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For a general phenotypic description and a discussion of genetic heterogeneity of lung cancer, see 211980.
Mapping
In a genomewide association study pooling data from 3 studies including 5,095 patients with lung cancer and 5,200 controls, Wang et al. (2008) found a significant association between susceptibility to lung cancer and rs3117582 on chromosome 6p21.33 within intron 1 of the BAT3 (142590) gene. The findings were replicated in an additional 2,484 cases and 3,036 controls (p value = 4.97 x 10(-10)). The C allele of rs3117582 was associated with increased disease risk. Another SNP (rs3131379) in the region showed significant association (p value = 1.91 x 10(-7)) and localized to intron 10 of the MSH5 (603382) gene.
*[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
|
LUNG CANCER SUSCEPTIBILITY 4
|
c2675479
| 25,500 |
omim
|
https://www.omim.org/entry/612593
| 2019-09-22T16:01:01 |
{"omim": ["612593"]}
|
For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Clinical Features
Barbet et al. (2003) reported a consanguineous family of French origin in which 4 sibs were affected with early-onset, slowly progressive isolated optic atrophy. All complained of visual impairment beginning between ages 2 and 6 years. Detailed examination showed optic atrophy without retinal degeneration. Disease progression was very slow, with adult visual acuity ranging from 1/10 to 2/10 for distant vision. Moderate photophobia and dyschromatopsia for red-green confusion were also noted. Nystagmus and optic neuropathy were not present.
Inheritance
Kjer (1959) reviewed the subject of an autosomal recessive form of optic atrophy in connection with his study of a dominant form (see 165500). Parental consanguinity was noted in earlier reports.
Moller (1992) reviewed 22 'old' papers suggesting the existence of a recessive form of simple optic atrophy and concluded that 'a very clear-cut well documented pedigree has yet to be published.' He pointed out that Fraser and Friedmann (1967) found no such cases in their classic survey on causes of blindness in children. A review through 18 years of registration of visually impaired Danish children, covering a population of more than 1 million Danes under 18 years of age, showed no case. Moller (1992) concluded that in genetic counseling of a consanguineous couple or other parents who have a child with a cryptogenic, monosymptomatic optic atrophy, there is little reason to suspect a simple, recessively inherited optic atrophy and there is probably a very small recurrence risk.
Mapping
By genomewide analysis of a large consanguineous French family with optic atrophy, Barbet et al. (2003) identified a candidate disease locus, referred to here as OPA6, within a 12-Mb region on chromosome 8q21-q22 between markers D8S1702 and D8S1794 (maximum lod score of 3.41 at marker D8S270). The authors referred to the locus as ROA1. Genetic analysis excluded mutations in the CNGB3 (605080), DECR1 (222745), and PDP1 (see PPM2C; 605993) genes.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Optic atrophy, isolated \- Photophobia, moderate \- Dyschromatopsia with red-green confusion \- Visual acuity for distant vision ranges from 1/10 to 2/10 as adult \- No retinal degeneration \- No nystagmus MISCELLANEOUS \- Onset in infancy or early childhood \- Slow progression ▲ 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
|
OPTIC ATROPHY 6
|
c1850281
| 25,501 |
omim
|
https://www.omim.org/entry/258500
| 2019-09-22T16:24:04 |
{"doid": ["5723"], "mesh": ["C537127"], "omim": ["258500"], "orphanet": ["98676"], "synonyms": ["OPTIC ATROPHY, CONGENITAL OR EARLY INFANTILE, AUTOSOMAL RECESSIVE", "Alternative titles", "Autosomal recessive non-syndromic optic atrophy"]}
|
Neurological movement disorder
Dystonia
A person with medication-induced dystonia
SpecialtyNeurology
Complicationsphysical disabilities (contractures, torticollis),[1] pain and fatigue[2]
Causeshereditary (DYT1); birth injury; head trauma; medication; infection; toxins
Diagnostic methodgenetic testing, electromyography, blood tests, MRI or CT scan
Treatmentmedication, physical therapy, botulinum toxin injection, deep brain stimulation
Medicationanticholinergics, dopamine agonists
Dystonia is a neurological hyperkinetic movement disorder syndrome in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures.[3] The movements may resemble a tremor. Dystonia is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles.[4]
The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to pharmaceutical drugs, particularly neuroleptics,[3] or stress. Treatment must be highly customized to the needs of the individual and may include oral medications, chemodenervation botulinum neurotoxin injections, physical therapy, or other supportive therapies, and surgical procedures such as deep brain stimulation.
## Contents
* 1 Classification
* 1.1 Types
* 1.2 Generalized dystonias
* 1.3 Focal dystonias
* 1.4 Segmental dystonias
* 1.5 Genetic/primary
* 2 Signs and symptoms
* 3 Causes
* 4 Treatment
* 4.1 Physical intervention
* 4.2 Medication
* 4.3 Surgery
* 5 History
* 6 See also
* 7 References
* 8 External links
## Classification[edit]
There are multiple types of dystonia, and many diseases and conditions may cause dystonia.
Dystonia is classified by:
1. Clinical characteristics such as age of onset, body distribution, nature of the symptoms, and associated features such as additional movement disorders or neurological symptoms, and
2. Cause (which includes changes or damage to the nervous system and inheritance).[4]
Physicians use these classifications to guide diagnosis and treatment.
### Types[edit]
* Generalized
* Focal
* Segmental
* Psychogenic
* Acute dystonic reaction[5]
* Vegetative-vascular
### Generalized dystonias[edit]
For example, dystonia musculorum deformans (Oppenhiem, Flatau-Sterling syndrome):[citation needed]
* Normal birth history and milestones
* Autosomal dominant
* Childhood onset
* Starts in lower limbs and spreads upwards
Also known as torsion dystonia or idiopathic torsion dystonia (old terminology "dystonia musculorum deformans").
### Focal dystonias[edit]
Main article: Focal dystonia
These most common dystonias are typically classified as follows:
Name Location Description
Anismus muscles of the rectum Causes painful defecation, constipation; may be complicated by encopresis.
Cervical dystonia (spasmodic torticollis) muscles of the neck Causes the head to rotate to one side, to pull down towards the chest, or back, or a combination of these postures.
Blepharospasm muscles around the eyes The sufferer experiences rapid blinking of the eyes or even their forced closure causing functional blindness.
Oculogyric crisis muscles of eyes and head An extreme and sustained (usually) upward deviation of the eyes often with convergence causing diplopia (double vision). It is frequently associated with backward and lateral flexion of the neck and either widely opened mouth or jaw clenching. Frequently a result of antiemetics such as the neuroleptics (e.g., prochlorperazine) or metoclopramide. Can be caused by Chlorpromazine.
Oromandibular dystonia muscles of the jaw and muscles of tongue Causes distortions of the mouth and tongue.
Spasmodic dysphonia/Laryngeal dystonia muscles of larynx Causes the voice to sound broken, become hoarse, sometimes reducing it to a whisper.
Focal hand dystonia (also known as musician's or writer's cramp). single muscle or small group of muscles in the hand It interferes with activities such as writing or playing a musical instrument by causing involuntary muscular contractions. The condition is sometimes "task-specific," meaning that it is generally apparent during only certain activities. Focal hand dystonia is neurological in origin and is not due to normal fatigue. The loss of precise muscle control and continuous unintentional movement results in painful cramping and abnormal positioning that makes continued use of the affected body parts impossible.
The combination of blepharospasmodic contractions and oromandibular dystonia is called cranial dystonia or Meige's syndrome.
### Segmental dystonias[edit]
Segmental dystonias affect two adjoining parts of the body:[citation needed]
* Hemidystonia affects an arm and foot on one side of the body.
* Multifocal dystonia affects many different parts of the body.
* Generalized dystonia affects most of the body, frequently involving the legs and back.
### Genetic/primary[edit]
Symbol OMIM Gene Locus Alt Name
DYT1 128100 TOR1A 9q34 Early-onset torsion dystonia
DYT2 224500 HPCA 1p35-p34.2 Autosomal recessive primary isolated dystonia
DYT3 314250 TAF1 Xq13 X-linked dystonia-parkinsonism
DYT4 128101 TUBB4[6] 19p13.12-13 Autosomal dominant whispering dysphonia
DYT5a 128230 GCH1 14q22.1-q22.2 Autosomal dominant dopamine-responsive dystonia
DYT5b 191290 TH 11p15.5 Autosomal recessive dopamine-responsive dystonia
DYT6 602629 THAP1 8p11.21 Autosomal dominant dystonia with cranio-cervical predilection
DYT7 602124 unknown 18p (questionable) Autosomal dominant primary focal cervical dystonia
DYT8 118800 MR1 2q35 Paroxysmal nonkinesigenic dyskinesia
DYT9 601042 SLC2A1 1p35-p31.3 Episodic choreoathetosis/spasticity (now known to be synonymous with DYT18)
DYT10 128200 PRRT2 16p11.2-q12.1 Paroxysmal kinesigenic dyskinesia
DYT11 159900 SGCE 7q21 Myoclonic dystonia
DYT12 128235 ATP1A3 19q12-q13.2 Rapid onset dystonia parkinsonism and alternating hemiplegia of childhood
DYT13 607671 unknown, near D1S2667[7] 1p36.32-p36.13 Autosomal dominant cranio-cervical/upper limb dystonia in one Italian family
DYT14 See DYT5
DYT15 607488 unknown 18p11[8] Myoclonic dystonia not linked to SGCE mutations
DYT16 612067 PRKRA 2q31.3 Autosomal recessive young onset dystonia parkinsonism
DYT17 612406 unknown, near D20S107[9] 20p11.2-q13.12 Autosomal recessive dystonia in one family
DYT18 612126 SLC2A1 1p35-p31.3 Paroxysmal exercise-induced dyskinesia
DYT19 611031 probably PRRT2 16q13-q22.1 Episodic kinesigenic dyskinesia 2, probably synonymous with DYT10
DYT20 611147 unknown 2q31 Paroxysmal nonkinesigenic dyskinesia 2
DYT21 614588 unknown 2q14.3-q21.3 Late-onset torsion dystonia
DYT24 610110 ANO3[10] 11p14.2 Autosomal dominant cranio-cervical dystonia with prominent tremor
There is a group called myoclonic dystonia where some cases are hereditary and have been associated with a missense mutation in the dopamine-D2 receptor. Some of these cases have responded well to alcohol.[11][12]
Other genes that have been associated with dystonia include CIZ1, GNAL, ATP1A3, and PRRT2.[13] Another report has linked THAP1 and SLC20A2 to dystonia.[14]
## Signs and symptoms[edit]
Play media
Hyperglycemia-induced involuntary movements, which, in this case, did not consist of typical hemiballismus but rather of hemichorea (dance-like movements of one side of the body; initial movements of the right arm in the video) and bilateral dystonia (slow muscle contraction in legs, chest, and right arm) in a 62-year-old Japanese woman with type 1 diabetes.
Symptoms vary according to the kind of dystonia involved. In most cases, dystonia tends to lead to abnormal posturing, in particular on movement. Many sufferers have continuous pain, cramping, and relentless muscle spasms due to involuntary muscle movements. Other motor symptoms are possible including lip smacking.[15]
Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, and dropped items), cramping pain with sustained use, and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to restless leg syndrome. Affected persons may notice trembling in the diaphragm while breathing, or the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and the constant movement to avoid pain may result in the grinding and wearing down of teeth, or symptoms similar to temporomandibular joint disorder. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping.[citation needed]
Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide a definitive diagnosis by showing pulsating nerve signals being transmitted to the muscles even when they are at rest. The brain appears to signal portions of fibers within the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate, tremble and contort. When called upon to perform an intentional activity, the muscles fatigue very quickly and some portions of the muscle groups do not respond (causing weakness) while other portions over-respond or become rigid (causing micro-tears under load). The symptoms worsen significantly with use, especially in the case of focal dystonia, and a "mirror effect" is often observed in other body parts: Use of the right hand may cause pain and cramping in that hand as well as in the other hand and legs that were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures can worsen symptoms.[citation needed]
Direct symptoms may be accompanied by secondary effects of the continuous muscle and brain activity, including disturbed sleep patterns, exhaustion, mood swings, mental stress, difficulty concentrating, blurred vision, digestive problems, and short temper. People with dystonia may also become depressed and find great difficulty adapting their activities and livelihood to a progressing disability. Side-effects from treatment and medications can also present challenges in normal activities.[citation needed]
In some cases, symptoms may progress and then plateau for years, or stop progressing entirely. The progression may be delayed by treatment or adaptive lifestyle changes, while forced continued use may make symptoms progress more rapidly. In others, the symptoms may progress to total disability, making some of the more risky forms of treatment worth considering. In some cases with patients who already have dystonia, a subsequent traumatic injury or the effects of general anethesia during an unrelated surgery can cause the symptoms to progress rapidly.[citation needed]
An accurate diagnosis may be difficult because of the way the disorder manifests itself. Sufferers may be diagnosed as having similar and perhaps related disorders including Parkinson's disease, essential tremor, carpal tunnel syndrome, temporomandibular joint disorder, Tourette's syndrome, conversion disorder or other neuromuscular movement disorders. It has been found that the prevalence of dystonia is high in individuals with Huntington's disease, where the most common clinical presentations are internal shoulder rotation, sustained fist clenching, knee flexion, and foot inversion.[16] Risk factors for increased dystonia in patients with Huntington's disease include long disease duration and use of antidopaminergic medication.[16]
## Causes[edit]
Primary dystonia is suspected when the dystonia is the only sign and there is no identifiable cause or structural abnormality in the central nervous system. Researchers suspect it is caused by a pathology of the central nervous system, likely originating in those parts of the brain concerned with motor function—such as the basal ganglia and the GABA (gamma-aminobutyric acid) producing Purkinje neurons. The precise cause of primary dystonia is unknown. In many cases it may involve some genetic predisposition towards the disorder combined with environmental conditions.[citation needed]
Secondary dystonia refers to dystonia brought on by some identified cause, such as head injury[citation needed], drug side effect (e.g. tardive dystonia), or neurological disease (e.g. Wilson's disease).
Meningitis and encephalitis caused by viral, bacterial, and fungal infections of the brain have been associated with dystonia. The main mechanism is inflammation of the blood vessels, causing restriction of blood flow to the basal ganglia. Other mechanisms include direct nerve injury by the organism or a toxin, or autoimmune mechanisms.[17]
Environmental and task-related factors are suspected to trigger the development of focal dystonias because they appear disproportionately in individuals who perform high precision hand movements such as musicians, engineers, architects, and artists.[citation needed] Chlorpromazine can also cause dystonia, which can be often misjudged as a seizure.[citation needed] Neuroleptic drugs often cause dystonia, including oculogyric crisis.[citation needed]
Malfunction of the sodium-potassium pump may be a factor in some dystonias. The Na+
-K+
pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons.[18] This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the cerebellum and the brain.[19] Indeed, an ouabain block of Na+
-K+
pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia.[20] Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations. A mutation in the Na+
-K+
pump (ATP1A3 gene) can cause rapid onset dystonia parkinsonism.[21] The parkinsonism aspect of this disease may be attributable to malfunctioning Na+
-K+
pumps in the basal ganglia; the dystonia aspect may be attributable to malfunctioning Na+
-K+
pumps in the cerebellum (that act to corrupt its input to the basal ganglia) possibly in Purkinje neurons.[18]
Cerebellum issues causing dystonia is described by Filip et al. 2013: "Although dystonia has traditionally been regarded as a basal ganglia dysfunction, recent provocative evidence has emerged of cerebellar involvement in the pathophysiology of this enigmatic disease. It has been suggested that the cerebellum plays an important role in dystonia etiology, from neuroanatomical research of complex networks showing that the cerebellum is connected to a wide range of other central nervous system structures involved in movement control to animal models indicating that signs of dystonia are due to cerebellum dysfunction and completely disappear after cerebellectomy, and finally to clinical observations in secondary dystonia patients with various types of cerebellar lesions. It is proposed that dystonia is a large-scale dysfunction, involving not only cortico-basal ganglia-thalamo-cortical pathways, but the cortico-ponto-cerebello-thalamo-cortical loop as well. Even in the absence of traditional "cerebellar signs" in most dystonia patients, there are more subtle indications of cerebellar dysfunction. It is clear that as long as the cerebellum's role in dystonia genesis remains unexamined, it will be difficult to significantly improve the current standards of dystonia treatment or to provide curative treatment."[22]
## Treatment[edit]
Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief, as does reducing stress, getting plenty of rest, moderate exercise, and relaxation techniques.[citation needed] Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression, or denervation.[citation needed] All current treatments have negative side-effects and risks. A geste antagoniste is a physical gesture or position (such as touching one's chin) that temporarily interrupts dystonia, it is also known as a sensory trick.[23] Patients may be aware of the presence of a geste antagoniste that provides some relief.[24] Therapy for dystonia can involve prosthetics that passively simulate the stimulation.[25]
### Physical intervention[edit]
While research in the area of effectiveness of physical therapy intervention for dystonia remains weak,[26] there is reason to believe that rehabilitation can benefit dystonia patients.[27] Physical therapy can be utilized to manage changes in balance, mobility and overall function that occur as a result of the disorder.[28] A variety of treatment strategies can be employed to address the unique needs of each individual. Potential treatment interventions include splinting,[29] therapeutic exercise, manual stretching, soft tissue and joint mobilization, postural training and bracing,[27] neuromuscular electrical stimulation, constraint-induced movement therapy, activity and environmental modification, and gait training.[28]
A patient with dystonia may have significant challenges in activities of daily living (ADL), an area especially suited for treatment by occupational therapy (OT). An occupational therapist (OT) may perform needed upper extremity splinting, provide movement inhibitory techniques, train fine motor coordination, provide an assistive device, or teach alternative methods of activity performance to achieve a patient's goals for bathing, dressing, toileting, and other valued activities.[citation needed]
Recent research has investigated further into the role of physiotherapy in the treatment of dystonia. A recent study showed that reducing psychological stress, in conjunction with exercise, is beneficial for reducing truncal dystonia in patients with Parkinson’s Disease.[30] Another study emphasized progressive relaxation, isometric muscle endurance, dynamic strength, coordination, balance, and body perception, seeing significant improvements to patients' quality of life after 4 weeks.[31]
Since the root of the problem is neurological, doctors have explored sensorimotor retraining activities to enable the brain to "rewire" itself and eliminate dystonic movements. The work of several doctors such as Nancy Byl and Joaquin Farias has shown that sensorimotor retraining activities and proprioceptive stimulation can induce neuroplasticity, making it possible for patients to recover substantial function that was lost due to Cervical Dystonia, hand dystonia, blepharospasm, oromandibular dystonia, dysphonia and musicians' dystonia.[32][33][34][35][36]
Some focal dystonias have been proven treatable through movement retraining in the Taubman approach, particularly in the case of musicians. However other focal dystonias may not respond and may even be made worse by this treatment.[citation needed]
Due to the rare and variable nature of dystonia, research investigating the effectiveness of these treatments is limited. There is no gold standard for physiotherapy rehabilitation.[30] To date, focal cervical dystonia has received the most research attention;[28] however, study designs are poorly controlled and limited to small sample sizes.[26]
### Medication[edit]
Different medications are tried in an effort to find a combination that is effective for a specific person. Not all people respond well to the same medications. Medications that have had positive results in some include: diphenhydramine, benzatropine and atropine. anti-Parkinsons agents (such as ropinirole and bromocriptine), and muscle relaxants (such as diazepam).[citation needed]
Anticholinergics
Medications such as anticholinergics (benztropine), which act as inhibitors of the neurotransmitter acetylcholine, may provide some relief. In the case of an acute dystonic reaction, diphenhydramine is sometimes used (though this drug is well known as an antihistamine, in this context it is being used primarily for its anticholinergic role).[citation needed]. See also Procyclidine. Another which in many has shown total control of symptoms, alone or taken with other medications,often clonazepam, is gabapentin. Noting, some are generic sensitive, as with other medications, and either have to sample test each one for a successful result, or take the original version.[citation needed]
Baclofen
A baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal cord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin. Baclofen can also be taken in tablet form[37]
Botulinum toxin injection
Botulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 3–6 months, depending on the kind of dystonia. Botox or Dysport injections have the advantage of ready availability (the same form is used for cosmetic surgery) and the effects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking of the toxin into adjacent muscle groups, causing weakness or paralysis in them. The injections must be repeated, as the effects wear off and around 15% of recipients develop immunity to the toxin. There is a Type A and a Type B toxin approved for treatment of dystonia; often, those that develop resistance to Type A may be able to use Type B.[38]
Muscle relaxants
Clonazepam, a benzodiazepine, is also sometimes prescribed. However, for most, their effects are limited and side-effects like mental confusion, sedation, mood swings, and short-term memory loss occur.[citation needed]
Parkinsonian drugs
Dopamine agonists: One type of dystonia, dopamine-responsive dystonia, can be completely treated with regular doses of L-DOPA in a form such as Sinemet (carbidopa/levodopa). Although this does not remove the condition, it does alleviate the symptoms most of the time. (In contrast, dopamine antagonists can sometimes cause dystonia.)[citation needed]
Ketogenic diet
One complex case study found that a ketogenic type diet may have been helpful in reducing symptoms associated with alternating hemiplegia of childhood (AHC) of a young child. However, as the researchers noted, their results could have been corollary in nature and not due to the diet itself, though future research is warranted.[39]
### Surgery[edit]
Schematic representation of a patient with cervical dystonia, with DBS electrodes implanted in the internal globus pallidus (GPi)
Surgery, such as the denervation of selected muscles, may also provide some relief; however, the destruction of nerves in the limbs or brain is not reversible and should be considered only in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proven successful in a number of cases of severe generalised dystonia.[40] DBS as treatment for medication-refractory dystonia, on the other hand, may increase the risk of suicide in patients. However, reference data of patients without DBS therapy are lacking.[41]
## History[edit]
The Italian Bernardino Ramazzini provided one of the first descriptions of task-specific dystonia in 1713 in a book of occupational diseases, The Morbis Artificum.[42] In chapter II of this book’s Supplementum, Ramazzini noted that "Scribes and Notaries" may develop "incessant movement of the hand, always in the same direction … the continuous and almost tonic strain on the muscles... that results in failure of power in the right hand". A report from the British Civil Service also contained an early description of writer’s cramp. In 1864, Solly coined the term "scrivener’s palsy" for this affliction. These historical reports usually attributed the etiology of the motor abnormalities to overuse. Then, dystonia were reported in detail in 1911, when Hermann Oppenheim,[43] Edward Flatau and Wladyslaw Sterling described some Jewish children affected by a syndrome that was retrospectively considered to represent familial cases of DYT1 dystonia. Some decades later, in 1975, the first international conference on dystonia was held in New York. It was then recognized that, in addition to severe generalized forms, the dystonia phenotype also encompasses poorly-progressive focal and segmental cases with onset in adulthood, such as blepharospasm, torticollis and writer’s cramp. These forms were previously considered independent disorders and were mainly classified among neuroses. A modern definition of dystonia was worded some years later, in 1984. During the following years it became evident that dystonia syndromes are numerous and diversified, new terminological descriptors (e.g., dystonia plus, heredodegenerative dystonias, etc.) and additional classification schemes were introduced. The clinical complexity of dystonia was then fully recognized.[44]
## See also[edit]
* Extrapyramidal symptoms
* Hypertonia
* Sydenham's chorea
* Ulegyria (brain condition with dystonia symptoms)
## References[edit]
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## External links[edit]
Classification
D
* ICD-10: G24.9
* ICD-10-CM: G24
* ICD-9-CM: 333
* OMIM: 128100
* MeSH: D004421
* DiseasesDB: 17912
* SNOMED CT: 250068003
External resources
* GeneReviews: Dystonia Overview
* A Boston Marathon record is about to be set – by a man with a movement disorder in The Washington Post
* GeneReview/NIH/UW entry on Dystonia Overview
* GeneReviews/NCBI/NIH/UW entry on Early-Onset Primary Dystonia
* Film on Dystonia from Public Broadcasting Service
* A story of one woman's struggle with dystonia at MSNBC.com
* 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
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* Encephalomyelitis
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encephalopathy
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movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
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* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
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* For more detailed coverage, see Template:Demyelinating diseases of CNS
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* For more detailed coverage, see Template:Sleep
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* Brain herniation
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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
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* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
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* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
Authority control
* NDL: 01025772
*[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
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*[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
|
Dystonia
|
c0393593
| 25,502 |
wikipedia
|
https://en.wikipedia.org/wiki/Dystonia
| 2021-01-18T18:46:37 |
{"mesh": ["D004421", "D020821"], "umls": ["C0393593"], "icd-9": ["333"], "icd-10": ["G24.924.9"], "orphanet": ["156159", "68363"], "wikidata": ["Q906492"]}
|
A rare unclassified acute myeloid leukemia characterized by an acute panmyeloid proliferation with blasts constituting more than 20% of cells in the bone marrow or peripheral blood, accompanied by fibrosis of the bone marrow. Patients typically present with acute onset of severe constitutional symptoms, bone pain, and pancytopenia. Splenomegaly is minimal or absent. The disease is rapidly progressive with poor therapy response.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Acute panmyelosis with myelofibrosis
|
c0334674
| 25,503 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86843
| 2021-01-23T18:36:51 |
{"gard": ["11907"], "umls": ["C0334674"], "icd-10": ["C94.4"], "synonyms": ["Acute myelodysplasia with myelofibrosis", "Acute myelofibrosis", "Acute myelosclerosis"]}
|
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Disability
Theory and models
* Disability theory
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Socioeconomic assistance
* Social Security Disability Insurance
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the Severely Handicapped
* Groups
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Attraction to disability is a sexualised interest in the appearance, sensation and experience of disability.[1] It may extend from normal human sexuality into a type of sexual fetishism. Sexologically, the pathological end of the attraction tends to be classified as a paraphilia.[2][3] (Note, however, that the very concept paraphilia continues to elude satisfactory definition and remains a subject of ongoing debate in both professional and lay communities[4][5]) Other researchers have approached it as a form of identity disorder.[6][7][8] The most common interests are towards amputations, prosthesis, and crutches.[1]
## Contents
* 1 History
* 2 As fetish subculture
* 3 In relationships
* 4 Explanations
* 4.1 Sexological
* 4.2 By DPWs
* 5 In media
* 6 See also
* 7 References
## History[edit]
Until the 1990s, it tended to be described mostly as acrotomophilia, at the expense of other disabilities, or of the wish by some to pretend or acquire disability. Bruno (1997) systematised the attraction as factitious disability disorder.[8] A decade on, others argue that erotic target location error is at play, classifying the attraction as an identity disorder.[7][9] In the standard psychiatric reference Diagnostic and Statistical Manual of Mental Disorders, text revision (DSM-IV-tr), the fetish falls under the general category of "Sexual and Gender Identity Disorders" and the more specific category of paraphilia, or sexual fetishes;[10] this classification is preserved in DSM-5.[11]
## As fetish subculture[edit]
Desires to pretend to be disabled and acquire a disability are extensions of the pathological disorder. About half of all devotees occasionally pretend (43 percent of Nattress [1996], sample of 50). Avowed "wannabes" seem to number not more than five percent of the devotee-wannabe population, though Nattress (1996) found 22 percent of his sample of 50 had wanted to become disabled. Accordingly, Bruno (1997) puts those afflicted with versions of the paraphilia under the broad heading of Devotees, Pretenders, and Wannabes (DPWs), as used here.[8]
Well over half of DPWs have felt this pathological attraction since childhood, as typical in paraphilias. The Amelotatist (see References) found that 75 percent of its sample of 195 were aware of the attraction by age fifteen. Those attracted often cherish early memories of a sexuoerotic tragedy (a "first sighting") involving an object of their future attention, often an older member of the opposite sex, as stereotypical in paraphilic etiology. About a quarter report discovering the paraphilia in puberty and a few in maturity.
The aforesaid has given grounds for the attraction to disability to be represented as the continuum Bruno (1997) termed factitious disability disorder.[8] At its less-intense devotee end, there is sexualised fascination with the existential aspects of disability and its appearance. In its middle pretending area is strong desire to reproduce the sensations of disability. At its intense wannabe end is an imperative to acquire a disability which may prompt self-harm.
According to DPW fetishists, their attraction does not appear to pose dangers to DPWs' partners or third parties. However, it can be noted that the DSM-IV includes this paraphilia within the diagnostic criteria of psychiatric pathology. Fetishists raise objections to the characterization of their preference as an aberrant pathology. However, objections have also been raised by members of the disabled community on the grounds that such fetishes objectify and dehumanize them. Some people with disabilities willingly participate in the fetish subculture, for example, contributing model photos (e.g., Debbie van der Putten).
## In relationships[edit]
The Amelotatist found that 55 percent of a sample of 195 DPWs had dated disabled people, 40 percent had been sexually intimate with disabled partners, and 5 percent had current disabled spouses. Nattress (1993) found that 41 percent of a sample of 50 DPWs had, or were in, relationships with disabled partners.[12]
Relationships between DPWs and disabled people tend to be reported as being ordinary, the attraction being sated by the fact of the partner's disability. It appears that the attraction to disability is undisclosed in a proportion of DPW-disabled relationships. DPWs may press disabled partners to put their disabilities to the fore in intimate situations and exhibit them in social ones. Sexually, some DPWs have been reported to engage in active tactile observation as much as in intercourse.
That DPWs find it hard to satisfy both sexual and emotional needs is borne out in findings by both Nattress (1996) and Dixon (1983).[13] They report that, despite reasonable success in obtaining sexual contact with disabled people, just 21 percent of DPWs had had long-term relationships with disabled partners.
About half of DPWs fail to establish relationships with disabled people. "Second-best" options for them are relationships with pretenders and wannabes. Practically all DPWs have experience of relationships with able-bodied partners. Such relationships are also reported to be ordinary despite the (mostly undisclosed) attraction to disability on the part of one partner.
Although it is not common knowledge within mainstream communities, the internet has revolutionized the process by which DPWs can meet each other while pursuing meaningful relationships. Some of these individuals, however, have expressed a level of concern when it comes to their first face to face encounters. While most of these encounters are completely safe, there are important guidelines to provide a sense of security to either party who may feel vulnerable.[14]
## Explanations[edit]
Psychology views sadism and masochism as interchangeable, with voyeurism and exhibitionism as their respective aspects. Devotees’ observation-based behavior and preference for display-minded partners seem to support explanations 2 to 4. Devotee pornography tends to display the appearance of disability across a range of activities rather than focus on sexual situations.
Recent neuroscientific research suggests that apotemnophilia has a neurological basis.[15][16][17]
### Sexological[edit]
Contemporary sexology does not consider the attraction problematic unless exercising it infringes the rights of one of the parties and/or those of third parties. Explanations include:
1. Imprinting or the influence of influential events on behaviour. Encountering visibly disabled people in childhood awakes strong emotions which may give rise to quasi-logical reasoning and a desire for people with the type of trauma encountered. Care received during hospital stays may awaken a wish to become disabled (as a way of ensuring continuous care), later projected onto others. Freud is credited with discovering conditioning ("imprinting" in sexology) in the context of fetishism;[citation needed]
2. Implied parental approval: if, on encountering someone disabled, a future DPW’s parents express admiration, the child may conclude that disability inspires regard, later ranking it among sexual preferences. This is among explanations mentioned by Dr John Money in Lovemaps;
3. Flight from pressure: strict parenting and/or onerous peer environments may cause the future devotee to seek respite in sickness and disability. With time, the wish to become disabled is "projected" onto others. The analogy with Munchausen Syndrome (simulating or inducing illness as a route to compassion and benefits) here is reasonably clear in wannabes. In them, projection has failed, leaving them to see themselves as more attractive if disabled. The fact that most DPWs feel the attraction since childhood also backs the above explanations. There are also suggestions that there are more DPWs in America, Europe, and the Far East due to specific parent/peer-driven achievement models there. This is another explanation mentioned in Lovemaps;
4. Inferiority complex causing projection: DPWs may have been made to feel inferior in childhood and may project their ambitions onto disabled people, who perforce have to overcome many barriers;
5. 'Darwinism': DPWs see disabled people as proven in natural selection, having cheated death and overcome adversity;
6. The unknown: children experience fascination with and fear of the unknown when encountering a disabled person. As adolescents, they may experience similar emotions when first approaching the opposite sex. This fascination with alienness may become associated with arousal over time through classical conditioning. Eventually, arousal will be triggered by the emotion;
7. "The missing phallus": When exposed to the nude female body, some men are fascinated by the fact that "the penis is missing", and there is an alternative and sexual organ (in fact, one reminiscent of a wound) in its place. This feeling of surprise may become a part of sexual attraction. The sight of a missing limb may evoke a similar feeling. Similar to 6 above, this explanation was proposed by Dr Anne Hooper in 1978;
8. Attention seeking and envy: Since disabled people tend to draw more than average attention, children observing them may conclude that one has to be disabled to enjoy attention. In puberty, disability would be included in their attractiveness criteria.
9. Erotic target location error: The desire of some male transvestites and transsexuals to assume the appearance of their sexual ideal was transposed by analogy to amputee wannabes by First (2005), who backs his claim with research by himself and others since 2000.[18] Since the condition of some wannabes appears not to be primarily sexual (except by association), the explanation defines the attraction to disability as an identity disorder. It is put forward within the narrow context of amputee wannabes, and the author does not address the DPW continuum discussed above. The wannabe community has always defined itself in terms very similar to those First and Lawrence (2006) use, with the indigenous label "transabled" gaining ground by 2005 at the expense of "wannabe."
### By DPWs[edit]
The DPW community constantly debates the origins of the attraction ("the Why?"). The Amelotatist, reporting a poll of 195 devotees was a community contribution and the first synthesis of explanations. A 2005 straw poll in two DPW fora revealed that in childhood many respondents (often first or only children) felt alienated from peers, forming solitary interests in inter alia, transportation, or collecting. This may indicate that empathy with the disabled, subject to exclusion in most cultures, is among the motivations for the attraction. It may also indicate that admiration is at play in the attraction, inasmuch as the disabled perforce overcome inhibitions similar to those many DPWs face, as hinted above.[need quotation to verify]
## In media[edit]
* Pumpkin, a sorority girl is drawn to a disabled man.
* Boxing Helena, a feature film concerning amputee fetishism
* American Horror Story: Freak Show features Elsa Mars (Jessica Lange), a German woman who had her legs amputated in an acrotomophilic film while working as a prostitute in Weimar Germany.
* Katawa Shoujo, a visual novel based on dating disabled girls.
## See also[edit]
* Abasiophilia – the fascination for disabled people who use leg-braces or other orthopaedic appliances
* Agalmatophilia – the desire for mannequins or for statue-like immobility, feigned or caused by illness or paralysis
* Acrotomophilia – the desire for partners with missing limbs
* Apotemnophilia – the desire to acquire a disability ("wannabeism," "transability", "transabled"); Body integrity identity disorder BIID
* Body dysmorphic disorder – the pathological dislike of one's own physique for subjective reasons
* Body modification – the deliberate altering of physique for non-medical reasons
* Disability pretenders – one who behaves as if disabled and/or alters their appearance so as to suggest they are disabled
* Handicap fetishism – another term for the broad range of attractions to disability
* Handicap principle – possible analogue from the animal kingdom
* Legbrace fetishism – the desire for partners who use leg braces; an aspect of abasiophilia
* Medical fetishism – a sexualised interest in observing medical practice and receiving medical treatment
* Munchhausen's syndrome – a psychological disorder whose sufferers feign illness and/or cause themselves self-harm
## References[edit]
1. ^ a b Limoncin, E.; Carta, R.; et al. (2014). "The sexual attraction toward disabilities: a preliminary internet-based study". International Journal of Impotence Research. 26 (2): 51–54. doi:10.1038/ijir.2013.34. PMID 24048013.
2. ^ Money, J.; Simcoe, K. W. (1984). "Acrotomophilia, sex and disability: New concepts and case report". Sexuality and Disability. 7 (1–2): 43–50. doi:10.1007/BF01101829.
3. ^ Money, J. (1991). "Paraphilia in Females". Journal of Psychology & Human Sexuality. 3 (2): 165–172. doi:10.1300/J056v03n02_11.
4. ^ Moser, C. (2011). "Yet Another Paraphilia Definition Fails". Archives of Sexual Behavior. 40 (3): 483–485. doi:10.1007/s10508-010-9717-x. PMID 21210203. [1]
5. ^ Balon, R. (2013). "Controversies in the Diagnosis and Treatment of Paraphilias". Journal of Sex & Marital Therapy. 39 (1): 7–20. doi:10.1080/0092623X.2012.709219. PMID 23152966.
