for scoliosis until the age of skeletal maturity * Annual evaluation and monitoring of hearing in first three years of life * Periodic reevaluation by a clinical geneticist to apprise the family of new developments and/or recommendations and facilitate long-term monitoring for emerging medical or mental health concerns ### Agents/Circumstances to Avoid Some medications used to treat behavioral problems (e.g., clozapine, olanzapine) may lead to excessive weight gain. When possible, use medications that are not associated with weight gain. ### 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 access to 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 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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	16p11.2 Recurrent Microdeletion	None	28,993	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK11167/	2021-01-18T21:46:10	{"synonyms": []}
Phosphate Nephropathy Other namesNephrocalcinosis SpecialtyNephrology SymptomsSimilar with Acute kidney disease ComplicationsAcute kidney disease and Chronic kidney disease TypesKidney injury CausesUse of sodium phosphate Risk factorsDevelopment of Acute kidney disease Diagnostic methodFormation of calcium phosphate crystals PreventionAlternative bowel-preparation agents TreatmentRenal replacement therapy Phosphate nephropathy or nephrocalcinosis[1] is an adverse renal condition that arises with a formation of phosphate crystals within the kidney's tubules. This renal insufficiency is associated with the use of oral sodium phosphate (OSP) such as C.B. Fleet's Phospho soda and Salix's Visocol, for bowel cleansing prior to a colonoscopy.[2] According to the U.S. Food and Drug Administration (FDA), the potential risk factors of this complication are pre-existing kidney disease, increased age, female gender, dehydration, comorbidities such as diabetes mellitus, hypertension,...concurrent treatment with hypertensive medications (ACE inhibitors and angiotensin receptor blockers) and medications that affect renal perfusion (Nonsteroidal anti-inflammatory drug or NSAIDs and diuretics).[2] This complication can be diagnosed with renal tests and biomarkers in laboratories including histochemical staining of renal biopsy specimens,[3] the measure of creatinine level, GFR level, and urine output,[4][5] urine microscopy,[1] CT scanning,[6] and urinalysis.[3] Phosphate nephropathy may also lead to further renal complications including acute kidney diseases and chronic kidney diseases, or the abrupt and gradual loss of kidney function over time.[7] Different management approaches involve the use of alternative bowel preparation agents and increasing patients' risk assessment among healthcare professionals, including nephrologists, gastroenterologists, and renal pathologists.[8] Other agents used for bowel preparation (e.g. magnesium citrate or PEG-3350 & electrolyte-based purgatives such as Colyte or Golytely) do not carry this risk.[4][8] According to the U.S. Food and Drug Administration (FDA), "acute phosphate nephropathy is a rare, serious adverse event that has been associated with the use of OSPs. The occurrence of these events was previously described in an Information for Healthcare Professionals sheet and an FDA Science Paper issued in May 2006. Additional cases of acute phosphate nephropathy have been reported to FDA and described in the literature since these were issued." [2] ## Contents * 1 Natural history * 2 Signs and symptoms * 3 Diagnosis * 3.1 Pathophysiology * 3.2 Types of assessment * 4 Risk factors * 5 Management * 5.1 Prevention * 5.2 Treatment * 6 References * 7 Further reading ## Natural history[edit] Mannitol and large volume of saline were first used as bowel preparation agents prior to colonoscopy.[6] As the use of Mannitol causes the production of methane, hydrogen, and other flammable gases, it was reported to be associated with colonic explosion.[6] Large volume of saline was also reported to significantly impact the electrolyte balance and net fluid within the body.[6] Later in the 1990, the polyethylene-glycol electrolyte lavage solution or PEG-ELS, was formulated with more effectiveness and safety to use.[7] PEG-ELS was not widely adopted due to its requirement of consuming an enormous volume.[6] Then, OSP (C.B. Fleet's Phospho soda) in the form of tablets with the same efficacy as PEG-ELS, was chosen as a safe alternative bowel preparation agent.[7] Later, in 1975, acute kidney injury and potential chronic kidney disease were first found to be related to the ingestion of OSP.[8] Then, in 2003, an adverse incident of calcium phosphate deposition within the renal tubules was first reported following the use of OSP.[8] This was linked to the tubular injury and other renal complications as well as the emergence of the term “phosphate nephropathy”.[8] ## Signs and symptoms[edit] Patients with phosphate nephropathy have variable outcomes, either being recognised as developing acute kidney injury, the abrupt loss in renal failure, or being undiagnosed.[4] As the deposition of calcium phosphate crystals are detected at the renal tubules following the use of OSP, the symptoms of phosphate nephropathy are similar to acute tubular necrosis, an intrinsic renal injury.[9] For example, events including diarrhea, vomiting, dehydration, sepsis, and hypotension following the colonoscopy, can indicate the risk of phosphate nephropathy and raise the concern for acute tubular necrosis.[9] The results of hypotension and dehydration are dry mucous membrane, decreased skin turgor, and cool extremities, which can be used to notify the abnormal renal perfusion.[9] As there is a gap between the first administration of OSP and recognisable symptoms, many phosphate nephropathy incidences are overlooked and not proceeded to biopsy for further investigation.[8] The transient hyperphosphatasemia, the electrolyte disorder with elevated phosphate level in the blood, is found to be correlated with the use of OSP after colonoscopy.[10] Significant electrolyte abnormalities including hypocalcemia, hypernatremia, and hypomagnesemia are also the outcomes of the use of OSP.[4] As these detection tests are mostly operated at the laboratory level, phosphate nephropathy incidents are widely under-recognized and overlooked.[10] Depiction of different adverse renal conditions. Phosphate nephropathy or deposition of calcium phosphate within renal tubules belongs to the urinary stone problems. ## Diagnosis[edit] ### Pathophysiology[edit] The efficient elimination of phosphorus depends on the kidney’s filtration rate and the phosphorus bioavailability in the blood.[6] Most renal phosphorus is absorbed at the proximal tubules in comparison to the distal nephron.[11] The elevated phosphorus load, or hyperphosphatemia, can reduce the phosphorus reabsorption in the kidney’s proximal tubular within minutes of OSP ingestion.[1] This leads to hypovolemia, a large distribution of phosphate at the distal nephron without being completely reabsorbed at the proximal tubules.[11] Hypovolemia results in an increase of proximal salt and water at the descending limb of the loop of Henle, where calcium and phosphate are unable to permeate.[11] Hypovolemia collectively combines with the ongoing water and salt reabsorption in the proximal tubules, enhances the calcium phosphate precipitation within the renal tubular lumen.[11][9] Parathyroid hormone-induced calcium precipitation also contributes to the formation of calcium phosphate crystals, which thus impairs the renal function.[1] An excess phosphorus triggers calcium precipitation and reduces calcium absorption in the gastrointestinal tract.[1] This reduces the ionized calcium concentration in blood, which further induces a compensatory parathyroid hormone response.[1] Parathyroid hormone is reported to accelerate urinary calcium load, which results in the formation of calcium phosphate crystals in the renal distal tubules and collecting ducts.[1] When the calcium phosphate crystals bind to the tubular epithelial cells, the reactive oxygen species are released, which further impair the renal excretory pathway.[1] The use of OSP causes an increase in phosphatemia and impairs renal perfusion, which later leads to acute kidney injury and chronic kidney disease.[6] The calcification of major arteries like coronary arteries and cardiovascular complication risks can be the result of impaired kidney function in excreting calcium and phosphate.[12] ### Types of assessment[edit] Phosphate nephropathy can be diagnosed via different types of assessment, most of which are also used to detect acute kidney injury and chronic kidney disease.[1] Most phosphate nephropathy incidents are diagnosed weeks or months after taking OSP, due to its clinical silence.[8] For example, these assessments include the measurement of serum phosphorus with an elevation of more than 3 mmol/L,[4] the finding of an elevated serum creatinine level and a decrease in glomerular filtration rate (GFR),[4] urine microscopy for crystallization detection,[1] the image of calcium phosphate crystals deposited through CT scanning,[6] urinalysis,[3] renal biopsy specimens with histochemical staining for calcium phosphate.[8][3] These assessments are generally carried out within the laboratory environment, in which longer waiting time is required to attain the results. The measurement of serum creatinine level and GFR are used to indicate the severity stage of acute kidney injury or the duration of impairment of kidney function, when early-onset phosphate nephropathy occurs.[13] The more than 1.5 fold increase in serum creatinine level, or the more than 25% decrease in GFR, or the decrease in urine output less than 0.5mL/kg/h within 6 hours, signify the risk of attaining acute kidney injury after ingestion of OPS.[5] Urine microscopy is reported to be an accurate diagnostic assessment for underlying crystalline-induced nephropathy, either endogenous or drug-induced calcium phosphate crystals.[14] Via examining the urinary sediments, calcium phosphate crystals are identified, and the associated phosphate nephropathy is determined.[14] As phosphate nephropathy results in acute kidney injury and chronic kidney disease, the impairment in kidney function can be measured via urinalysis.[3] The presence of non-dysmorphic erythrocytes, modest proteinuria or protein within urine, pyuria or pus within urine, and leukocyte cast indicates acute tubular necrosis and acute tubulointerstitial nephritis.[3] For phosphate nephropathy with nonspecific symptoms, renal biopsy is reported as an important diagnosis due to the normal levels of both calcium and phosphorus.[13] Following renal biopsy, the calcium phosphate crystals are distinguished from calcium oxalate crystals via staining with haematoxylin and eosin, as calcium phosphate deposits lack birefringence under polarized light.[3] Then, the positive staining with the von Kossa stains can be used to display the presence of abnormal calcium and phosphate deposits respectively via light illumination.[8] ## Risk factors[edit] According to the FDA, caution is required to consider prior use of OSP, especially in patients with the following potential risk factors. For instance, people older than 55, female gender,[6] people with a history of kidney diseases if their GFR level is less than 60 mL/min,[1] people who recurrently on antihypertensive treatment with NSAIDs, ARBs, ACEIs, and diuretics, people who have lower fluid intake and less bowel movements,[2][1] people who have underlying systemic and gastrointestinal diseases,[1] and a short interval between OSP administrations (less than 12 hours interval).[11] The risk of acquiring phosphate nephropathy was reported to increase in parallel with the number of these listed risk factors.[11] Older people are particularly at risk when using OSP for colonoscopy, as they have lower fluid intake, have intrinsically less bowel movements, and often have antihypertensive or nephrotoxic drugs.[1] It is also reported that people with comorbidities including diabetes mellitus, hypertension, and other metabolic syndromes will have a higher risk of phosphate nephropathy.[13] ## Management[edit] ### Prevention[edit] As phosphate nephropathy is considered an irreversible complication when starting to progress into acute kidney injury and chronic kidney disease, prevention strategies can help to avoid the undesired outcomes.[1] According to the FDA, it is recommended for both healthcare professionals and patients, particularly high-risk individuals, to obtain adequate information about the adverse effect of OSP before administering and consuming this agent.[2] Monitoring of renal function weeks or months after the administration of OSP also helps to early detect and treat the condition appropriately.