6. ^ Blom, R. M.; Hennekam, R. C.; Denys, D. (2012). Harrison, Ben J (ed.). "Body Integrity Identity Disorder". PLOS ONE. 7 (4): e34702. doi:10.1371/journal.pone.0034702. PMC 3326051. PMID 22514657.
7. ^ a b Lawrence, A. A. (2006). "Clinical and Theoretical Parallels Between Desire for Limb Amputation and Gender Identity Disorder". Archives of Sexual Behavior. 35 (3): 263–278. doi:10.1007/s10508-006-9026-6. PMID 16799838. [2]
8. ^ a b c d Bruno, Richard L. (1997), "Devotees, Pretenders, & Wannabes: Two Cases of Factitious Disability Disorder", The Journal of Sexuality & Disability, 15 (4): 243–260, doi:10.1023/A:1024769330761
9. ^ Lawrence, A. A. (2009). "Erotic Target Location Errors: An Underappreciated Paraphilic Dimension". Journal of Sex Research. 46 (2–3): 194–215. doi:10.1080/00224490902747727. PMID 19308843.
10. ^ McRuer, Robert & Anna Mollow (2012). Sex and Disability. Duke University Press. pp. 360–1. ISBN 9780822351542.
11. ^ Blanchard, Ray (2009-06-25). "Paraphilias and the DSM-V: General Diagnostic Issues and Options Exemplified with Pedohebephilic Disorder. Paper presented at 19th WAS World Congress for Sexual Health, June 25, 2009, Göteborg, Sweden". Retrieved 2013-07-05.
12. ^ Disabled Dating
13. ^ Dixon, D. (1983). "An erotic attraction to amputees". Sexuality and Disability. 6: 3–6. doi:10.1007/BF01119844.
14. ^ Safe Amputee Dating Archived June 28, 2009, at the Wayback Machine
15. ^ Brang, D.; McGeoch, P. D.; Ramachandran, V. S. (2008). "Apotemnophilia: A neurological disorder". NeuroReport. 19 (13): 1305–1306. doi:10.1097/WNR.0b013e32830abc4d. PMID 18695512. [3]
16. ^ Hilti, L. M.; Hanggi, J.; Vitacco, D. A.; Kraemer, B.; Palla, A.; Luechinger, R.; Jancke, L.; Brugger, P. (2012). "The desire for healthy limb amputation: Structural brain correlates and clinical features of xenomelia". Brain. 136 (Pt 1): 318–29. doi:10.1093/brain/aws316. PMID 23263196. [4]
17. ^ Blanke, O.; Morgenthaler, F. D.; Brugger, P.; Overney, L. S. (2009). "Preliminary evidence for a fronto-parietal dysfunction in able-bodied participants with a desire for limb amputation". Journal of Neuropsychology. 3 (2): 181–200. doi:10.1348/174866408X318653. PMID 19338723. [5][permanent dead link]
18. ^ First, M. B. (2005). "Desire for amputation of a limb: Paraphilia, psychosis, or a new type of identity disorder". Psychological Medicine. 35 (6): 919–928. doi:10.1017/S0033291704003320. PMID 15997612. "Archived copy" (PDF). Archived from the original (PDF) on 2008-11-20. Retrieved 2013-07-07.CS1 maint: archived copy as title (link)
* The Amelotatist: A Statistical Profile, Ampix [exeunt], Lawndale, California, 1979
* Baril, A. and K. Trevenen (2014). “Exploring Ableism and Cisnormativity in the Conceptualization of Identity and Sexuality ‘Disorders’”, Annual Review of Critical Psychology, 11, p. 389-416. Read online
* Elman, R. Amy, "Disability Pornography: The Fetishization of Women's Vulnerabilities," Violence Against Women, 3.3 (June 1997), pp. 257–270
* Everaerd, W., "A Case of Apotemnophilia: A Handicap as Sexual Preference," The American Journal of Psychotherapy, 37, pp. 285–293, 1983
* Fleischl, M. F., "A Man's Fantasy of a Crippled Girl," The American Journal of Psychotherapy, 14, pp. 471–748, 1960
* Hooper, A., "The Amputee Fetish," Forum [exeunt], June 1978, Penthouse Publications Ltd, London
* Lamacz, M., J. Money, Vandalized Lovemaps: Paraphilic Outcome of seven Cases in Pediatric Sexology, Prometheus, Buffalo, N.Y., 1989
* London, L. S., Dynamic Psychiatry: Transvestism-Desire for Crippled Women, Vol. 2, New York, Corinthian, 1952
* Money, J.; Jobaris, R.; Furth, G. (1977). "Apotemnophilia: Two Cases of Self-demand Amputation as a Paraphilia". The Journal of Sexuality Research. 13 (2): 115–125. doi:10.1080/00224497709550967.
* Money, J., Lovemaps: Clinical Concepts of Sexual/Erotic Health and Pathology, Paraphilia, and Gender Transposition in Childhood, Adolescence, and Maturity, Irvington, New York, N.Y., 1986
* Money, J., The Adam Principle, Prometheus, Buffalo, N.Y., 1993
* Michel Eyquem de Montaigne, "Of the Lame or Crippel," Chapter xi, Booke iii, Essays, (translated from the original French)
* Nattress, L., Jr., "The Female Amputee as an Object of Interest and Sexual Attraction," in Pfeiffer, David, Stephen C. Hey, Gary Kiger — Eds., The Disability Perspective: Variations on a Theme, Salem, Oregon, USA, The Society for Disability Studies and Willamette University, 1993
* Nattress, L., Jr., Amelotasis: A Descriptive Study (second edition), unpublished doctoral dissertation, 1996
* "Steiner, Dr Karl," readers' queries, Men Only, Paul Raymond Publications, London, February 1978 et seq.
* Storrs, B (1997). "Devotees of Disability". New Mobility. 6: 50–53.
* Storrs, B., "Amputees, Inc.: Amputees pitching Products and Themselves to Devotees of Disability," New Mobility 7, pp. 26–31, 1997
* Taylor, B, "Amputee Fetishism: An Exclusive Journal Interview with Dr. John Money of Johns Hopkins," The Maryland State Medical Journal, pp. 35–38, March, 1976
* various, Forum (readers' letters), "One-Legged Appeal" and "Monopede Mania," Penthouse, Penthouse Publications, London, June 1974 et seq.
* Wakefield, P. L., Frank, A., Meyers, R. W., "The Hobbyist: A Euphemism for Self-Mutilation and Fetishism," Bull Menninger Clinic, 41, pp. 539–552, 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
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Attraction to disability
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None
| 25,504 |
wikipedia
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https://en.wikipedia.org/wiki/Attraction_to_disability
| 2021-01-18T18:57:57 |
{"wikidata": ["Q4818692"]}
|
## Description
Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a subtype of acute leukemia, a cancer of the white blood cells. Somatically acquired mutations in several genes have been identified in ALL lymphoblasts, cells in the early stages of differentiation. Germline variation in certain genes may also predispose to susceptibility to ALL (Trevino et al., 2009).
### Genetic Heterogeneity of Acute Lymphoblastic Leukemia
A susceptibility locus for acute lymphoblastic leukemia (ALL1) has been mapped to chromosome 10q21. See also ALL2 (613067), which has been mapped to chromosome 7p12.2; and ALL3 (615545), which is caused by mutation in the PAX5 gene (167414) on chromosome 9p.
Mapping
In a genomewide association study of 317 patients with ALL and 17,958 controls, Trevino et al. (2009) found an association between ALL and 2 SNPs on chromosome 10q21: rs10821936 (p = 1.4 x 10(-15), odds ratio (OR) of 1.91) and rs10994982 (p = 5.7 x 10(-9), OR of 1.62.) The SNPs were in linkage disequilibrium with each other and located in intron 3 of the ARID5B gene (608538). The patient cohort included 67 patients with T-cell leukemia. In addition, these SNPs also distinguished B-hyperdiploid ALL from other subtypes (rs10821936; p = 1.62 x 10(-5), OR of 2.17; rs10994982; p = 0.003, OR of 1.72). These specific findings were replicated in an independent validation cohort of 124 children with ALL (p = 0.003 and p = 0.0008, ORs of 2.45 and 2.86, respectively). The risk alleles were also associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. Trevino et al. (2009) concluded that germline variants can affect susceptibility to, and characteristics of, ALL and specific ALL subtypes.
In a genomewide association study of 2 case-control series, totaling 907 ALL cases and 2,398 controls, Papaemmanuil et al. (2009) also found an association between development of ALL and a SNP at 10q21.2 in the ARID5B gene (rs7089424, OR of 1.65, p = 6.69 x 10(-19)). The 10q21.2 risk association was selective for the B-hyperdiploid subtype. These data suggested that common low-penetrance susceptibility alleles may contribute to the risk of developing childhood ALL.
By genotyping 1,384 cases of precursor B-cell childhood ALL and 1,877 controls from Germany and the United Kingdom, Prasad et al. (2010) found a significant association between ALL and the ARID5B SNP rs7089424 (OR of 1.80; p = 5.90 x 10(-28)). This finding replicated the independent susceptibility locus for ALL at chromosome 10q21.2 previously reported by Trevino et al. (2009) and Papaemmanuil et al. (2009). The ALL2 locus on chromosome 7p12.2 and a locus on chromosome 14q11.2 (see below) were also replicated. Although there was no evidence of interactive effects between any of the 3 pairs of loci, the risk of ALL increased with an increasing number of risk alleles for the 3 loci. Prasad et al. (2010) concluded that these variants may underlie the risk of ALL in approximately 64% of cases.
### Associations Pending Confirmation
In a genomewide association study of 2 case-control series, totaling 907 ALL cases and 2,398 controls, Papaemmanuil et al. (2009) found a suggestive association with a SNP at chromosome 14q11.2 in the CEBPE gene (600749) (rs2239633, OR of 1.34, p = 2.88 x 10(-7)).
By genotyping 1,384 cases of precursor B-cell childhood ALL and 1,877 controls from Germany and the United Kingdom, Prasad et al. (2010) found a significant association between ALL and CEBPE SNP rs2239633 (OR of 1.27; p = 4.90 x 10(-6)). This finding replicated the independent susceptibility locus for ALL at chromosome 14q11.2 previously reported by Papaemmanuil et al. (2009).
Pathogenesis
### ETV6-RUNX1 ALL
The ETV6/RUNX1 fusion gene (see 600618), found in 25% of childhood ALL cases, is acquired in utero but requires additional somatic mutations for overt leukemia. Papaemmanuil et al. (2014) used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG (see 179615)-mediated deletions emerged as the dominant mutational process, characterized by recombination signal sequence motifs near breakpoints, incorporation of nontemplated sequence at junctions, approximately 30-fold enrichment at promoters and enhancers of genes actively transcribed in B-cell development, and an unexpectedly high ratio of recurrent to nonrecurrent structural variants. Single-cell tracking showed that this mechanism is active throughout leukemic evolution, with evidence of localized clustering and reiterated deletions. Integration of data on point mutations and rearrangements identified ATF7IP (613644) and MGA (616061) as tumor-suppressor genes in ALL. Papaemmanuil et al. (2014) concluded that a remarkably parsimonious mutational process transforms ETV6/RUNX1-positive lymphoblasts, targeting the promoters, enhancers, and first exons of genes that normally regulate B-cell differentiation.
### PAX5 and IKZF1 Mutations
Lesions in the PAX5 (167414) and IKZF1 (602023) genes, encoding B-lymphoid transcription factors, occur in over 80% of cases of pre-B-cell ALL. By combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, Chan et al. (2017) identified a novel B-lymphoid program for transcriptional repression of glucose and energy supply. The metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK (see 602739). Dominant-negative mutants of PAX5 and IKZF1 however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a nonpermissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (138040), encoding the glucocorticoid receptor, TXNIP (605051), encoding a glucose feedback sensor, and CNR2 (605051), encoding a cannabinoid receptor, as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukemic transformation. Conversely, pharmacologic TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2, and AMPK as potential therapeutic targets. Furthermore, these results provided a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation.
### Central Nervous System Metastasis
In mice, Yao et al. (2018) showed that ALL cells in the circulation are unable to breach the blood-brain barrier; instead, they migrate into the central nervous system (CNS) along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin (see 150320), which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor alpha-6 integrin (ITGA6; 147556) is expressed in most cases of ALL. Yao et al. (2018) found that alpha-6 integrin-laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3K-delta (PIK3CD; 602839) inhibitor, which decreased alpha-6 integrin expression on ALL cells, or specific alpha-6 integrin-neutralizing antibodies, and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid, and CNS disease symptoms despite minimally decreased bone marrow disease burden. Yao et al. (2018) concluded that alpha-6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.
Molecular Genetics
### Somatic Mutations
A t(9;22) translocation occurs in greater than 90% of chronic myelogeneous leukemia (CML; 608232), 25 to 30% of adult and 2 to 10% of childhood acute lymphoblastic leukemia, and rare cases of acute myelogenous leukemia. The translocation, known as the Philadelphia chromosome, results in the head-to-tail fusion of the BCR (151410) and ABL1 (189980) genes (see review of Chissoe et al., 1995). Clark et al. (1987) demonstrated that Philadelphia chromosome-positive ALL cells express unique Abl-derived tyrosine kinases of 185 and 180 kD that are distinct from the Bcr, Abl-derived 210-kD protein of CML. In ALL, Fainstein et al. (1987) found that ABL is translocated into the 5-prime region of the BCR gene. The consequence of this is the expression of a fused transcript in which the first exon of BCR is linked to the second ABL exon. This transcript encodes a 190-kD protein kinase.
Kurzrock et al. (1987) found a novel Abl protein product in Philadelphia chromosome-positive acute lymphoblastic leukemia. They suggested that alternative mechanisms of activation of Abl exist and that a different mechanism may apply in human acute lymphoid leukemia as opposed to myeloid malignancies.
In T-cell acute lymphoblastic leukemia (T-ALL), transcription factors are known to be deregulated by chromosomal translocations. Graux et al. (2004) described the extrachromosomal (episomal) amplification of ABL1 in 5 of 90 (5.6%) individuals with T-ALL. Molecular analyses delineated the amplicon as a 500-kb region from band 9q34, containing the oncogenes ABL1 and NUP214 (114350). They detected the ABL1/NUP214 fusion transcript in cell lines derived from 5 individuals with the ABL1 amplification, in cell lines from 5 of 85 (5.8%) additional individuals with T-ALL, and in 3 of 22 T-ALL cell lines. The constitutively phosphorylated tyrosine kinase ABL1/NUP214 was found to be sensitive to the tyrosine kinase inhibitor imatinib. The recurrent cryptic ABL1/NUP214 rearrangement was associated with increased expression of HOX11 (186770) and HOX11L2 (604640) and deletion of CDKN2A (600160), consistent with a multistep pathogenesis of T-ALL.
Somatic mutations in the FLT3 (136351) and BAX (600040) genes have been identified in cell lines from patients with acute lymphocytic leukemia. Meijerink et al. (1998) found that approximately 21% of human hematopoietic malignancy cell lines had somatic mutations in the BAX gene, perhaps most commonly in acute lymphoblastic leukemia. Both T-cell and B-cell lines contained BAX somatic mutations. Approximately half were nucleotide insertions or deletions within a deoxyguanosine (G8) tract (see 600040.0004), resulting in a proximal frameshift and loss of immunodetectable BAX protein.
Armstrong et al. (2004) found that 6 (25%) of 25 hyperdiploid ALL samples had somatic mutations in the FLT3 gene (see 136351.0003; 136351.0007; 136351.0009). Three mutations were novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. In 3 samples from patients whose disease would relapse, FLT3 mutations were identified. These data suggested that patients with hyperdiploid or relapsed ALL in childhood might be considered candidates for therapy with small-molecule inhibitors of FLT3.
In a genomewide analysis of leukemic cells from 242 pediatric ALL patients using high resolution SNP arrays and genomic DNA sequencing, Mullighan et al. (2007) identified mutations in genes encoding principal regulators of B-lymphocyte development and differentiation in 40% of B-progenitor ALL cases. Deletions were detected in IKZF1 (603023), IKZF3 (606221),TCF3 (147141), EBF1 (164343), and LEF1 (153245). The PAX5 (167414) gene was the most frequent target of somatic mutation, being altered in 31.7% of cases.
Mullighan et al. (2009) reported a recurring interstitial deletion of pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that juxtaposes the first, noncoding exon of P2RY8 (300525) with the coding region of CRLF2 (300357). They identified the P2RY8/CRLF2 fusion in 7% of individuals with B-progenitor ALL and 53% of individuals with ALL associated with Down syndrome. CRLF2 alteration was associated with activating JAK mutations, and expression of human P2RY8/CRLF2 together with mutated mouse Jak2 (147796) resulted in constitutive JAK-STAT activation and cytokine-independent growth of Ba/F3 cells overexpressing IL7 receptor-alpha (IL7R; 146661). Mullighan et al. (2009) concluded that rearrangement of CRLF2 and JAK mutations together contribute to leukemogenesis in B-progenitor ALL.
Van Vlierberghe et al. (2010) identified somatic inactivating mutations and deletions of the PHF6 gene in 16% of pediatric and 38% of adult primary T-ALL samples, most of which were derived from male patients. The authors noted that T-ALL shows an increased incidence in males. Loss of PHF6 was associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 (186770) and TLX3 (604640). The findings suggested that PHF6 is an X-linked tumor suppressor in T-ALL.
Anderson et al. (2011) examined the genetic architecture of cancer at the subclonal and single-cell level and in cells responsible for cancer clone maintenance and propagation in childhood acute lymphoblastic leukemia in which the ETV6 (600618)/RUNX1 (151385) gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or driver copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to 8 genetic abnormalities could be detected in single cells, a genetic signature of subclones identified, and a composite picture of subclonal architecture and putative ancestral trees assembled. Anderson et al. (2011) observed that subclones in acute lymphoblastic leukemia have variegated genetics and complex nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukemia-propagating cells, assayed by serial transplantation in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) IL2R-gamma (308380)-null mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo.
Mullighan et al. (2011) resequenced 300 genes in matched diagnosis and relapse samples from 23 patients with ALL. This identified 52 somatic nonsynonymous mutations in 32 genes, many of which were novel, including the transcriptional coactivators CREBBP (600140) and NCOR1 (600849), the transcription factors ERG (165080), SPI1 (165170), TCF4 (602272), and TCF7L2 (602228), components of the Ras signaling pathway (see 190070), histone genes (e.g., 602810), genes involved in histone modification (CREBBP and CTCF, 604167), and genes previously shown to be targets of recurring DNA copy number alteration in ALL. Analysis of an extended cohort of 71 diagnosis-relapse cases and 270 acute leukemia cases that did not relapse found that 18.3% of relapse cases had sequence or deletion mutations of CREBBP, which encodes the transcriptional coactivator and histone acetyltransferase CREB-binding protein. The mutations were either present at diagnosis or acquired at relapse, and resulted in truncated alleles or deleterious substitutions in conserved residues of the histone acetyltransferase domain. Functionally, the mutations impaired histone acetylation and transcriptional regulation of CREBBP targets. Several mutations acquired at relapse were detected in subclones at diagnosis, suggesting that the mutations may confer resistance to therapy.
Zenatti et al. (2011) identified heterozygous somatic mutations in the IL7R (146661) gene on chromosome 5p13 in 17 (9%) of 201 T-cell acute lymphoblastic leukemia samples from 3 independent cohorts. All mutations affected exon 6, in the juxtamembrane-transmembrane domain at the interface with the extracellular region, and were shown in several cell lines to result in ligand-independent constitutive activation of IL7R-mediated downstream signaling pathways, most prominently PI3K-Akt (see 164730), JAK1 (147795), and STAT5 (601511). JAK3 (600173) signaling was not involved. Most IL7R mutations (14/17; 82%) created an unpaired cysteine residue in the interface, leading to homotypic dimerization and/or oligomerization and thus bypassing the requirement for ligand-dependent activation. These mutations were enriched in the T-ALL subgroup comprising TLX3 (604640)-rearranged and HOXA (614060)-deregulated cases. In vitro and in vivo mouse studies demonstrated the oncogenic potential of the IL7R mutants. T-ALL cells carrying the IL7R mutations were sensitive to inhibition of the JAK-STAT pathway, suggesting therapeutic implications.
Ntziachristos et al. (2012) reported the presence of loss-of-function mutations and deletions of the EZH2 (601573) and SUZ12 (606245) genes, which encode crucial components of the polycomb repressive complex-2 (PRC2), in 25% of T-ALLs. To further study the role of PRC2 in T-ALL, Ntziachristos et al. (2012) used NOTCH1 (190198)-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark lys27 trimethylation of histone-3 (H3K27me3) by antagonizing the activity of PRC2. Ntziachristos et al. (2012) concluded that their studies suggested a tumor suppressor role for PRC2 in human leukemia and suggested a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation.
Using exome sequencing in 67 T-cell ALLs, De Keersmaecker et al. (2013) detected protein-altering mutations in 508 genes. Consideration of genes that were mutated in at least 2 samples and were significantly more mutated than the local background mutation rate identified 15 candidate oncogenic driver genes, 7 of which were novel. Adult (15 years of age or older) samples showed 2.5 times more somatic protein-altering mutations than those from children (21.1 vs 8.2), and 2.7 times more mutations in candidate driver genes than those from children. De Keersmaecker et al. (2013) identified CNOT3 (604910) as a tumor suppressor mutated in 7 of 89 (7.9%) adult T-ALLs; its knockdown caused tumors in a sensitized Drosophila eye cancer model in which the Notch ligand Delta (see 606582) is overexpressed in the developing eyes. In addition, De Keersmaecker et al. (2013) identified mutations affecting the ribosomal proteins RPL5 (603634) and RPL10 (312173) in 12 of 122 (9.8%) pediatric T-ALLs, with recurrent alterations in RPL10 of arg98, an invariant residue from yeast to human. Yeast and lymphoid cells expressing the RPL10 arg98 to ser mutant showed a ribosome biogenesis defect.
Jaffe et al. (2013) profiled global histone modifications in 115 cancer cell lines from the Cancer Cell Line Encyclopedia. One signature was characterized by increased H3K36me2, exhibited by several lines harboring translocations in the NSD2 methyltransferase (WHSC1; 602952). An NSD2 glu1099-to-lys (E1099K) variant was identified in nontranslocated ALL cell lines sharing this signature. Ectopic expression of the variant induced a chromatin signature characteristic of NSD2 hyperactivation and promoted transformation. NSD2 knockdown selectively inhibited the proliferation of NSD2-mutant lines and impaired the in vivo growth of an NSD2-mutant ALL xenograft. Sequencing analysis of greater than 1,000 pediatric cancer genomes identified the NSD2 E1099K alteration in 14% of t(12;21) ETV6-RUNX1-containing ALLs.
Ntziachristos et al. (2014) delineated the role of the H3K27 demethylases JMJD3 (KDM6B; 611577) and UTX (KDM6A; 300128) in T-ALL. The authors showed that JMJD3 is essential for the initiation and maintenance of T-ALL, as it controls important oncogenic gene targets by modulating H3K27 methylation. By contrast, they found that UTX functions as a tumor suppressor and is frequently genetically inactivated in T-ALL. Moreover, Ntziachristos et al. (2014) demonstrated that the small molecule inhibitor GSKJ4 affects T-ALL growth by targeting JMJD3 activity. Ntziachristos et al. (2014) concluded that 2 proteins with a similar enzymatic function can have opposing roles in the context of the same disease, paving the way for treating hematopoietic malignancies with a novel category of epigenetic inhibitors.
For discussion of an association between ALL and somatic mutation in the GNB1 gene, see 139380.
Heterozygous activating mutations in NT5C2 (600417) are present in about 20% of relapsed pediatric T-cell ALL and in 3 to 10% of relapsed B-precursor ALL, and an arg367-to-gln (R367Q) change is the most common NT5C2 mutation found in relapsed ALL. Tzoneva et al. (2018) used a conditional and inducible leukemia model to demonstrate that expression of NT5C2(R367Q) induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukemia cell growth and leukemia-initiating cell activity. The loss-of-fitness phenotype of NT5C2 +/R367Q mutant cells was associated with excess export of purines to the extracellular space and depletion of the intracellular purine-nucleotide pool. Consequently, blocking guanosine synthesis by inhibition of inosine-5-prime-monophosphate dehydrogenase (IMPDH) induced increased cytotoxicity against NT5C2-mutant leukemia lymphoblasts. Tzoneva et al. (2018) concluded that these results identified the fitness cost of NT5C2 mutation and resistance to chemotherapy as key evolutionary drivers that shape clonal evolution in relapsed ALL and supported a role for IMPDH inhibition in the treatment of ALL.
### Somatic Mutations in Early T-Cell Precursor ALL
Zhang et al. (2012) performed whole-genome sequencing of 12 early T-cell precursor (ETP) ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell ALL cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signaling (67% of cases; NRAS, 164790; KRAS, 190070; FLT3, 136351; IL7R, JAK3, JAK1, SH2B3, 605093; and BRAF, 164757), inactivating lesions disrupting hematopoietic development (58%; GATA3, 131320; ETV6, 600618; RUNX1, 151385; IKZF1, 603023; and EP300, 602700), and histone-modifying genes (48%; EZH2, 601573; EED, 605984; SUZ12, 606245; SETD2, 612778; and EP300). Zhang et al. (2012) also identified new targets of recurrent mutation including DNM2 (602378), ECT2L, and RELN (600514). The mutational spectrum is similar to myeloid tumors, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukemia hematopoietic stem cells. Zhang et al. (2012) concluded that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.
Clinical Management
Resistance to tyrosine kinase inhibitors (TKIs) develops in virtually all cases of Philadelphia chromosome-positive acute lymphoblastic leukemia. Duy et al. (2011) reported the discovery of a novel mechanism of drug resistance that is based on protective feedback signaling of leukemia cells in response to treatment with TKIs. In Philadelphia chromosome-positive acute lymphoblastic leukemia cells, Duy et al. (2011) identified BCL6 (109565) as a central component of this drug-resistance pathway and demonstrated that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukemia-initiating subclones.
Mutations that deregulate NOTCH1 (190198) and RAS/PI3K (see 601232)/AKT signaling are prevalent in T-ALL and often coexist. Dail et al. (2014) showed that the PI3K inhibitor GDC-0941 is active against primary T-ALLs from wildtype and Kras(G12D) mice; addition of the MEK (see 176872) inhibitor PD0325901 increases its efficacy. Mice invariably relapsed after treatment with drug-resistant clones, most of which unexpectedly showed reduced levels of activated NOTCH1 protein, downregulated many NOTCH1 target genes, and exhibited cross-resistance to gamma-secretase inhibitors. Multiple resistant primary T-ALLs that emerged in vivo did not contain somatic NOTCH1 mutations present in the parental leukemia, and resistant clones upregulated PI3K signaling. Consistent with these data, inhibition of NOTCH1 activated the PI3K pathway, providing a likely mechanism for selection against oncogenic NOTCH1 signaling. Dail et al. (2014) concluded that these studies validated PI3K as a therapeutic target in T-ALL and raised the unexpected possibility that dual inhibition of PI3K and NOTCH1 signaling could promote drug resistance in T-ALL.
Methotrexate is used as the standard of care in the treatment of the most common pediatric malignancy, acute lymphoblastic leukemia (ALL), with relatively high success rates that unfortunately are accompanied by severe toxicity. Kanarek et al. (2018) found that young patients with ALL that showed high expression of HAL (609457) in the ALL cells have significantly higher survival rates compared to patients in the same study with low HAL expression. Expression levels of expression levels of SLC19A1 (600424), which encodes the transporter for methotrexate, as well as the genes AMDHD1 and FTCD (606806), encoding histidine degradation pathway enzymes, showed no significant association with patient survival. Kanarek et al. (2018) concluded that endogenous expression levels of HAL, which encodes the rate-limiting enzyme of the histidine degradation pathway, are associated with the sensitivity of cancer cell lines to methotrexate, and the overall survival of patients with ALL who are treated with methotrexate. These findings suggested that HAL expression might serve as a clinical predictor for better responders to methotrexate treatment among patients with ALL and may be informative for decisions regarding therapy strategies. Furthermore, both genetic perturbation and dietary enhancement of the pathway changed the sensitivity of hematopoietic cancer cells to the chemotherapy. As standard protocols for administering methotrexate are often accompanied by severe toxicity, Kanarek et al. (2018) suggested that dietary supplementation with histidine could represent a relatively low-risk intervention that might enable reduced dosing of this toxic agent and therefore a greater clinical benefit.
*[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
|
LEUKEMIA, ACUTE LYMPHOBLASTIC
|
c0023449
| 25,505 |
omim
|
https://www.omim.org/entry/613065
| 2019-09-22T15:59:52 |
{"doid": ["9952"], "omim": ["613065"], "orphanet": ["513"]}
|
A number sign (#) is used with this entry because of evidence that EDICT syndrome is caused by heterozygous mutation in the MIR184 gene (613146) on chromosome 15q25.
Description
EDICT syndrome is an autosomal dominant syndromal anterior segment dysgenesis characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and thinning of the corneal stroma (Iliff et al., 2012).
Syndromes with overlapping features have been reported, including cornea guttata with anterior polar cataracts (121390) and congenital corneal opacities, cornea guttata, and corectopia (608484).
Clinical Features
Akpek et al. (2002) reported an 81-year-old man with bilateral aphakia, diffuse corneal haze, and corneal thinning associated with guttae. Both pupils were miotic and slightly eccentric with focal areas of iris stromal atrophy. There was a 'beaten-metal' appearance and guttae of the endothelium as well as deep posterior vesicles. Corneal topography revealed bilateral steepening of the corneas, but no apparent cone. There were 8 additional affected family members over the subsequent 2 generations with congenital cataracts and corneal abnormalities, 2 of whom were examined. A 55-year-old daughter had undergone bilateral cataract extractions at 6 years of age. Examination revealed bilateral microcornea (9.5 mm vertically and 10 mm horizontally) as well as symmetric changes of the corneas with uniform steepening and thinning; however, corneal topography did not demonstrate a cone. The pupils were small and mildly eccentric with ectropion pupillae. Specular biomicroscopy revealed normal endothelial cell count, shape, and size. A 16-year-old grandson was diagnosed with bilateral congenital cataracts and myopia at 6 years of age, and with posterior polymorphous dystrophy diagnosed at 7 years of age. Examination showed bilateral thinning of the cornea and mild anterior polar cataracts, and corneal topography revealed rather diffuse steepening of the corneas without a cone. Specular biomicroscopy showed vesicle-like lesions of the endothelium. He also had bilateral small pupils with mild ectropion pupillae. Akpek et al. (2002) concluded that this constellation of autosomal dominantly inherited ocular findings, including corneal endothelial and stromal anomalies with congenital cataracts and iris abnormalities, represented a novel anterior segment disorder.
Hughes et al. (2003) examined 30 members of a large 3-generation Northern Irish family segregating autosomal dominant keratoconus and cataract on 2 occasions at an interval of 5 years. Examination of younger individuals indicated that onset of progressive astigmatism predated onset of lens opacities by 1 to 2 years. Astigmatism manifested around the age of 8 years, and although there was some intrafamilial variation, cones were generally detectable around the age of 9 to 12 years. Individuals who exhibited neither progressive astigmatism nor lens opacities by age 13 years appeared to remain unaffected. Corrective surgery was usually necessary in early adulthood for both keratoconus and cataract.
Dash et al. (2006) restudied the Northern Irish family with autosomal dominant keratoconus and cataract that was originally reported by Hughes et al. (2003). Affected individuals had no abnormalities or signs of anterior segment dysgenesis at birth, with the corneal and lens changes developing after the age of 5 years. Sequential examination of family members indicated that the anterior polar cataract and keratoconus were developmental rather than congenital.
Mapping
In a 3-generation pedigree with an autosomal dominant anterior segment dysgenesis involving corneal steepening and thinning, microcornea, endothelial abnormalities, iris hypoplasia, and congenital anterior polar cataracts, originally reported by Akpek et al. (2002), Jun et al. (2002) performed linkage analysis and obtained a lod score of 2.71 on chromosome 15q22.1-q25.3, between markers D15S993 and D15S202. Jun et al. (2002) proposed the designation 'EDICT' syndrome to represent the clinical findings of endothelial dystrophy, iris hypoplasia, congenital cataract, and corneal stromal thinning.
Hughes et al. (2003) performed genomewide linkage analysis in a large 3-generation Northern Irish family segregating autosomal dominant keratoconus and cataract and found evidence of linkage on chromosome 15, with a maximum 2-point lod score of 3.99 (theta = 0.11) with D15S131. Fine mapping with additional microsatellite markers and recombination analysis defined a 6.5-Mb critical interval flanked by CYP11A (118485) and D15S211, with a maximum 2-point lod score of 8.13 with IREB2 (147582) at chromosome 15q25.1. The authors noted that this is an exceedingly gene-rich region, containing approximately 95 known or predicted genes; 4 positional candidate genes were screened but no causative mutations were found.
In the large 3-generation Northern Irish family segregating autosomal dominant severe keratoconus and early-onset anterior polar cataract, previously studied by Hughes et al. (2003), Dash et al. (2006) refined the linkage region to an approximately 5.5-Mb interval flanked by the MAN2C1 gene (154580) and the D15S211 marker on chromosome 15q. The refined interval excluded 28 candidate genes, and a further 23 candidate genes were excluded by direct sequencing.
Molecular Genetics
In a 3-generation Northern Irish family in which 18 of 38 individuals had an autosomal dominant form of severe anterior keratoconus and early-onset anterior polar cataract, originally reported by Hughes et al. (2003), Hughes et al. (2011) identified a heterozygous mutation in the seed region of the MIR184 gene (57C-T; 613146.0001) that segregated with disease in the family and was not found in 167 unscreened controls.
In 8 affected members of a multigenerational family segregating an autosomal dominant anterior segment dysgenesis (EDICT syndrome) mapping to chromosome 15q22.1-q25.3, originally reported by Akpek et al. (2002), Iliff et al. (2012) analyzed 24 candidate genes and 4 microRNAs residing within the critical interval and identified heterozygosity for the same 57C-T mutation in the seed region of the MIR184 gene as had been found in a family with keratoconus and anterior polar cataract by Hughes et al. (2011). The mutation was not found in 2 unaffected family members, 282 patients with Fuchs corneal dystrophy (see FECD1, 136800), 283 control individuals without corneal dystrophy, or the 1000 Genomes database.
Noting the differences in corneal phenotype between affected members of the 2 families found to carry the same 57C-T mutation in the MIR184 gene (Hughes et al., 2011; Iliff et al., 2012), Iliff et al. (2012) stated that they had performed next-generation sequencing that ruled out any potential coding variant that might modify the phenotype caused by the mutation. In response, Hughes et al. (2012) noted that the 2 families clearly had a very closely related phenotype arising from the same mutation, and suggested that the most useful investigation of genetic modifiers of the corneal-ectasia phenotype would be direct genetic comparison of the 2 affected families.