[1] Withholding the antihypertensive medications (ARBs, ACEIs), diuretic medications, and NSAIDs before and after the use of OSP for colonoscopy, is reported to minimize the risk of phosphate nephropathy.[4] As ingestion of OPS can potentially induce osmotic diarrhea and result in depletion of body fluid, adequate hydration is recommended before and after the procedure to prevent episodes of hypotension.[10] It is unknown whether water or electrolyte-containing solutions would adequately compensate the electrolyte imbalance following the use of OSP.[6] The recommended volume of fluid when using OSP as a bowel preparation agent varies from 0.7 to 2.2 L, with the optimal amount greater than 3.7 L.[6] It is still unknown whether lowering the standard doses of OSP from 45/45 ml to 45/30 mL in 9–12 hours apart would be safer to use, as lower OSP dose was reported to cause moderate elevation of serum phosphorus.[6][15] In addition, there are other relevant bowel-preparation agents that can be used in line with the colonoscopy guidelines including electrolyte-based purgatives such as Golytely, Polyethylene glycol (PEG), sodium picosulfate,[8] and sodium laxatives.[4] These bowel preparation alternatives show the same efficacy with OSP and cause less frequently and significantly side effects and complications than OSP.[15] ### Treatment[edit] Upon the early detection, phosphate nephropathy can be treated with a timely renal replacement therapy such as haemodialysis or peritoneal dialysis in order to decelerate the calcium phosphate crystallization process.[8] Haemodialysis is performed to assist the renal excretion via removing accumulated toxins, especially the overproduction of reactive oxygen species at the damaged tubular epithelial cells.[12] The complete recovery of renal function after phosphate nephropathy progression to acute kidney injury or to chronic kidney disease, was reported to be rare.[3] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p Honore, Patrick; Lochy, Stijn; Jacobs, Rita; De Waele, Elisabeth; Joannes-Boyau, Olivier; De Regt, Jouke; Van Gorp, Viola; Spapen, Herbert (March 2013). "Phosphate induced crystal acute kidney injury – an under-recognized cause of acute kidney injury potentially leading to chronic kidney disease: case report and review of the literature". International Journal of Nephrology and Renovascular Disease. 6: 61–4. doi:10.2147/IJNRD.S41428. ISSN 1178-7058. PMC 3605970. PMID 23662071. 2. ^ a b c d e Research, Center for Drug Evaluation and (2018-11-03). "Information on Oral Sodium Phosphate (OSP) Products for Bowel Cleansing (marketed as Visicol and OsmoPrep, and oral sodium phosphate products available without a prescription)". FDA. 3. ^ a b c d e f g h Monfared, A; Habibzadeh, S.M; Mesbah, S.A (2014). "Acute phosphate nephropathy". Iranian Journal of Kidney Diseases. 8 (3): 246–249. PMID 24878951. 4. ^ a b c d e f g h Abcar, Antoine (2009-07-01). "Acute Phosphate Nephropathy". The Permanente Journal. 13 (3). doi:10.7812/TPP/08-069. PMID 20740089. 5. ^ a b Makris, Konstantinos; Spanou, Loukia (May 2016). "Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes". The Clinical Biochemist Reviews. 37 (2): 85–98. ISSN 0159-8090. PMC 5198510. PMID 28303073. 6. ^ a b c d e f g h i j k l Heher, Eliot C.; Thier, Samuel O.; Rennke, Helmut; Humphreys, Benjamin D. (September 2008). "Adverse Renal and Metabolic Effects Associated with Oral Sodium Phosphate Bowel Preparation". Clinical Journal of the American Society of Nephrology. 3 (5): 1494–1503. doi:10.2215/CJN.02040408. ISSN 1555-9041. PMC 4571150. PMID 18596115. 7. ^ a b c Markowitz, Glen S; Nasr, Samih H; Klein, Philip; Anderson, Herman; Stack, Jay I; Alterman, Lloyd; Price, Barbara; Radhakrishnan, Jai; D’agati, Vivette D (June 2004). "Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing". Human Pathology. 35 (6): 675–684. doi:10.1016/j.humpath.2003.12.005. PMID 15188133. 8. ^ a b c d e f g h i j k Davies, Matthew R. P.; Williams, David; Niewiadomski, Olga D. (September 2018). "Phosphate nephropathy: an avoidable complication of bowel preparation for colonoscopy: Brief Communications". Internal Medicine Journal. 48 (9): 1141–1144. doi:10.1111/imj.14015. PMID 30182391. 9. ^ a b c d Hanif, Muhammad O.; Bali, Atul; Ramphul, Kamleshun (2020), "Acute Renal Tubular Necrosis", StatPearls, StatPearls Publishing, PMID 29939592, retrieved 2020-05-29 10. ^ a b c Markowitz, Glen S.; Stokes, M. Barry; Radhakrishnan, Jai; D’Agati, Vivette D. (2005-11-01). "Acute Phosphate Nephropathy following Oral Sodium Phosphate Bowel Purgative: An Underrecognized Cause of Chronic Renal Failure". Journal of the American Society of Nephrology. 16 (11): 3389–3396. doi:10.1681/ASN.2005050496. ISSN 1046-6673. PMID 16192415. 11. ^ a b c d e f Markowitz, Glen S.; Perazella, Mark A. (November 2009). "Acute phosphate nephropathy". Kidney International. 76 (10): 1027–1034. doi:10.1038/ki.2009.308. PMID 19675530. 12. ^ a b Vadakedath, Sabitha; Kandi, Venkataramana (2017-08-23). "Dialysis: A Review of the Mechanisms Underlying Complications in the Management of Chronic Renal Failure". Cureus. 9 (8): e1603. doi:10.7759/cureus.1603. ISSN 2168-8184. PMC 5654453. PMID 29067226. 13. ^ a b c Rocuts, Alexander K.; Waikar, Sushrut S.; Alexander, Mariam P.; Rennke, Helmut G.; Singh, Ajay K. (May 2009). "Acute phosphate nephropathy". Kidney International. 75 (9): 987–991. doi:10.1038/ki.2008.293. PMID 18580858. 14. ^ a b Luciano, R. L.; Perazella, M. A. (2015-04-01). "Crystalline-induced kidney disease: a case for urine microscopy". Clinical Kidney Journal. 8 (2): 131–136. doi:10.1093/ckj/sfu105. ISSN 2048-8505. PMC 4370296. PMID 25815167. 15. ^ a b Moon, Won (2013-05-31). "Optimal and Safe Bowel Preparation for Colonoscopy". Clinical Endoscopy. 46 (3): 219–223. doi:10.5946/ce.2013.46.3.219. ISSN 2234-2400. PMC 3678056. PMID 23767029. ## Further reading[edit] * "Acute phosphate nephropathy and renal failure". New England Journal of Medicine. 2003 Sep 4;349(10):1006-7. * "Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing". Human Pathology. 2004 Jun;35(6):675-84. * "Renal failure following bowel cleansing with a sodium phosphate purgative". Nephrology Dialysis Transplantation. 2005 Apr;20(4):850-1. * "Acute Phosphate Nephropathy following Oral Sodium Phosphate Bowel Purgative: An Underrecognized Cause of Chronic Renal Failure". Journal of the American Society of Nephrology. 2005 Nov 1;16(11). * v * t * e Diseases of the urinary system (N00–N39, 580–599) Kidney disease Glomerules Primarily nephrotic Non-proliferative * Minimal change * Focal segmental * Membranous Proliferative * Mesangial proliferative * Endocapillary proliferative * Membranoproliferative/mesangiocapillary By condition * Diabetic * Amyloidosis Primarily nephritic, RPG Type I RPG/Type II hypersensitivity * Goodpasture's syndrome Type II RPG/Type III hypersensitivity * Post-streptococcal * Lupus * DPGN * IgA/Berger's Type III RPG/Pauci-immune * Granulomatosis with polyangiitis * Microscopic polyangiitis * Eosinophilic granulomatosis with polyangiitis General * glomerulonephritis * glomerulonephrosis Tubules * Renal tubular acidosis * proximal * distal * Acute tubular necrosis * Genetic * Fanconi syndrome * Bartter syndrome * Gitelman syndrome * Liddle's syndrome Interstitium * Interstitial nephritis * Pyelonephritis * Balkan endemic nephropathy General General syndromes * Nephritis * Nephrosis * Renal failure * Acute renal failure * Chronic kidney disease * Uremic pericarditis * Uremia * Diabetes insipidus * Nephrogenic * Renal papilla * Renal papillary necrosis * Major calyx/pelvis * Hydronephrosis * Pyonephrosis * Reflux nephropathy Vascular * Renal artery stenosis * Renal ischemia * Hypertensive nephropathy * Renovascular hypertension * Renal cortical necrosis Other * Analgesic nephropathy * Renal osteodystrophy * Nephroptosis * Abderhalden–Kaufmann–Lignac syndrome Urinary tract Ureter * Ureteritis * Ureterocele * Megaureter Bladder * Cystitis * Interstitial cystitis * Hunner's ulcer * Trigonitis * Hemorrhagic cystitis * Neurogenic bladder dysfunction * Bladder sphincter dyssynergia * Vesicointestinal fistula * Vesicoureteral reflux Urethra * Urethritis * Non-gonococcal urethritis * Urethral syndrome * Urethral stricture/Meatal stenosis * Urethral caruncle Any/all * Obstructive uropathy * Urinary tract infection * Retroperitoneal fibrosis * Urolithiasis * Bladder stone * Kidney stone * Renal colic * Malakoplakia * Urinary incontinence * Stress * Urge * Overflow [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Phosphate nephropathy	None	28,994	wikipedia	https://en.wikipedia.org/wiki/Phosphate_nephropathy	2021-01-18T18:35:13	{"wikidata": ["Q7187433"]}
Usual interstitial pneumonia Other namesUsual interstitial pneumonitis (UIP) CT scan of a patient with UIP. There is interstitial thickening, architectural distortion, honeycombing and bronchiectasis. SpecialtyRespirology Usual interstitial pneumonia (UIP) is a form of lung disease characterized by progressive scarring of both lungs.[1] The scarring (fibrosis) involves the supporting framework (interstitium) of the lung. UIP is thus classified as a form of interstitial lung disease. ## Contents * 1 Terminology * 2 Signs and symptoms * 3 Causes * 4 Diagnosis * 4.1 Radiology * 4.2 Histology * 4.3 Differential diagnosis * 5 Management * 6 Prognosis * 7 History * 8 See also * 9 References * 10 External links ## Terminology[edit] The term "usual" refers to the fact that UIP is the most common form of interstitial fibrosis. "Pneumonia" indicates "lung abnormality", which includes fibrosis and inflammation. A term previously used for UIP in the British literature is cryptogenic fibrosing alveolitis (CFA), a term that has fallen out of favor since the basic underlying pathology is now thought to be fibrosis, not inflammation. The term usual interstitial pneumonitis (UIP) has also often been used, but again, the -itis part of that name may overemphasize inflammation. ## Signs and symptoms[edit] The typical symptoms of UIP are progressive shortness of breath and cough for a period of months. In some patients, UIP is diagnosed only when a more acute disease supervenes and brings the patient to medical attention. ## Causes[edit] The cause of the scarring in UIP may be known (less commonly) or unknown (more commonly). Since the medical term for conditions of unknown cause is "idiopathic", the clinical term for UIP of unknown cause is idiopathic pulmonary fibrosis (IPF).[2] Examples of known causes of UIP include connective tissue diseases (primarily rheumatoid arthritis), drug toxicity, chronic hypersensitivity pneumonitis, asbestosis and Hermansky–Pudlak syndrome.[2] ## Diagnosis[edit] Usual interstitial pneumonia seen on CT scan. Honeycomb fibrosis is seen at the bases of both lungs. UIP may be diagnosed by a radiologist using computed tomography (CT) scan of the chest, or by a pathologist using tissue obtained by a lung biopsy. ### Radiology[edit] Radiologically, the main feature required for a confident diagnosis of UIP is honeycomb change in the periphery and the lower portions (bases) of the lungs.[3] On high-resolution computed tomography (HRCT), the following categories, depending on imaging findings, have been recommended by a collaborative effort by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society:[4] * UIP pattern:[4] * Honeycombing, with or without peripheral traction bronchiectasis or bronchiolectasis * Predominantly subpleural and basal * Often heterogenous distribution, being occasionally diffuse, and may be asymmetrical There may be superimposed CT features such as mild ground-glass opacity, reticular pattern and pulmonary ossification. * Probable UIP pattern:[4] * Predominantly subpleural and basal * Often hererogenous distribution * Reticular pattern with peripheral traction bronchiectasis or bronchiolectasis * There may be mild ground-glass opacity * Indeterminate for UIP:[4] * Predominantly subpleural and basal * Subtle reticular pattern * May have mild ground-glass opacity or distortion (“early UIP pattern”) * Findings suggestive of another diagnosis, including:[4] * Other predominant distribution: * Peribronchovascular * Perilymphatic * Upper or mid-lung * Cysts * Marked mosaic pattern * Predominant ground-glass opacity * Profuse micronodules * Nodules, especially centrilobular * Consolidation * Pleural plaques (indicating asbestosis) * Dilated esophagus (indicating connective tissue disease) * Distal clavicular erosions (indicating rheumatoid arthritis) * Extensive lymph node enlargement * Pleural effusion * Pleural thickening (indicating connective tissue disease/drugs) ### Histology[edit] The histologic hallmarks of UIP, as seen in lung tissue under a microscope by a pathologist, are interstitial fibrosis in a "patchwork pattern", honeycomb change and fibroblast foci (see images below).