Nomenclature
Giasin et al. (2012) suggested that the reported corneal phenotype in EDICT syndrome falls within the keratoconus/keratoglobus spectrum. Iliff et al. (2012) responded that the corneal thinning in EDICT is uniform, without the increased central thinning of keratoconus or increased peripheral thinning of keratoglobus, noting that in EDICT patients the corneal steepening is uniform, diffuse, and nonectatic, without a cone or globular contour. In addition, Iliff et al. (2012) stated that there are histopathologic differences between keratoconus/keratoglobus and EDICT, with disruption of the Bowman layer and Descemet membrane in the former and changes resembling Fuchs corneal dystrophy (see FECD1, 136800) and posterior polymorphous corneal dystrophy (see PPCD1, 122000) in the latter.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Corneal thinning and steepening \- Keratoconus, severe anterior (in some patients) \- Microcornea \- Astigmatism \- Decreased visual acuity \- Cataract, anterior polar, congenital or early-onset (in some patients) \- Corneal endothelial dystrophy (in some patients) \- Small pupils (in some patients) \- Slightly eccentric pupils (in some patients) \- Iris stromal atrophy (rare) \- Corneal haze (rare) MOLECULAR BASIS \- Caused by mutation in microRNA 184 gene (MIR184, 613146.0001 ) ▲ 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
|
EDICT SYNDROME
|
c3280392
| 25,506 |
omim
|
https://www.omim.org/entry/614303
| 2019-09-22T15:55:44 |
{"omim": ["614303"], "orphanet": ["293936"], "synonyms": ["KERATOCONUS, FAMILIAL, WITH EARLY-ONSET ANTERIOR POLAR CATARACT", "Familial keratoconus with cataract", "Alternative titles", "ENDOTHELIAL DYSTROPHY, IRIS HYPOPLASIA, CONGENITAL CATARACT, AND STROMAL THINNING SYNDROME", "Endothelial dystrophy-iris hypoplasia-congenital cataract-stromal thinning syndrome", "KTCNCT", "Autosomal dominant keratoconus with early-onset anterior polar cataracts", "KERATOCONUS WITH CATARACT"]}
|
Gougerot–Blum syndrome
Other namesPigmented purpuric lichenoid dermatitis,[1] and Pigmented purpuric lichenoid dermatitis of Gougerot and Blum[1]
SpecialtyDermatology
Gougerot–Blum syndrome is a variant of pigmented purpuric dermatitis, a skin condition characterized by minute, rust-colored to violaceous, lichenoid papules that tend to fuse into plaques of various hues.[2]:829 Relative to other variants, it is characterized clinically by a male predominance, pruritus, with a predilection for the legs, and histologically, it features a densely cellular lichenoid infiltrate.[3]
It was characterized in 1925.[4]
Gougerot–Blum syndrome is named after the French dermatologists Henri Gougerot (1881–1955) and Paul Blum (1878–1933).
## See also[edit]
* Pigmentary purpuric eruptions
* Skin lesion
* List of cutaneous conditions
## References[edit]
1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
3. ^ Barnhill RL and Crowson AN (eds) Textbook of Dermatopathology, second edition, McGraw-Hill, 2004: 211-212
4. ^ synd/2079 at Who Named It?
## External links[edit]
Classification
D
* DiseasesDB: 30753
* v
* t
* e
Pigmentation disorders/Dyschromia
Hypo-/
leucism
Loss of
melanocytes
Vitiligo
* Quadrichrome vitiligo
* Vitiligo ponctué
Syndromic
* Alezzandrini syndrome
* Vogt–Koyanagi–Harada syndrome
Melanocyte
development
* Piebaldism
* Waardenburg syndrome
* Tietz syndrome
Loss of melanin/
amelanism
Albinism
* Oculocutaneous albinism
* Ocular albinism
Melanosome
transfer
* Hermansky–Pudlak syndrome
* Chédiak–Higashi syndrome
* Griscelli syndrome
* Elejalde syndrome
* Griscelli syndrome type 2
* Griscelli syndrome type 3
Other
* Cross syndrome
* ABCD syndrome
* Albinism–deafness syndrome
* Idiopathic guttate hypomelanosis
* Phylloid hypomelanosis
* Progressive macular hypomelanosis
Leukoderma w/o
hypomelanosis
* Vasospastic macule
* Woronoff's ring
* Nevus anemicus
Ungrouped
* Nevus depigmentosus
* Postinflammatory hypopigmentation
* Pityriasis alba
* Vagabond's leukomelanoderma
* Yemenite deaf-blind hypopigmentation syndrome
* Wende–Bauckus syndrome
Hyper-
Melanin/
Melanosis/
Melanism
Reticulated
* Dermatopathia pigmentosa reticularis
* Pigmentatio reticularis faciei et colli
* Reticulate acropigmentation of Kitamura
* Reticular pigmented anomaly of the flexures
* Naegeli–Franceschetti–Jadassohn syndrome
* Dyskeratosis congenita
* X-linked reticulate pigmentary disorder
* Galli–Galli disease
* Revesz syndrome
Diffuse/
circumscribed
* Lentigo/Lentiginosis: Lentigo simplex
* Liver spot
* Centrofacial lentiginosis
* Generalized lentiginosis
* Inherited patterned lentiginosis in black persons
* Ink spot lentigo
* Lentigo maligna
* Mucosal lentigines
* Partial unilateral lentiginosis
* PUVA lentigines
* Melasma
* Erythema dyschromicum perstans
* Lichen planus pigmentosus
* Café au lait spot
* Poikiloderma (Poikiloderma of Civatte
* Poikiloderma vasculare atrophicans)
* Riehl melanosis
Linear
* Incontinentia pigmenti
* Scratch dermatitis
* Shiitake mushroom dermatitis
Other/
ungrouped
* Acanthosis nigricans
* Freckle
* Familial progressive hyperpigmentation
* Pallister–Killian syndrome
* Periorbital hyperpigmentation
* Photoleukomelanodermatitis of Kobori
* Postinflammatory hyperpigmentation
* Transient neonatal pustular melanosis
Other
pigments
Iron
* Hemochromatosis
* Iron metallic discoloration
* Pigmented purpuric dermatosis
* Schamberg disease
* Majocchi's disease
* Gougerot–Blum syndrome
* Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis
* Lichen aureus
* Angioma serpiginosum
* Hemosiderin hyperpigmentation
Other
metals
* Argyria
* Chrysiasis
* Arsenic poisoning
* Lead poisoning
* Titanium metallic discoloration
Other
* Carotenosis
* Tar melanosis
Dyschromia
* Dyschromatosis symmetrica hereditaria
* Dyschromatosis universalis hereditaria
See also
* Skin color
* Skin whitening
* Tanning
* Sunless
* Tattoo
* removal
* Depigmentation
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Gougerot–Blum syndrome
|
c0263396
| 25,507 |
wikipedia
|
https://en.wikipedia.org/wiki/Gougerot%E2%80%93Blum_syndrome
| 2021-01-18T19:00:39 |
{"umls": ["C0263396"], "wikidata": ["Q5588184"]}
|
Abortion in Benin is only legal if the abortion will save the woman's life.[1] A select list of experts are allowed to examine a pregnancy to determine whether the only option for saving the woman's life is to induce abortion.[1]
## Impact of strict abortion laws[edit]
Self-induced abortions have been growing in Benin, especially among students in high school or university, and the average age of abortion recipients is 19.[1]
## References[edit]
1. ^ a b c Abortion Policies: Oman to Zimbabwe. United Nations Publications. 2001. ISBN 9789211513653. Retrieved 4 December 2014.
* v
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This abortion-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Abortion in Benin
|
None
| 25,508 |
wikipedia
|
https://en.wikipedia.org/wiki/Abortion_in_Benin
| 2021-01-18T18:41:32 |
{"wikidata": ["Q19568847"]}
|
This article needs attention from an expert in Molecular and Cellular Biology. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Molecular and Cellular Biology may be able to help recruit an expert. (October 2011)
Urticarial vasculitis
SpecialtyDermatology, immunology
Urticarial vasculitis (also known as "chronic urticaria as a manifestation of venulitis", "hypocomplementemic urticarial vasculitis syndrome", "hypocomplementemic vasculitis" and "unusual lupus-like syndrome")[1] is a skin condition characterized by fixed urticarial lesions that appear histologically as a vasculitis.[2]:834
## Contents
* 1 Mechanism
* 1.1 C1q
* 1.2 Impaired classical complement pathway
* 2 Diagnosis
* 3 Treatment
* 4 Popular culture
* 5 See also
* 6 References
* 7 External links
## Mechanism[edit]
Antibodies are usually raised against foreign proteins, such as those made by a replicating virus or invading bacterium. Virus or bacteria with antibodies opsonized or "stuck" to them highlight them to other cells of the immune system for clearance.
Antibodies against self proteins are known as autoantibodies, and are not found in healthy individuals. These autoantibodies can be used to detect certain diseases.
### C1q[edit]
C1q is an integral component within the complement pathway – a complicated cascade of protein interactions, culminating in an immune response against a broad variety of pathogens. The anti-C1q antibodies found in patients with hypocomplementemic urticarial vasculitis activate C1q, which instigates activation of the entire complement pathway. Consequently, levels of all complement proteins become low.
### Impaired classical complement pathway[edit]
C1 complex comprising C1q, C1r and C1s
The complement pathway is composed of several subset pathways: the lectin/mannose pathway, alternative pathway and the classical pathway. All pathways culminate in the production of a C3 convertase, which catalyses C3 into its constitutive parts (better detailed here – classical complement pathway).[3]
In brief, the crucial role of C1q in the pathway is its importance as the first protein to start the complement cascade (which ends in the destruction of the invading bacteria or virus), and its ability to link the two important arms of the immune system – the innate immune system: a broad defence system; and the adaptive immune system: the strong immune response capable of remembering previous infections, allowing fast response against recurrent infections, meaning that people with a normal immune system don't continually catch the same cold or same strain of flu repeatedly.[3]
Case studies of individuals with HUV have also highlighted other potential complicating factors which it seems the anti-C1q antibodies play a role in. This can mean in some cases the deposition of large immune complexes in the kidney which cannot be cleared by the usual cells of the immune system (e.g. macrophages which are unable to bind the Fc portion of the C1q antibody), leading to further complications.[4] This seems to be rare, but can occur when a pre-existing renal condition is apparent. Also, there has been some speculation as to an additional autoantibody against an inhibitor protein (in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement pathway and one protein that builds up controls angioedema (vessel – swelling),[4] resulting in excess water building up under the skin (the weal appearance).
## Diagnosis[edit]
A rare autoimmune disease characterized by recurrent urticaria (nettle rash), first described in the 1970s. There is no defined paradigm for the syndrome aetiology and severity in progression. Diagnosis is confirmed with the identification of at least two conditions from: venulitis on skin biopsy, arthritis, ocular inflammation, abdominal pain or positive C1q antibodies to immune complexes.[5] It is this last category, anti-C1q antibodies, that all HUV patients test positive for.[4] In vitro experiments and mouse models of the disease have not thoroughly determined the link between these antibodies and the disease, even though the link is so pronounced.
## Treatment[edit]
Unfortunately there are no known specific therapies for HUV. The regime of prescription steroids and other immunosuppressive drugs aims to dampen the body's production of anti-C1q antibodies.[5] However, this again renders the individual immunocompromised.
## Popular culture[edit]
Urticarial vasculitis is featured prominently in the 2010 documentary film Fat, Sick and Nearly Dead.[6] The main character and narrator suffers from the disease.
## See also[edit]
* Cutaneous small-vessel vasculitis
* 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 978-1-4160-2999-1.
2. ^ James, William D.; Berger, Timothy G.; Arthur Hawley Sanford; et al. (2006). Andrews' Diseases of the Skin clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.CS1 maint: multiple names: authors list (link)
3. ^ a b Janeway, Travers, Walport and Shlomchik. Immunobiology, 6th Edition, Chapter 2; pp 55–75
4. ^ a b c [Kallenberg Cees G.M. Autoimmunity Reviews 7 (2008) pp612-615]
5. ^ a b [Ozen S. Education Review. Journal of Pediatric Nephrology (2010) 25:pp1633-1639]
6. ^ "Fat, Sick & Nearly Dead". 1 September 2014 – via www.imdb.com.
## External links[edit]
Classification
D
* ICD-10: L95.8 (ILDS L95.810)
External resources
* eMedicine: article/1085087
* v
* t
* e
Cutaneous vasculitis and other vascular-related cutaneous conditions
Cutaneous vasculitis
* Erythema elevatum diutinum
* Capillaritis
* Urticarial vasculitis
* Nodular vasculitis
Microvascular occlusion
* Calciphylaxis
* Cryoglobulinemic purpura/Cryoglobulinemic vasculitis
* vascular coagulopathy: Livedoid vasculitis
* Livedoid dermatitis
* Perinatal gangrene of the buttock
* Malignant atrophic papulosis
* Sneddon's syndrome
Purpura
* Nonthrombocytopenic purpura: Cryofibrinogenemic purpura
* Drug-induced purpura
* Food-induced purpura
* IgA vasculitis
* Obstructive purpura
* Orthostatic purpura
* Purpura fulminans
* Purpura secondary to clotting disorders
* Purpuric agave dermatitis
* Pigmentary purpuric eruptions
* Solar purpura
* Traumatic purpura
* Waldenström hyperglobulinemic purpura
* Painful bruising syndrome
* ungrouped: Paroxysmal hand hematoma
* Postcardiotomy syndrome
* Deep vein thrombosis
* Superficial thrombophlebitis
* Mondor's disease
* Blueberry muffin baby
* Fibrinolysis syndrome
Systemic vasculitis
* see Template:Systemic vasculitis
Vascular malformations
* Arteriovenous malformation
* Bonnet–Dechaume–Blanc syndrome
* Cobb syndrome
* Parkes Weber syndrome
* Sinusoidal hemangioma
* lymphatic malformation
* Hennekam syndrome
* Aagenaes syndrome
* telangiectasia: Generalized essential telangiectasia
* Hereditary hemorrhagic telangiectasia
* Unilateral nevoid telangiectasia
Ulcer
* Venous ulcer
* Arterial insufficiency ulcer
* Hematopoietic ulcer
* Neuropathic ulcer
* Acroangiodermatitis
Lymphedema
* see Template:Lymphatic vessel disease
Ungrouped
vascular-related
cutaneous conditions
* Raynaud's phenomenon
* Thromboangiitis obliterans
* Erythromelalgia
* Septic thrombophlebitis
* Arteriosclerosis obliterans
* Bier spots/Marshall–White syndrome
* Cholesterol embolus
* Reactive angioendotheliomatosis
* Trousseau's 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
|
Urticarial vasculitis
|
c1304408
| 25,509 |
wikipedia
|
https://en.wikipedia.org/wiki/Urticarial_vasculitis
| 2021-01-18T18:56:56 |
{"gard": ["6725"], "umls": ["C1304408"], "icd-10": ["L95.8"], "orphanet": ["36412"], "wikidata": ["Q7901365"]}
|
A 46, XY disorder of sex development (DSD) is a condition in which an individual with one X chromosome and one Y chromosome in each cell, the pattern normally found in males, have genitalia that is not clearly male or female. Infants with this condition tend to have penoscrotal hypospadias, abnormal development of the testes, and reduced to no sperm production. Some individuals with 46, XY DSD have fully to underdeveloped female reproductive organs (e.g., uterus and fallopian tubes), while others do not. People with with 46, XY DSD may be raised as males or females. Treatment involves surgery and hormone replacement therapy. People with 46, XY DSD are at an increased risk for gonadal tumors and benefit from regular surveillance or surgery to remove abnormally developed gonads.
*[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
|
46, XY disorders of sexual development
|
c0432470
| 25,510 |
gard
|
https://rarediseases.info.nih.gov/diseases/8538/46-xy-disorders-of-sexual-development
| 2021-01-18T17:56:59 |
{"mesh": ["C536769"], "umls": ["C0432470"], "orphanet": ["98085"], "synonyms": ["46, XY DSD", "46, XY female", "XY female"]}
|
Thanatophoric dysplasia, type 2 (TD2) is a form of TD (see this term) characterized by micromelia, straight long-bones, macrocephaly, brachydactyly, shortened ribs and a clover-leaf skull (kleeblattschaedel).
## Epidemiology
The prevalence is unknown but it is less common than TD1 (see this term).
## Clinical description
TD2 presents in the prenatal period (in the first to second trimester) with micromelia, long-bones (femurs) that are straight and not as short as those seen in TD type 1, platyspondyly of the vertebrae, narrow thorax, and a cloverleaf (trilobed) skull. Distinctive facial features include macrocephaly, frontal bossing, low nasal bridge, large anterior fontanel and proptosis. Polyhydramnios is common. Neonates usually die shortly after birth due to respiratory insufficiency and/or spinal cord/brain stem compression.
## Etiology
TD2 is caused by a single missense mutation (K650E) in the fibroblast growth factor receptor 3 (FGFR3) gene, located to chromosome 4p16.3.
## Genetic counseling
TD2 is inherited autosomal dominantly but the majority of cases are due to a de novo mutation in the proband. Genetic counseling allows families who have already had one child with TD2 to know that recurrence rate is about 2%, so their risk of having a healthy child is high. Expert reviewers: Dr. Michael Bober and Ms. Angie Duker
*[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
|
Thanatophoric dysplasia type 2
|
c1300257
| 25,511 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93274
| 2021-01-23T17:50:24 |
{"gard": ["1402"], "mesh": ["C536508"], "omim": ["156830", "187601"], "umls": ["C1300257", "C1834928"], "icd-10": ["Q77.1"], "synonyms": ["Cloverleaf skull-micromelic bone dysplasia syndrome", "TD2", "Thanatophoric dwarfism type 2", "Thanatophoric dwarfism-cloverleaf skull syndrome"]}
|
## Clinical Features
Morand et al. (1977) described 2 brothers with cardiomyopathy. One died at the age of 17 years of heart failure. The second was asymptomatic but had muscle cramps on effort; his skeletal musculature was completely normal. Cardiac examination showed apical systolic murmur, a globular hypokinetic heart, and electrocardiographic changes typical of those seen in Duchenne muscular dystrophy. Serum creatine kinase was greatly elevated, carnosinuria was demonstrated on a meat-free diet and microscopic changes of dystrophy were demonstrated on muscle biopsy. The mother and 1 of 2 sisters had elevated serum creatine kinase.
INHERITANCE \- X-linked CARDIOVASCULAR Heart \- Cardiomyopathy \- Apical systolic murmur \- Abnormal electrocardiograph \- Globular hypokinetic heart NEUROLOGIC Central Nervous System \- Normal neurologic status LABORATORY ABNORMALITIES \- Elevated serum creatine phosphokinase \- Carnosinuria ▲ 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
|
MUSCULAR DYSTROPHY, CARDIAC TYPE
|
c1442927
| 25,512 |
omim
|
https://www.omim.org/entry/309930
| 2019-09-22T16:17:37 |
{"mesh": ["C563247"], "omim": ["309930"]}
|
Lenz microphthalmia syndrome
Other namesLMS
Lenz microphthalmia syndrome is a very rare inherited disorder characterized by abnormal smallness of one or both eyes (microphthalmos) sometimes with droopy eyelids (blepharoptosis), resulting in visual impairment or blindness. Eye problems may include coloboma, microcornea, and glaucoma. Some affected infants may have complete absence of the eyes (anophthalmia). Most affected infants have developmental delay and intellectual disability, ranging from mild to severe. Other physical abnormalities associated with this disorder can include an unusually small head (microcephaly), and malformations of the teeth, ears, fingers or toes, skeleton, and genitourinary system. The range and severity of findings vary from case to case. Formal diagnosis criteria do not exist.
Lenz microphthalmia syndrome is also known as LMS, Lenz syndrome, Lenz dysplasia, Lenz dysmorphogenetic syndrome, or microphthalmia with multiple associated anomalies (MAA: OMIM 309800). It is named after Widukind Lenz, a German geneticist and dysmorphologist.
## Contents
* 1 Genetics
* 2 Diagnosis
* 2.1 Differential diagnosis
* 3 Management
* 4 References
## Genetics[edit]
Lenz microphthalmia syndrome is inherited as an X-linked recessive genetic trait and is fully expressed in males only. Females who carry one copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder, such as an abnormally small head (microcephaly), short stature, or malformations of the fingers or toes. Molecular genetic testing of BCOR (MCOPS2 locus), the only gene known to be associated with Lenz microphthalmia syndrome, is available on a clinical basis. One additional locus on the X chromosome (MCOPS1) is known to be associated with LMS.
## Diagnosis[edit]
### Differential diagnosis[edit]
A somewhat similar X-linked syndrome of microphthalmia, called oculofaciocardiodental syndrome (OFCD) is associated with mutations in BCOR. OFCD syndrome is inherited in an X-linked dominant pattern with male lethality.
## Management[edit]
This section is empty. You can help by adding to it. (March 2019)
## References[edit]
* Lenz Microphthalmia 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
|
Lenz microphthalmia syndrome
|
c0796016
| 25,513 |
wikipedia
|
https://en.wikipedia.org/wiki/Lenz_microphthalmia_syndrome
| 2021-01-18T19:07:35 |
{"gard": ["87"], "mesh": ["C537464"], "umls": ["C0796016"], "orphanet": ["568"], "wikidata": ["Q6523439"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of MCDR, see MCDR1 (136550).
Clinical Features
Michaelides et al. (2003) reported a 4-generation, nonconsanguineous British family with autosomal dominant macular dystrophy characterized by early onset of retinal changes confined to the macular region. The macular abnormalities varied from mild retinal pigment epithelium (RPE) pigmentary change to atrophy. Drusen-like deposits were present to various degrees and were characteristic of the phenotype. Subretinal neovascular membrane was a complication. The authors noted phenotypic similarity to North Carolina macular dystrophy (MCDR1, NCMD; 136550).
Rosenberg et al. (2010) studied a 3-generation Danish family in which 10 members exhibited features consistent with North Carolina macular dystrophy. The proband was a 13-year-old girl who presented with photophobia. Kinetic visual fields were slightly constricted, and automated perimetry showed bilateral defects in the lower right quadrant. She had normal color vision. Funduscopy revealed slightly oval-shaped bilateral macular lesions consisting of fine, densely packed, grainy depigmentations resembling small laminar drusen. Scotopic and photopic full-field electroretinography (ffERG) showed normal waveforms with normal amplitudes and implicit times. At follow-up 2 years later, her findings were unchanged. Examination of her 2 older sisters and a younger brother, who had no visual complaints, revealed the same macular lesions. A paternal uncle had a history of subnormal vision that was detected at 7 years of age on a screening test at school, at which time 'toxoplasmosis-like' macular scars were noted in both eyes. At age 33, he had no visual complaints but on close questioning, he reported difficulties with words disappearing while reading. Color vision was normal, and Golmann perimetry showed normal outer boundaries. Ophthalmoscopy revealed small round heavily pigmented foveal scars surrounded by small drusen-like changes. Rosenberg et al. (2010) stated that the appearance of characteristic macular lesions coupled with the autosomal dominant transmission, normal color vision, and normal ffERG, strongly supported a diagnosis of NCMD.
Audere et al. (2016) reported a Latvian family in which 8 members over 3 generations had dystrophic changes in the macula consistent with NCMD. Visual acuity was decreased in all 6 patients examined, and all had normal color vision. There was no progression of macular lesions; visual field testing, performed in 1 patient, showed bilateral small central scotomata. The authors observed that there was considerable variability in visual acuity between individuals of the same age group, and that there was no overlap between severity of disease and family generation. In addition, the authors noted that the phenotype in this family, with normal color vision and no progression of macular lesions, was reminiscent of MCDR1, and that MCDR3 is more often characterized by color vision defects and progression of disease. However, citing the NCMD-affected family reported by Michaelides et al. (2003) that exhibited a mixed phenotype, with mild color vision abnormalities and 1 patient with disease progression, Audere et al. (2016) concluded that the MCDR1 and MCDR3 phenotypes overlap more than previously thought.
Cipriani et al. (2017) performed fundus autofluorescence and optical coherence tomography (OCT) in an affected individual from each of 2 British families (designated GC15626 and GC15119, respectively) with 'typical' NCMD. The patient from family GC15626, a large 4-generation family previously reported by Michaelides et al. (2003), showed bilateral well-demarcated and relatively symmetric areas of macular chorioretinal atrophy. In contrast, the patient from family GC15119 exhibited a mild form of the disease, with bilateral relatively symmetric hyperfluorescent drusen-like deposits concentrated within the macular region, and otherwise normal OCT findings.
Mapping
In a 4-generation British family with retinal macular dystrophy, Michaelides et al. (2003) found linkage of the disorder, which they designated MCDR3, to 5p15.33-p13.1 (maximum lod of 3.61 at a recombination fraction of 0.00 for marker D5S630) between flanking markers D5S1981 and D5S2031.
Using a panel of STRP markers, Rosenberg et al. (2010) excluded the chromosome 6 MCDR1 locus in a 3-generation Danish family segregating autosomal dominant macular dystrophy. Genomewide linkage analysis with SNP microarrays identified a region on chromosome 5p with a maximum nonparametric linkage score of 9.88. Affected family members shared an allele of 1,081 consecutive SNPs spanning 13.96 Mb between the telomere and rs13154455. Linkage was confirmed by genotyping all 10 affected family members with 7 STRP markers spanning the region. The maximum 2-point parametric lod score of 2.69 (theta = 0) was obtained with markers D5S406, D5S1987, and D5S2505. Rosenberg et al. (2010) noted that the linked region overlapped with the previously described MCDR3 locus; the combined data narrowed the critical region from 20.0 Mb to 12.75 Mb.
In 5 affected members of a large 3-generation Latvian family (GC19806) with NCMD, previously reported by Audere et al. (2016), Cipriani et al. (2017) identified heterozygosity for a 45-kb tandem duplication at the MCDR3 locus (chr5:4,391,377-4,436,535; GRCh37) that was not found in an unaffected member of the family. In 25 affected individuals from 9 additional British families with NCMD, including a family (GC15626) that was originally reported by Michaelides et al. (2003), Cipriani et al. (2017) identified heterozygosity for a 43-kb tandem duplication in the same region (chr5:4,396,927-4,440,442). The duplications segregated with disease in the families, and neither was found in 16 controls, 650 patients with inherited retinal disease, or a public CNV database. The authors stated that the 2 duplications overlap the previously described duplication identified in a Danish family with NCMD by Small et al. (2016) (see MOLECULAR GENETICS), and further refine the MCDR3 locus to a 39-kb shared region in a gene desert located 800 kb downstream of the IRX1 gene (606197) and 693.9 kb upstream of the ADAMTS16 gene (607510).
Molecular Genetics
In a 3-generation Danish family segregating autosomal dominant macular dystrophy mapping to chromosome 5, originally studied by Rosenberg et al. (2010), Small et al. (2016) performed whole-genome sequencing and identified heterozygosity for a 900-kb tandem duplication that included the entire coding sequence of the IRX1 gene. The duplication segregated with disease in the family and was not found in 261 unrelated controls. However, Small et al. (2016) noted that smaller duplications in the same region, some of which included the entire coding sequence of IRX1, had been found in normal individuals, suggesting that the disease-causing element is not the IRX1 coding sequence itself.
### Exclusion Studies
In a 3-generation Latvian family segregating autosomal dominant NCMD, in which linkage analysis was inconclusive but was stronger for 5p15 than chromosome 6, Audere et al. (2016) analyzed 39 genes within the 5p15 region but did not find any causative mutations.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Decreased visual acuity \- Central scotomata (in some patients) \- Mild color vision defects (in some patients) \- Drusen-like macular deposits \- Macular retinal pigment epithelium atrophy \- Macular retinal pigment epithelium pigmentation \- Subretinal neovascular membrane (in some patients) \- Normal electroretinography MISCELLANEOUS \- Onset in first decade of life \- Disease is nonprogressive in most patients ▲ 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
|
MACULAR DYSTROPHY, RETINAL, 3
|
c3888009
| 25,514 |
omim
|
https://www.omim.org/entry/608850
| 2019-09-22T16:07:05 |
{"omim": ["608850"]}
|
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2018)
Stasis papillomatosis
Stasis papillomatosis is a disease characterized by chronic congestion of the extremities, with blood circulation interrupted in a specific area of the body.[citation needed] A consequence of this congestion and inflammation is long-term lymphatic obstruction.[1] It is also typically characterized by the appearance of numerous papules.[2] Injuries can range from small to large plates composed of brown or pink, smooth or hyperkeratotic papules.[3] The most typical areas where injuries occur are the back of the feet, the toes, the legs, and the area around a venous ulcer formed in the extremities, although the latter is the rarest of all.[1] These injuries include pachydermia (thickening of the skin), lymphedema, lymphomastic verrucusis and elephantosis verracosa. The disease can be either localized or generalized; the localized form makes up 78% of cases.[1] Treatment includes surgical and pharmaceutical intervention; indications for partial removal include advanced fibrotic lymphedema and elephantiasis.[4] Despite the existence of these treatments, chronic venous edema, which is a derivation of stasis papillomatosis, is only partially reversible. The skin is also affected and its partial removal may mean that the skin and the subcutaneous tissue are excised.[5] A side effect of the procedure is the destruction of existing cutaneous lymphatic vessels. It also risks papillomatosis, skin necrosis and edema exacerbation.[6]
All etiologies lead to local dermal lymphostasis pathogenesis. A maximum variation was observed after the resection of block subcutaneous tissue in patients suffering from congenital lymphedema. Signals that the current condition are different, either in the dermis or in the subcutaneous area.[7] In dermis, principal signs found are precollectors initial nodes, injection tank, the reticular distribution, cutaneous reflexes, and lymphatic cysts. On other hand in the subcutaneous area principal signs are; collectors, thinning, ectatic, tortuous, rest offs, reflux dermal, sclerosis, calcifications.[6]
## Contents
* 1 Presentation
* 1.1 Complications
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 References
## Presentation[edit]
### Complications[edit]
Chronic inflammation can cause long term lymphatic obstruction.[3] Typically, patients have disorders that present local nodes, primary lymphedema and chronic venous insufficiency. Erysipelas and trauma are major risk factors. Lymphatic edema can be developed in many acral cases accompanied by a thickening of the folds of the skin, hyperkeratosis and papillomatosis.[1] Chronic venous edema is only partially reversible and soon becomes hard, especially confirming tenderness. All structures of the skin are affected. Dilated dermal lymphatic vessels with consequent superior organization and fibrosis result in papillomatosis. As dermal lymphatic stasis progreses, these skin changes become more marked and known as elephantiasis. Occasionally, tissue fibrosis and thickening may become so marked in the later stages of lymphedema that pitting is absent. Recurrent cellulitis, erysipelas and dermato-LAM-adenitis are complications of chronic lymphedema.[6]
## Causes[edit]
The reason for its occurrence is unknown. Investigations have suspected that obesity and preceding psoriatic lesions cause local lymphatic disturbances, followed by the development of stasis papillomatosis.[7] On the other hand, genetic or environmental factors may play a role. Some investigators have speculated that it represents an allergic response to an epidermal protein antigen created through increased hydrostatic pressure, whereas others believe that the skin has been compromised and is more susceptible to irritation and trauma.[4]
The age is an important factor, because as some people get older the veins which carry blood from the legs back to the heart do not work as well as they use to. This causes fluid to settle in the lower legs.[8]
The most important cause of this condition is insufficient lymphatic drainage, causing soft tissue swelling due to fluid accumulation. Obstruction of lymphatic tissue causes increased intravascular tissue protein; this will increase the production of fibroblasts and mast cells.[2][5] Lymphatic obstruction due to any cause can increase the amount of proteins in the intravascular tissue, either by root osmotic pressure, or because it absorbs a little liquid. The further roteins increase the vascular fluid, fibroblasts and promote the ploriferation of mast cells which produce the clinical symptoms of nonpitting edema. The epidermis may be hyperkeratotic and warty and this predisposes to tissue cracks and allows secondary infection.[3]
## Diagnosis[edit]
Stasis Papillomatosis is similar to AGEP (Acute generalized exanthematous pustulosis) from pustular psoriasis; criteria for histopathologic distinction have been proposed: papillary edema, vasculitis, exocytosis of eosinophils and single-cell necrosis of keratinocytes in AGEP and acanthosis and papillomatosis in pustular psoriasis.[1]
An example that illustrates the difference between SP and Stasis Papillomatosis and the histology diagnosis is … “a markedly obese, 41-year-old Japanese man who had suffered from psoriasis vulgaris for several years visited hospital with elephantiasis-like swelling of his lower legs of three months' duration. His right lower leg showed marked papillomatosis with thick scales, and the left lower leg was eroded and papillomatous.[5] Although direct lymphography of his lower extremities showed no abnormality, indirect lymphography revealed local lymphatic damage in the involved skin”.[3] Histological examination showed hyperkeratosis, marked papillomatosis, proliferation of capillaries in the upper dermis, and lymphectasia in the lower dermis. It was suspected that obesity and the preceding psoriatic lesions caused local lymphatic disturbances, followed by the development of stasis papillomatosis.[6]
## Treatment[edit]
This disease is caused by problems in the circulatory system; thus, the legs should be elevated as much as possible to help the return of the blood. At night it is advisable to sleep with a pillow under the lower legs.[6] In the evening, it is not unusual for legs to be swollen. The volume of the lower leg can increase to up to 100ml after a long working day or up to 200ml after a long-haul flight without moving.[2][3]
In the example of the 41-year-old Japanese man the lesions were much improved by washing and topical use of corticosteroids for two months, also oral antibiotics like cephalexin are used if cellulitis is present. Moist exudative inflammation and moist ulcers respond to tepid wet compresses of Burow’s solution or just saline or water for 30 to 60 minutes several times a day.[9] But in worse cases, edema that does not disappear spontaneously within a few hours or after a walk, is described as pathological, so it needs to have a special treatment. It is very important to say that Papillamitosis, bilateral and marked edema with few symptoms is mostly caused by the systemic circulation (heart, kidneys, liver).[3]
Papillamitosis is associated with symptoms and/or clinical signs such as dilated superficial veins, varicose veins and changes in the skin.[3] Edema and its complication Papillamitosis are only partially reversible and soon becomes hard, which is mainly confirmed on palpation. All skin structures are affected and this is characterized by the term. Lymphoedema may develop in many cases accompanied by acral thickening of the skin folds, hyperkeratosis and papillomatosis.[3][5]
## References[edit]
1. ^ a b c d e Schultz-Ehrenburg U, Niederauer HH, Tiedjen KU (May 1993). "Stasis papillomatosis. Clinical features, etiopathogenesis and radiological findings". The Journal of Dermatologic Surgery and Oncology. 19 (5): 440–6. doi:10.1111/j.1524-4725.1993.tb00371.x. PMID 8496488.
2. ^ a b c Schultz-Ehrenburg (2011). Dermatol Surg Oncol.[full citation needed]
3. ^ a b c d e f g h Mockenhaupt M (February 2009). "Severe drug-induced skin reactions: Clinical pattern, diagnostics and therapy". Journal der Deutschen Dermatologischen Gesellschaft. 7 (2): 142–60, quiz 161–2. doi:10.1111/j.1610-0387.2008.06878.x. PMID 19371237.
4. ^ a b "Venous Disorders, Diagnosis and Treatment | Three-dimensional Regenerative Ambulatory Phlebotherapy". phlebotherapy.eu. Retrieved 2016-06-06.
5. ^ a b c d Clinical Key. Obtenido de Clinical Key.[full citation needed]
6. ^ a b c d e Sato T, Katagiri K, Itami S, Takayasu S (May 1996). "A case of stasis papillomatosis associated with psoriasis vulgaris". The Journal of Dermatology. 23 (5): 352–6. doi:10.1111/j.1346-8138.1996.tb04030.x. PMID 8675828.
7. ^ a b Szuba A, Rockson SG (1998). "Lymphedema: classification, diagnosis and therapy". Vascular Medicine. 3 (2): 145–56. doi:10.1177/1358836X9800300209. PMID 9796078.
8. ^ Sadeghian G, NilfroushZadeh MA, Siadat AH, Ziaei H (2008). "Nodular fibrosis: a rare complication of non filarial lymph edema". Dermatology Online Journal. 14 (3): 20. PMID 18627721.
9. ^ Rivas. "Guide for lymphedema".[full citation needed]
*[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
|
Stasis papillomatosis
|
None
| 25,515 |
wikipedia
|
https://en.wikipedia.org/wiki/Stasis_papillomatosis
| 2021-01-18T18:42:16 |
{"wikidata": ["Q17155503"]}
|
A number sign (#) is used with this entry because of evidence that systemic lupus erythematosus-16 (SLEB16) can be caused by homozygous mutation in the DNASE1L3 gene (602244) on chromosome 3p14.3.
For a general phenotypic description and discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Clinical Features
Al-Mayouf et al. (2011) studied 7 Arab families in which at least 2 sibs had systemic lupus erythematosus and healthy consanguineous parents. All affected individuals had pediatric onset of SLE, and there was high frequency of anti-neutrophil cytoplasmic antibodies and lupus nephritis.
Mapping
In 7 consanguineous Arab families in which at least 2 sibs had systemic lupus erythematosus, Al-Mayouf et al. (2011) performed autozygome analysis and, in 6 of the families, identified overlapping autozygous intervals of varying lengths on chromosome 3p14.3. Linkage analysis confirmed the locus with a lod score of 6.6.
Molecular Genetics
In 6 consanguineous Arab families with SLE mapping to chromosome 3p14.3, Al-Mayouf et al. (2011) analyzed the candidate gene DNASE1L3 (602244) and identified a 1-bp deletion (602244.0001) that segregated with disease in all 6 families. Haplotype analysis confirmed this to be a founder mutation. Al-Mayouf et al. (2011) noted that the International Consortium for Systemic Lupus Erythematosus Genetics et al. (2008) observed a GWAS peak on chromosome 3p14.3, which was tentatively attributed to the PXK gene (611450); given that DNASE1L3 is only 140 kb upstream of PXK, Al-Mayouf et al. (2011) suggested that the signal might have been generated by variants in DNASE1L3.
INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Nephritis IMMUNOLOGY \- Systemic lupus erythematosus, childhood onset LABORATORY ABNORMALITIES \- Anti-neutrophil cytoplasmic antibodies MOLECULAR BASIS \- Caused by mutation in the deoxyribonuclease I-like 3 gene (DNASE1L3, 602244.0001 ) ▲ 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
|
SYSTEMIC LUPUS ERYTHEMATOSUS 16
|
c3280742
| 25,516 |
omim
|
https://www.omim.org/entry/614420
| 2019-09-22T15:55:21 |
{"doid": ["9074"], "omim": ["614420"], "orphanet": ["300345"], "synonyms": ["Autosomal SLE", "Familial SLE", "Familial systemic lupus erythematosus"]}
|
Oncocytoma
Micrograph of a parotid gland oncocytoma (right of image). Normal parotid gland is also present (left of image). H&E stain.
SpecialtyOncology
An oncocytoma is a tumor made up of oncocytes, epithelial cells characterized by an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm.[1][2] The cells and the tumor that they compose are often benign but sometimes may be premalignant or malignant.
## Contents
* 1 Presentation
* 2 Renal oncocytoma
* 3 Salivary gland oncocytoma
* 3.1 Symptoms
* 4 Thyroid oncocytoma
* 4.1 Symptoms
* 5 Additional images
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
An oncocytoma is an epithelial tumor composed of oncocytes, large eosinophilic cells having small, round, benign-appearing nuclei with large nucleoli.
Oncocytoma can arise in a number of organs.
## Renal oncocytoma[edit]
Main article: Renal oncocytoma
Renal oncocytoma is thought to arise from the intercalated cells of collecting ducts of the kidney. It represents 5% to 15% of surgically resected renal neoplasms.
## Salivary gland oncocytoma[edit]
Oncocytoma of the salivary gland. This lesion presented as a lateral anterior neck mass. At surgery, it was found to be a soft 3.0 × 2.1 × 1.8 cm tumor of the submandibular salivary gland. The photo shows the characteristic dark color of an oncocytoma, a rare type of benign neoplasm, at the left side of the image (the normal lobulated salivary gland tissue is to the right).
The salivary gland oncocytoma is a well-circumscribed, benign neoplastic growth also called an oxyphilic adenoma. It comprises about 1% of all salivary gland tumors. The histopathology is marked by sheets of large swollen polyhedral epithelial oncocytes, which are granular acidophilic parotid cells with centrally located nuclei. The granules are created by the mitochondria.
### Symptoms[edit]
Salivary gland oncocytomas are most common in ages 70–80, females, the parotid gland (85–90%), and are firm, slowly growing, painless masses of less than 4 cm. They may be bilateral.
## Thyroid oncocytoma[edit]
Thyroid oncocytomas can be benign (adenomas) or malignant (carcinomas). Also known as Hürtle cell tumours. Grossly, oncocytic adenomas are encapsulated, solid nodules with a characteristic brown cut surface. The gross appearance of a minimally invasive oncocytic carcinoma is indistinguishable to that of an adenoma, while widely invasive oncocytic carcinomas are obviously invasive macroscopically and display pervasive vascular invasion with multifocal involvement of the thyroid gland. There are no reliable cytologic features which distinguish oncocytic adenomas from carcinomas and the only criterion for a diagnosis of malignancy is the identification of transcapsular or vascular invasion.
### Symptoms[edit]
Patients with thyroid oncocytomas present with a thyroid nodule, usually with normal thyroid function. If the tumor is big or invasive, there may be other symptoms such as difficulty swallowing or talking.
## Additional images[edit]
* Micrograph of a renal oncocytoma. H&E stain.
* Micrograph of a renal oncocytoma. H&E stain.
* Gross appearance of the cut surface of a nephrectomy specimen containing a renal oncocytoma. Note the rounded contour, the mahogany colour and the central scar.
## See also[edit]
* Kidney
* Renal cell carcinoma
* Hurthle cell
## References[edit]
1. ^ Coburn V, Radfar A, Snook D, Mahalingam M (2007). "Cutaneous oncocytoma - a report of three cases and review of the literature". J. Cutan. Pathol. 34 (4): 355–59. doi:10.1111/j.1600-0560.2006.00620.x. PMID 17381809.
2. ^ "Atlas of Genetics and Cytogenetics in Oncology and Haematology - Thyroid:oncocytic tumors". Retrieved 2009-02-01.
## External links[edit]
Classification
D
* ICD-O: M8290/0
* MeSH: D018249
* DiseasesDB: 31956
External resources
* eMedicine: med/1045
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
* v
* t
* e
Tumors of lip, oral cavity and pharynx / head and neck cancer
Oral cancer
Salivary gland
malignant epithelial tumors
* Acinic cell carcinoma
* Mucoepidermoid carcinoma
* Adenoid cystic carcinoma
* Salivary duct carcinoma
* Epithelial-myoepithelial carcinoma
* Polymorphous low-grade adenocarcinoma
* Hyalinizing clear cell carcinoma
benign epithelial tumors
* Pleomorphic adenoma
* Warthin's tumor
ungrouped:
* Oncocytoma
Tongue
* Leukoplakia
* Rhabdomyoma
* Oropharynx
* v
* t
* e
Tumors of the urinary and genital systems
Kidney
Glandular and epithelial neoplasm
* Renal cell carcinoma
* Renal oncocytoma
Mixed tumor
* Wilms' tumor
* Mesoblastic nephroma
* Clear-cell sarcoma of the kidney
* Angiomyolipoma
* Cystic nephroma
* Metanephric adenoma
by location
* Renal medullary carcinoma
* Juxtaglomerular cell tumor
* Renal medullary fibroma
Ureter
* Ureteral neoplasm
Bladder
* Transitional cell carcinoma
* Squamous-cell carcinoma
* Inverted papilloma
Urethra
* Transitional cell carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma
* Melanoma
Other
* Malignant fibrous histiocytoma
*[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
|
Oncocytoma
|
c1510502
| 25,517 |
wikipedia
|
https://en.wikipedia.org/wiki/Oncocytoma
| 2021-01-18T18:39:21 |
{"mesh": ["D018249"], "umls": ["C1510502"], "wikidata": ["Q1760202"]}
|
A number sign (#) is used with this entry because familial hemophagocytic lymphohistiocytosis-5 (FHL5) is caused by homozygous or compound heterozygous mutation in the syntaxin-binding protein-2 gene (STXBP2; 601717) on chromosome 19p13.
For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis, see 267700.
Mapping
Zur Stadt et al. (2009) performed genomewide linkage analysis and homozygosity mapping in 1 Saudi Arabian and 14 unrelated Turkish probands, all from consanguineous backgrounds, who had familial hemophagocytic lymphohistiocytosis but did not have mutations in the 3 known FHL genes. A maximum heterogeneity lod (hlod) score of 5.9 was obtained on chromosome 19p; fine mapping yielded a hlod of 8.3 at rs634968, and detailed genotype analysis revealed an overlapping region of homozygosity in 7 of the 15 cases, a 1,040-kb interval containing 36 genes. Whole-genome analysis of another consanguineous FHL family from Saudi Arabia with 2 affected and 3 unaffected sibs revealed 3 homozygous regions with lod scores greater than 2.0, 1 of which overlapped with the previously identified interval on chromosome 19p.
In 8 patients from 6 consanguineous families with FHL in which known causes had been excluded by genetic analysis, Cote et al. (2009) performed genomewide SNP analysis and found a common region of homozygosity on chromosome 19p13.2-p13.3; of 40 genes within the interval, the STXBP2 gene appeared to be the most plausible candidate.
Molecular Genetics
In 8 unrelated probands with familial hemophagocytic lymphohistiocytosis mapping to chromosome 19p, from 2 Saudi Arabian and 6 Turkish consanguineous families, zur Stadt et al. (2009) identified homozygous mutations in the STXBP2 gene in all 8 patients (see, e.g., 601717.0001-601717.0003). Sequence analysis in other patients from nonconsanguineous FHL families revealed homozygosity or compound heterozygosity for additional mutations in the STXBP2 gene in 4 patients from Germany and the Czech Republic (see, e.g., 601717.0004-601717.0006), 2 of whom had previously been reported (Beutel et al., 2009; Sparber-Sauer et al., 2009). Corresponding heterozygous mutations were found in all available unaffected parents, and none of the mutations were detected in 210 chromosomes from ethnically matched controls. The 7 patients who were homozygous for missense mutations or a 3-bp deletion had early-onset disease, diagnosed before 1 year of age, whereas the remaining 5 patients, who were homozygous for a splice site mutation or compound heterozygous for the splice site mutation and another mutation, had disease that developed after 1 year of age. Zur Stadt et al. (2009) identified STX11 (605014), mutations in which causes FHL4 (603552), as an interaction partner of STXBP2, and demonstrated that this interaction is eliminated by the missense mutations identified in the FHL5 patients, leading to decreased stability of both proteins. Analysis of CD107 degranulation in 3 early-onset and 2 late-onset patients demonstrated marked reduction or absence of natural killer and cytotoxic T-cell activity.
In affected members of 6 consanguineous families with FHL mapping to chromosome 19p13.2-p13.3, Cote et al. (2009) sequenced the STXBP2 gene and identified homozygosity for the P477L mutation (601717.0001) in 3 Saudi Arabian families and for the IVS14 splice site mutation (601717.0003) in 3 families of Turkish, Palestinian Arab, and Iranian origin, respectively. In all patients with the P477L mutation, FHL was early in onset and rapidly led to death in 3 of 5 patients, whereas FHL manifestations occurred several years later in patients with the splice site mutation, and 1 individual homozygous for the splice site mutation was asymptomatic at 32 months of age. Cote et al. (2009) confirmed STX11 as the main partner of STXBP2 in lymphocytes, with STXBP2 being required for its expression.
Cetica et al. (2010) analyzed the STXBP2 gene in 28 FHL families in which mutations in known FHL genes had been excluded by sequence analysis, and identified homozygosity for 4 different missense mutations in the STXBP2 gene in 4 (14%) of the 28 families, originating from Italy, England, Kuwait, and Pakistan, respectively (see, e.g., 601717.0001 and 601717.0007). Cetica et al. (2010) noted that the presenting features of these FHL5 patients appeared largely comparable to those of other FHL subgroups, in particular FHL2 (603553) and FHL3 (608898).
*[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
|
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 5
|
c0272199
| 25,518 |
omim
|
https://www.omim.org/entry/613101
| 2019-09-22T15:59:39 |
{"doid": ["0110925"], "mesh": ["D051359"], "omim": ["613101"], "orphanet": ["540"], "genereviews": ["NBK1444"]}
|
Congenital stromal corneal dystrophy is an inherited eye disorder. This condition primarily affects the cornea, which is the clear outer covering of the eye. In people with this condition, the cornea appears cloudy and may have an irregular surface. These corneal changes lead to visual impairment, including blurring, glare, and a loss of sharp vision (reduced visual acuity). Visual impairment is often associated with additional eye abnormalities, including "lazy eye" (amblyopia), eyes that do not look in the same direction (strabismus), involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia).
## Frequency
Congenital stromal corneal dystrophy is probably very rare; only a few affected families have been reported in the medical literature.
## Causes
Congenital stromal corneal dystrophy is caused by mutations in the DCN gene. This gene provides instructions for making a protein called decorin, which is involved in the organization of collagens. Collagens are proteins that strengthen and support connective tissues such as skin, bone, tendons, and ligaments. In the cornea, well-organized bundles of collagen make the cornea transparent. Decorin ensures that collagen fibrils in the cornea are uniformly sized and regularly spaced.
Mutations in the DCN gene lead to the production of a defective version of decorin. This abnormal protein interferes with the organization of collagen fibrils in the cornea. As poorly arranged collagen fibrils accumulate, the cornea becomes cloudy. These corneal changes lead to reduced visual acuity and related eye abnormalities.
### Learn more about the gene associated with Congenital stromal corneal dystrophy
* DCN
## 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.
*[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
|
Congenital stromal corneal dystrophy
|
c1864738
| 25,519 |
medlineplus
|
https://medlineplus.gov/genetics/condition/congenital-stromal-corneal-dystrophy/
| 2021-01-27T08:25:47 |
{"mesh": ["C566452"], "omim": ["610048"], "synonyms": []}
|
Todd's paresis
Other namesTodd's paralysis, or Todd's palsy
SpecialtyNeurology
Todd's paresis (or postictal paresis/paralysis, "after seizure") is focal weakness in a part or all of the body after a seizure. This weakness typically affects appendages and is localized to either the left or right side of the body. It usually subsides completely within 48 hours. Todd's paresis may also affect speech, eye position (gaze), or vision.
The condition is named after Robert Bentley Todd (1809–1860), an Irish-born London physiologist who first described the phenomenon in 1849.[1][2] It may occur in up to 13% of seizure cases.[3] It is most common after a focal motor seizure affecting one limb or one side of the body.[4] The generally postulated cause is the exhaustion of the primary motor cortex, although no conclusive evidence is available to support this.
## Contents
* 1 Presentation
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 References
* 7 External links
## Presentation[edit]
Robert Bentley Todd
The classic presentation of Todd's paresis is a transient weakness of a hand, arm, or leg after focal seizure activity within that limb. The weakness may range in severity from mild to complete paralysis.[citation needed]
When seizures affect areas other than the motor cortex, other transient neurological deficits can take place. These include sensory changes if the sensory cortex is involved by the seizure, visual field defects if the occipital lobe is involved, and aphasia if speech, comprehension or conducting fibers are involved.[citation needed]
Postictal paresis (PP), although familiar to neurologists, has not been well-studied. One retrospective observational study evaluated 328 selected patients from ages 16 to 57 years who had prolonged video-electroencephalogram (EEG) monitoring for medically intractable epilepsy and focal seizure onset; those with nonepileptic seizures, status epilepticus, and Lennox-Gastaut syndrome were excluded.[5] The following observations were made:[citation needed]
* PP occurred in 44 patients (13.4 percent)
* PP was always unilateral and always contralateral to the seizure focus
* The mean duration of PP was 174 seconds (range 11 seconds to 22 minutes)
Of all seizures followed by PP, the following features were noted:[citation needed]
* Obvious ictal motor activity was seen in 78 percent (Todd's paresis is more common after any clonic seizure activity)[3]
* Very slight ictal motor activity was seen in 10 percent
* No ictal motor activity was seen in nearly 10 percent
* The most common ictal lateralizing sign was unilateral clonic activity in 56 percent
* Ictal dystonic posturing occurred in 48 percent
* Ictal limb immobility occurred in 25 percent
The results of this study are valuable because few other data exist on the frequency, duration, and seizure characteristics associated with PP. However, the study is likely biased by the inclusion only of patients with medically intractable seizures who had undergone video-EEG monitoring, and the results may not extrapolate to a general epilepsy population.[citation needed]
Other post-ictal neurological findings that do not involve activity of the area affected by the seizure have been described. They are thought to be caused by a different mechanism than Todd's paresis, and including paralysis of the contralateral limb,[6] and rare genetic causes of hemiplegia and seizures.[7]
## Causes[edit]
The cause of Todd's paresis has been attributed to the affected cortex being ‘exhausted’ or silenced due to increased inhibition, but these conjectures are not supported. It has been observed that the impairments that follow seizures are similar to those that follow strokes, where for a period of time blood flow to certain areas of the brain is restricted and these areas are starved of oxygen.[8]
## Diagnosis[edit]
The most significant issue regarding the Todd's paresis is its differentiation from a stroke. The issue is further complicated by the fact that some strokes trigger a focal seizure during the acute phase. A Todd's paresis in this context may overestimate the extent of neurological deficit due to the vascular process itself resulting in erroneous decisions with regards to acute stroke therapy such as thrombolysis. For this reason a seizure during an acute stroke is generally accepted to be a relative contraindication to thrombolytic therapy, especially in the absence of documented cerebrovascular occlusion using vascular imaging techniques.[9]
An infant with Todd's paresis does not necessarily preclude the diagnosis of a febrile convulsion. This view is as a result of a recent study that showed the incidence of Todd's paresis to be in 0.4% of infants that have been diagnosed with a febrile convulsion.[10]
## Treatment[edit]
There is no treatment for Todd's paralysis. Individuals must rest as comfortably as possible until the paralysis disappears.[citation needed]
## Prognosis[edit]
An occurrence of Todd's paralysis indicates that a seizure has occurred. The prognosis for the patient depends upon the effects of the seizure, not the occurrence of the paralysis.[citation needed]
## References[edit]
1. ^ Todd RB (1849). "On the pathology and treatment of convulsive diseases". London Med Gaz. 8: 668.
2. ^ Pearce JM (March 1994). "Robert Bentley Todd (1809-60) and Todd's paralysis". J. Neurol. Neurosurg. Psychiatry. 57 (3): 315. doi:10.1136/jnnp.57.3.315. PMC 1072820. PMID 8158178.
3. ^ a b Gallmetzer P, Leutmezer F, Serles W, Assem-Hilger E, Spatt J, Baumgartner C (June 2004). "Postictal paresis in focal epilepsies--incidence, duration, and causes: a video-EEG monitoring study". Neurology. 62 (12): 2160–4. doi:10.1212/wnl.62.12.2160. PMID 15210875.
4. ^ Uptodate: Evaluation of the first seizure in adults
5. ^ Gallmetzer P, Leutmezer F, Serles W, Assem-Hilger E, Spatt J, Baumgartner C (June 2004). "Postictal paresis in focal epilepsies--incidence, duration, and causes: a video-EEG monitoring study". Neurology. 62 (12): 2160–4. doi:10.1212/wnl.62.12.2160. PMID 15210875.
6. ^ Oestreich L, Berg M, Bachmann D, Burchfiel J, Erba G (1995). "Ictal contralateral paresis in complex partial seizures". Epilepsia. 36 (7): 671–5. doi:10.1111/j.1528-1157.1995.tb01044.x. PMID 7555983.
7. ^ Mikati M, Maguire H, Barlow C, Ozelius L, Breakefield X, Klauck S, Korf B, O'Tuama S, Dangond F (1992). "A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations". Neurology. 42 (12): 2251–7. doi:10.1212/wnl.42.12.2251. PMID 1361034.
8. ^ name="Farrell et al., 2016">Farrell, Jordan S; Gaxiola-Valdez, Ismael; Wolff, Marshal D; David, Laurence S; Dika, Haruna I; Geeraert, Bryce L; Wang, X Rachel; Singh, Shaily; Spanswick, Simon C; Dunn, Jeff F; Antle, Michael C; Federico, Paolo; Teskey, G Campbell (2016). "Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent". eLife. 5. doi:10.7554/eLife.19352. PMC 5154758. PMID 27874832.
9. ^ Sylaja PN, Dzialowski I, Krol A, Roy J, Federico P, Demchuk AM (2006). "Role of CT angiography in thrombolysis decision-making for patients with presumed seizure at stroke onset". Stroke. 37 (3): 915–7. doi:10.1161/01.STR.0000202678.86234.84. PMID 16456124.
10. ^ Nelson K, Ellenberg J; Prognosis in Children With Febrile Seizures Paediatrics; 61, 5: 720-727
## External links[edit]
Classification
D
* ICD-10: G83.8
* ICD-9-CM: 344.89
* MeSH: D010243
* v
* t
* e
Seizures and epilepsy
Basics
* Seizure types
* Aura (warning sign)
* Postictal state
* Epileptogenesis
* Neonatal seizure
* Epilepsy in children
Management
* Anticonvulsants
* Investigations
* Electroencephalography
* Epileptologist
Personal issues
* Epilepsy and driving
* Epilepsy and employment
Seizure types
Focal
Seizures
Simple partial
Complex partial
Gelastic seizure
Epilepsy
Temporal lobe epilepsy
Frontal lobe epilepsy
Rolandic epilepsy
Nocturnal epilepsy
Panayiotopoulos syndrome
Vertiginous epilepsy
Generalised
* Tonic–clonic
* Absence seizure
* Atonic seizure
* Automatism
* Benign familial neonatal seizures
* Lennox–Gastaut syndrome
* Myoclonic astatic epilepsy
* Epileptic spasms
Status epilepticus
* Epilepsia partialis continua
* Complex partial status epilepticus
Myoclonic epilepsy
* Progressive myoclonus epilepsy
* Dentatorubral–pallidoluysian atrophy
* Unverricht–Lundborg disease
* MERRF syndrome
* Lafora disease
* Juvenile myoclonic epilepsy
Non-epileptic seizure
* Febrile seizure
* Psychogenic non-epileptic seizure
Related disorders
* Sudden unexpected death in epilepsy
* Todd's paresis
* Landau–Kleffner syndrome
* Epilepsy in animals
Organizations
* Citizens United for Research in Epilepsy (US)
* Epilepsy Action (UK)
* Epilepsy Action Australia
* Epilepsy Foundation (US)
* Epilepsy Outlook (UK)
* Epilepsy Research UK
* Epilepsy Society (UK)
*[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
|
Todd's paresis
|
c0234544
| 25,520 |
wikipedia
|
https://en.wikipedia.org/wiki/Todd%27s_paresis
| 2021-01-18T18:45:53 |
{"mesh": ["D010243"], "umls": ["C0234544"], "icd-10": ["G83.8"], "wikidata": ["Q495068"]}
|
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-51 (RP51) is caused by homozygous mutation in the TTC8 gene (608132) on chromosome 14q31.
Mutation in the TTC8 gene can also cause Bardet-Biedl syndrome-8 (BBS8; 615985), in which retinitis pigmentosa is one of the primary features.
For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical Features
Riazuddin et al. (2010) studied 4 affected and 7 unaffected members of a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa (RP). Medical records of the 4 affected individuals were suggestive of early-onset RP, with diagnoses made between 2 years and 4 years of age. Fundus photographs showed typical changes of RP, including attenuation of retinal arteries and bone spicule pigment deposits in the midperiphery of the retina. The diagnosis was confirmed by electroretinography (ERG), which showed typical RP changes with loss of both rod and cone responses in affected individuals but not in unaffected sibs or in the unaffected mother. None of the affected individuals had evidence of syndromic disease; specifically, there were no features consistent with Bardet-Biedl syndrome (BBS8; see 209900), which is also caused by TTC8 mutation. None had renal problems, and their body mass indices were within the normal range. There were no signs of polydactyly or midline defects or facies reminiscent of BBS, and no evidence of developmental delay, appreciable cognitive impairment, or inappropriate social behavior.
Goyal et al. (2016) studied a 4-generation consanguineous family of North Indian origin in which 2 brothers and their male cousin had RP. The proband was a 22-year-old man who had noticed night blindness and photophobia since age 17 years, with loss of central vision at age 18. His affected brother lost central vision at age 16 years, and their cousin had onset of RP at age 2 years with loss of central vision at age 5. Funduscopy in all 3 showed attenuated retinal vessels, bone spicule-like pigmentation in the midperiphery of the retina, macular degeneration, retinal pigment epithelium (RPE) degeneration, and waxy pallor of the optic disc. Visual acuity was reduced, and all 3 had high myopia. OCT in the proband's affected brother showed fraying of the rod and cone layers, hyperflexed areas in the RPE layer due to accumulation of pigments, and macular degeneration; ERG testing showed extinguished rod and cone responses. None of the affected individuals exhibited any extraocular characteristics of BBS, and thus were considered to represent nonsyndromic autosomal recessive RP with macular degeneration.
Mapping
In a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa, Riazuddin et al. (2010) performed a genomewide scan and obtained a 2-point lod score of 3.12 at marker D14S256 (theta = 0.0). Recombination events defined a 13.4-cM (5.6-Mb) critical interval between D14S612 and D14S1050 on chromosome 14q, harboring more than 100 annotated genes.
Molecular Genetics
In a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa (RP) mapping to chromosome 14q, Riazuddin et al. (2010) sequenced candidate genes and identified a homozygous splice site mutation in the TTC8 gene (608132.0005) that segregated with disease and was not found in 384 Pakistani control chromosomes or 384 chromosomes of northern European descent.
In the proband from a consanguineous North Indian family with RP and macular degeneration mapping to chromosome 14q, Goyal et al. (2016) performed whole-exome sequencing and identified homozygosity for a missense mutation in the TTC8 gene (Q449H; 608132.0006). The mutation segregated with disease in the family and was not found in 100 ethnically matched controls.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Night blindness \- Photophobia \- Reduced visual acuity \- High myopia \- Attenuation of retinal vessels \- Macular degeneration \- Bone spicule-like pigmentation in midperiphery of retina \- Degeneration of retinal pigment epithelium (RPE) \- Waxy pallor of optic disc \- Fraying of rod and cone layers on optical coherence tomography (OCT) \- Bulged areas in RPE layer due to accumulation of pigment on OCT \- Macular degeneration on OCT \- Extinguished rod and cone responses on electroretinography MISCELLANEOUS \- Affected individuals do not exhibit any features of Bardet-Biedl syndrome (see 615985 ) \- One large consanguineous Pakistani family has been reported (last curated May 2016) MOLECULAR BASIS \- Caused by mutation in the tetratricopeptide repeat domain-containing protein-8 gene (TTC8, 608132.0005 ) ▲ 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
|
RETINITIS PIGMENTOSA 51
|
c0035334
| 25,521 |
omim
|
https://www.omim.org/entry/613464
| 2019-09-22T15:58:35 |
{"doid": ["0110398"], "mesh": ["D012174"], "omim": ["613464"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
|
Human infectious disease
Chagas disease
Other namesAmerican trypanosomiasis
Photomicrograph of Giemsa-stained Trypanosoma cruzi
Pronunciation
* /ˈtʃɑːɡəs/, Portuguese pronunciation: [ˈʃaɡɐs]
SpecialtyInfectious disease
SymptomsFever, large lymph nodes, headache[1]
ComplicationsHeart failure, enlarged esophagus, enlarged colon[1]
CausesTrypanosoma cruzi spread by kissing bugs[1]
Diagnostic methodFinding the parasite, its DNA, or antibodies in the blood[2]
PreventionEliminating kissing bugs and avoiding their bites[1]
MedicationBenznidazole, nifurtimox[1]
Frequency6.2 million (2017)[3]
Deaths7,900 (2017)[4]
Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by Trypanosoma cruzi.[1] It is spread mostly by insects known as Triatominae, or "kissing bugs".[1] The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or swelling at the site of the bite.[1] After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms.[2][5] Up to 45% of people with chronic infection develop heart disease 10–30 years after the initial illness, which can lead to heart failure.[2] Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.[2]
T. cruzi is commonly spread to humans and other mammals by the bite of a kissing bug.[6] The disease may also be spread through blood transfusion, organ transplantation, eating food contaminated with the parasites, and vertical transmission (from a mother to her baby).[1] Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its DNA by polymerase chain reaction.[5] Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood.[7] It affects more than 150 types of animals.[8]
Prevention focuses on eliminating kissing bugs and avoiding their bites.[1] This may involve the use of insecticides or bed-nets.[9] Other preventive efforts include screening blood used for transfusions.[1] As of 2019[update], a vaccine has not been developed.[1] Early infections are treatable with the medications benznidazole or nifurtimox, which usually cure the disease if given shortly after the person is infected, but become less effective the longer a person has had Chagas disease.[1] When used in chronic disease, medication may delay or prevent the development of end–stage symptoms.[1] Benznidazole and nifurtimox often cause side effects, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued.[1][2] As of 2019[update], new drugs for Chagas disease are under development, and experimental vaccines have been studied in animal models.[10][11]
It is estimated that 6.2 million people, mostly in Mexico, Central America and South America, have Chagas disease as of 2017,[1][3] resulting in an estimated 7,900 deaths.[4] Most people with the disease are poor,[12] and most do not realize they are infected.[13] Large-scale population migrations have carried Chagas disease to new regions, which now include the United States and many European countries.[1]
The disease was first described in 1909 by Brazilian physician Carlos Chagas, after whom it is named.[1] Chagas disease is classified as a neglected tropical disease.[14]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Transmission
* 3 Pathophysiology
* 4 Diagnosis
* 5 Prevention
* 6 Management
* 6.1 Complications
* 7 Epidemiology
* 7.1 Non-endemic countries
* 8 History
* 9 Research
* 9.1 Treatments
* 9.2 Diagnostic tests
* 10 See also
* 11 References
* 12 External links
## Signs and symptoms[edit]
An acute Chagas disease infection with swelling of the right eye (Romaña's sign)
Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years.[2][5][15] The acute stage is often symptom-free.[2] When present, the symptoms are typically minor and not specific to any particular disease.[5] Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes.[1][2][5] Rarely, people develop a swollen nodule at the site of infection, which is called "Romaña's sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin.[5][16] In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can cause life-threatening fluid accumulation around the heart, or inflammation of the heart or brain and surrounding tissues.[2] The acute phase typically lasts four to eight weeks and resolves without treatment.[2]
Unless treated with antiparasitic drugs, individuals remain chronically infected with T. cruzi after recovering from the acute phase.[2] Most chronic infections are asymptomatic, which is referred to as indeterminate chronic Chagas disease.[2] However, over decades with chronic Chagas disease, 30–40% of people develop organ dysfunction (determinate chronic Chagas disease), which most often affects the heart or digestive system.[2][5]
The most common manifestation is heart disease, which occurs in 14–45% of people with chronic Chagas disease.[2] People with Chagas heart disease often experience heart palpitations and sometimes fainting due to irregular heart function.[17] By electrocardiogram, people with Chagas heart disease most frequently have arrhythmias.[17] As the disease progresses, the heart's ventricles become enlarged (dilated cardiomyopathy), which reduces its ability to pump blood.[17] In many cases the first sign of Chagas heart disease is heart failure, thromboembolism, or chest pain associated with abnormalities in the microvasculature.[17]
Also common in chronic Chagas disease is damage to the digestive system, particularly enlargement of the esophagus or colon, which affects 10–21% of people.[2] Those with enlarged esophagus often experience pain (odynophagia) or trouble swallowing (dysphagia), acid reflux, cough, and weight loss.[2] Individuals with enlarged colon often experience constipation, which can lead to severe blockage of the intestine or its blood supply.[2] Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered reflexes or movement.[2] While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.[17]
Signs and symptoms differ for people infected with T. cruzi through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, vomiting, shortness of breath, cough, and pain in the chest, abdomen, and muscles.[2] Those infected congenitally typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as jaundice, respiratory distress, and heart problems.[2] People infected through organ transplant or blood transfusion tend to have symptoms similar to those of vector-borne disease, but the symptoms may not manifest for anywhere from a week to five months.[2] Chronically infected individuals who become immunosuppressed due to HIV infection can suffer particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or brain abscesses.[5] Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage.[18] Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum.[5]
## Cause[edit]
Life cycle and transmission of T. cruzi
Chagas disease is caused by infection with the protozoan parasite T. cruzi, which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs".[5] At the bite site, motile T. cruzi forms called trypomastigotes invade various host cells.[6] Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication.[6] The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream.[2] Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate.[2] Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.[2]
### Transmission[edit]
Triatoma infestans, a common vector of T. cruzi[19]
T. cruzi can be transmitted by various triatomine bugs in the genera Triatoma, Panstrongylus, and Rhodnius.[2] The primary vectors for human infection are the species of triatomine bugs that inhabit human dwellings, namely Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata and Panstrongylus megistus.[19] These insects are known by a number of local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, and chipo in Venezuela.[20] The bugs tend to feed at night, preferring moist surfaces near the eyes or mouth.[15][19] A triatomine bug can become infected with T. cruzi when it feeds on an infected host.[15] T. cruzi replicates in the insect's intestinal tract and is shed in the bug's feces.[15] When an infected triatomine feeds, it pierces the skin and takes in a blood meal, defecating at the same time to make room for the new meal.[15] The bite is typically painless, but causes itching.[15] Scratching at the bite introduces the T. cruzi-laden feces into the bite wound, initiating infection.[15]
In addition to classical vector spread, Chagas disease can be transmitted through food or drink contaminated with triatomine insects or their feces.[21] Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection.[21] This route of transmission has been implicated in several outbreaks, where it led to unusually severe symptoms, likely due to infection with a higher parasite load than from the bite of a triatomine bug.[7][21]
T. cruzi can also be transmitted independent of the triatomine bug during blood transfusion, following organ transplantation, or across the placenta during pregnancy.[2] Transfusion with the blood of an infected donor infects the recipient 10–25% of the time.[2] To prevent this, blood donations are screened for T. cruzi in many countries with endemic Chagas disease, as well as the United States.[7] Similarly, transplantation of solid organs from an infected donor can transmit T. cruzi to the recipient.[2] This is especially true for heart transplant, which transmits T. cruzi 75–100% of the time, and less so for transplantation of the liver (0–29%) or a kidney (0–19%).[2] An infected mother can also pass T. cruzi to her child through the placenta; this occurs in up to 15% of births by infected mothers.[22] As of 2019, 22.5% of new infections occurred through congenital transmission.[23]
## Pathophysiology[edit]
Large scale anatomy of a heart damaged by chronic Chagas disease
In the acute phase of the disease, signs and symptoms are caused directly by the replication of T. cruzi and the immune system's response to it.[2] During this phase, T. cruzi can be found in various tissues throughout the body and circulating in the blood.[2] During the initial weeks of infection, parasite replication is brought under control by production of antibodies and activation of the host's inflammatory response, particularly cells that target intracellular pathogens such as NK cells and macrophages, driven by inflammation-signaling molecules like TNF-α and IFN-γ.[2]
During chronic Chagas disease, long-term organ damage develops over years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, T. cruzi is found frequently in the striated muscle fibers of the heart.[24] As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat.[24] Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically macrophages and T cells.[24] Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.[24]
In the heart, colon, and esophagus, chronic disease also leads to a massive loss of nerve endings.[17] In the heart, this may contribute to arrythmias and other cardiac dysfunction.[17] In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction.[17] Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.[17]
## Diagnosis[edit]
T. cruzi trypomastigotes seen in a blood smear
The presence of T. cruzi is diagnostic of Chagas disease. During the acute phase of infection, it can be detected by microscopic examination of fresh anticoagulated blood, or its buffy coat, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa, for direct visualization of parasites.[5][7] Blood smear examination detects parasites in 34–85% of cases. Techniques such as microhematocrit centrifugation can be used to concentrate the blood, which makes the test more sensitive.[2] On microscopic examination, T. cruzi trypomastigotes have a slender body, often in the shape of an S or U, with a flagellum connected to the body by an undulating membrane.[25]
Alternatively, T. cruzi DNA can be detected by polymerase chain reaction (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy,[23] and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by transfer of antibodies against T. cruzi from a mother to her baby (passive immunity).[26] PCR is also used to monitor T. cruzi levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage.[2][5][23]
During the chronic phase, microscopic diagnosis is unreliable and PCR is less sensitive because the level of parasites in the blood is low.[2] Chronic Chagas disease is usually diagnosed using serological tests, which detect immunoglobulin G antibodies against T. cruzi in the person's blood.[7] The most common test methodologies are ELISA, indirect immunofluorescence, and indirect hemagglutination.[27] Two positive serology results, using different test methods, are required to confirm the diagnosis.[5] If the test results are inconclusive, additional testing methods such as Western blot can be used.[2] T. cruzi antigens may also be detected in tissue samples using immunohistochemistry techniques.[7]
Various rapid diagnostic tests for Chagas disease are available. These tests are easily transported and can be performed by people without special training.[28] They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low,[2] and it is recommended that a second method is used to confirm a positive result.[28][29]
T. cruzi can be isolated from samples through blood culture or xenodiagnosis, or by inoculating animals with the person's blood. In the blood culture method, the person's red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. It can take up to six months to obtain the result. Xenodiagnosis involves feeding the person's blood to triatomine insects, then examining their feces for the parasite 30 to 60 days later.[28] These methods are not routinely used, as they are slow and have low sensitivity.[27][28]
## Prevention[edit]
Bed nets can be used in endemic areas to prevent bites from triatomine bugs.[15]
Efforts to prevent Chagas disease have largely focused on vector control to limit exposure to triatomine bugs. Insecticide-spraying programs have been the mainstay of vector control, consisting of spraying homes and the surrounding areas with residual insecticides.[30] This was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids.[30] These programs have drastically reduced transmission in Brazil and Chile,[15] and eliminated major vectors from certain regions: Triatoma infestans from Brazil, Chile, Uruguay, and parts of Peru and Paraguay, as well as Rhodnius prolixus from Central America.[17] Vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs.[30] In response, vector control programs have implemented alternative insecticides (e.g. fenitrothion and bendiocarb in Argentina and Bolivia), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches.[30] In areas with triatomine bugs, transmission of T. cruzi can be prevented by sleeping under bed nets and by housing improvements that prevent triatomine bugs from colonizing houses.[15]
Blood transfusion was formerly the second-most common mode of transmission for Chagas disease.[31] T. cruzi can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood, packed red blood cells, granulocytes, cryoprecipitate, and platelets.[31] The development and implementation of blood bank screening tests has dramatically reduced the risk of infection during blood transfusion.[31] Nearly all blood donations in Latin American countries undergo Chagas screening.[31] Widespread screening is also common in non-endemic nations with significant populations of immigrants from endemic areas including the United Kingdom (implemented in 1999), Spain (2005), the United States (2007), France and Sweden (2009), Switzerland (2012), and Belgium (2013).[32] Blood is tested using serological tests, typically ELISAs, to detect antibodies against T. cruzi proteins.[31]
Other modes of transmission have also been targeted by Chagas disease prevention programs. Treating T. cruzi-infected mothers during pregnancy reduces the risk of congenital transmission of the infection.[22] To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for T. cruzi infection, and the World Health Organization recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease.[1][33] Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests.[2]
There is no vaccine against Chagas disease.[1] Several experimental vaccines have been tested in animals infected with T. cruzi and were able to reduce parasite numbers in the blood and heart,[34] but no vaccine candidates had undergone clinical trials in humans as of 2016.[35]
## Management[edit]
A bottle of nifurtimox tablets
Chagas disease is managed using antiparasitic drugs to eliminate T. cruzi from the body and symptomatic treatment to address the effects of the infection.[7] As of 2018, benznidazole and nifurtimox were the antiparasitic drugs of choice for treating Chagas disease,[2] though benznidazole is the only drug available in most of Latin America.[36] For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days.[2] Antiparasitic treatment is most effective early in the course of infection: it eliminates T. cruzi from 50 to 80% of people in the acute phase, but only 20–60% of those in the chronic phase.[7] Treatment of chronic disease is more effective in children than in adults, and the cure rate for congenital disease approaches 100% if treated in the first year of life.[2] Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission.[1] Elimination of T. cruzi does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately.[7] Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy.[17]
Benznidazole is usually considered the first-line treatment because it has milder adverse effects than nifurtimox and its efficacy is better understood.[2][23] Both benznidazole and nifurtimox have common side effects that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems, decreased appetite, weakness, headache, and sleeping problems. These side effects can sometimes be treated with antihistamines or corticosteroids, and are generally reversed when treatment is stopped.[2] However, benzidazole is discontinued in up to 29% of cases.[2] Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug.[2] The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various neurological disorders including mood changes, insomnia, paresthesia and peripheral neuropathy.[2] Treatment is discontinued in up to 75% of cases.[2][23] Both drugs are contraindicated for use in pregnant women and people with liver or kidney failure.[1] As of 2019, resistance to these drugs has been reported.[36]
### Complications[edit]
In the chronic stage, treatment involves managing the clinical manifestations of the disease. The treatment of Chagas cardiomyopathy is similar to that of other forms of heart disease.[2] Beta blockers and ACE inhibitors may be prescribed, but some people with Chagas disease may not be able to take the standard dose of these drugs because they have low blood pressure or a low heart rate.[2][17] To manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as amiodarone, or have a pacemaker implanted.[5] Blood thinners may be used to prevent thromboembolism and stroke.[17] Chronic heart disease caused by Chagas is a common reason for heart transplantation surgery.[15] Because transplant recipients take immunosuppressive drugs to prevent organ rejection, they are monitored using PCR to detect reactivation of the disease. People with Chagas disease who undergo heart transplantation have higher survival rates than the average heart transplant recipient.[17]
Mild gastrointestinal disease can be treated symptomatically, such as by using laxatives for constipation, or taking a prokinetic drug like metoclopramide before meals to relieve esophageal symptoms.[5][37] Surgery to sever the muscles of the lower esophageal sphincter (cardiomyotomy) is indicated in more severe cases of esophageal disease,[37] and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.[5][27]
## Epidemiology[edit]
Epidemiology of Chagas disease circa 2011: red is endemic countries where spread is through vectors; yellow is endemic countries where spread is occasionally through vectors; blue is non-endemic countries where spread is through blood transfusions[38]
Disability-adjusted life years due to Chagas disease in 2016. Grey indicates no data. Otherwise, colors get increasingly dark red for each order of magnitude increase in DALY burden: 0, white. Up to 1,000 DALYs, yellow. 1,001 to 10,000 DALYs, orange. 10,001 to 100,000 DALYs, light red. Greater than 100,000 DALYs, dark red.[39]
In 2017, an estimated 6.2 million people worldwide had Chagas disease, with approximately 162,000 new infections and 7,900 deaths each year.[3][4] This resulted in a global annual economic burden estimated at US$7.2 billion, 86% of which is borne by endemic countries.[32][40] Chagas disease results in the loss of over 800,000 disability-adjusted life years each year.[2]
Chagas is endemic to 21 countries in continental Latin America: Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela.[1][2] The endemic area ranges from the southern United States to northern Chile and Argentina, with Bolivia (6.1%), Argentina (3.6%), and Paraguay (2.1%) exhibiting the highest prevalence of the disease.[2] In endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010.[2][41] Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006),[41] and in Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces.[42] During Venezuela's humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted and Chagas disease seroprevalence rates have increased.[43] Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission.[2]
While the rate of vector-transmitted Chagas disease has declined throughout most of Latin America, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species.[21][44][45] Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.[43]
Chagas exists in two different ecological zones: In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where T. cruzi also circulates in wild and domestic animals.[46] T. cruzi commonly infects more than 100 species of mammals across Latin America including opossums, armadillos, marmosets, bats, and various rodents, all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals.[47]
### Non-endemic countries[edit]
Though Chagas is traditionally considered a disease of rural Latin America, international migration has dispersed those suffering from the disease to numerous non-endemic countries, primarily in North America and Europe.[1][32] As of 2020, approximately 300,000 infected people are living in the United States,[48] about 30,000 to 40,000 of whom have Chagas cardiomyopathy.[17] The vast majority of Chagas infections in the United States occur in immigrants from Latin America,[17][23] but local transmission is possible. Eleven triatomine species are native to the United States and some southern states have persistent cycles of disease transmission between insect vectors and animal reservoirs,[2][23] which include woodrats, possums, raccoons, armadillos and skunks.[49] However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015.[2][48] As of 2013, the cost of treatment in the United States was estimated to be US$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers.[40]
Chagas disease affects approximately 68,000 to 123,000 people in Europe as of 2019.[50] Spain, which has a high rate of immigration from Latin America, has the highest prevalence of the disease. It is estimated that 50,000 to 70,000 Spanish people are living with the disease, which accounts for 75% of European cases.[51] The prevalence of Chagas varies widely within European countries due to differing immigration patterns.[50] Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.[51]
## History[edit]
Carlos Chagas, in his laboratory at Instituto Oswaldo Cruz
T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent.[52] T. cruzi has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the Atacama Desert, to remains of various ages in Minas Gerais, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the Rio Grande.[52] Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), Luís Gomes Ferreira [pt] (1735), and Theodoro J. H. Langgaard (1842).[52]
The formal description of Chagas disease was made by Carlos Chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver.[52] Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named Trypanosoma cruzi in honor of his mentor, Brazilian physician Oswaldo Cruz.[52] He sent infected triatomine bugs to Cruz in Rio de Janeiro, who showed the bite of the infected triatomine could transmit T. cruzi to marmoset monkeys as well.[52] In just two years, 1908 and 1909, Chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection.[53][54][55] Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the Faculdade de Medicina do Rio de Janeiro [pt], the disease was widely referred to as "Chagas disease".[53] Chagas' discovery brought him national and international renown, but in highlighting the inadequacies of the Brazilian government's response to the disease, Chagas attracted criticism to himself and to the disease that bore his name, stifling research on his discovery and likely frustrating his nomination for the Nobel Prize in 1921.[53][56]
In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentina's Chaco Province.[52] In Argentina, the disease is known as mal de Chagas-Mazza in his honor.[57] Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with T. cruzi was widespread across Latin America.[52] This, combined with successes eliminating the malaria vector through insecticide use, spurred the creation of public health campaigns focused on treating houses with insecticides to eradicate triatomine bugs.[30][52] The 1950s saw the discovery that treating blood with crystal violet could eradicate the parasite, leading to its widespread use in transfusion screening programs in Latin America.[52] Large-scale control programs began to take form in the 1960s, first in São Paulo, then various locations in Argentina, then national-level programs across Latin America.[58] These programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains or odors after application and were longer-lasting and more cost-effective.[52][58] Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004).[30]
## Research[edit]
### Treatments[edit]
Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain.[36][59] Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models.[11][60]
A number of experimental vaccines have been tested in animals. Some approaches have used inoculation with dead or attenuated T. cruzi parasites or non-pathogenic organisms that share antigens with T. cruzi, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored. As of 2019, vaccine research has mainly been limited to small animal models, and further testing in large animals is needed.[10]
### Diagnostic tests[edit]
As of 2018, standard diagnostic tests for Chagas disease were limited in their ability to measure response to antiparasitic treatment. Serological tests, for example, may remain positive for years after T. cruzi is eliminated from the body, and PCR may give false negative results when parasitemia is low. Various potential biomarkers of treatment response are under investigation, such as immunoassays against specific T. cruzi antigens, flow cytometry testing to detect antibodies against different life stages of T. cruzi, and markers of physiological changes caused by the parasite, such as alterations in coagulation and lipid metabolism.[17]
Another research area is the use of biomarkers to predict the progression of chronic Chagas disease. Blood levels of tumor necrosis factor alpha, brain and atrial natriuretic peptide, and angiotensin converting enzyme 2, markers of heart damage and inflammation, have been found to correlate with the severity of Chagas cardiomyopathy. Endothelin-1 has been studied as a prognostic marker in animal models.[61]
T. cruzi shed acute-phase antigen (SAPA), which can be detected in blood using ELISA or Western blot,[22] has been used as an indicator of early acute and congenital infection.[61] A novel assay for T. cruzi antigens in urine has been developed to diagnose congenital disease.[22]
## See also[edit]
* Drugs for Neglected Diseases Initiative
* Chagas: Time to Treat campaign
* Association for the Promotion of Independent Disease Control in Developing Countries
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33. ^ Bonney KM (March 2014). "Chagas disease in the 21st century: a public health success or an emerging threat". Parasite. 21 (11): 11. doi:10.1051/parasite/2014012. PMC 3952655. PMID 24626257.