[5] * Pathological findings in usual interstitial pneumonia (UIP) * Appearance of usual interstitial pneumonia (UIP) in a surgical lung biopsy at low magnification. The tissue is stained with hematoxylin (purple dye) and eosin (pink dye) to make it visible. The pink areas in this picture represent lung fibrosis (collagen stains pink). Note the "patchwork" (quilt-like) pattern of the fibrosis. * Appearance of honeycomb change in a surgical lung biopsy at low magnification. The dilated spaces seen here are filled with mucin. Hematoxylin-eosin stain, low magnification. * A fibroblast focus in a surgical lung biopsy of UIP. Hematoxylin-eosin stain, high magnification. The white space to the left is an airspace. The pale area to the right is a fibroblast focus. It is an area of active fibroblast proliferation within the interstitium of the lung. ### Differential diagnosis[edit] The differential diagnosis includes other types of lung disease that cause similar symptoms and show similar abnormalities on chest radiographs. Some of these diseases cause fibrosis, scarring or honeycomb change. The most common considerations include: * chronic hypersensitivity pneumonitis * non-specific interstitial pneumonia * sarcoidosis * pulmonary Langerhans cell histiocytosis * asbestosis [6] ## Management[edit] Oxygen therapy may assist with daily living. In case of idiopathic pulmonary fibrosis, certain medications like nintedanib and pirfenidone can help slow the progression.[7] Lastly, lung transplants may help. ## Prognosis[edit] Regardless of cause, UIP is relentlessly progressive, usually leading to respiratory failure and death without a lung transplant.[citation needed] Some patients do well for a prolonged period of time, but then deteriorate rapidly because of a superimposed acute illness (so-called "accelerated UIP"). The outlook for long-term survival is poor. In most studies, the median survival is 3 to 4 years.[citation needed] Patients with UIP in the setting of rheumatoid arthritis have a slightly better prognosis than UIP without a known cause (IPF). ## History[edit] UIP, as a term, first appeared in the pathology literature. It was coined by Averill Abraham Liebow.[8] ## See also[edit] * Pneumoconiosis * Silicosis * Asbestosis * Idiopathic pulmonary fibrosis * Pulmonary fibrosis * Emphysema ## References[edit] 1. ^ Travis WD, King TE, Bateman ED, et al. (2002). "ATS/ERS international multidisciplinary consensus classification of idiopathic interstitial pneumonias. General principles and recommendations". American Journal of Respiratory and Critical Care Medicine. 165 (5): 277–304. doi:10.1164/ajrccm.165.2.ats01. PMID 11790668. 2. ^ a b Wuyts, W. A.; Cavazza, A.; Rossi, G.; Bonella, F.; Sverzellati, N.; Spagnolo, P. (2014). "Differential diagnosis of usual interstitial pneumonia: when is it truly idiopathic?". European Respiratory Review. 23 (133): 308–319. doi:10.1183/09059180.00004914. ISSN 0905-9180. 3. ^ Sumikawa H, et al. (2008). "Computed tomography findings in pathological usual interstitial pneumonia: relationship to survival". American Journal of Respiratory and Critical Care Medicine. 177 (4): 433–439. doi:10.1164/rccm.200611-1696OC. PMID 17975197. 4. ^ a b c d e Raghu, Ganesh; Remy-Jardin, Martine; Myers, Jeffrey L.; Richeldi, Luca; Ryerson, Christopher J.; Lederer, David J.; Behr, Juergen; Cottin, Vincent; Danoff, Sonye K.; Morell, Ferran; Flaherty, Kevin R.; Wells, Athol; Martinez, Fernando J.; Azuma, Arata; Bice, Thomas J.; Bouros, Demosthenes; Brown, Kevin K.; Collard, Harold R.; Duggal, Abhijit; Galvin, Liam; Inoue, Yoshikazu; Jenkins, R. Gisli; Johkoh, Takeshi; Kazerooni, Ella A.; Kitaichi, Masanori; Knight, Shandra L.; Mansour, George; Nicholson, Andrew G.; Pipavath, Sudhakar N. J.; Buendía-Roldán, Ivette; Selman, Moisés; Travis, William D.; Walsh, Simon L. F.; Wilson, Kevin C. (2018). "Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline". American Journal of Respiratory and Critical Care Medicine. 198 (5): e44–e68. doi:10.1164/rccm.201807-1255ST. ISSN 1073-449X. 5. ^ Katzenstein AL, Mukhopadhyay S, Myers JL (2008). "Diagnosis of usual interstitial pneumonia and distinction from other fibrosing interstitial lung diseases". Human Pathology. 39 (9): 1275–1294. doi:10.1016/j.humpath.2008.05.009. PMID 18706349. 6. ^ Leslie, Kevin O; Wick, Mark R. (2005). Practical pulmonary pathology: a diagnostic approach. Edinburgh: Churchill Livingstone. ISBN 0-443-06631-0. OCLC 156861539. 7. ^ Reviewed and approved by the American Lung Association Scientific and Medical Editorial Review Panel. Last reviewed February 5, 2018. 8. ^ Averill Abraham Liebow at Who Named It? ## External links[edit] Classification D * ICD-10: J84.1 * ICD-9-CM: 515 * DiseasesDB: 4815 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Usual interstitial pneumonia	c1800706	28,995	wikipedia	https://en.wikipedia.org/wiki/Usual_interstitial_pneumonia	2021-01-18T18:48:11	{"mesh": ["D054990"], "wikidata": ["Q17147306"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Pulmonary agenesis" – news · newspapers · books · scholar · JSTOR (April 2020) Pulmonary agenesis Chest radiograph of a woman with unilateral pulmonary agenesis SpecialtyPulmonology Pulmonary agenesis is an inborn lung underdevelopment that is rare and potentially lethal.[1] The disorder is caused by a complete developmental arrest of the primitive lung during embryonic life, and it is often associated with other developmental defects.[2] Bilateral and unilateral pulmonary agenesis are classified, depending on whether one side of the lung or both sides are affected. Bilateral pulmonary agenesis is lethal, while the mortality rate of unilateral pulmonary agenesis is higher than 50%.[3] Depending on the severity, the symptom ranges from none to various respiratory complaints.[4] It is detectable prenatally, however, its nonspecific clinical features act as the obstacle for diagnosing.[2] The exact cause of pulmonary agenesis is still obscure. However, theories have been raised regarding the vascular, iatrogenic, viral and genetic causes of pulmonary agenesis in an attempt to explain the pathogenesis of the disorder.[5] In most cases of pulmonary agenesis, surgical resection is performed to remove the malformed lobe or the entire defected lung of the patient depending on the severity of the respiratory impairment.[6] ## Contents * 1 Signs and symptoms * 1.1 Bilateral pulmonary agenesis * 1.2 Unilateral pulmonary agenesis * 1.3 Associated anomalies * 2 Causes * 3 Diagnosis * 3.1 Prenatal * 3.2 After birth * 4 Treatment * 5 Prognosis * 6 History * 7 References ## Signs and symptoms[edit] Pulmonary agenesis is the complete absence of lung tissue, including bronchial tree, lung parenchyma, and supporting vasculatures.