34. ^ Dumonteil E, Herrera C, Buekens P (January 2019). "A therapeutic preconceptional vaccine against Chagas disease: A novel indication that could reduce congenital transmission and accelerate vaccine development". PLOS Neglected Tropical Diseases. 13 (1): e0006985. doi:10.1371/journal.pntd.0006985. PMC 6354953. PMID 30703092.
35. ^ Beaumier CM, Gillespie PM, Strych U, et al. (June 2016). "Status of vaccine research and development of vaccines for Chagas disease". Vaccine. 34 (26): 2996–3000. doi:10.1016/j.vaccine.2016.03.074. PMID 27026146.
36. ^ a b c Ribeiro V, Dias N, Paiva T, et al. (December 2019). "Current trends in the pharmacological management of Chagas disease". Int J Parasitol Drugs Drug Resist (Review). 12: 7–17. doi:10.1016/j.ijpddr.2019.11.004. PMC 6928327. PMID 31862616.
37. ^ a b de Oliveira EC, da Silveira ABM, Luquetti AO (9 September 2019). "Gastrointestinal Chagas Disease". In Marcelo Altcheh J, Freilij H (eds.). Chagas Disease: A Clinical Approach. Birkhäuser Advances in Infectious Diseases. Switzerland: Springer Nature. pp. 243–62. doi:10.1007/978-3-030-00054-7_12. ISBN 978-3-030-00054-7. ISSN 2504-3811.
38. ^ Liu Q, Zhou XN (December 2015). "Preventing the transmission of American trypanosomiasis and its spread into non-endemic countries". Infectious Diseases of Poverty. 4: 60. doi:10.1186/s40249-015-0092-7. PMC 4693433. PMID 26715535.
39. ^ World Health Organization. "Disease burden and mortality estimates". Archived from the original on 10 February 2020. Retrieved 27 April 2020.
40. ^ a b Lee BY, Bacon KM, Bottazzi ME, Hotez PJ (April 2013). "Global economic burden of Chagas disease: a computational simulation model". The Lancet Infectious Diseases. 13 (4): 342–8. doi:10.1016/S1473-3099(13)70002-1. PMC 3763184. PMID 23395248.
41. ^ a b Moncayo A, Silveria AC (2017). "Current epidemiological trends of Chagas disease in Latin America and future challenges: epidemiology, surveillance, and health policies". American Trypanosomiasis – Chagas Disease (2 ed.). Elsevier. pp. 59–88. doi:10.1016/B978-0-12-801029-7.00004-6.
42. ^ "The Southern Cone Initiative: an update". Special Programme for Research and Training in Tropical Diseases (TDR) (Press release). WHO. 2004. Archived from the original on 22 September 2009. Retrieved 29 August 2008.
43. ^ a b Grillet ME, Hernández-Villena JV, Llewellyn MS, et al. (May 2019). "Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region" (PDF). Lancet Infect Dis (Review). 19 (5): e149–e161. doi:10.1016/S1473-3099(18)30757-6. PMID 30799251.
44. ^ Alarcón de Noya B, Noya Gonzáles O (9 September 2019). "Orally Transmitted Chagas Disease: Biology, Epidemiology, and Clinical Aspects of a Foodborne Infection". In Marcelo Altcheh J, Freilij H (ed.). Chagas Disease: A Clinical Approach. Birkhäuser Advances in Infectious Diseases. Switzerland: Springer Nature. pp. 225–241. doi:10.1007/978-3-030-00054-7_11. ISBN 978-3-030-00054-7. ISSN 2504-3811.
45. ^ Hotez PJ, Basáñez MG, Acosta-Serrano A, Grillet ME (2017). "Venezuela and its rising vector-borne neglected diseases". PLOS Neglected Tropical Diseases. 11 (6): e0005423. doi:10.1371/journal.pntd.0005423. ISSN 1935-2735. PMC 5490936. PMID 28662038.
46. ^ Morel CM, Lazdins J (October 2003). "Chagas disease". Nat Rev Microbiol. 1 (1): 14–5. doi:10.1038/nrmicro735. PMID 15040175. S2CID 29869370.
47. ^ Jansen AM, Roque ALR (2010). "11 - Domestic and Wild Mammalian Reservoirs". In Telleria J, Tibayrenc M (eds.). American Trypanosomiasis. Elsevier. pp. 249–276. doi:10.1016/B978-0-12-384876-5.00011-3. ISBN 978-0-123-84876-5.
48. ^ a b Turabelidze G, Vasudevan A, Rojas-Moreno C, et al. (2020). "Autochthonous Chagas Disease — Missouri, 2018". MMWR. Morbidity and Mortality Weekly Report. 69 (7): 193–195. doi:10.15585/mmwr.mm6907a4. ISSN 0149-2195. PMC 7043387. PMID 32078594.
49. ^ Montgomery SP, Starr MC, Cantey PT, Edwards MS, Meymandi SK (2014). "Neglected Parasitic Infections in the United States: Chagas Disease". Am J Trop Med Hyg. 90 (5): 814–818. doi:10.4269/ajtmh.13-0726. PMC 4015570. PMID 24808250.
50. ^ a b Alonso-Padilla J, Pinazo MJ, Gascón J (9 September 2019). "Chagas Disease in Europe". In Marcelo Altcheh J, Freilij H (ed.). Chagas Disease: A Clinical Approach. Birkhäuser Advances in Infectious Diseases. Switzerland: Springer Nature. pp. 111–123. doi:10.1007/978-3-030-00054-7_5. ISBN 978-3-030-00054-7. ISSN 2504-3811.
51. ^ a b Velasco M, Gimeno-Feliú LA, Molina I, et al. (February 2020). "Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology". Euro Surveill. (Review). 25 (8). doi:10.2807/1560-7917.ES.2020.25.8.1900393. PMC 7055039. PMID 32127121.
52. ^ a b c d e f g h i j k Steverding D (July 2014). "The history of Chagas disease". Parasites & Vectors. 7: 317. doi:10.1186/1756-3305-7-317. PMC 4105117. PMID 25011546.
53. ^ a b c Kropf SP, Sá MR (July 2009). "The discovery of Trypanosoma cruzi and Chagas disease (1908–1909): tropical medicine in Brazil" (PDF). Hist Cienc Saude Manguinhos. 16 (Suppl 1): 13–34. doi:10.1590/s0104-59702009000500002. PMID 20027916. S2CID 36106351.
54. ^ Chagas C (1909). "Neue Trypanosomen". Vorläufige Mitteilung Arch Schiff Tropenhyg. 13: 120–2.
55. ^ Chagas C (1909). "Nova tripanozomiase humana: Estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem [New human trypanosomiasis. Studies about the morphology and life-cycle of Schizotripanum cruzi, etiological agent of a new morbid entity of man]". Mem Inst Oswaldo Cruz. 1 (2): 159–218. doi:10.1590/S0074-02761909000200008. ISSN 0074-0276. (in Portuguese with German full translation as "Ueber eine neue Trypanosomiasis des Menschen.")
56. ^ Bestetti RB, Martins CA, Cardinalli-Neto A (May 2009). "Justice where justice is due: A posthumous Nobel Prize to Carlos Chagas (1879–1934), the discoverer of American Trypanosomiasis (Chagas' disease)". International Journal of Cardiology. 134 (1): 9–16. doi:10.1016/j.ijcard.2008.12.197. PMID 19185367.
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61. ^ a b Balouz V, Agüero F, Buscaglia CA (2017). "Chagas disease diagnostic applications: present knowledge and future steps". Adv. Parasitol. (Review). 97: 1–45. doi:10.1016/bs.apar.2016.10.001. PMC 5363286. PMID 28325368.
## External links[edit]
Wikimedia Commons has media related to Chagas disease.
Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app.
* Chagas disease at Curlie
* Chagas information at the U.S. Centers for Disease Control
* Chagas information from the Drugs for Neglected Diseases initiative
* Chagas disease information for travellers from the International Association for Medical Assistance to Travellers
Classification
D
* ICD-10: B57
* ICD-9-CM: 086
* MeSH: D014355
* DiseasesDB: 13415
External resources
* MedlinePlus: 001372
* eMedicine: med/327
* Patient UK: Chagas disease
* Scholia: Q649558
* v
* t
* e
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Parasitic disease caused by Excavata protozoa
Discicristata
Trypanosomatida
Trypanosomiasis
* T. brucei
* African trypanosomiasis
* T. cruzi
* Chagas disease
Leishmaniasis
* Leishmania major / L. mexicana / L. aethiopica / L. tropica
* Cutaneous leishmaniasis
* L. braziliensis
* Mucocutaneous leishmaniasis
* L. donovani / infantum
* Visceral leishmaniasis
Schizopyrenida
* Naegleria fowleri
* Primary amoebic meningoencephalitis
Trichozoa
Diplomonadida
* Giardia lamblia (Giardiasis)
Trichomonadida
* Trichomonas vaginalis
* Trichomoniasis
* Dientamoeba fragilis
* Dientamoebiasis
*[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
|
Chagas disease
|
c0041234
| 25,522 |
wikipedia
|
https://en.wikipedia.org/wiki/Chagas_disease
| 2021-01-18T18:51:58 |
{"gard": ["6030"], "mesh": ["D014355"], "umls": ["C0041234"], "orphanet": ["3386"], "wikidata": ["Q649558"]}
|
A rare subtype of cerebrofacial arteriovenous metameric syndrome characterized by unilateral arteriovenous malformations involving the cerebellum, pons, and mandible (lateral rhombencephalic group). The condition manifests in childhood. Common presenting signs and symptoms are progressive neurological deficit, hemorrhage, and cosmetic complaints like facial asymmetry.
*[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
|
Cerebrofacial arteriovenous metameric syndrome type 3
|
c3838691
| 25,523 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141199
| 2021-01-23T18:56:24 |
{"icd-10": ["Q28.2"], "synonyms": ["CAMS3"]}
|
14q11.2 microduplication syndrome is a rare chromosomal anomaly characterized by developmental delay, mild to severe intellectual disability with speech impairment and epilepsy. Additionally, it may include dysmorphic features (such as hypo- or hypertelorism, dysplastic ears, short palpebral fissures), microcephaly or macrocephaly, behavioral abnormalities, stereotyped hand movements, ataxia, hypotonia, cleft palate.
*[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
|
14q11.2 microduplication syndrome
|
None
| 25,524 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261229
| 2021-01-23T19:10:30 |
{"icd-10": ["Q92.3"], "synonyms": ["Dup(14)(q11.2)", "Trisomy 14q11.2"]}
|
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. (November 2008) (Learn how and when to remove this template message)
Vossius ring (also called Vossius's ring or Vossius' ring) is due to blunt trauma to the eye. When the eye is injured, a circular ring of fainted or stippled opacity is seen on the anterior surface of the lens due to brown amorphous granules of pigment lying on the capsule. It has the same diameter as the contracted pupil, and is due to impression of the iris on the lens as a result of the force of a concussion injury, which drives the cornea and iris backward.
It is named after German ophthalmologist Adolf Vossius, who first described the condition in 1906.[1]
## References[edit]
1. ^ Vossius' ring at Who Named It
## External links[edit]
* NIH website
This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This medical symptom 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
|
Vossius ring
|
c0271169
| 25,525 |
wikipedia
|
https://en.wikipedia.org/wiki/Vossius_ring
| 2021-01-18T18:39:00 |
{"umls": ["C0271169"], "icd-10": ["S05.1"], "wikidata": ["Q7942061"]}
|
Autosomal recessive spastic ataxia of Charlevoix-Saguenay
Other namesAutosomal recessive spastic ataxia type 6
This condition is inherited in an autosomal recessive manner
SpecialtyNeurology
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare neurodegenerative genetic disorder that primarily affects people from the Charlevoix and Saguenay–Lac-Saint-Jean regions of Quebec or descendants of native settlers in this region.[1][2] This disorder has also been demonstrated in people from various other countries including India, Turkey, Japan, the Netherlands, Italy, Belgium, France and Spain.[3][4] The prevalence has been estimated at about 1 in 1,900 in Quebec, but it is very rare elsewhere.[4]
## Contents
* 1 Symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Prognosis
* 5 References
* 6 External links
## Symptoms[edit]
ARSACS is usually diagnosed in early childhood, approximately 12–24 months of age when a child begins to take their first steps. At this time, it manifests as a lack of coordination and balance resulting in frequent falls. Some of the signs and symptoms include:[5]
* stiffness of the legs
* appendicular and trunk ataxia
* hollow foot and hand deformities
* ataxic dysarthria
* distal muscle wasting
* horizontal gaze nystagmus
* spasticity[6]
## Genetics[edit]
The inheritance pattern is autosomal recessive. The disorder is caused by mutations in the SACS gene on chromosome 13.[7] It is unclear as to how these mutations affect the central nervous system (CNS) and skeletal muscles presenting in the signs and symptoms of ARSACS.[8]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (March 2018)
## Prognosis[edit]
Most patients begin to use a wheelchair for movement around age 30–40.[9] Death usually occurs in their 60s, but some have been reported to live longer.[4]
## References[edit]
1. ^ Bouchard JP, Richter A, Mathieu J, Brunet D, Hudson TJ, Morgan K, Melançon SB (October 1998). "Autosomal recessive spastic ataxia of Charlevoix-Saguenay". Neuromuscular Disorders. 8 (7): 474–9. doi:10.1016/S0960-8966(98)00055-8. PMID 9829277. S2CID 21219526.
2. ^ Bouchard JP, Barbeau A, Bouchard R, Bouchard RW (February 1978). "Autosomal recessive spastic ataxia of Charlevoix-Saguenay". The Canadian Journal of Neurological Sciences. 5 (1): 61–9. doi:10.1017/S0317167100024793. PMID 647499.
3. ^ Menon M, Shaji C, Kabeer K, Parvathy G (2016). "SACS gene-related autosomal recessive spastic ataxia of Charlevoix-Saguenay from South India". Archives of Medicine and Health Sciences. 4: 122–4. doi:10.4103/2321-4848.183359.
4. ^ a b c "Autosomal recessive spastic ataxia of Charlevoix Saguenay". www.orpha.net. Retrieved 2017-01-19.
5. ^ "Muscular Dystrophy Canada:Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)" (PDF). Archived from the original (PDF) on 2011-07-25. Retrieved 2011-05-12.
6. ^ Vermeer S, van de Warrenburg BP, Kamsteeg EJ, et al. (1993–2020). "ARSACS". In Adam MP, Ardinger HH, Pagon RA, et al. (eds.). GeneReviews® [Internet]. University of Washington, Seattle. PMID 20301432. NBK1255.
7. ^ "270550 - SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE; SACS". omim.org. Retrieved 2017-01-19.
8. ^ "Genetics Home Reference: SACS". U.S. National Library of Medicine. Retrieved 2011-05-12.
9. ^ Reference, Genetics Home. "ARSACS". Genetics Home Reference. Retrieved 2017-01-19.
## External links[edit]
Classification
D
* ICD-10: G11.1
* OMIM: 270550
* MeSH: C536787 C536787, C536787
External resources
* Orphanet: 98
* ARSACS at OMIM
* ARSACS at Orpha.net
*[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
|
Autosomal recessive spastic ataxia of Charlevoix-Saguenay
|
c1849140
| 25,526 |
wikipedia
|
https://en.wikipedia.org/wiki/Autosomal_recessive_spastic_ataxia_of_Charlevoix-Saguenay
| 2021-01-18T18:48:43 |
{"gard": ["4910"], "mesh": ["C536787"], "umls": ["C1849140"], "icd-10": ["G11.1"], "orphanet": ["98"], "wikidata": ["Q2868786"]}
|
12q14 microdeletion syndrome is a genetic syndrome caused by a missing piece of chromosome 12. The signs and symptoms depend on the size of the missing piece and the genes involved, but generally include growth delay, short stature and feeding difficulties. When this syndrome is inherited, it is passed on in a dominant pattern. It can be diagnosed through a genetic test, either a chromosomal microarray or whole exome sequencing.
*[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
|
12q14 microdeletion syndrome
|
c4305140
| 25,527 |
gard
|
https://rarediseases.info.nih.gov/diseases/13390/12q14-microdeletion-syndrome
| 2021-01-18T18:02:27 |
{"synonyms": ["Osteopoikilosis-short stature-intellectual disability syndrome", "Del(12)(q14)", "Deletion 12q14", "Monosomy 12q14"]}
|
A number sign (#) is used with this entry because holoprosencephaly-5 (HPE5) is caused by heterozygous mutation in the ZIC2 gene (603073) on chromosome 13q32.
For a phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).
Clinical Features
Holoprosencephaly is the most common structural anomaly of the human brain and is one of the anomalies seen in patients with deletions and duplications of chromosome 13. On the basis of molecular analysis of a series of patients with hemizygous deletions of the long arm of chromosome 13, Brown et al. (1993, 1995) defined a discrete 1-Mb region in band 13q32 where a deletion leads to major developmental anomalies (the 13q32 deletion syndrome). Patients in whom this region is deleted usually have major congenital malformations, including brain anomalies such as HPE or exencephaly, as well as digital anomalies such as absent thumbs.
Brown et al. (2001) reported that central nervous system malformations seen in patients with ZIC2 mutations ranged from alobar HPE (most common) to middle interhemispheric fusion defect (1 case). Additionally, all of the patients with ZIC2 mutations had relatively normal faces, suggesting that ZIC2 mutations represent a large proportion of HPE cases without facial malformation.
Solomon et al. (2010) retrospectively reviewed the clinical features of 157 individuals from 119 unrelated kindreds with HPE5, including 141 patients with intragenic ZIC2 mutations and 16 with deletions involving the ZIC2 gene. The alobar and semilobar types of HPE were the most common among those with point mutations, occurring in 20% and 34% of patients, respectively. A majority (67%) of patients did not display typical HPE facial features, such as the combination of hypotelorism, midface hypoplasia, cleft palate, and single maxillary central incisor, and none had features at the severe end of the spectrum, including cyclopia or a proboscis. Instead, patients with HPE5 had a more subtle common facial phenotype consisting of bitemporal narrowing (53%), upslanting palpebral fissures (97%), a flat nasal bridge (33%), a short nose with anteverted nares (73%), a broad and deep philtrum (43%), and a subjective appearance of large ears (37%). Facial clefts were described in 10%, while 17% had high-arched palates. Hydrocephalus was present in 12%, neural tube defects in 4%, and skeletal anomalies in 14%. There was no consistent pattern of extraneurologic features.
In 2 half sisters with holoprosencephaly and partial rhombencephalosynapsis, Ramocki et al. (2011) identified a heterozygous truncating mutation in the ZIC2 gene (603073.0006). One of the girls had macrocephaly and scaphocephaly, and the other had microcephaly. Both had severe mental retardation and motor disability. The mother did not carry the deletion in her peripheral blood, suggesting germline mosaicism. Although these findings suggested that rhombencephalosynapsis may be related to HPE, no ZIC2 mutations were identified in 11 additional cases of rhombencephalosynapsis. Guleria (2011) disagreed with the diagnosis of partial rhombencephalosynapsis in the patients reported by Ramocki et al. (2011), and suggested that the appearance of the contiguous cerebellar folial pattern likely resulted from a small posterior fossa and crowding of the structures. Ramocki et al. (2011) responded that the interpretation of neuroimaging regarding the diagnosis of partial rhombencephalosynapsis is controversial, and maintained that their patients were correctly diagnosed.
By detailed ophthalmologic examination of a 5-year-old girl with genetically confirmed HPE5, Pineda-Alvarez et al. (2011) found hyperopia, astigmatism, and microcornea. The patient was part of a cohort of 10 patients with genetically confirmed HPE. All had at least 2 ophthalmologic anomalies, including refractive errors, microcornea, microphthalmia, blepharoptosis, exotropia, and coloboma. The findings contributed to the understanding of the phenotypic variability of the HPE spectrum and showed that subtle intraocular abnormalities can occur in HPE.
Mapping
HPE5 results from mutations in the ZIC2 gene, which maps to chromosome 13q32.
Molecular Genetics
Brown et al. (1998) reported that heterozygous mutations in the human ZIC2 gene, a homolog of the Drosophila 'odd-paired' (opa) gene, are associated with HPE. Haploinsufficiency of ZIC2 is likely to cause the brain malformation seen in 13q deletion patients. Brown et al. (1998) used SSCP to screen for ZIC2 mutations in DNA samples from 150 patients with sporadic HPE and 63 patients with familial HPE. One patient with sporadic HPE showed a 56-bp head-to-tail repeat insertion in the first exon of the gene (603073.0001). In a second sporadic case, a 1-bp C insertion caused a frameshift that altered the last 90 amino acids, or approximately 20%, of the protein (603073.0002). In a third family with 2 sibs affected with HPE, Brown et al. (1998) determined that both had a 30-bp insertion in the third exon of ZIC2 (603073.0003). This insertion was a head-to-tail repeat and expanded the alanine tract normally present at that position from 15 to 25 alanine residues. In a fourth family with a single child affected with HPE, Brown et al. (1998) found a 7-bp deletion in the zinc finger region that destroyed the reading frame (603073.0004).
Brown et al. (2001) found 15 ZIC2 mutations within a cohort of 509 isolated holoprosencephaly cases. Seven mutations were frameshifts that were predicted to result in loss of function, further supporting the idea that ZIC2 haploinsufficiency can result in HPE. One mutation, an alanine tract expansion which is caused by the expansion of an imperfect trinucleotide repeat, occurred in 7 patients from 6 different families. In 3 of those families, the father was found to be apparently mosaic for the mutation. The authors hypothesized that this mutation may arise through errors in somatic recombination, an extremely unusual mutation mechanism.
In 30 unrelated children with holoprosencephaly, Orioli et al. (2001) analyzed for mutations in the SIX3 (603714), SHH (600725), TGIF (602630), and ZIC2 genes. They identified 3 novel mutations, 2 in the SHH gene and 1 in the ZIC2 gene. Their results explained 8% (2 of 26 newborn samples) of the HPE cases in the South American population studied.
Among 94 fetuses with HPE and a normal karyotype, Bendavid et al. (2006) used quantitative multiplex PCR of short fluorescent fragments (QMPSF) to screen for microdeletions in the 4 major HPE genes, SHH, SIX3, ZIC2, and TGIF. Microdeletions were identified in 8 (8.5%) fetuses: 2 in SHH, 2 in SIX3, 3 in ZIC2, and 1 in TGIF. Further analysis showed that the entire gene was missing in each case. Point mutations in 1 of the 4 genes were identified in 13 of the fetuses. Combining the instances of point mutations and microdeletions for the 94 cases yielded the following percentages: SHH (6.3%), ZIC2 (8.5%), SIX3 (5.3%), and TGIF (2%). Bendavid et al. (2006) reported the use of 2 complementary assays for HPE-associated submicroscopic deletions: a multicolor fluorescence in situ hybridization (FISH) assay using probes for the 4 major HPE genes and 2 candidate genes (DISP1, 607502 and FOXA2, 600288) followed by quantitative PCR to selected samples. Microdeletions for SHH, ZIC2, SIX3, or TGIF were found in 16 of 339 severe HPE cases (i.e., with CNF findings; 4.7%). In contrast, no deletions were found in 85 patients at the mildest end of the HPE spectrum. Based on their data, Bendavid et al. (2006) suggested that microdeletion testing should be considered as part of an evaluation of holoprosencephaly, especially in severe HPE cases.
Solomon et al. (2010) found ZIC2 mutations in 49 (8.4%) of 582 probands with HPE. These results were combined with other reports of ZIC2-related HPE from testing areas. In a cohort of 65 families with ZIC2 mutations in whom parents were available for testing, ZIC2 mutations occurred de novo in 72%. The majority of mutations (98%) were predicted or proven to result in loss of function.
Genotype/Phenotype Correlations
Among 34 patients with holoprosencephaly, Dubourg et al. (2004) observed that mutation in ZIC2 was associated with anencephaly.
Mercier et al. (2011) reported the clinical and molecular features of a large European series of 645 HPE probands (51% fetuses) and 699 relatives in order to examine genotype/phenotype correlations. The facial features were assigned to 4 categories: categories 1 and 2 had severe facial defects, whereas microforms were listed as 3 and 4. ZIC2 mutations were found in 53 (8.2%) probands, and the phenotype tended to include severe alobar or semilobar HPE with few facial features. Other associated findings included neural tube defects (9%) and neuronal migration abnormalities (15%). Two patients had rachischisis. There was a high proportion of associated extracraniofacial malformations (40%), mostly visceral abnormalities and abnormalities of the extremities; 8 cases had multiple congenital malformations. There was a high ratio of female:male affected (1.8:1), suggesting that ZIC2 mutations may be embryonically lethal in males. Although heritability was low (30%), microforms were reported in 36% of parents with ZIC2 mutations. Statistical analysis did not show a positive correlation between the severity of the brain malformation and facial features for those with ZIC2 mutations, and those with ZIC2 mutations tended to have the most severe HPE types compared to those with mutations in other genes. Based on these results, Mercier et al. (2011) proposed an algorithm for molecular analysis in HPE.
Population Genetics
In a targeted screening study of 4 genes in 86 Dutch patients with holoprosencephaly, Paulussen et al. (2010) found that 21 (24%) had heterozygous mutations in 1 of 3 of the genes. Three (3.5%) had mutations in the SHH gene (600725), 9 (10.5%) had mutations in the ZIC2 gene, and 9 (10.5%) had mutations in the SIX3 gene (603714). None had mutations in the TGIF gene (602630). Two deletions were detected, 1 encompassing the ZIC2 gene and another encompassing the SIX3 gene. About half of the mutations were de novo; 1 was germline mosaic. There was marked clinical variability, but those with ZIC2 mutations tended to have less severe facial malformations. Five of 7 parental carriers were asymptomatic, and 2 had minor HPE signs.
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Bitemporal narrowing (53%) \- Tall, broad forehead Face \- Broad, deep philtrum (43%) Ears \- Large ears (37%) Eyes \- Upslanting palpebral fissures (97%) \- Synophrys \- Hypotelorism (19%) \- Hypertelorism (12%) Nose \- Flat nasal bridge (33%) \- Short nose with anteverted nares (73%) Mouth \- Cleft lip/palate (10%) \- High-arched palate (17%) SKIN, NAILS, & HAIR Hair \- Synophrys NEUROLOGIC Central Nervous System \- Mental retardation \- Hydrocephalus (12%) \- Neural tube defects (4%) MISCELLANEOUS \- High occurrence of de novo mutations \- Subtle facial phenotype compared to other types of HPE MOLECULAR BASIS \- Caused by mutation in the zinc finger protein of cerebellum 2 gene (ZIC2, 603073.0001 ) ▲ 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
|
HOLOPROSENCEPHALY 5
|
c0751617
| 25,528 |
omim
|
https://www.omim.org/entry/609637
| 2019-09-22T16:05:45 |
{"doid": ["0110878"], "mesh": ["D016142"], "omim": ["609637"], "orphanet": ["93926", "280195", "220386", "93925", "280200", "93924", "2162"], "synonyms": ["MIH type HPE", "Middle interhemispheric fusion variant", "MIH", "Syntelencephaly", "Middle interhemispheric variant of holoprosencephaly", "MIHF", "Septopreoptic HPE", "MIHV"], "genereviews": ["NBK1530"]}
|
## Clinical Features
Among the children of a consanguineous mating, Mutchinick (1972) described 2 with an apparently distinctive syndrome of mental and physical retardation, peculiar facies, and heart and renal malformations. True microcephaly and Seckel dwarfism were suggested but for one or another reason did not satisfy the features of these cases.
Doerfler et al. (1997) examined 2 brothers from the Ruhr area in Germany with a phenotype similar to that described by Mutchinick (1972). A third brother with multiple malformations had died in infancy. On further investigation they found that the 2 sib pairs, that from Argentina and that from Germany, now living some 12,000 km apart, originated from the same geographic region in Poland. The 3 brothers described by Doerfler et al. (1997) came from a nonconsanguineous family and showed microcephaly, mental and physical retardation, speech disorder, facial anomalies, and internal hydrocephalus. The youngest brother died at the age of 5 months. He had situs abdominalis inversus and atrial septal defect, and had been operated on for internal hydrocephalus and atresia of the biliary duct.
Tonoki et al. (1999) described a Japanese girl with Mutchinick syndrome, indicating that it is not restricted to descendants of individuals from East Prussia.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Microcephaly Face \- High forehead \- Prognathism Ears \- Low-set ears \- Protruding ears Eyes \- Strabismus \- Myopia \- Hypertelorism \- Ptosis \- Downslanting palpebral fissure \- Long, curly eyelashes \- Light blue irides Nose \- Prominent nose \- Broad nasal bridge Mouth \- Large mouth \- Thin upper lip \- High-arched palate Teeth \- Dental malocclusion \- Irregular ridges on incisors \- Carious teeth CARDIOVASCULAR Heart \- Atrial septal defect CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum \- Pectus carinatum ABDOMEN \- Situs abdominalis inversus Biliary Tract \- Intrahepatic atresia of biliary duct Gastrointestinal \- Feeding problems GENITOURINARY External Genitalia (Male) \- Hypospadias Kidneys \- Calyceal dilation SKELETAL Spine \- Cuboid-shaped thoracolumbar vertebral bodies Hands \- Fifth finger clinodactyly \- Hyperconvex thumb nails Feet \- Pes planus SKIN, NAILS, & HAIR Nails \- Hyperconvex thumb nails Hair \- Long, curly eyelashes \- Blond hair NEUROLOGIC Central Nervous System \- Mental retardation \- Hydrocephalus \- Partial agenesis of corpus callosum \- Spastic gait ▲ 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
|
MENTAL RETARDATION, BUENOS AIRES TYPE
|
c0796080
| 25,529 |
omim
|
https://www.omim.org/entry/249630
| 2019-09-22T16:25:28 |
{"mesh": ["C563095"], "omim": ["249630"], "orphanet": ["3079"], "synonyms": ["Alternative titles", "MUTCHINICK SYNDROME"]}
|
Spinocerebellar ataxia (SCA) is a term referring to a group of hereditary ataxias that are characterized by degenerative changes in the part of the brain related to the movement control (cerebellum), and sometimes in the spinal cord. There are many different types of SCA, and they are classified according to the mutated (altered) gene responsible for the specific type of SCA. The types are described using "SCA" followed by a number, according to their order of identification: SCA1 through SCA40 (and the number continues to grow). The signs and symptoms may vary by type but are similar, and may include an uncoordinated walk (gait), poor hand-eye coordination, and abnormal speech (dysarthria). SCA is inherited in an autosomal dominant manner. However, the term "spinocerebellar" may be found with other diseases, such as the autosomal recessive spinocerebellar ataxias (SCAR). Treatment is supportive and based on the signs and symptoms present in the person with SCA.
*[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
|
Spinocerebellar ataxia
|
c0087012
| 25,530 |
gard
|
https://rarediseases.info.nih.gov/diseases/10748/spinocerebellar-ataxia
| 2021-01-18T17:57:37 |
{"mesh": ["D020754"], "synonyms": ["SCA"]}
|
A number sign (#) is used with this entry because of evidence that kuru is an acquired form of prion disease, associated with variation in the PRNP gene (176640).
Description
Kuru, a fatal neurodegenerative condition, is a human prion disease that primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning ('transumption'). The incidence has fallen dramatically since the cessation of cannibalism in the 1950s (summary by Wadsworth et al., 2008).
Clinical Features
Collinge et al. (2006) identified 11 patients with kuru in Papua New Guinea who were all born before the cessation of cannibalism. The most likely incubation period in men ranged from 39 to 56 years. Most of the patients were homozygous at the PRNP 129 residue (M129V; 176640.0005). The findings indicated that kuru can have a very long incubation time, which may affect epidemiologic studies of other prion diseases.
Molecular Genetics
By PRNP genotyping of frozen blood samples from 92 patients with kuru, Cervenakova et al. (1998) found that homozygosity at codon 129 (M129V; 176640.0005), particularly for methionine, was associated with significantly earlier age at onset and a shorter duration of illness compared to heterozygosity at codon 129. However, other clinical characteristics were similar for all genotypes at codon 129. Cervenakova et al. (1998) noted that all cases of variant Creutzfeldt-Jakob disease (vCJD; see 123400), which is caused by oral ingestion of infected tissue, have been shown to be homozygous for met129. As kuru is the most appropriate transmissible prion disease for comparison to vCJD by virtue of its oral and/or mucocutaneous route of infection, the authors hypothesized that evolution of vCJD may be associated with genetic heterogeneity at PRNP codon 129.
Mead et al. (2009) identified a gly127-to-val (G127V; 176640.0028) SNP in inhabitants of the Eastern Highlands of Papua New Guinea. Genotyping of more than 3,000 individuals, including 709 who participated in cannibalistic mortuary feasts of whom 152 subsequently died of kuru, found that heterozygosity (127GV) for the G127V polymorphism conferred protection against kuru. The val127 variant was invariably linked to the met129 (176640.0005) polymorphism and was found exclusively in people from the Purosa Valley and neighboring villages, where kuru was prevalent. The frequency of the 127GV genotype was 0.08. Thirty-six of 48 patients with kuru who were younger than 20 years of age carried the 127GG/129MM or 127GG/129VV genotype compared to 36 of 125 elderly women who were resistant to kuru (p = 3.4 x 10(-8)) and 27 of 104 patients with kuru who were older than 20 years (p = 1.2. x 10(-8)), indicating that heterozygosity at these SNPs confers protection. In addition, the 127GV genotype was not found in any patients with kuru, suggesting that it may provide complete resistance to the disease. Approximately 50% of the 51 127V-containing chromosomes shared a common haplotype, indicating a common ancestor about 10 generations ago. The findings were consistent with selection pressure.
Population Genetics
Kuru is largely restricted to the Fore linguistic group of the Papua New Guinea Eastern Highlands and was transmitted during endocannibalistic feasts (Mead et al., 2003). Heterozygosity for a common polymorphism in the human prion protein gene confers relative resistance to prion diseases. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are, in marked contrast to younger unexposed Fore, predominantly PRNP 129 heterozygotes. Kuru imposed strong balancing selection on the Fore, essentially eliminating PRNP 129 homozygotes. Mead et al. (2003) cited evidence suggesting that cannibalism was widespread in many prehistoric populations and may have provided the setting for selection pressure as protection against prion disease. Worldwide PRNP haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans.
Kreitman and Di Rienzo (2004) and Soldevila et al. (2005) suggested that the findings reported by Mead et al. (2003) were due to ascertainment bias and did not reflect balancing selection. In an analysis of 174 individuals worldwide genotyped for the PRNP 129 polymorphism, Soldevila et al. (2006) found no evidence for selective forces other than purifying selection. The findings disputed the hypothesis suggested by Mead et al. (2003).
Hardy et al. (2006) found significantly higher frequencies of the PRNP val129 allele in several Central and South American populations compared to the very low frequencies among East Asian populations from which they derived. The authors noted that cannibalism has been documented in the Americas, particularly among the Aztecs. The authors agreed with the hypothesis suggested by Mead et al. (2003) of selection pressure at the prion locus, and hypothesized that a devastating kuru-like epidemic may have occurred in the Americas, resulting in increased frequency of the val129 allele.
Pathogenesis
Reproduction of the disease clinically and histopathologically in chimpanzees injected with material from the brain of human cases (Gajdusek et al. (1966, 1967)) suggested that kuru is due to a 'slow virus.' Whether significant genetic factors are also involved remains uncertain. ('Scrapie' is a chronic neurologic disease of sheep in which involvement of a 'slow virus' has also been proposed; however, genetic factors may also be involved.) Bennett et al. (1959) had suggested that affected males were homozygous and affected females either homozygous or heterozygous for a single gene for kuru. However, many later studies clearly showed that kuru, scrapie, and other encephalopathies such as Creutzfeldt-Jakob disease (CJD; 123400) are not caused by 'slow virus' infection but arise through horizontal infection and accumulation of aberrant prion protein (176640) in the brains of affected individuals (e.g., Kingsbury, 1990). The cerebellar prion protein is converted into an aberrant isoform by posttranslational modification. For review, see Prusiner and Hsaio (1994).
Animal Model
Wadsworth et al. (2008) found that the conformation of pathogenic PrP(Sc) fragments isolated from the brains of 3 individuals with kuru were similar to those seen in classic sporadic CJD. Kuru-inoculated transgenic mice carrying human homozygous PRNP val129 showed transmission rates similar to those of classic CJD, not variant CJD. All 3 kuru isolates resulted in 100% rates of prion infection with clinical disease and a mean incubation time of about 200 days. Kuru-inoculated and sporadic CJD-inoculated transgenic mice showed similar neuropathologic changes that were distinct from variant CJD. The findings were consistent with the theory that kuru originated from chance consumption of an individual with sporadic CJD.
In contrast to the findings of Wadsworth et al. (2008), Manuelidis et al. (2009) concluded that the kuru infectious agent is a unique geographic isolate distinct from CJD and scrapie. Manuelidis et al. (2009) transmitted primate kuru to mice expressing normal and increased levels of the murine prion protein. Features of mice transmitted with sporadic CJD, variant CJD (BSE), and scrapie were clearly different from the features of mice transmitted with kuru with respect to incubation time, brain neuropathology, lymphoreticular involvement, and clinical signs. Differences between the pathogenic agents were also observed in in vitro studies using monotypic GT1 cells. The incubation time of kuru was shortened significantly in transgenic mice with increased levels of the murine prion protein, suggesting that host variability can influence susceptibility and virulence, and that the kuru infectious agent can adapt rapidly.
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KURU, SUSCEPTIBILITY TO
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https://www.omim.org/entry/245300
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Cognitive disorder of face perception
Prosopagnosia
Other namesFace blindness
The fusiform face area, the part of the brain associated with facial recognition
Pronunciation
* /ˌprɒsəpæɡˈnoʊzɪə/[1]
SpecialtyNeurology
Prosopagnosia (from Greek prósōpon, meaning "face", and agnōsía, meaning "non-knowledge"), also called face blindness,[2] is a cognitive disorder of face perception in which the ability to recognize familiar faces, including one's own face (self-recognition), is impaired, while other aspects of visual processing (e.g., object discrimination) and intellectual functioning (e.g., decision-making) remain intact. The term originally referred to a condition following acute brain damage (acquired prosopagnosia), but a congenital or developmental form of the disorder also exists, with a prevalence rate of 2.5%.[3] The specific brain area usually associated with prosopagnosia is the fusiform gyrus,[4] which activates specifically in response to faces. The functionality of the fusiform gyrus allows most people to recognize faces in more detail than they do similarly complex inanimate objects. For those with prosopagnosia, the new method for recognizing faces depends on the less sensitive object-recognition system. The right hemisphere fusiform gyrus is more often involved in familiar face recognition than the left. It remains unclear whether the fusiform gyrus is only specific for the recognition of human faces or if it is also involved in highly trained visual stimuli.
Acquired prosopagnosia results from occipito-temporal lobe damage and is most often found in adults. This is further subdivided into apperceptive and associative prosopagnosia. In congenital prosopagnosia, the individual never adequately develops the ability to recognize faces.[5]
Though there have been several attempts at remediation, no therapies have demonstrated lasting real-world improvements across a group of prosopagnosics. Prosopagnosics often learn to use "piecemeal" or "feature-by-feature" recognition strategies. This may involve secondary clues such as clothing, gait, hair color, skin color, body shape, and voice. Because the face seems to function as an important identifying feature in memory, it can also be difficult for people with this condition to keep track of information about people, and socialize normally with others. Prosopagnosia has also been associated with other disorders that are associated with nearby brain areas: left hemianopsia (loss of vision from left side of space, associated with damage to the right occipital lobe), achromatopsia (a deficit in color perception often associated with unilateral or bilateral lesions in the temporo-occipital junction) and topographical disorientation (a loss of environmental familiarity and difficulties in using landmarks, associated with lesions in the posterior part of the parahippocampal gyrus and anterior part of the lingual gyrus of the right hemisphere).[6]
The opposite of prosopagnosia is the skill of superior face recognition ability. People with this ability are called "super recognizers".[7]
## Contents
* 1 Types
* 1.1 Apperceptive
* 1.2 Associative
* 1.3 Developmental
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 History
* 7 Children
* 8 Notable people with prosopagnosia
* 9 See also
* 10 References
* 11 Further reading
* 12 External links
## Types[edit]
### Apperceptive[edit]
Apperceptive prosopagnosia has typically been used to describe cases of acquired prosopagnosia with some of the earliest processes in the face perception system. The brain areas thought to play a critical role in apperceptive prosopagnosia are right occipital temporal regions.[8] People with this disorder cannot make any sense of faces and are unable to make same–different judgments when they are presented with pictures of different faces. They are unable to recognize both familiar and unfamiliar faces. In addition, apperceptive sub-types of prosopagnosia struggle recognizing facial emotion.[9] However, they may be able to recognize people based on non-face clues such as their clothing, hairstyle, skin color, or voice.[10] Apperceptive prosopagnosia is believed to be associated with impaired fusiform gyrus.[11] It is interesting that experiments on the formation of new face detectors in adults on face-like stimuli (learning to distinguish the faces of cats) indicate that such new detectors are formed not in the fusiform, but in the lingual gyrus.[12]
### Associative[edit]
Associative prosopagnosia has typically been used to describe cases of acquired prosopagnosia with spared perceptual processes but impaired links between early face perception processes and the semantic information we hold about people in our memories. Right anterior temporal regions may also play a critical role in associative prosopagnosia.[8] People with this form of the disorder may be able to tell whether photos of people's faces are the same or different and derive the age and sex from a face (suggesting they can make sense of some face information) but may not be able to subsequently identify the person or provide any information about them such as their name, occupation, or when they were last encountered.[8] Associative prosopagnosia is thought to be due to impaired functioning of the parahippocampal gyrus.[13][14]
### Developmental[edit]
Developmental prosopagnosia (DP), also called congenital prosopagnosia (CP), is a face-recognition deficit that is lifelong, manifesting in early childhood, and that cannot be attributed to acquired brain damage. While developmental prosopagnosia begins early in life, many people do not realize that they have DP until later in their adult lives. A number of studies have found functional deficits in DP both on the basis of EEG measures and fMRI. It has been suggested that a genetic factor is responsible for the condition. The term "hereditary prosopagnosia" was introduced if DP affected more than one family member, essentially accenting the possible genetic contribution of this condition. To examine this possible genetic factor, 689 randomly selected students were administered a survey in which seventeen developmental prosopagnosics were quantifiably identified. Family members of fourteen of the DP individuals were interviewed to determine prosopagnosia-like characteristics, and in all fourteen families, at least one other affected family member was found.[15]
In 2005, a study led by Ingo Kennerknecht showed support for the proposed congenital disorder form of prosopagnosia. This study provides epidemiological evidence that congenital prosopagnosia is a frequently occurring cognitive disorder that often runs in families. The analysis of pedigree trees formed within the study also indicates that the segregation pattern of hereditary prosopagnosia (HPA) is fully compatible with autosomal dominant inheritance. This mode of inheritance explains why HPA is so common among certain families (Kennerknecht et al. 2006).[16]
## Cause[edit]
Prosopagnosia can be caused by lesions in various parts of the inferior occipital areas (occipital face area), fusiform gyrus (fusiform face area), and the anterior temporal cortex.[8] Positron emission tomography (PET) and fMRI scans have shown that, in individuals without prosopagnosia, these areas are activated specifically in response to face stimuli.[6] The inferior occipital areas are mainly involved in the early stages of face perception and the anterior temporal structures integrate specific information about the face, voice, and name of a familiar person.[8]
Acquired prosopagnosia can develop as the result of several neurologically damaging causes. Vascular causes of prosopagnosia include posterior cerebral artery infarcts (PCAIs) and hemorrhages in the infero-medial part of the temporo-occipital area. These can be either bilateral or unilateral, but if they are unilateral, they are almost always in the right hemisphere.[6] Recent studies have confirmed that right hemisphere damage to the specific temporo-occipital areas mentioned above is sufficient to induce prosopagnosia. MRI scans of patients with prosopagnosia showed lesions isolated to the right hemisphere, while fMRI scans showed that the left hemisphere was functioning normally.[6] Unilateral left temporo-occipital lesions result in object agnosia, but spare face recognition processes, although a few cases have been documented where left unilateral damage resulted in prosopagnosia. It has been suggested that these face recognition impairments caused by left hemisphere damage are due to a semantic defect blocking retrieval processes that are involved in obtaining person-specific semantic information from the visual modality.[8]
Other less common etiologies include carbon monoxide poisoning, temporal lobectomy, encephalitis, neoplasm, right temporal lobe atrophy, injury, Parkinson's disease, and Alzheimer's disease.[6]
## Diagnosis[edit]
There are few neuropsychological assessments that can definitively diagnose prosopagnosia. One commonly used test is the famous faces tests, where individuals are asked to recognize the faces of famous persons. However, this test is difficult to standardize. The Benton Facial Recognition Test (BFRT) is another test used by neuropsychologists to assess face recognition skills. Individuals are presented with a target face above six test faces and are asked to identify which test face matches the target face. The images are cropped to eliminate hair and clothes, as many people with prosopagnosia use hair and clothing cues to recognize faces. Both male and female faces are used during the test. For the first six items only one test face matches the target face; during the next seven items, three of the test faces match the target faces and the poses are different. The reliability of the BFRT was questioned when a study conducted by Duchaine and Nakayama showed that the average score for 11 self-reported prosopagnosics was within the normal range.[17]
The test may be useful for identifying patients with apperceptive prosopagnosia, since this is mainly a matching test and they are unable to recognize both familiar and unfamiliar faces. They would be unable to pass the test. It would not be useful in diagnosing patients with associative prosopagnosia since they are able to match faces.[citation needed]
The Cambridge Face Memory Test (CFMT) was developed by Duchaine and Nakayama to better diagnose people with prosopagnosia. This test initially presents individuals with three images each of six different target faces. They are then presented with many three-image series, which contain one image of a target face and two distracters. Duchaine and Nakayama showed that the CFMT is more accurate and efficient than previous tests in diagnosing patients with prosopagnosia. Their study compared the two tests and 75% of patients were diagnosed by the CFMT, while only 25% of patients were diagnosed by the BFRT. However, similar to the BFRT, patients are being asked to essentially match unfamiliar faces, as they are seen only briefly at the start of the test. The test is not currently widely used and will need further testing before it can be considered reliable.[17]
The 20-item Prosopagnosia Index (PI20)[18][19][20] is a freely available and validated self-report questionnaire that can be used alongside computer-based face recognition tests to help identify individuals with prosopagnosia. It has been validated using objective measures of face perception ability including famous face recognition tests and the Cambridge Face Memory Test. Less than 1.5% of the general population score above 65 on the PI20 and less than 65% on the CFMT.[20]
## Treatment[edit]
There are no widely accepted treatments.[21]
## Prognosis[edit]
Management strategies for acquired prosopagnosia, such as a person who has difficulty recognizing people's faces after a stroke, generally have a low rate of success.[21] Acquired prosopagnosia sometimes spontaneously resolves on its own.[21]
## History[edit]
Selective inabilities to recognize faces were documented as early as the 19th century, and included case studies by Hughlings Jackson and Charcot. However, it was not named until the term prosopagnosia was first used in 1947 by Joachim Bodamer [de], a German neurologist. He described three cases, including a 24-year-old man who suffered a bullet wound to the head and lost his ability to recognize his friends, family, and even his own face. However, he was able to recognize and identify them through other sensory modalities such as auditory, tactile, and even other visual stimuli patterns (such as gait and other physical mannerisms). Bodamer gave his paper the title Die Prosop-Agnosie, derived from Classical Greek πρόσωπον (prósōpon) meaning "face" and αγνωσία (agnōsía) meaning "non-knowledge". In October 1996, Bill Choisser began popularizing the term face blindness for this condition;[2] the earliest-known use of the term is in an 1899 medical paper.[22]
A case of a prosopagnosia is "Dr P." in Oliver Sacks' 1985 book The Man Who Mistook His Wife for a Hat, though this is more properly considered to be one of a more general visual agnosia. Although Dr P. could not recognize his wife from her face, he was able to recognize her by her voice. His recognition of pictures of his family and friends appeared to be based on highly specific features, such as his brother's square jaw and big teeth. Oliver Sacks himself suffered from prosopagnosia, but did not know it for much of his life.[23]
The study of prosopagnosia has been crucial in the development of theories of face perception. Because prosopagnosia is not a unitary disorder (i.e., different people may show different types and levels of impairment), it has been argued that face perception involves a number of stages, each of which can cause qualitative differences in impairment that different persons with prosopagnosia may exhibit.[24]
This sort of evidence has been crucial in supporting the theory that there may be a specific face perception system in the brain. Most researchers agree that the facial perception process is holistic rather than featural, as it is for perception of most objects. A holistic perception of the face does not involve any explicit representation of local features (i.e., eyes, nose, mouth, etc.), but rather considers the face as a whole.[8][25][26] Because the prototypical face has a specific spatial layout (eyes are always located above nose, and nose located above mouth), it is beneficial to use a holistic approach to recognize individual/specific faces from a group of similar layouts. This holistic processing of the face is exactly what is damaged in prosopagnosics.[8] They are able to recognize the specific spatial layout and characteristics of facial features, but they are unable to process them as one entire face. This is counterintuitive to many people, as not everyone believes faces are "special" or perceived in a different way from other objects in the rest of the world. Though evidence suggests that other visual objects are processed in a holistic manner (e.g., dogs in dog experts), the size of these effects are smaller and are less consistently demonstrated than with faces. In a study conducted by Diamond and Carey, they showed this to be true by performing tests on dog-show judges. They showed pictures of dogs to the judges and to a control group and they then inverted those same pictures and showed them again. The dog-show judges had greater difficulty in recognizing the dogs once inverted compared to the control group; the inversion effect, the increased difficulty in recognizing a picture once inverted, was shown to be in effect. It was previously believed that the inversion effect was associated only with faces, but this study shows that it may apply to any category of expertise.[27]
It has also been argued that prosopagnosia may be a general impairment in understanding how individual perceptual components make up the structure or gestalt of an object. Psychologist Martha Farah has been particularly associated with this view.[28][29]
## Children[edit]
Developmental prosopagnosia can be a difficult thing for a child to both understand and cope with. Many adults with developmental prosopagnosia report that for a long time they had no idea that they had a deficit in face processing, unaware that others could distinguish people solely on facial differences.[30]
Prosopagnosia in children may be overlooked; they may just appear to be very shy or slightly odd due to their inability to recognize faces. They may also have a hard time making friends, as they may not recognize their classmates. They often make friends with children who have very clear, distinguishing features.[citation needed]
Children with prosopagnosia may also have difficulties following the plots of television shows and movies, as they have trouble recognizing the different characters. They tend to gravitate towards cartoons, in which characters have simple but well-defined characteristics, and tend to wear the same clothes, may be strikingly different colours or even different species. Prosopagnosiac children even have a hard time telling family members apart, or recognizing people out of context (e.g., the teacher in a grocery store).[31] Some have difficulty recognising themselves in group photographs.[citation needed]
Additionally, children with prosopagnosia can have a difficult time at school, as many school professionals are not well versed in prosopagnosia, if they are aware of the disorder at all.[32] Recently, a database of children's faces and test for child face perception has been developed, which may offer professionals a way to evaluate if a child has prosopagnosia. [33] [34]
## Notable people with prosopagnosia[edit]
* Robert Gascoyne-Cecil, 3rd Marquess of Salisbury (1830–1903)[35]
* Margaret Kerry (born 1929), American actress and reference model for Tinker Bell[36]
* Oliver Sacks (1933–2015), British neurologist[37]
* Jane Goodall (born 1934), English primatologist[38]
* Karl Kruszelnicki (born 1948), Australian science communicator[39]
* Chuck Close (born 1949), American painter[40]
* Duncan Bannatyne (born 1949), Scottish entrepreneur[41]
* Steve Wozniak (born 1950), American computer engineer and co-founder of Apple Inc.[42]
* John Hickenlooper (born 1952), US Senator and former Governor of Colorado[43]
* Jim Woodring (born 1952), American cartoonist[44][45]
* Stephen Fry (born 1957), English actor[46][47]
* Mary Ann Sieghart (born 1961), English journalist and radio presenter[48]
* Markos Moulitsas (born 1971), American blogger and former member of the military[49]
* Victoria, Crown Princess of Sweden (born 1977)[50][51]
* Sara Benincasa (born 1980) American comedian and author[52]
## See also[edit]
* Alexithymia
* Amygdala
* Aphantasia
* Cognitive neuropsychology
* Covert facial recognition
* Face perception
* Faces in the Crowd (film)
* Fregoli delusion
* N170
* Mirrored-self misidentification
* Prosopamnesia
* Recognition of human individuals
* Super recognisers
* Temporal lobe epilepsy
* Thatcher effect
## References[edit]
1. ^ prosopagnosia. collinsdictionary.com
2. ^ a b Davis, Joshua (November 2006). "Face Blind". Wired. Retrieved 31 December 2014. ("[Bill] Choisser had even begun to popularize a name for the condition: face blindness.")
3. ^ Grüter T, Grüter M, Carbon CC (2008). "Neural and genetic foundations of face recognition and prosopagnosia". J Neuropsychol. 2 (1): 79–97. CiteSeerX 10.1.1.571.9472. doi:10.1348/174866407X231001. PMID 19334306.
4. ^ "Face blindness not just skin deep". CNN. Retrieved 19 November 2015.
5. ^ Behrmann M, Avidan G (April 2005). "Congenital prosopagnosia: face-blind from birth". Trends Cogn. Sci. (Regul. Ed.). 9 (4): 180–7. CiteSeerX 10.1.1.379.4935. doi:10.1016/j.tics.2005.02.011. PMID 15808500. S2CID 12029388.
6. ^ a b c d e Mayer, Eugene; Rossion, Bruno (2007). Olivier Godefroy; Julien Bogousslavsky (eds.). Prosopagnosia (PDF). The Behavioral and Cognitive Neurology of Stroke (1 ed.). New York: Cambridge University Press. pp. 315–334. doi:10.1017/CBO9780511544880.017. ISBN 978-0521842617. OCLC 468190971. Archived from the original (PDF) on 1 July 2013. Retrieved 19 December 2012.
7. ^ Barry, Elen (5 September 2018). "From Mountain of CCTV Footage, Pay Dirt: 2 Russians Are Named in Spy Poisoning". The New York Times. Retrieved 6 September 2018.
8. ^ a b c d e f g h Gainotti G, Marra C (2011). "Differential contribution of right and left temporo-occipital and anterior temporal lesions to face recognition disorders". Front Hum Neurosci. 5: 55. doi:10.3389/fnhum.2011.00055. PMC 3108284. PMID 21687793.
9. ^ Biotti, Federica; Cook, Richard (2016). "Impaired perception of facial emotion in developmental prosopagnosia" (PDF). Cortex. 81: 126–136. doi:10.1016/j.cortex.2016.04.008. PMID 27208814. S2CID 35052467.
10. ^ Barton, Jason J.S.; Cherkasova, Mariya v.; Press, Daniel Z.; Intriligator, James M.; O'Connor, Margaret (2004). "Perception functions in Prosopagnosia". Perception. 33 (8): 939–956. doi:10.1068/p5243. PMID 15521693. S2CID 25242447.
11. ^ Kanwisher N, McDermott J, Chun MM (1 June 1997). "The fusiform face area: a module in human extrastriate cortex specialized for face perception". J. Neurosci. 17 (11): 4302–4311. doi:10.1523/JNEUROSCI.17-11-04302.1997. PMC 6573547. PMID 9151747.
12. ^ Kozlovskiy, Stanislav; Popova, Alla; Shirenova, Sophie; Kiselnikov, Andrey; Chernorizov, Alexander; Danilova, Nina (October 2016). "Formation of Face-Selective Detectors: ERP- And Dipole-Source Localization Study". International Journal of Psychophysiology. 108: 68. doi:10.1016/j.ijpsycho.2016.07.223.
13. ^ Kozlovskiy, S.A.; Vartanov, A.V.; Shirenova, S.D.; Neklyudova, A.K. (2017). "Brain mechanisms of the Tip-of-the-Tongue state:An electroencephalography-based source localization study". Psychology in Russia: State of the Art. 10 (3): 218–230. doi:10.11621/pir.2017.0315. ISSN 2074-6857.
14. ^ Kozlovskiy, SA; Shirenova, SD; Vartanov, AV; Kiselnikov, AA; Marakshina, JA (October 2016). "Retrieval from Long-Term Memory: Dipole Sources Localization Study". International Journal of Psychophysiology. 108: 98. doi:10.1016/j.ijpsycho.2016.07.300.
15. ^ Grueter M, Grueter T, Bell V, Horst J, Laskowski W, Sperling K, Halligan PW, Ellis HD, Kennerknecht I (2007). "Hereditary Prosopagnosia: The First Case Series" (PDF). Cortex. 43 (6): 734–749. doi:10.1016/S0010-9452(08)70502-1. PMID 17710825. S2CID 4477925.
16. ^ Kennerknecht, I.; Grueter, T.; Welling, B.; Wentzek, S.; Horst, J. R.; Edwards, S.; Grueter, M. (August 2006). "First report of prevalence of non-syndromic hereditary prosopagnosia (HPA)" (PDF). American Journal of Medical Genetics. 140A (15): 1617–1622. doi:10.1002/ajmg.a.31343. PMID 16817175. S2CID 2401.
17. ^ a b Duchaine B, Nakayama K (2006). "The Cambridge Face Memory Test: results for neurologically intact individuals and an investigation of its validity using inverted face stimuli and prosopagnosic participants". Neuropsychologia. 44 (4): 576–585. doi:10.1016/j.neuropsychologia.2005.07.001. PMID 16169565. S2CID 799553.
18. ^ Shah, Punit; Gaule, Anne; Sowden, Sophie; Bird, Geoffrey; Cook, Richard (24 June 2015). "The 20-item prosopagnosia index (PI20): a self-report instrument for identifying developmental prosopagnosia". Royal Society Open Science. 2 (6): 140343. Bibcode:2015RSOS....240343S. doi:10.1098/rsos.140343. PMC 4632531. PMID 26543567.
19. ^ Shah, Punit; Sowden, Sophie; Gaule, Anne; Catmur, Caroline; Bird, Geoffrey (1 November 2015). "The 20 item prosopagnosia index (PI20): relationship with the Glasgow face-matching test". Royal Society Open Science. 2 (11): 150305. Bibcode:2015RSOS....250305S. doi:10.1098/rsos.150305. ISSN 2054-5703. PMC 4680610. PMID 26715995.
20. ^ a b Gray, Katie; Bird, Geoffrey; Cook, Richard (1 March 2017). "Robust associations between the 20-item prosopagnosia index and the Cambridge Face Memory Test in the general population". Royal Society Open Science. 4 (3): 160923. Bibcode:2017RSOS....460923G. doi:10.1098/rsos.160923. PMC 5383837. PMID 28405380.
21. ^ a b c DeGutis, Joseph M.; Chiu, Christopher; Grosso, Mallory E.; Cohan, Sarah (5 August 2014). "Face processing improvements in prosopagnosia: successes and failures over the last 50 years". Frontiers in Human Neuroscience. 8: 561. doi:10.3389/fnhum.2014.00561. ISSN 1662-5161. PMC 4122168. PMID 25140137.
22. ^ Inglis, David (May 1899). "Moral Imbecility". Transactions of the Michigan State Medical Society. 23: 377–387.
23. ^ Katz, Neil (26 August 2010). "Prosopagnosia: Oliver Sacks' Battle with "Face Blindness"". CBS News. Retrieved 3 February 2010.
24. ^ Young, Andrew W.; Newcombe, F.; de Hanncombe, E.H.F.; Small, M. (1998). Andrew W. Young (ed.). Dissociable deficits after brain injury. Face and Mind. Oxford; New York: Oxford University Press. pp. 181–208. doi:10.1093/acprof:oso/9780198524205.003.0006. ISBN 978-0198524212. OCLC 38014705.
25. ^ Richler JJ, Cheung OS, Gauthier I (April 2011). "Holistic processing predicts face recognition". Psychol Sci. 22 (4): 464–471. doi:10.1177/0956797611401753. PMC 3077885. PMID 21393576.
26. ^ Richler JJ, Wong YK, Gauthier I (April 2011). "Perceptual Expertise as a Shift from Strategic Interference to Automatic Holistic Processing". Curr Dir Psychol Sci. 20 (2): 129–134. doi:10.1177/0963721411402472. PMC 3104280. PMID 21643512.
27. ^ Diamond, R.; Carey, S. (June 1986). "Why faces are and are not special: an effect of expertise". Journal of Experimental Psychology: General. 115 (2): 107–117. doi:10.1037/0096-3445.115.2.107. PMID 2940312.
28. ^ Farah MJ, Wilson KD, Drain M, Tanaka JN (July 1998). "What is "special" about face perception?". Psychol Rev. 105 (3): 482–498. doi:10.1037/0033-295X.105.3.482. PMID 9697428.
29. ^ Farah, Martha J. (2004). Visual agnosia. Cambridge, Mass: MIT Press. ISBN 978-0-262-56203-4. OCLC 474679492.
30. ^ Nancy L. Mindick (2010). Understanding Facial Recognition Difficulties in Children: Prosopagnosia Management Strategies for Parents and Professionals (JKP Essentials). Jessica Kingsley Pub. ISBN 978-1-84905-802-5. OCLC 610833680.
31. ^ Schmalzl L, Palermo R, Green M, Brunsdon R, Coltheart M (July 2008). "Training of familiar face recognition and visual scan paths for faces in a child with congenital prosopagnosia". Cogn Neuropsychol. 25 (5): 704–729. doi:10.1080/02643290802299350. PMID 18720102. S2CID 29278660.
32. ^ Wilson, C. Ellie; Palermo, Romina; Schmalzl, Laura; Brock, Jon (February 2010). "Specificity of impaired facial identity recognition in children with suspected developmental prosopagnosia". Cognitive Neuropsychology. 27 (1): 30–45. doi:10.1080/02643294.2010.490207. PMID 20623389. S2CID 35860566.