[7] The only remaining part is rudimentary bronchus.[7] Hence, the affected areas lose their function of gas exchange.[7] This malformation is thought to involve the proliferation arrest of lung buds during embryo development, while the causes are still debatable. In many cases, it is associated with the occurrence of other inborn malformations.[7] The estimated prevalence of pulmonary agenesis is 34/1,000,000 live births, with a slightly higher possibility in the female population.[8] Two types of pulmonary agenesis are classified based on the severity of underdevelopment: bilateral and unilateral pulmonary agenesis.[citation needed] ### Bilateral pulmonary agenesis[edit] Bilateral pulmonary agenesis means that both sides of the lung are absent, its occurrence is rare compared to unilateral pulmonary agenesis.[9] The fetus losses the ability to do gas change, and is hence incompatible with life after birth.[9] ### Unilateral pulmonary agenesis[edit] The severity of unilateral pulmonary agenesis varies depending on the area of tissue affected, being either a single lobe or a whole lung.[4] The clinical features varies in individuals from asymptomatic to various respiratory complaints.[4] The occurrences of symptoms also vary from infant stage to childhood, teenager, and adult life.[4] Frequently seen clinical features includes dyspnea, respiratory distress, recurrent pulmonary infections, and limited exercise tolerance.[4] Rapid heartbeat, cyanosis, chest asymmetry, dullness may also be present.[4] Lung function is significantly affected in cases of pulmonary agenesis, demonstrated by reduction in forced expiratory volume and forced vital capacity.[4] This reduction in total lung volume sets limits on patients’ exercise tolerance, and contribute to shortness of breath after exercises.[4] The retention of bronchial secretions often leads to recurrent pulmonary infections, adding to damage in lung function, hence causing respiratory stress.[10] ### Associated anomalies[edit] Considering the fact that a large proportion of mortality cases of pulmonary agenesis are partly due to the presence of associated malformations, it is common to find other congenital anomalies associated with this type of disorder. Although some cases of bilateral pulmonary agenesis were reported as an isolated finding, most cases of pulmonary agenesis are associated with other anomalies, especially in the gastrointestinal, genitourinary and ocular systems. Frequently associated congenital anomalies include tracheal stenosis, esophageal atresia, tracheoesophageal fistula, bronchogenic cysts, patent ductus arteriosus, tetralogy of Fallot and anomalies of the great vessels.[11] ## Causes[edit] Although pulmonary agenesis, aplasia and hypoplasia are lethal congenital disorders all resulting from underdevelopment of lungs, pulmonary agenesis and aplasia differ from pulmonary hypoplasia in their underlying cause.[12] Unlike pulmonary hypoplasia which in most cases result from the incomplete development of lung during prenatal development,[13] pulmonary agenesis and aplasia result from a complete developmental arrest of the primitive lung during embryonic life.[12] Whether the disorder is bilateral or unilateral depends on the stage in which the arrest occurs during the embryonic stage of lung development.[12] The earlier the occurrence of developmental arrest, the more severe the defect and the more likely that the agenesis will be bilateral.[12] Bilateral pulmonary agenesis is highly rare and it is caused by the complete failure in the development of respiratory primordium,[11] the primary structure developed in the earliest stage of embryonic development that gives rise to the entire respiratory tract.[14] In this case, the absence of lung buds or pleural cavities is observed,[11] thus making the case of bilateral pulmonary agenesis highly lethal. On the other hand, unilateral pulmonary agenesis is caused by the imbalance in the development of lung buds. Either one side of the lung fails completely, leading to pulmonary aplasia, or one side of the lung is underdeveloped, leading to dysplasia or hypoplasia.[11] These defects occur during the early stage of lung development, although not as early as bilateral pulmonary agenesis, when respiratory primordium bifurcates into right and left primitive lung buds at the end of the fourth week of gestation.[11] Although the exact cause of the disorder remains obscure, theories have been advanced throughout history to explain the pathogenesis of lung agenesis.[15] Based on an in vitro experiment done in rats, researchers observed lung aplasia in animals that were fed with a diet deficient in vitamin A.[16] From the result of this experiment, a theory was raised that vitamin A deficiency during pregnancy may cause pulmonary agenesis. Some authors have suggested vascular cause of pulmonary agenesis similar to the causes for intestinal atresia[15] and others suggested Iatrogenic and viral factors as potential causes of pulmonary agenesis.[15] Genetic cause for pulmonary agenesis has also been raised. It has been said that the gene responsible for the cause of pulmonary agenesis may have variable expressivity and penetrance.[15] ## Diagnosis[edit] The symptoms of pulmonary agenesis are unspecific, and their occurrence varies between individuals.[2] These factors increased the difficulty for physicians to diagnose. So, there is a considerable time delay for the disease to be diagnosed, though it's capable of detection since birth or even prenatally.[2] ### Prenatal[edit] Prenatal diagnosis of pulmonary agenesis is yet to be reached satisfaction, due to the technical difficulties in differentiating this disorder with other malformation.[2] Only a few cases of reported cases are diagnosed before birth.[2] Prenatal sonographic evaluation, also known as Biophysical profile is frequently used for prenatal testing. High frequency of associated abnormalities (see the section - "Associated Abnormalities" for details) may also lead to suspicion of pulmonary agenesis.[2] 2‐dimensional color Doppler imaging could visually capture the blood flow, hence determine the existence of pulmonary vasculature.[2] It is also a frequently used technique for pulmonary agenesis diagnosis.