33. ^ Dalrymple, Kirsten A.; Gomez, Jesse; Duchaine, Brad (14 November 2013). "The Dartmouth Database of Children's Faces: Acquisition and Validation of a New Face Stimulus Set". PLOS ONE. 8 (11): e79131. Bibcode:2013PLoSO...879131D. doi:10.1371/journal.pone.0079131. PMC 3828408. PMID 24244434.
34. ^ Croydon, Abigail; Pimperton, Hannah; Ewing, Louise; Duchaine, Brad C.; Pellicano, Elizabeth (1 September 2014). "The Cambridge Face Memory Test for Children (CFMT-C): A new tool for measuring face recognition skills in childhood". Neuropsychologia. 62: 60–67. doi:10.1016/j.neuropsychologia.2014.07.008. PMID 25054837. S2CID 10641959.
35. ^ Grüter, Thomas. "Prosopagnosia in biographies and autobiographies" (PDF). Retrieved 24 February 2020.
36. ^ Rembulat, Vince (2 July 2019). "THE 'REAL' TINKER BELL". Manteca Bulletin. Manteca, CA. Retrieved 29 April 2020.
37. ^ Katz, Neil (26 August 2010). "Prosopagnosia: Oliver Sacks' Battle with "Face Blindness"". CBS News. Retrieved 3 February 2010.
38. ^ "Photos: The faces of those who don't recognize faces". CNN. 23 May 2013.
39. ^ "Dr Karl on what it's like to live with face blindness". abc.net.au. ABC. Retrieved 12 November 2018.
40. ^ "Mosaic Art NOW: Prosopagnosia: Portraitist Chuck Close". mosaicartnow.com. Archived from the original on 21 August 2017. Retrieved 20 August 2017.
41. ^ Tobin, Lucy (20 June 2011). "Researchers explore problems of 'face blindness'". The Guardian. London. Retrieved 23 July 2012.
42. ^ Kelion, Leo (9 September 2015). "Steve Wozniak: Shocked and amazed by Steve Jobs movie". BBC. Retrieved 9 September 2015.
43. ^ "John Hickenlooper didn't mean to forget who you are: How face blindness has affected his political career". CNN. 26 June 2019.
44. ^ https://www.lambiek.net/artists/w/woodring.htm
45. ^ Jim Woodring speech Making Light VASD Program, around the 32:00 mark. 24 March 2016.
46. ^ Sieghart, Mary Ann (1 July 2016). "Who Are You Again?". BBC Radio 4.
47. ^ Hepworth, David (25 June 2016). "Who are you again? What it's like to never remember a face". The Guardian. Retrieved 1 July 2016.
48. ^ Kelly Strange "Everyone looks the same to me", Mirror.co.uk website, 9 November 2007. Retrieved 15 April 2008.
49. ^ "Photos: The faces of those who don't recognize faces". CNN. 23 May 2013.
50. ^ "Princess Victoria's face confession".
51. ^ "The Art of Living Magazine – Art, Culture and Wealth Management". The Art of Living Magazine. Archived from the original on 14 May 2017. Retrieved 30 April 2017.
52. ^ https://twitter.com/SaraJBenincasa/status/1308296067574722561
## Further reading[edit]
* Bruce, V.; Young, A. (2000). In the Eye of the Beholder: The Science of Face Perception. Oxford University Press. ISBN 978-0-19-852439-7.
* Duchaine, BC; Nakayama, K (April 2006). "Developmental prosopagnosia: a window to content-specific face processing". Current Opinion in Neurobiology. 16 (2): 166–173. doi:10.1016/j.conb.2006.03.003. PMID 16563738. S2CID 14102858.
* Farah, Martha J. (1990). Visual agnosia: disorders of object recognition and what they tell us about normal vision. Cambridge: M.I.T. Press. ISBN 978-0-262-06135-3. OCLC 750525204.
* Oliver Sacks (30 August 2010). "Prosopagnosia, the science behind face blindness". The New Yorker. Retrieved 10 August 2014.
* Heather Sellers (2010). You Don't Look Like Anyone I Know. Riverhead Hardcover. ISBN 978-1-59448-773-6. OCLC 535490485.
* Lyall, Sarah (27 November 2017). "Face Blindness: Sarah Lyall on a curious condition". Five Dials. Retrieved 31 August 2019.
* Dingfelder, Sadie (21 August 2019). "My life with face blindness: I spent decades unable to recognize people. Then I learned why". Washington Post. Retrieved 31 August 2019.
## External links[edit]
Look up prosopagnosia in Wiktionary, the free dictionary.
Wikiversity has learning resources about Prosopagnosia
* Face Blind! – The online book on face blindness by Bill Choisser, San Francisco.
Classification
D
* ICD-10: R48.8
* ICD-10-CM: R48.3
* ICD-9-CM: 368.16
* OMIM: 610382
* MeSH: D020238
* v
* t
* e
Symptoms, signs and syndromes associated with lesions of the brain and brainstem
Brainstem
Medulla (CN 8, 9, 10, 12)
* Lateral medullary syndrome/Wallenberg
* PICA
* Medial medullary syndrome/Dejerine
* ASA
Pons (CN 5, 6, 7, 8)
* Upper dorsal pontine syndrome/Raymond-Céstan syndrome
* Lateral pontine syndrome (AICA) (lateral)
* Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar)
* Locked-in syndrome
* Internuclear ophthalmoplegia
* One and a half syndrome
Midbrain (CN 3, 4)
* Weber's syndrome
* ventral peduncle, PCA
* Benedikt syndrome
* ventral tegmentum, PCA
* Parinaud's syndrome
* dorsal, tumor
* Claude's syndrome
Other
* Alternating hemiplegia
Cerebellum
* Latearl
* Dysmetria
* Dysdiadochokinesia
* Intention tremor)
* Medial
* Cerebellar ataxia
Basal ganglia
* Chorea
* Dystonia
* Parkinson's disease
Cortex
* ACA syndrome
* MCA syndrome
* PCA syndrome
* Frontal lobe
* Expressive aphasia
* Abulia
* Parietal lobe
* Receptive aphasia
* Hemispatial neglect
* Gerstmann syndrome
* Astereognosis
* Occipital lobe
* Bálint's syndrome
* Cortical blindness
* Pure alexia
* Temporal lobe
* Cortical deafness
* Prosopagnosia
Thalamus
* Thalamic syndrome
Other
* Upper motor neuron lesion
* Aphasia
*[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
|
Prosopagnosia
|
c0234512
| 25,532 |
wikipedia
|
https://en.wikipedia.org/wiki/Prosopagnosia
| 2021-01-18T18:30:19 |
{"mesh": ["D020238"], "umls": ["C0234512"], "wikidata": ["Q244438"]}
|
A rare cardiac disease characterized by acute occurrence of heart failure after an emotional or physical trigger however, recovery of the wall motion abnormalities are observed within months. Symptoms are similar to acute coronary syndrome (ACS).
## Epidemiology
Takotsubo syndrome (TTS) is found in about 1-3% of all patients with symptoms of ACS; however, the prevalence is likely underestimated. Around 90% of TTS patients are women, typically postmenopausal but male and younger patients are diagnosed increasingly due to raised awareness of the syndrome.
## Clinical description
In the acute phase, clinical presentation, electrocardiography (ECG) and cardiac biomarkers are similar to those of ACS. Typical symptoms are acute chest pain or dyspnea. Further symptoms can arise from complications of TTS, e.g. heart failure, cardiogenic shock, or cardiac arrest. New ECG changes or elevated cardiac biomarkers may or may not be present.
## Etiology
The underlying mechanisms of this syndrome remain incompletely understood. Recent findings show that specific alterations in neurological response and sympathetic activation after emotional stimuli are present in TTS. These findings confirm the importance of brain-heart interaction in the development of this process. Microcirculatory constriction is also proposed as an underlying mechanism.
## Diagnostic methods
Diagnosis is often challenging due to the similarity with ACS. Coronary angiography with left ventriculography is considered the gold standard diagnostic tool. The InterTAK (international takotsubo) Diagnostic Criteria have been developed to improve diagnosis and include the following: 1) transient left ventricular dysfunction presenting as either apical, midventricular, basal or focal wall motion abnormalities with possible right ventricular involvement, 2) a preceding emotional, physical, or combined trigger (although not obligatory), 3) neurological disorders can be possible triggers, 4) presence of new ECG abnormalities (ST-segment elevation or depression, T-wave inversion, or QTc prolongation), 5) elevated cardiac markers (especially brain natriuretic peptide), 6) significant coronary artery disease can coexist, 7) absence of myocarditis.
## Differential diagnosis
Differential diagnoses include AMI, myocarditis, spontaneous coronary artery dissection, or peripartum cardiomyopathy.
## Management and treatment
Due to difficulty in distinguishing TTS from ACS, patients should be transferred to a chest pain unit upon presentation and receive guideline based treatment of ACS. There are no randomized clinical trials to support specific acute or long term treatment recommendations in TTS. However, the consensus statement from an international TTS expert panel provides recommendations for optimal treatment of TTS patients. Electrocardiogram monitoring is essential as a prolonged QT-interval may trigger malignant ventricular arrhythmias (torsades de pointes) or atrioventricular-block. Cardiogenic shock or post cardiac arrest requires intensive care with treatment according to the presence or absence of pulmonary edema, low left ventricular ejection fraction, hypotension and bradycardia. In all cases, inotropic substances should be avoided. For long term treatment, angiotensin converting-enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) are recommended as they are associated with improved survival and lower recurrence rates. Echocardiography should be performed during the acute phase to exclude right ventricular involvement, left ventricular outflow tract obstruction or intraventricular thrombus. A follow-up echocardiography should be performed after discharge to confirm recovery.
## Prognosis
The spectrum of TTS is wide and ranges from low to very high risk. In-hospital mortality and long-term outcome in TTS are similar compared to ACS. Recovery of the left ventricular regional systolic dysfunction is usually observed after 4-8 weeks. The risk of recurrence is around 5%.
*[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
|
Tako-Tsubo cardiomyopathy
|
c1739395
| 25,533 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66529
| 2021-01-23T19:08:30 |
{"gard": ["9400"], "mesh": ["D054549"], "umls": ["C1168291", "C1739395"], "icd-10": ["I42.8"], "synonyms": ["Ampulla cardiomyopathy", "Apical ballooning syndrome", "Ballooning cardiomyopathy", "Broken heart syndrome", "Stress cardiomyopathy", "Tako-Tsubo syndrome", "Takotsubo cardiomyopathy", "Takotsubo syndrome", "Transient left ventricular apical ballooning syndrome"]}
|
Holoprosencephaly-hypokinesia syndrome is an extremely rare and fatal central nervous system malformation occurring during embryogenesis, presenting prenatally with holoprosencephaly and fetal hypokinesia as major features. Other manifestations include microcephaly, multiple contractures and intrauterine growth restriction. There have been no further descriptions in the literature since 1988.
*[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
|
Lethal intrauterine growth restriction-cortical malformation-congenital contractures syndrome
|
c1844016
| 25,534 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2570
| 2021-01-23T18:02:44 |
{"gard": ["3788"], "mesh": ["C564409"], "omim": ["306990"], "umls": ["C1844016"], "icd-10": ["Q04.2"], "synonyms": ["Morse-Rawnsley-Sargent syndrome"]}
|
## Clinical Features
The spondyloepimetaphyseal dysplasias are disorders characterized by involvement of the epiphyses, metaphyses, and vertebral bodies. Rao et al. (1997) described an apparently new form of SEMD, inherited as an autosomal recessive, and associated with abnormal dentition. In addition to generalized platyspondyly with epiphyseal and metaphyseal involvement, a 16-year-old girl and her 11-year-old brother showed thin tapering fingers with accentuated palmar creases and abnormal dentition (oligodontia and pointed incisors). The parents were first cousins.
INHERITANCE \- Autosomal recessive GROWTH Height \- Proportionate short stature HEAD & NECK Eyes \- Blue sclerae Teeth \- Oligodontia (reduced number of molars and premolars) \- Pointed lower central incisors \- Discolored lateral incisors \- Wide gap between upper and lower central incisors SKELETAL \- Spondyloepimetaphyseal dysplasia Spine \- Platyspondyly \- Irregular vertebral endplates Pelvis \- Narrow iliac wings \- Short, broad femoral necks Limbs \- Genu valgum \- Mildly flared irregular metaphyses \- Small, flat irregularly ossified epiphyses Hands \- Thin, tapering fingers \- Accentuated palmar creases \- Fifth finger camptodactyly \- Pseudoepiphyses (1st and 5th metacarpals) SKIN, NAILS, & HAIR Skin \- Dry palmar skin NEUROLOGIC Central Nervous System \- Normal intelligence ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH ABNORMAL DENTITION
|
c1866507
| 25,535 |
omim
|
https://www.omim.org/entry/601668
| 2019-09-22T16:14:27 |
{"mesh": ["C566644"], "omim": ["601668"], "orphanet": ["168451"]}
|
This article needs attention from an expert in Pathology. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Pathology may be able to help recruit an expert. (November 2008)
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: "Metabolic bone disease" – news · newspapers · books · scholar · JSTOR (October 2020)
Metabolic bone disease (MBD)
SpecialtyRheumatology, endocrinology
Metabolic bone disease is an abnormality of bones caused by a broad spectrum of disorders. Most commonly these disorders are caused by deficiencies of minerals such as calcium, phosphorus, magnesium or vitamin D leading to dramatic clinical disorders that are commonly reversible once the underlying defect has been treated. These disorders are to be differentiated from a larger group of genetic bone disorders where there is a defect in a specific signaling system or cell type that causes the bone disorder. There may be overlap. For example, genetic or hereditary hypophosphatemia may cause the metabolic bone disorder osteomalacia. Although there is currently no treatment for the genetic condition, replacement of phosphate often corrects or improves the metabolic bone disorder.
## Contents
* 1 Conditions considered to be metabolic bone disorders
* 2 References
* 3 External links
## Conditions considered to be metabolic bone disorders[edit]
* osteoporosis
* osteomalacia (adults) & rickets (children)
* osteitis fibrosa cystica
* Paget's disease of bone
* pyramiding (turtles)
Osteoporosis is due to causal factors like atrophy of disuse and gonadal deficiency. Hence osteoporosis is common in postmenopausal women and in men above 50 yrs. Hypercorticism may also be a causal factor, as osteoporosis may be seen as a feature of Cushing's syndrome.
## References[edit]
## External links[edit]
Classification
D
* MeSH: D001851
* v
* t
* e
Bone and joint disease
Bone
Inflammation
endocrine:
* Osteitis fibrosa cystica
* Brown tumor
infection:
* Osteomyelitis
* Sequestrum
* Involucrum
* Sesamoiditis
* Brodie abscess
* Periostitis
* Vertebral osteomyelitis
Metabolic
* Bone density
* Osteoporosis
* Juvenile
* Osteopenia
* Osteomalacia
* Paget's disease of bone
* Hypophosphatasia
Bone resorption
* Osteolysis
* Hajdu–Cheney syndrome
* Ainhum
* Gorham's disease
Other
* Ischaemia
* Avascular necrosis
* Osteonecrosis of the jaw
* Complex regional pain syndrome
* Hypertrophic pulmonary osteoarthropathy
* Nonossifying fibroma
* Pseudarthrosis
* Stress fracture
* Fibrous dysplasia
* Monostotic
* Polyostotic
* Skeletal fluorosis
* bone cyst
* Aneurysmal bone cyst
* Hyperostosis
* Infantile cortical hyperostosis
* Osteosclerosis
* Melorheostosis
* Pycnodysostosis
Joint
Chondritis
* Relapsing polychondritis
Other
* Tietze's syndrome
Combined
Osteochondritis
* Osteochondritis dissecans
Child
leg:
* hip
* Legg–Calvé–Perthes syndrome
* tibia
* Osgood–Schlatter disease
* Blount's disease
* foot
* Köhler disease
* Sever's disease
spine
* * Scheuermann's_disease
arm:
* wrist
* Kienböck's disease
* elbow
* Panner 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
|
Metabolic bone disease
|
c0005944
| 25,536 |
wikipedia
|
https://en.wikipedia.org/wiki/Metabolic_bone_disease
| 2021-01-18T19:03:36 |
{"mesh": ["D001851"], "wikidata": ["Q6822340"]}
|
Intermediate nemaline myopathy is a type of nemaline myopathy (NM; see this term) that shows features of typical NM (see this term) in neonates with a more severe progression.
## Epidemiology
The annual incidence of NM has been estimated at 1/50,000 live births, and intermediate NM might represent 20% of all cases.
## Clinical description
Neonates with intermediate NM present with spontaneous anti-gravity movements and active respiratory muscles, but with a progressive generalized weakness which prevents achievement of gross motor milestones or leads to loss of ambulation and/or independent respiration by age 11 years. Children often develop joint contractures.
## Etiology
The ACTA1 (1q42.13), NEB (2q22) or TPM3 (1q21.2) genes have been associated with intermediate NM and the transmission pattern of the disease is autosomal recessive or dominant.
*[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
|
Intermediate nemaline myopathy
|
c3711389
| 25,537 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171433
| 2021-01-23T17:37:16 |
{"gard": ["12823"], "mesh": ["C579880"], "omim": ["161800", "256030", "609284", "615731"], "icd-10": ["G71.2"]}
|
A number sign (#) is used with this entry because of evidence that diarrhea-7 (DIAR7) is caused by homozygous mutation in the DGAT1 gene (604900). One such family has been reported.
For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
Clinical Features
Haas et al. (2012) reported a family of Ashkenazi Jewish descent with 2 of 3 children affected by congenital diarrhea. Both affected children presented 3 days after birth with severe intractable diarrhea; 1 child died from complications at age 17 months. The second child showed marked improvement, with resolution of most symptoms at 10 to 12 months of age. The first affected child was a girl who had a normal birth weight of 3.18 kg. Three days after birth, she developed vomiting, colicky pain, and nonbloody watery diarrhea 8 to 10 times per day. She was treated with oral rehydration solution, and her formula was changed to soy-based formula from breast milk and cow's milk formula, but diarrhea continued. All cultures were negative. She exhibited protein-losing enteropathy and hypoalbuminemia, and required total parenteral nutrition (TPN). Stomach, duodenum, and colon biopsies were negative for chronic granulomatous disease (CGD), autoimmune enteropathy, food protein-induced enterocolitis, microvillous inclusion disease, and tufting enteropathy. Neuroendocrine cells were present in intestinal biopsies. There was no evidence of congenital lymphangiectasia by CT scan. There was evidence of dystrophic microvilli in the duodenum. The child had hyperlipidemia, with a fasting serum TG level of 325 at 1 month of age; her mother and father also had elevated fasting TG levels. At 14 months of age, the girl was below the first percentile for weight and had recurrent episodes of sepsis secondary to a venous catheter. She died at 17 months of age from complications of malnutrition and sepsis. The second affected child was a boy who weighed 3.7 kg at birth. He had a remarkably similar presentation to his sister, but he exhibited metabolic acidosis and hyponatremia at 6 days of age. He also had protein-losing enteropathy. Combined hyperlipidemia was treated with cholestyramine when the boy was 27 months of age, and fasting serum lipid levels decreased. He was thriving at 46 months of age on an unrestricted diet. Haas et al. (2012) showed villous atrophy and microvillous dystrophy in patchy areas next to normal morphology in jejunal biopsies.
Molecular Genetics
Both patients in the family reported by Haas et al. (2012) were homozygous for a splice site mutation resulting in the skipping of exon 8 in the DGAT1 gene (604900.0001). Molecular analysis of the mutant allele indicated a total loss of function, with no detectable DGAT1 protein or activity produced. Both parents and an unaffected sib were heterozygous for the mutation. This variant was found in 3 individuals from 12,500 control exomes; Haas et al. (2012) estimated the probability of homozygosity to be 1 in approximately 50 to 100 million births.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive secondary to congenital diarrhea ABDOMEN Gastrointestinal \- Vomiting \- Watery diarrhea, congenital \- Patchy areas of dystrophic microvilli in duodenum \- Patchy areas of villous atrophy \- Protein-losing enteropathy \- Parenteral nutritional support required LABORATORY ABNORMALITIES \- Hypoalbuminemia \- Hyperlipidemia \- Elevated fasting triglycerides (seen in heterozygotes as well) \- Elevated total cholesterol (seen in heterozygotes as well) MISCELLANEOUS \- Two patients in one Ashkenazi Jewish family described (last curated June 2014) \- One patient died at 17 months of age \- One patient showed improvement and was thriving at 46 months of age MOLECULAR BASIS \- Caused by mutation in the diacylglycerol O-acyltransferase 1 gene (DGAT1, 604900.0001 ) ▲ 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
|
DIARRHEA 7, PROTEIN-LOSING ENTEROPATHY TYPE
|
c4014516
| 25,538 |
omim
|
https://www.omim.org/entry/615863
| 2019-09-22T15:50:47 |
{"doid": ["0060778"], "omim": ["618183", "615863"], "orphanet": ["329242"], "synonyms": ["Congenital chronic diarrhea with exudative enteropathy"]}
|
## Description
Hereditary primary lymphedema is caused by anatomic or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes, such as nail dysplasia or papillomatosis. Onset is usually at birth or in early childhood but can occur later, and the severity is variable (summary by Gordon et al., 2013 and Balboa-Beltran et al., 2014).
For a discussion of genetic heterogeneity of lymphatic malformation, see 153100.
Clinical Features
Malik and Grzeschik (2008) reported a large consanguineous Pakistani family in which 25 individuals spanning 5 generations had lymphedema confined to the lower limbs. Despite consanguinity, detailed pedigree analysis indicated autosomal dominant inheritance with reduced penetrance. Onset occurred in early childhood and showed maximum manifestations at puberty. The phenotype was variable, ranging from swelling of a foot to severe bilateral lymphedema of the lower legs below the knee. Some, but not all, patients had papillomatosis over the affected areas. Swelling began to subside by age 30 years and became unremarkable in the following 12 to 15 years. The phenotype was similar to that seen in hereditary lymphedema type 1 (LMPHM1; 153100).
Mapping
By genomewide linkage analysis of a large Pakistani family with lymphedema, Malik and Grzeschik (2008) identified a candidate locus on chromosome 6q16.2-q22.1 (maximum 2-point lod score of 3.19 at D6S1671; multipoint lod score of 3.75 at 108 cM). Haplotype analysis delineated a 17.26-cM interval between D6S1716 and D6S303. Genetic analysis excluded mutations in the FOXO3A gene (602681).
INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Papillomatosis of affected area MUSCLE, SOFT TISSUES \- Lymphedema of the lower limbs (swelling is confined to below the knees) MISCELLANEOUS \- Onset in early childhood or infancy \- Progressive, with full manifestations at puberty \- Swelling starts to fade by age 30 years and gradually becomes unremarkable \- Reduced penetrance ▲ 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
|
LYMPHATIC MALFORMATION 2
|
c1704423
| 25,539 |
omim
|
https://www.omim.org/entry/611944
| 2019-09-22T16:02:37 |
{"doid": ["0070211"], "mesh": ["D008209"], "omim": ["611944"], "orphanet": ["79452"], "synonyms": ["Alternative titles", "LYMPHEDEMA, HEREDITARY, IB, FORMERLY"]}
|
Aglossia (aglossia congenita) is a congenital defect resulting in a partial development or complete absence of a tongue.
Aglossia is commonly associated with craniofacial and limb defects (Adactylia syndrome) and is thought to belong to a family of oromandibular limb hypogenesis syndrome or OLHS. It is believed to be caused by heat-induced vascular disruption near the fourth week of embryonic development.
The first known case was reported in the early 18th century by a member of the prominent De Jussieu family in France and cases to this day remain rare.[1]
## References[edit]
1. ^ Gupta, SR (2012). "Isolated aglossia congenita: A rare case of oromandibular limb hypogenesis syndrome type I B". J Oral Maxillofac Pathol. 16: 414–9. doi:10.4103/0973-029X.102504. PMC 3519220. PMID 23248477.
## External links[edit]
* Experience: I was born without a tongue, Kelly Rogers, The Guardian, 1 December 2017.
*[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
|
Aglossia
|
c0158663
| 25,540 |
wikipedia
|
https://en.wikipedia.org/wiki/Aglossia
| 2021-01-18T18:36:58 |
{"umls": ["C0158663"], "wikidata": ["Q9588048"]}
|
Charcot-Marie-Tooth disease type 1A (CMT1A) is a type of inherited neurological disorder that affects the peripheral nerves. People with this disease experience weakness and wasting (atrophy) of the muscles of the lower legs beginning in adolescence; later they can also have hand weakness and sensory loss. In CMT1A, abnormal nerve conduction studies can be found in babies or toddlers, but the symptoms that are characteristic of the disease may not occur until 20 years of age or later. CMT1A is caused by having an extra copy (a duplication) of the PMP22 gene. It is inherited in an autosomal dominant manner. Treatment for this condition may include physical therapy; occupational therapy; braces and other orthopedic devices; orthopedic surgery; and pain medications. The severity and degree of disability varies very much among the affected people.
*[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
|
Charcot-Marie-Tooth disease type 1A
|
c0270911
| 25,541 |
gard
|
https://rarediseases.info.nih.gov/diseases/1245/charcot-marie-tooth-disease-type-1a
| 2021-01-18T18:01:32 |
{"mesh": ["D002607"], "omim": ["118220"], "umls": ["C0270911"], "orphanet": ["101081"], "synonyms": ["Charcot-Marie-Tooth disease, demyelinating, type 1A", "CMT 1A", "Hereditary motor and sensory neuropathy 1A", "HMSN 1A", "Charcot Marie Tooth disease type 1A"]}
|
A rare congenital disorder of copper metabolism with severe multisystemic manifestations that are primarily characterized by progressive neurodegeneration and marked connective tissue anomalies. A pathognomonic feature is the typical sparse, abnormal steely hair.
## Epidemiology
Prevalence at birth is estimated at 1/300,000 and 1/360,000 in Europe and Japan, respectivley. In Australia, the birth prevalence is much higher (1/50,000-100,000), likely due to a founder effect. The disorder is X-linked and thus primarily affects males.
## Clinical description
Menkes disease (MD) manifests in the neonatal period. Most patients are born at term with appropriate birth measurements. Cephalohematomas and spontaneous fractures are occasionally observed at birth. In the early neonatal period, patients may present with prolonged jaundice, hypothermia, hypoglycemia and feeding difficulties. Pectus excavatum and umbilical and inguinal hernias have also been reported. Unusual sparse and dull scalp hair is often the initial observation at the age of 1-2 months. Characteristically, the hair appears hypopigmented/depigmented, resembles steel wool and is friable, especially in the areas of the scalp subjected to friction. Additional symptoms are failure to thrive, poor eating, vomiting, and diarrhea. The appearance of pale skin, frontal or occipital bossing, micrognathia and pudgy cheeks may be observed. Patients develop gradual motor dysfunction and seizures. Muscular hypotonia in early life is replaced later-on by spasticity and weakness of the extremities. The clinical course is usually severe. Variable forms exist with occipital horn syndrome (OHS) being the mildest recognized form, which further presents with prominent bony exostoses and bladder diverticula.
## Etiology
MD is caused by pathogenic variants in ATP7A (Xq21.1) encoding a membrane bound copper-transport protein (Cu2+-transporting ATPase-alpha polypeptide). To date, about 300 different variants in this gene have been reported. There is no obvious correlation between the variants and the clinical course.
## Diagnostic methods
Initial diagnosis is based on clinical features (typical hair changes associated with hypotonia and delayed neuromotor development) and supported by demonstration of reduced levels of serum copper and ceruloplasmin. However, in the neonatal period these markers should be interpreted with caution, as their levels are also low in healthy newborns. In this period, plasma catecholamine analysis (ratio of DOPA to dihydroxyphenylglycol), indicative of dopamine beta-hydroxylase deficiency, may be used as a diagnostic test when the clinical diagnosis suggests MD. Although not specific, other laboratory investigations are useful to complete the clinical work up, these include light microscopy (for hair), radiological imaging (for generalized osteoporosis, metaphyseal flaring and spurs in the long bones, diaphyseal periosteal reaction and thickening, and Wormian bones in the cranial sutures), and arteriography (arterial tortuosity, especially of the intracranial arteries). Definitive diagnosis is based on molecular genetic testing.
## Differential diagnosis
Differential diagnosis includes Ehlers-Danlos syndrome, Marfan syndrome, cutis laxa syndromes, mitochondrial disorders, osteogenesis imperfecta and child abuse.
## Antenatal diagnosis
Prenatal diagnosis is possible where the pathogenic variant has previously been identified in a family member and the preferred situation is to determine the carrier status of the mother prior to pregnancy and prenatal diagnosis.
## Genetic counseling
Transmission is X-linked recessive. Genetic counseling should be offered to couples where the mother is a carrier of a pathogenic variant, informing them that the risk for a male fetus to be affected is 50% at each pregnancy. In rare cases, a female fetus may be affected (manifesting heterozygote) and this possibility should also be considered during genetic counselling. Similarly, germ-line mosaicism has been described and, although probably infrequent, it should also be discussed when counselling non-carrier mothers of singleton cases.
## Management and treatment
Treatment is mainly symptomatic. Early parenteral copper-histidine supplementation may modify disease progression and some symptoms by providing extra copper to tissue and to copper-dependent enzymes. Oral administration of copper is ineffective as it is trapped in the intestines.
## Prognosis
Prognosis is poor and patients usually die in early childhood. However, careful medical care, and possibly copper administration, may extend life span.
* 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
|
Menkes disease
|
c0022716
| 25,542 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=565
| 2021-01-23T17:52:32 |
{"gard": ["1521"], "mesh": ["D007706"], "omim": ["309400"], "umls": ["C0022716"], "icd-10": ["E83.0"], "synonyms": ["MD", "Menkes kinky hair disease", "Menkes syndrome"]}
|
## Summary
### Clinical characteristics.
The spectrum of ADAMTSL4-related eye disorders is a continuum that includes the phenotypes known as "autosomal recessive isolated ectopia lentis" and "ectopia lentis et pupillae" as well as more minor eye anomalies with no displacement of the pupil and very mild displacement of the lens. Typical eye findings are dislocation of the lens, congenital abnormalities of the iris, refractive errors that may lead to amblyopia, and early-onset cataract. Increased intraocular pressure and retinal detachment may occur on occasion. Eye findings can vary within a family and between the eyes in an individual. In general, no additional systemic manifestations are observed, although skeletal features have been reported in a few affected individuals.
### Diagnosis/testing.
The diagnosis is established in individuals with characteristic eye findings by the identification of biallelic pathogenic variants in ADAMTSL4 by molecular genetic testing.
### Management.
Treatment of manifestations: In children, the main objective is to prevent amblyopia by early correction of refractive errors and patching. Surgery should be considered in individuals with cataracts, those at risk for complications caused by the dislocated lens, those in whom patching does not result in improvement of visual acuity, those in whom the lens edge is in the middle of the pupil, and those with insufficient correction of refractive errors, in particular large degrees of astigmatism. While lensectomy with anterior vitrectomy and correction of the aphakia with contact lenses or secondary intraocular lens (IOL) replacement has been the usual procedure in the past, capsule-sparing lens surgery has recently been introduced. Sphincterotomy can benefit individuals with small and highly displaced pupils. Increased intraocular pressure can in most cases be controlled by topical anti-glaucoma medication. Retinal detachment is treated in the usual manner by vitrectomy and scleral buckling if necessary.
Surveillance: Assessment of visual acuity, refractive error, and intraocular pressure one to three times per year; adults who are stable may be examined annually, whereas children require more frequent examinations. Ultrasonography may be necessary to evaluate for retinal detachment if the view of the fundus is limited.
Agents/circumstances to avoid: Care during contact sports to avoid trauma to the head. Avoid boxing and martial arts.
Evaluation of relatives at risk: Sibs of a proband should undergo complete ophthalmologic evaluation (determination of visual acuity, measurement of intraocular pressure, slit lamp examination, and ophthalmoscopy) to allow for early diagnosis and treatment of findings, primarily to prevent amblyopia. If the pathogenic variants in a family are known, molecular genetic testing is likely to be more helpful in clarifying the genetic status of at-risk sibs given the wide variability even within the same family.
### Genetic counseling.
ADAMTSL4-related eye disorders are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the pathogenic variants in the family are known.
## Diagnosis
The spectrum of ADAMTSL4-related eye disorders is a continuum that includes the phenotypes known as autosomal recessive isolated ectopia lentis and ectopia lentis et pupillae as well as more minor eye anomalies with no displacement of the pupil and very mild displacement of the lens. Variability in the eye findings is observed among affected individuals in a family and between the eyes of the same individual. No formal diagnostic criteria have been published.
### Suggestive Findings
ADAMTSL4-related eye disorders should be suspected in individuals with the following characteristics:
* Mild to severe dislocation of the lens due to loss of zonular fibers without any preceding trauma. The lens may be displaced in any direction. Spherophakia, lens coloboma, and iridodonesis may be present.
* Mild to severe displacement of the pupil; in some instances the pupils are normal. If the pupil is displaced, the lens is usually displaced in the opposite direction.
* Enlarged iris processes; seen in most affected individuals, causing an anomalous iridocorneal angle
* A deep anterior chamber and a thin and flat iris with loss of iris crypts accompanied by iris transillumination; seen in individuals with prominent displacement of the pupil
* Fibrosis of iris tissue surrounding the pupil resulting in poor dilatation of the pupil in response to mydriatics
* Presence of a pupillary membrane, with small strands extending from the pupillary margin visible after dilatation of the pupil. A fibrous membrane, visible on ultrasound biomicroscopy, may cover the posterior part of the iris.
* Family history consistent with autosomal recessive inheritance
### Establishing the Diagnosis
The diagnosis of an ADAMTSL4-related eye disorder is established in a proband with characteristic eye findings by the identification of biallelic pathogenic variants in ADAMTSL4 on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of an ADAMTSL4-related eye disorder is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with ectopia lentis and/or pupillary displacement or those in whom the diagnosis of an ADAMTSL4-related eye disorder has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic findings suggest the diagnosis of an ADAMTSL4-related eye disorder, molecular genetic testing approaches can include single-gene testing or use of a multigene panel.
* Single-gene testing. Sequence analysis of ADAMTSL4 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found gene-targeted deletion/duplication analysis can be considered; however, to date no large deletions or complex rearrangements involving ADAMTSL4 have been reported.
* A multigene panel that includes ADAMTSL4 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other inherited disorders characterized by ectopia lentis and/or pupillary displacement or if the diagnosis of an ADAMTSL4-related eye disorder is not considered because an individual has atypical phenotypic features comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in ADAMTSL4-Related Eye Disorders
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
ADAMTSL4Sequence analysis 3100% 4
Gene-targeted deletion/duplication analysis 5None reported 4
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Overwater et al [2017]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
## Clinical Characteristics
### Clinical Description
The spectrum of ADAMTSL4-related eye disorders is a continuum that includes the phenotypes known as autosomal recessive isolated ectopia lentis and ectopia lentis et pupillae as well as more minor eye anomalies with no displacement of the pupil and very mild displacement of the lens. Variability in the eye findings described in detail in Diagnosis is observed among affected individuals in a family and even between eyes in the same individual.
Presentation. The diagnosis of ectopia lentis is usually made in early childhood although dislocation of the lens may be present at birth [Neuhann et al 2011]. When ectopia lentis is accompanied by severe ectopia pupillae, the diagnosis is usually made at birth; in mild cases, the findings may not be recognized until adulthood. The clinical presentation in ADAMTSL4-related eye disorders is considered to be more severe than that seen in individuals with other nonsyndromic forms of ectopia lentis [Chandra et al 2012].
Refractive errors are common:
* Hyperopia (+5 D to +15 D) occurs when the lens is dislocated out of the visual axis resulting in a functionally aphakic eye.
* Myopia (-5 D to >-15 D) may result from increased axial growth of the eye, or because of abnormalities like spherophakia and lens coloboma.
* Various degrees of astigmatism, sometimes quite large, are frequently observed.
In children, uncorrected refractive errors and anisometropia (unequal refractive errors between the two eyes) may lead to amblyopia. One study found that the risk for amblyopia was highest when the lens was still covering the visual axis and the edge of the lens was within 0.3-2.3 mm of the center of the pupil [Romano et al 2002].
Cataract can be seen at an early age. In the study by Christensen et al [2010], all affected individuals older than age 45 years had undergone cataract surgery.