[2] Congenital diaphragmatic hernia (CDH), in this case, the upward displacement of the diaphragm and abdominal organs, is a possible clinical outcome detectable before birth.[7] The displacement is caused by organ herniation occupying the empty space in the chest wall, while this space is created by the absence of lung tissue.[7] However, it's important to note that a list of other disorders could also be the cause of CDH.[7] ### After birth[edit] Several techniques are frequently involved in the diagnosis of pulmonary agenesis after birth: * Chest X-ray is effective in detecting the traits of lung herniation.[1] The unaffected side of lung tends to undergo hypertrophy, and move towards the empty space in the chest wall on the opposite side.[1] This herniation could be indicated by fluoroscopy.[1] With age increasing, the herniation progresses and ease its detection.[1] * Pulmonary angiography assists in detecting the presence of pulmonary artery branches, differentiating pulmonary agenesis to hypoplasia and aplasia.[4] * Electrocardiogram is useful in detecting dextrocardia, a possible outcome when agenesis is present on the right lung.[1] With empty space in the chest wall, the heart rotates in clockwise direction, shifting the location for apex beat occurrence.[1] Hence cardiac physical examination also helps as heart sounds is heard best at right chest with dextrocardia.[1][4] In the condition of left side agenesis, heart sounds will appear to be louder than normal.[1][4] * Chest asymmetry, as a possible trait for pulmonary agenesis, is found to be more obvious in adult patients, especially in males.[4] Breast development in females tends to make it less obvious for the observance of asymmetry, though it could still be indicated by a more conical shape and slightly higher location of the breast on the affected side.[4] * CT scan, bronchoscopy, bronchography and Magnetic resonance imaging also contributes to the observation of patients’ lung anatomy.[4] ## Treatment[edit] The treatment is dependent on the severity of respiratory impairment and the underlying etiology of the disorder.[13] In most cases, surgical resection is performed to remove the nonfunctioning lobe or the entire defected lung.[13] Removing the malformed part of the lung helps reduce symptoms and chances of lung infection.[17] In the past, patients underwent pulmonary plombage to render the empty hemithorax.[17] Plombage, also known as extraperiosteal or extrapleural pneumonolysis, is a historical treatment procedure for cavity tuberculosis of upper lobes of lungs used between the 1930s and 1950s.[18] During the operation, a cavity is created by the intrathoracic placement of inert materials, commonly Lucite (acrylic) balls, ping pong balls, oils, rubber sheets, paraffin wax, and gauze.[18] As a result, the mediastinal and skeletal shift toward the volume loss side.[13] Chest radiograph of a 3-year-old who underwent right pulmonary plombage with insertion of three Ping-Pong balls 1 year earlier.[13] Recent approach involves the implantation of tissue expander either via open thoracotomy or thoracoscopically in an attempt to shift the mediastinum back to its anatomical location.[19] Such surgical procedure involving the implantation of tissue expander for treating pulmonary agenesis was first reported in Berlin, Germany which was then followed by reports from Bordeaux, France and Verona, Italy.[19] The main focus of the treatment procedure is to preserve the remaining functional tissue[13] and prevent significant musculoskeletal disfigurement that may arise as a side effect of tissue expander implantation, as the mediastinal and skeletal shift towards the volume-loss side.[13] If the defect is extensive but there is a chance for the fetus to live, an exo-utero intrapartum treatment (EXIT) may be performed to salvage the potential life.[17] EXIT technique involves partial delivery of a baby through an incision in the uterus while remaining attached to their mother's placenta.[18] Such procedure is necessary for babies who require airway support so that they are provided with a functioning airway before they are detached from their mother's placenta.[18] The EXIT procedure is used to perform lung resection for babies with extensive lung defects in a relatively stabilized condition after birth.[20] ## Prognosis[edit] Prognosis of pulmonary agenesis depends on the degree of pulmonary involvement during the embryonic stage of lung development, as well as the patient's history of pulmonary infections and the presence of associated anomalies.[17] The majority of patients diagnosed with bilateral pulmonary agenesis die in utero or within the first few hours after birth.[21] Numerous cases of bilateral pulmonary agenesis, where both lungs have been affected, have been reported previously.[18] On the other hand, the hypertrophy of the remaining lung to compensate for the lost lung is common in the case of unilateral pulmonary agenesis.[21] However, the mortality rate still exceeds 50%. Most causes of death are because of the presence of associated anomalies and malformations, which are common for pulmonary agenesis especially involving right-sided defects. Those suffering right-sided defects normally have poorer prognosis than those with left-sided defects, partly because the right side of the lung is usually more prone to infection considering the standard anatomical position of right bronchus, and also because cases with right-sided lung disorders have shown higher association rates with other anomalies.[17] In fact, it has been suggested that right-sided defects produce a more severe mediastinal shift, distorting the trachea and great vessels.[17] ## History[edit] Pulmonary agenesis was a confusing term before Boyden's classification was published. Before that, the term agenesis was used frequently when reporting cases related to underdeveloped lungs, regardless of the degree of the underdevelopment.[1] In 1955, Boyden classified pulmonary agenesis into 3 groups: agenesis, aplasia, and hypoplasia, which has been adopted by most researchers nowadays.[1] As a clarification, the term “pulmonary agenesis” in this Wikipedia page will only be referring to the agenesis in Boyden's classification, hence the information contained may not be valid for pulmonary aplasia or hypoplasia unless specifically mentioned.[4] ## References[edit] 1. ^ a b c d e f g h i j k Maltz, David; Nadas, Alexander (1968). "Presentation of Eight New Cases and Review of the Literature". Pediatrics. 42 (1): 175–88. 2. ^ a b c d e f g h i Meller, Cesar; Morris, Katie; Desai, Tarak; Kilby, Mark (2012). "Prenatal Diagnosis of Isolated Right Pulmonary Agenesis Using Sonography Alone". Journal of Ultrasound in Medicine. 31 (12): 2017–23. doi:10.7863/jum.2012.31.12.2017. PMID 23197556. 3. ^ Pediatric critical care. Fuhrman, Bradley P. (4th ed.). Philadelphia, PA: Elsevier Saunders. 2011. ISBN 978-0-323-08170-2. OCLC 722808791.CS1 maint: others (link) 4. ^ a b c d e f g h i j k l m n o Booth, J.B.; Berry, C.L. (1967). "Unilateral Pulmonary Agenesis". Arch Dis Child. 42 (224): 361–74. doi:10.1136/adc.42.224.361. PMC 2019767. PMID 4951635. 5. ^ Dordea Leonte, Laura (2013). "Fetology. Diagnosis and Management of the Fetal Patient". Acta Endocrinologica (Bucharest). 9 (4): 657. doi:10.4183/aeb.2013.657. ISSN 1841-0987. 6. ^ Holder, Tom; Ashcraft, Keith (2010), "Dedication", Ashcraft's Pediatric Surgery, Elsevier, pp. v, doi:10.1016/b978-1-4160-6127-4.00084-7, ISBN 978-1-4160-6127-4 7. ^ a b c d e f g Vettraino, Ivana; Tawil, Abir; Comstock, Christine (2003). "Bilateral Pulmonary Agenesis". American Institute of Ultrasound in Medicine. 22 (7): 723–6. doi:10.7863/jum.2003.22.7.723. PMID 12862273. 8. ^ J. E., Skandalakis; S. W., Gray; P, Symbas (1994). Embryology for Surgeons (2 ed.). pp. 429–32. 9. ^ a b D. R., Biyyam; T, Chapman; M. R., Ferguson; G, Deutsch; M. K., Dighe (2010). "Congenital lung abnormalities: embryologic features, prenatal diagnosis, and postnatal radiologic-pathologic correlation". Radiographics : A Review Publication of the Radiological Society of North America, Inc (6 ed.). 30 (6): 1721–38. doi:10.1148/rg.306105508. PMID 21071385. 10. ^ Nikam, Vasudha; Nagure, Pramod (2018). "Agenesis of Right Lung: A Rare Congenital Disorder". Int J Pediatr. 6 (4): 7473–78. doi:10.22038/ijp.2018.29561.2593. 11. ^ a b c d e Susan E, Wert (2004). Fetal and Neonatal Physiology (3rd ed.). 12. ^ a b c d Bradley P. Fuhrman and Jerry J. Zimmerman. (2011). Pediatric Critical Care (4th ed.). p. 599. ISBN 978-0-323-07307-3. 13. ^ a b c d e f g Ashcraft, K. W., Holcomb, G. W., Murphy, J. P., & Ostlie, D. J. (2010). Ashcraft's pediatric surgery (5th ed.). Philadelphia: Saunders/Elsevier. 14. ^ respiratory primordium. (n.d.). Retrieved April 4, 2020, from https://medical-dictionary.thefreedictionary.com/respiratory primordium. 15. ^ a b c d Fetology: Diagnosis and Management of the Fetal Patient, 2e. (n.d.). Retrieved April 4, 2020, from https://obgyn.mhmedical.com/content.aspx?bookid=1306§ionid 16. ^ Josef Warkany, Carolyn B. Roth (1948). Congenital Malformations Induced in Rats by Maternal Vitamin A Deficiency: II. Effect of Varying the Preparatory Diet Upon the Yield of Abnormal Young: Four Figures, The Journal of Nutrition, Volume 35, Issue 1, January 1948, Pages 1–11, https://doi.org/10.1093/jn/35.1.1 17. ^ a b c d e f Bradley P. Fuhrman and Jerry J. Zimmerman (2011). Pediatric Critical Care (4th ed.). ISBN 978-0-323-07307-3. 18. ^ a b c d e Lee, Kyung A; Cho, Jeong Yeon; Lee, Seung Mi; Jun, Jong Kwan; Kang, Jieun; Seo, Jeong-Wook (2010). "Prenatal Diagnosis of Bilateral Pulmonary Agenesis: a Case Report". Korean Journal of Radiology. 11 (1): 119–122. doi:10.3348/kjr.2010.11.1.119. PMC 2799641. PMID 20046503. 19. ^ a b Plombage: Radiology Reference Article. (2018). Retrieved April 4, 2020, from https://radiopaedia.org/articles/plombage 20. ^ Ex-Utero Intrapartum Treatment: Johns Hopkins Center for Fetal Therapy in Baltimore, Md. (May 7, 2019). Retrieved April 4, 2020, from https://www.hopkinsmedicine.org/gynecology_obstetrics/specialty_areas/fetal_therapy/fetal-interventions-procedures/ex_utero_intrapartum_t reatment.html 21. ^ a b Sadiqi, Jamshid; Hamidi, Hidayatullah (October 30, 2018). "CT features of lung agenesis – a case series (6 cases)". BMC Medical Imaging. 18 (1): 37. doi:10.1186/s12880-018-0281-5. PMC 6208179. PMID 30376819. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Pulmonary agenesis	c0265780	28,996	wikipedia	https://en.wikipedia.org/wiki/Pulmonary_agenesis	2021-01-18T18:42:20	{"gard": ["9119"], "mesh": ["C562992"], "umls": ["C0265780"], "icd-10": ["Q33.3"], "orphanet": ["984"], "wikidata": ["Q16526734"]}
Annular erythema of infancy SpecialtyDermatology Annular erythema of infancy is a skin condition reported in children roughly six months in age, characterized by transitory skin lesions that resolved without treatment within eleven months.[1]:143 ## See also[edit] * List of cutaneous conditions ## 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. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Annular erythema of infancy	c0457000	28,997	wikipedia	https://en.wikipedia.org/wiki/Annular_erythema_of_infancy	2021-01-18T18:56:03	{"umls": ["C0457000"], "wikidata": ["Q4769714"]}
A rare premature aging syndrome characterized by atrophy of the skin and subcutaneous tissue involving predominantly the distal parts of the extremities, resulting in prematurely aged appearance of the hand and feet. Another prominent feature is the characteristic facies with hollow cheeks, beaked nose, and owl-like eyes. Additional, non-dermatological manifestations, like bone anomalies have been described in some patients. Mode of inheritance has not been definitively established. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Acrogeria	c0406584	28,998	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2500	2021-01-23T18:45:45	{"gard": ["6543"], "mesh": ["C538187"], "omim": ["201200"], "umls": ["C0238590", "C0406584"], "icd-10": ["L90.8"], "synonyms": ["Acrogeria, Gottron type", "Acrometageria", "Gottron syndrome"]}
Sinoatrial node dysfunction and deafness is a rare genetic disease characterized by congenital severe to profound deafness with no evidence of vestibular dysfunction, associated with sinoatrial node dysfunction with pronounced bradycardia and increased variability of heart rate at rest and episodic syncopes that may be triggered by enhanced physical activity and stress. [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-hydroxybutyric 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 [FSH]: Follicle-stimulating hormone	Sinoatrial node dysfunction and deafness	c3554018	28,999	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324321	2021-01-23T17:06:19	{"omim": ["614896"], "synonyms": ["Sinoatrial node dysfunction and hearing loss"]}

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