Elevated intraocular pressure (IOP) is seen in up to 20%-25% of affected individuals [Christensen et al 2010, Neuhann et al 2011]. In the event of anterior subluxation of the lens, an acute rise in intraocular pressure may occur. Of note, the central corneal thickness can be increased (median value 589 μm; range 528-630 μm) [Christensen et al 2010], which may explain, to some extent, why some individuals have moderately elevated intraocular pressure, but few have glaucomatous damage of the optic nerve head.
Retinal detachment occurs more frequently than in the general population; in some individuals retinal detachment as well as elevated IOP could be the consequence of lensectomy or cataract surgery [Christensen et al 2010, Neuhann et al 2015, Overwater et al 2017].
Progression of the lens displacement and development of cataract may occur over time, whereas the pupillary displacement is fairly stable.
Visual acuity varies from light perception to 20/20 depending on the degree of amblyopia, the presence of cataract, or sequelae after retinal detachment or glaucoma. Surprisingly, some individuals with highly displaced pupils may have normal visual acuity.
Non-ocular findings. Individuals with ADAMTSL4-related eye disorders have, in general, no additional systemic manifestations although there have been some reports of skeletal features including craniosynostosis, pes planus, pectus carinatum, scoliosis, and/or joint laxity in a few affected individuals [Christensen et al 2010, Chandra et al 2013a, Overwater et al 2017].
### Genotype-Phenotype Correlations
No genotype-phenotype correlations have been noted.
* The phenotype may vary significantly from one individual to another within a family.
* The phenotype may vary significantly between eyes in the same individual.
* The same pathogenic variant can be associated with ectopia lentis and ectopia lentis et pupillae.
### Prevalence
In studies of individuals with nonsyndromic ectopia lentis, the proportion of those having a pathogenic variant in ADAMTSL4 ranges from 0% in a group of Chinese individuals to 50% in several groups of European individuals [Aragon-Martin et al 2010, Chandra et al 2012, Li et al 2014, Overwater et al 2017, van Bysterveldt et al 2017].
Pathogenic variants frequently associated with ADAMTSL4-related eye disorders vary across populations. The ADAMTSL4 c.767_786del pathogenic variant is common across Europe and probably represents a founder variant. In western Norway, three of 190 blood donors were heterozygous for this variant, suggesting that the frequency of homozygous individuals in this population is around 1:16,000 (with wide confidence intervals) [Christensen et al 2010].
In a German study, two of 360 ethnically matched anonymous individuals were heterozygous for this pathogenic variant [Neuhann et al 2011].
In Polynesians (Maori) the c.2237G>A (p.Arg746His) variant is common with an observed frequency in carriers of 1:132 [van Bysterveldt et al 2017]. In Bukharian Jews originating from Kazakhstan and Tajikistan, the most common variant is c.2594G>A (p.Arg865His; reported as c.2663G>A [p.Arg888His]) with a carrier frequency of 1:48 predicting a frequency of homozygous individuals around 1:9,000 [Reinstein et al 2016].
## Differential Diagnosis
### Table 2.
Disorders with Ectopia Lentis and/or Iris Anomalies to Consider in the Differential Diagnosis of ADAMTSL4-Related Eye Disorders
View in own window
DisorderGene(s)MOIDistinguishing Clinical Features of This Disorder
Ectopia lentis
(OMIM 129600)FBN1 1ADMay be accompanied by the systemic features of Marfan syndrome
Homocystinuria caused by cystathionine beta-synthase deficiencyCBSAR
* Tall, thin stature
* High-arched feet
* Chest anomalies
* Intellectual disability
* Seizures
* Arterial atheroma formation
Isolated sulfite oxidase deficiencySUOXAR
* Seizures
* Ataxia
* Dystonia
* Choreoathetotic movements
Weill-Marchesani syndrome (WMS)ADAMTS10
FBN1
LTPBP2AD 2
AR 2
* Proportionate short stature
* Brachydactyly
* Joint stiffness
WMS-like syndrome
(OMIM 613195)ADAMTS17ARBrachydactyly
MSPKA
(OMIM 251750)LTBP2AR
* Megalocornea
* Glaucoma
* Microspherophakia
* Axial myopia
* Marfanoid features
AniridiaPAX6AD
* Iris hypoplasia
* Foveal dysplasia
* Optic nerve hypoplasia
* Nystagmus
Axenfeld-Rieger syndrome type 1
(OMIM 180500)PITX2AD
* Embryotoxon posterior
* Iridocorneal adhesions
* Iris anomalies
Iridocorneal endothelial syndrome 3NA 4NA 4
* Corneal edema
* Corneal endothelial irregularities
* Polycoria
* Iris nevus
Iris coloboma>30AD
AR
XLVariable 5
Anterior segment dysgeneses
(OMIM PS107250)CPAMD8
CYP1B1
FOXC1
FOXE3
PAX6
PITX2
PITX3
PXDNAD
AR
* Microphthalmia
* Embryotoxon posterior
* Corneal opacities
* Sclerocornea
* Iris hypoplasia
* Iridocorneal adhesions
* Glaucoma
Posterior polymorphous corneal dystrophy
(OMIM PS122000)COL8A2
OVOL2
ZEB1AD
* Posterior corneal opacities
* Iridocorneal adhesions
* Glaucoma
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; MSPKA = microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma; XL= X-linked
1\.
Ectopia lentis most frequently occurs as an autosomal dominant disorder in association with pathogenic variants in FBN1 (OMIM 134797) that may (OMIM 154700) or may not (OMIM 129600) be accompanied by the systemic features of Marfan syndrome.
2\.
Pathogenic variants in ADAMTS10 are known to cause autosomal recessive WMS. Biallelic pathogenic variants in LTPBP2 have been reported in one family with autosomal recessive inheritance [Haji-Seyed-Javadi et al 2012]. A heterozygous pathogenic variant in FBN1 has been identified in one family with autosomal dominant WMS [Faivre et al 2003].
3\.
Silva et al [2018]
4\.
This is an acquired disorder and rarely seen in children.
5\.
There are many genes associated with iris coloboma, and accompanying features can be quite complex.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and the needs of an individual diagnosed with an ADAMTSL4-related eye disorder, routine ophthalmologic examination that includes the following is recommended if it has not already been completed:
* Determination of visual acuity and refractive error
* Measurement of intraocular pressure
Note: Affected individuals may have increased central corneal thickness that could explain, to some extent, why some individuals have moderately elevated intraocular pressure, but few have glaucomatous damage of the optic nerve head.
* Slit lamp examination
* Dilated fundus examination
The following may also provide important information:
* Orthoptic examination, particularly in children
* Measurement of axial length
* Anterior segment examination with optical coherence tomography and in selected individuals ultrasound biomicroscopy
* Corneal topography including measurement of corneal diameter and central corneal thickness
* Gonioscopy
Consultation with a clinical geneticist and/or genetic counselor is also recommended.
### Treatment of Manifestations
Refractive errors. In children, the main objective is to prevent amblyopia by early correction of refractive errors. Patching is necessary when correction of the refractive error is insufficient in restoring vision.
Lens abnormality. Surgery should be considered in individuals with cataracts, those at risk for complications caused by the dislocated lens (e.g., endocorneal contact, pupillary block), those in whom patching does not result in improvement of visual acuity, those in whom the lens edge is in the middle of the pupil, and those with insufficient correction of refractive errors, in particular large degrees of astigmatism [Anteby et al 2003, Wu-Chen et al 2005]. Surgery is rarely needed in children. Most individuals undergoing surgery are adolescents or young adults. Following lens removal, improvement of visual acuity has been observed even in individuals older than age seven years [Speedwell & Russell-Eggitt 1995].
In the past, lensectomy with anterior vitrectomy and correction of the aphakia with contact lenses or secondary intraocular lens (IOL) replacement has been the usual procedure. More recently, capsule-sparing lens surgery has been introduced. "Bag in the lens" (BIL) IOL implantation combined with capsular rings or lasso suture is an efficient procedure for the treatment of lens dislocation [Boonstra 2019]. Should BIL fail, the authors suggest removing the capsule and implanting a three-piece IOL by the technique described by Yamane et al [2017], at least in individuals from age four to five years and older.
Surgical treatment must be weighed against loss of accommodation and the risk for secondary glaucoma and retinal detachment. Aphakia correction in children imposes challenges with respect to the use of contact lenses and IOL implantation, particularly in individuals with unilateral involvement. Special care should be taken in the youngest children (age <2 years) as the growth of the eye will give a myopic shift. All surgical procedures should therefore be planned individually by an experienced ophthalmic surgeon [Hoffman et al 2013].
Pupil displacement. Sphincterotomy (widening of the pupil by incision of the iris at the pupillary margin) can benefit individuals with small and highly displaced pupils.
Increased intraocular pressure can in most cases be controlled by topical anti-glaucoma medication.
Retinal detachment. It is not clear if pathogenic variants in ADAMTSL4 increase the risk for retinal detachment. However, after lensectomy or cataract surgery, retinal detachment may occur. If typical signs (e.g., floaters, lightning, a diminished visual field) appear, evaluation by an ophthalmologist should be sought as soon as possible. Treatment of retinal detachment is by standard techniques using vitrectomy and scleral buckling if necessary. It is important to examine the fellow eye for retinal degeneration.
### Surveillance
Assess visual acuity, refractive error, and intraocular pressure one to three times per year: adults who are stable may be examined yearly, whereas children require more frequent examinations. Ultrasonography may be necessary to evaluate for retinal detachment if the view of the fundus is limited.
### Agents/Circumstances to Avoid
Care must be taken during contact sports to avoid blunt trauma to the eye and head. Affected individuals should not participate in activities like boxing or martial arts.
### Evaluation of Relatives at Risk
Sibs of a proband with an ADAMTSL4-related eye disorder should undergo complete ophthalmologic evaluation (determination of visual acuity, measurement of intraocular pressure, slit lamp examination, and ophthalmoscopy) to allow for early diagnosis and treatment of findings, primarily to prevent amblyopia.
If the pathogenic variants in a family are known, molecular genetic testing is likely to be more helpful than clinical examination in clarifying the genetic status of at-risk sibs, given the wide phenotypic variability even within the same family.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
ADAMTSL4-Related Eye Disorders
|
None
| 25,543 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK84111/
| 2021-01-18T21:45:36 |
{"synonyms": []}
|
A number sign (#) is used with this entry because X-linked syndromic mental retardation-14 (MRXS14) is caused by mutation in the UPF3B gene (300298), which is involved in nonsense-mediated decay of mRNA transcripts, on chromosome Xq24. Some patients have nonsyndromic mental retardation.
Clinical Features
Tarpey et al. (2007) reported 4 unrelated families with X-linked mental retardation. Although the phenotype was variable, common features included mild to severe mental retardation, autistic features, slender build, poor musculature, long, thin face, high-arched palate, high nasal bridge, and pectus deformities. Two families had been diagnosed as having Lujan-Fryns syndrome (309520) and 1 as having Opitz-Kaveggia syndrome (OKS; 305450). One of the families had been reported by Graham et al. (1998).
Xu et al. (2013) reported a large Chinese family in which 3 living males and 1 deceased male had nonsyndromic mild mental retardation. None of the affected individuals was known to have additional physical abnormalities. Carrier females were unaffected.
Inheritance
The transmission pattern of mental retardation in the families reported by Tarpey et al. (2007) and Xu et al. (2013) was consistent with X-linked recessive inheritance.
Molecular Genetics
In affected members of 4 unrelated families with X-linked syndromic mental retardation, Tarpey et al. (2007) identified hemizygous mutations in the UPF3B gene (300298.0001-300298.0004).
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation. They identified 3 separate nonrecurring truncating mutations in UPF3B that segregated absolutely with the phenotype. In addition to the X-linked mental retardation, affected family members had elements of the Opitz-Kaveggia and Lujan-Fryns syndromes.
By exome sequencing of a Chinese family with nonsyndromic X-linked mental retardation, Xu et al. (2013) identified a hemizygous mutation in the UPF3B gene (R430X; 300298.0003). X-chromosome inactivation studies in 3 carrier mothers showed that only 18%, 17%, and 13% of lymphocytes, respectively, expressed the mutant allele. PCR analysis of patient cells showed decreased levels of mutant mRNA in the patients, suggesting that it undergoes nonsense-mediated mRNA decay. Patient cells showed higher expression of the GADD45B gene (604948), a component of the classical nonsense-mediated decay pathway compared to controls, suggesting that the UPF3B mutation caused dysregulation of this pathway.
INHERITANCE \- X-linked recessive GROWTH Height \- Tall, thin habitus HEAD & NECK Head \- Macrocephaly Face \- Long, thin face \- Prominent forehead \- Maxillary hypoplasia \- Prominent jaw Nose \- High nasal bridge Mouth \- High-arched palate CHEST External Features \- Pectus excavatum \- Pectus carinatum \- Narrow chest SKELETAL Spine \- Kyphosis \- Scoliosis Hands \- Long hands \- Long fingers Feet \- Long feet MUSCLE, SOFT TISSUES \- Poor musculature NEUROLOGIC Central Nervous System \- Mental retardation, mild to severe Behavioral Psychiatric Manifestations \- Autistic features VOICE \- Hypernasal voice MOLECULAR BASIS \- Caused by mutation in the UPF3, B, yeast homolog gene (UPF3B, 300298.0001 ) ▲ 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
|
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
|
c0796022
| 25,544 |
omim
|
https://www.omim.org/entry/300676
| 2019-09-22T16:19:50 |
{"doid": ["0060821"], "mesh": ["C537724"], "omim": ["300676"], "orphanet": ["776"]}
|
A number sign (#) is used with this entry because of evidence that peeling skin syndrome-3 (PSS3) is caused by mutation in the carbohydrate sulfotransferase-8 (CHST8; 610190) gene on chromosome 19q13. One such family has been reported.
Description
Peeling skin syndrome-3 is characterized by asymptomatic lifelong and continuous shedding of the stratum corneum of the epidermis. Symptoms start during the second half of the first decade of life and consist of generalized white scaling occurring over the upper and lower extremities (Cabral et al. (2012)).
For a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).
Clinical Features
Cabral et al. (2012) described a 4-generation consanguineous Pakistani family with peeling skin syndrome. The 7 affected family members exhibited features of noninflammatory, painless peeling skin evidenced by generalized white scaling, most prominent over the upper and lower limbs. Their hair was normal. Affected individuals did not have a history of erythema, pruritis, or atopy; however, they reported irritation when in contact with water, dust, or sand.
Inheritance
The consanguineous Pakistani family described by Cabral et al. (2012) segregated autosomal recessive peeling skin syndrome.
Mapping
By SNP genomic mapping and microsatellite linkage analysis, Cabral et al. (2012) mapped PSS3 with a lod score of 10.9 to a 16-Mb region on chromosome 19q13 flanked by markers D19S414 and D19S412.
Molecular Genetics
Cabral et al. (2012) performed whole-exome sequencing on a single affected family member with PSS3 and identified a homozygous variant in exon 4 of the CHST8 gene, resulting in an arg227-to-trp (R77W) substitution (610190.0001). The variant was not present in any public databases or in 400 chromosomes from 200 unrelated healthy controls. By Sanger sequencing, Cabral et al. (2012) identified the same mutation in homozygous state in the other 6 affected family members and in heterozygous state in carrier individuals, demonstrating complete cosegregation of the mutation with the phenotype.
INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- White scaling skin, most prominent over upper and lower extremities \- No erythema \- No pruritis Hair \- Normal hair MISCELLANEOUS \- Onset in second half of the first decade of life \- One consanguineous Pakistani family has been described (last curated March 2015) MOLECULAR BASIS \- Caused by mutation in the carbohydrate sulfotransferase 8 gene (CHST8, 610190.0001 ) ▲ 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
|
PEELING SKIN SYNDROME 3
|
c1849193
| 25,545 |
omim
|
https://www.omim.org/entry/616265
| 2019-09-22T15:49:27 |
{"mesh": ["C564818"], "omim": ["270300", "616265", "618084"], "orphanet": ["263548", "263543"], "synonyms": ["PSS type A", "Non-inflammatory peeling skin syndrome type A", "Generalized deciduous skin", "Generalized deciduous skin type A", "Non-inflammatory generalized peeling skin syndrome type A.", "Generalized PSS", "Generalized peeling skin syndrome type A"]}
|
A rare genetic skin disease characterized by childhood onset of follicular keratotic papules slowly progressing to characteristic ''honeycomb'' atrophy on the cheeks, preauricular area, and forehead. Less frequently, the condition may affect also the upper lip, ears, or limbs. Additional features include facial erythema, milia, and follicular plugs.
*[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
|
Atrophoderma vermiculata
|
c0263429
| 25,546 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79100
| 2021-01-23T18:11:03 |
{"gard": ["9744"], "mesh": ["C537412"], "omim": ["209700", "604093"], "umls": ["C0263429"], "icd-10": ["L66.4"], "synonyms": ["Folliculitis ulerythematosa reticulate"]}
|
A number sign (#) is used with this entry because resistance to systemic lupus erythematosus is associated with a polymorphism in the Toll-like receptor-5 gene (TLR5; 603031).
Mapping
The genetic basis for systemic lupus erythematosus (SLE; 152700) is complex. Tsao et al. (1997) cited reports demonstrating that certain MHC class II alleles, as well as homozygosity for deficiency of complement genes C1Q (120550), C2 (613927), and C4 (120810), are associated with SLE in most ethnic groups studied. Polymorphism of the FCGR2A gene (146790) has been associated with the glomerulonephritis of SLE in some studies and possible linkage of the locus with lupus identified. Tsao et al. (1997) tested a candidate region on human 1q homologous to a murine SLE susceptibility region identified in NZB mice. They found that the tested markers located on 1q41-q42 showed linkage to SLE, as well as to the presence of IgG antichromatin antibodies. They studied a total of 43 families having at least 2 sibs with SLE. There were 52 affected sib pairs. Thirty families were from southern California, 8 from Taiwan, 2 from England, 2 from China, and 1 from Korea. Tsao et al. (1997) concluded that the 1q41-q42 region probably contains a susceptibility gene that confers risk for SLE in multiple ethnic groups. Kotzin (1997) reviewed their findings. He stated that the homologous locus on distal mouse chromosome 1 is termed Nba2 for 'New Zealand black autoimmunity-2.' Nba2 appears to be the most important non-MHC locus linked to nephritis and death in NZB mice. He commented that future analysis of a separate group of lupus families will be necessary to confirm whether there is a locus at 1q41-q42 with strong contributions to disease risk.
Moser et al. (1998) screened the human genome for linkage to SLE in 94 pedigrees containing 220 affecteds and 533 total subjects. The 31 African American and 55 European American pedigrees were analyzed separately as well as combined into a total collection of 94 pedigrees. They reported evidence for linkage to 16 potential SLE susceptibility loci, including a lod score of 3.37 in African Americans for the FCGR2A polymorphism (R131H; 146790.0001) on 1q23, previously shown to be associated with lupus nephritis in African Americans. Linkage to several other loci, including SLEB1, was found in African Americans, in European-Americans, and in all pedigrees combined.
Molecular Genetics
### Resistance to Systemic Lupus Erythematosus
TLR5, the innate immune receptor for bacterial flagellin, maps to chromosome 1q41 and contains a common 1147C-T polymorphism that encodes a premature stop codon (R392X; 603031.0001) associated with increased susceptibility to Legionnaire disease (608556). Using transmission disequilibrium testing in an SLE cohort containing 199 affected patients and their 75 unaffected sibs and 326 parents, Hawn et al. (2005) found that allele 1174C of TLR5, but not allele 1174T, which encodes the premature stop codon, was preferentially transmitted to SLE-affected offspring. Alleles of 3 other TLR5 SNPs were not preferentially transmitted. The allele frequency of 1174T in probands was 3.2% compared with 5.8% in unaffected individuals, consistent with a protective association. Individuals with the TLR5 stop codon produced significantly lower levels of proinflammatory cytokines than individuals with the wildtype genotype. Hawn et al. (2005) concluded that the TLR5 stop codon polymorphism is associated with resistance to SLE development, particularly in those seronegative for anti-dsDNA autoantibodies. They proposed that flagellated bacteria and the innate immune response may have a role in SLE development.
Animal Model
Mohan et al. (1998) pursued genetic studies in the NZM2410 lupus strain of mice that had implicated genomic intervals on chromosomes 1 (Sle1), 4 (Sle2), and 7 (Sle3) as conferring strong lupus susceptibility. B6 mice that were congenic for Sle1 had elevated IgG antichromatin antibodies. Mohan et al. (1998) explored the antinuclear antibody fine specificities and underlying cellular defects in these mice. On the B6 background, Sle1 by itself was sufficient to generate a strong, spontaneous, humoral antinuclear antibody (ANA) response, staining Hep-2 nuclei homogeneously and reacting primarily with H2A/H2B/DNA subnucleosomes. Sle1 also led to an expanded pool of histone-reactive T cells. Mohan et al. (1998) hypothesized that Sle1 may lead to the presentation of chromatin in an immunogenic fashion or directly impact tolerance of chromatin-specific B cells. They commented on the work of Tsao et al. (1997) demonstrating in human lupus a chromosome 1 interval (syntenic to murine Sle1) that is linked to high-serum IgG antichromatin ANAs. They suggested that all of these studies advance Sle1 on murine chromosome 1 as a major player in orchestrating selective loss of B-cell and T-cell tolerance to chromatin. This is in sharp contrast to the more generalized (not nuclear antigen restricted) immunophenotypes that Sle2 and Sle3 lead to. The process of generating congenic recombinants and screening them for anti-H2A/H2B/DNA antibodies should allow investigators to narrow the Sle1 interval and permit positional cloning of the causative gene. They stated that 'until then, one thing seems certain: Enshrouded in the Sle1 interval is the quintessential lupus gene responsible for the 'L.E.' phenomenon Hargraves discovered 50 years ago.'
In a fine-mapping analysis of the location of Sle1 on the mouse chromosome, Morel et al. (2001) determined that 3 loci within this congenic interval, termed Sle1a, Sle1b, and Sle1c, can independently cause a loss of tolerance to chromatin, a necessary step for full disease induction. The epistatic interactions of Sle1 with other susceptibility loci to cause severe nephritis cannot be accounted for, however, by these 3 loci alone, suggesting the existence of an additional locus, termed Sle1d.
Kumar et al. (2006) noted that the z allele of Sle1 and its component sublocus Sle1b, derived from a lupus-prone mouse strain, are linked to a variety of lupus-related disease phenotypes, including antinuclear antibodies, splenomegaly, and glomerulonephritis. SLAM gene family members are located within the Sle1bz sublocus and have been linked to murine spontaneous lupus. Analysis of mice expressing Sle1z/Sle1bz showed impaired B-cell anergy, receptor revision, and deletion. Among SLAM family members, the Ly108.1 isoform of Ly108 (SLAMF6; 606446) was most highly expressed in immature B cells from lupus-prone Sle1z mice. The normal allele, Ly108.2, but not Ly108.1, sensitized immature B cells to deletion and Rag (see 179615) reexpression. Kumar et al. (2006) concluded that some of the genes causing murine lupus may function by crippling multiple B-cell tolerance mechanisms. They suggested that Ly108 isoforms may function as molecular rheostats, determining the stringency with which self-reactive B cells are censored during early development.
*[v]: View this template
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
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*[NC]: neurogenic claudication
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*[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
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*[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
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*[LH]: luteinizing hormone
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*[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
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*[XO]: Xanthine oxidase
*[[*]]: Article is not yet available in this wiki.
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*[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
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*[m.]: married
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*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
|
SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 1
|
c1866373
| 25,547 |
omim
|
https://www.omim.org/entry/601744
| 2019-09-22T16:14:22 |
{"omim": ["601744"]}
|
Neurological impairment of voluntary muscle movement
For other uses, see Ataxia (disambiguation).
Ataxia
SpecialtyNeurology, Psychiatry
Symptoms
* Lack of coordination
* Slurred speech
* Trouble eating and swallowing
* Deterioration of fine motor skills
* Difficulty walking
* Gait abnormalities
* Eye movement abnormalities
* Tremors
* Heart problems
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum. Ataxia can be limited to one side of the body, which is referred to as hemiataxia. Several possible causes exist for these patterns of neurological dysfunction. Dystaxia is a mild degree of ataxia. Friedreich's ataxia has gait abnormality as the most commonly presented symptom.[1] The word is from Greek α- [a negative prefix] + -τάξις [order] = "lack of order".
## Contents
* 1 Types
* 1.1 Cerebellar
* 1.2 Sensory
* 1.3 Vestibular
* 2 Causes
* 2.1 Focal lesions
* 2.2 Exogenous substances (metabolic ataxia)
* 2.3 Radiation poisoning
* 2.4 Vitamin B12 deficiency
* 2.5 Hypothyroidism
* 2.6 Causes of isolated sensory ataxia
* 2.7 Non-hereditary cerebellar degeneration
* 2.8 Hereditary ataxias
* 2.9 Arnold–Chiari malformation (congenital ataxia)
* 2.10 Succinic semialdehyde dehydrogenase deficiency
* 2.11 Wilson's disease
* 2.12 Gluten ataxia
* 2.13 Potassium pump
* 2.14 Cerebellar ataxia associated with anti-GAD antibodies
* 3 Diagnosis
* 4 Treatment
* 5 Other uses
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Types[edit]
### Cerebellar[edit]
See also: Cerebellar ataxia
The term cerebellar ataxia is used to indicate ataxia due to dysfunction of the cerebellum.[2] The cerebellum is responsible for integrating a significant amount of neural information that is used to coordinate smoothly ongoing movements and to participate in motor planning. Although ataxia is not present with all cerebellar lesions, many conditions affecting the cerebellum do produce ataxia.[3] People with cerebellar ataxia may have trouble regulating the force, range, direction, velocity, and rhythm of muscle contractions.[4] This results in a characteristic type of irregular, uncoordinated movement that can manifest itself in many possible ways, such as asthenia, asynergy, delayed reaction time, and dyschronometria.[5] Individuals with cerebellar ataxia could also display instability of gait, difficulty with eye movements, dysarthria, dysphagia, hypotonia, dysmetria, and dysdiadochokinesia.[3] These deficits can vary depending on which cerebellar structures have been damaged, and whether the lesion is bi- or unilateral.
People with cerebellar ataxia may initially present with poor balance, which could be demonstrated as an inability to stand on one leg or perform tandem gait. As the condition progresses, walking is characterized by a widened base and high stepping, as well as staggering and lurching from side to side.[3] Turning is also problematic and could result in falls. As cerebellar ataxia becomes severe, great assistance and effort are needed to stand and walk.[3] Dysarthria, an impairment with articulation, may also be present and is characterized by "scanning" speech that consists of slower rate, irregular rhythm, and variable volume.[3] Also, slurring of speech, tremor of the voice, and ataxic respiration may occur. Cerebellar ataxia could result with incoordination of movement, particularly in the extremities. Overshooting (or hypermetria) occurs with finger-to-nose testing and heel to shin testing; thus, dysmetria is evident.[3][6] Impairments with alternating movements (dysdiadochokinesia), as well as dysrhythmia, may also be displayed. Tremor of the head and trunk (titubation) may be seen in individuals with cerebellar ataxia.[3]
Dysmetria is thought to be caused by a deficit in the control of interaction torques in multijoint motion.[7] Interaction torques are created at an associated joint when the primary joint is moved. For example, if a movement required reaching to touch a target in front of the body, flexion at the shoulder would create a torque at the elbow, while extension of the elbow would create a torque at the wrist. These torques increase as the speed of movement increases and must be compensated and adjusted for to create coordinated movement. This may, therefore, explain decreased coordination at higher movement velocities and accelerations.
* Dysfunction of the vestibulocerebellum (flocculonodular lobe) impairs balance and the control of eye movements. This presents itself with postural instability, in which the person tends to separate his/her feet upon standing, to gain a wider base and to avoid titubation (bodily oscillations tending to be forward-backward ones). The instability is, therefore, worsened when standing with the feet together, regardless of whether the eyes are open or closed. This is a negative Romberg's test, or more accurately, it denotes the individual's inability to carry out the test, because the individual feels unstable even with open eyes.[citation needed]
* Dysfunction of the spinocerebellum (vermis and associated areas near the midline) presents itself with a wide-based "drunken sailor" gait (called truncal ataxia),[8] characterised by uncertain starts and stops, lateral deviations, and unequal steps. As a result of this gait impairment, falling is a concern in patients with ataxia. Studies examining falls in this population show that 74–93% of patients have fallen at least once in the past year and up to 60% admit to fear of falling.[9][10]
* 'Dysfunction of the cerebrocerebellum' (lateral hemispheres) presents as disturbances in carrying out voluntary, planned movements by the extremities (called appendicular ataxia).[8] These include:
* Intention tremor (coarse trembling, accentuated over the execution of voluntary movements, possibly involving the head and eyes, as well as the limbs and torso)
* Peculiar writing abnormalities (large, unequal letters, irregular underlining)
* A peculiar pattern of dysarthria (slurred speech, sometimes characterised by explosive variations in voice intensity despite a regular rhythm)
* Inability to perform rapidly alternating movements, known as dysdiadochokinesia, occurs, and could involve rapidly switching from pronation to supination of the forearm. Movements become more irregular with increases of speed.[11]
* Inability to judge distances or ranges of movement happens. This dysmetria is often seen as undershooting, hypometria, or overshooting, hypermetria, the required distance or range to reach a target. This is sometimes seen when a patient is asked to reach out and touch someone's finger or touch his or her own nose.[11]
* The rebound phenomenon, also known as the loss of the check reflex, is also sometimes seen in patients with cerebellar ataxia, for example, when patients are flexing their elbows isometrically against a resistance. When the resistance is suddenly removed without warning, the patients' arms may swing up and even strike themselves. With an intact check reflex, the patients check and activate the opposing triceps to slow and stop the movement.[11]
* Patients may exhibit a constellation of subtle to overt cognitive symptoms, which are gathered under the terminology of Schmahmann's syndrome.[12]
### Sensory[edit]
The term sensory ataxia is used to indicate ataxia due to loss of proprioception, the loss of sensitivity to the positions of joint and body parts. This is generally caused by dysfunction of the dorsal columns of the spinal cord, because they carry proprioceptive information up to the brain. In some cases, the cause of sensory ataxia may instead be dysfunction of the various parts of the brain that receive positional information, including the cerebellum, thalamus, and parietal lobes.
Sensory ataxia presents itself with an unsteady "stomping" gait with heavy heel strikes, as well as a postural instability that is usually worsened when the lack of proprioceptive input cannot be compensated for by visual input, such as in poorly lit environments.
Physicians can find evidence of sensory ataxia during physical examination by having patients stand with their feet together and eyes shut. In affected patients, this will cause the instability to worsen markedly, producing wide oscillations and possibly a fall; this is called a positive Romberg's test. Worsening of the finger-pointing test with the eyes closed is another feature of sensory ataxia. Also, when patients are standing with arms and hands extended toward the physician, if the eyes are closed, the patients' fingers tend to "fall down" and then be restored to the horizontal extended position by sudden muscular contractions (the "ataxic hand").
### Vestibular[edit]
The term vestibular ataxia is used to indicate ataxia due to dysfunction of the vestibular system, which in acute and unilateral cases is associated with prominent vertigo, nausea, and vomiting. In slow-onset, chronic bilateral cases of vestibular dysfunction, these characteristic manifestations may be absent, and dysequilibrium may be the sole presentation.
## Causes[edit]
The three types of ataxia have overlapping causes, so can either coexist or occur in isolation. Cerebellar ataxia can have many causes despite normal neuroimaging.
### Focal lesions[edit]
Any type of focal lesion of the central nervous system (such as stroke, brain tumor, multiple sclerosis, inflammatory [such as sarcoidosis], and "chronic lymphocytyc inflammation with pontine perivascular enhancement responsive to steroids syndrome" [CLIPPERS[13]]) will cause the type of ataxia corresponding to the site of the lesion: cerebellar if in the cerebellum; sensory if in the dorsal spinal cord...to include cord compression by thickened ligamentum flavum or stenosis of the boney spinal canal...(and rarely in the thalamus or parietal lobe); or vestibular if in the vestibular system (including the vestibular areas of the cerebral cortex).
### Exogenous substances (metabolic ataxia)[edit]
Exogenous substances that cause ataxia mainly do so because they have a depressant effect on central nervous system function. The most common example is ethanol (alcohol), which is capable of causing reversible cerebellar and vestibular ataxia. Other examples include various prescription drugs (e.g. most antiepileptic drugs have cerebellar ataxia as a possible adverse effect), Lithium level over 1.5mEq/L, synthetic cannabinoid HU-211 ingestion[14] and various other medical and recreational drugs (e.g. ketamine, PCP or dextromethorphan, all of which are NMDA receptor antagonists that produce a dissociative state at high doses). A further class of pharmaceuticals which can cause short term ataxia, especially in high doses, are benzodiazepines.[15][16] Exposure to high levels of methylmercury, through consumption of fish with high mercury concentrations, is also a known cause of ataxia and other neurological disorders.[17]
### Radiation poisoning[edit]
Ataxia can be induced as a result of severe acute radiation poisoning with an absorbed dose of more than 30 grays.
### Vitamin B12 deficiency[edit]
Vitamin B12 deficiency may cause, among several neurological abnormalities, overlapping cerebellar and sensory ataxia.
### Hypothyroidism[edit]
Symptoms of neurological dysfunction may be the presenting feature in some patients with hypothyroidism. These include reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Most of the neurological complications improve completely after thyroid hormone replacement therapy.[18][19]
### Causes of isolated sensory ataxia[edit]
Peripheral neuropathies may cause generalised or localised sensory ataxia (e.g. a limb only) depending on the extent of the neuropathic involvement. Spinal disorders of various types may cause sensory ataxia from the lesioned level below, when they involve the dorsal columns.[20][21][22]
### Non-hereditary cerebellar degeneration[edit]
Non-hereditary causes of cerebellar degeneration include chronic alcohol abuse, head injury, paraneoplastic and non-paraneoplastic autoimmune ataxia,[23][24][25] high altitude cerebral oedema, coeliac disease, normal pressure hydrocephalus and infectious or post-infectious cerebellitis.
### Hereditary ataxias[edit]
Ataxia may depend on hereditary disorders consisting of degeneration of the cerebellum or of the spine; most cases feature both to some extent, and therefore present with overlapping cerebellar and sensory ataxia, even though one is often more evident than the other. Hereditary disorders causing ataxia include autosomal dominant ones such as spinocerebellar ataxia, episodic ataxia, and dentatorubropallidoluysian atrophy, as well as autosomal recessive disorders such as Friedreich's ataxia (sensory and cerebellar, with the former predominating) and Niemann Pick disease, ataxia-telangiectasia (sensory and cerebellar, with the latter predominating), and abetalipoproteinaemia. An example of X-linked ataxic condition is the rare fragile X-associated tremor/ataxia syndrome or FXTAS.
### Arnold–Chiari malformation (congenital ataxia)[edit]
Arnold–Chiari malformation is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of cerebrospinal fluid outflow.
### Succinic semialdehyde dehydrogenase deficiency[edit]
Succinic semialdehyde dehydrogenase deficiency is an autosomal-recessive gene disorder where mutations in the ALDH5A1 gene results in the accumulation of gamma-Hydroxybutyric acid (GHB) in the body. GHB accumulates in the nervous system and can cause ataxia as well as other neurological dysfunction.[26]
### Wilson's disease[edit]
Wilson's disease is an autosomal-recessive gene disorder whereby an alteration of the ATP7B gene results in an inability to properly excrete copper from the body.[27] Copper accumulates in the nervous system and liver and can cause ataxia as well as other neurological and organ impairments.[28]
### Gluten ataxia[edit]
Play media
A male with gluten ataxia: previous situation and evolution after three months of a gluten-free diet
Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten.[29][30] Early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression. The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of neurons in the cerebellum as a result of gluten exposure is irreversible.[29][31] It accounts for 40% of ataxias of unknown origin and 15% of all ataxias.[31] Less than 10% of people with gluten ataxia present any gastrointestinal symptom, yet about 40% have intestinal damage.[29][31] In some cases, the immune ataxia remains of unknown origin and lacks biomarkers. This entity is called primary auto-immune ataxia (PACA).[32]
### Potassium pump[edit]
Malfunction of the sodium-potassium pump may be a factor in some ataxias. The Na+
-K+
pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons.[33] This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the cerebellum and the brain.[34] Indeed, an ouabain block of Na+
-K+
pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia.[35] Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations.
### Cerebellar ataxia associated with anti-GAD antibodies[edit]
Antibodies against the enzyme glutamic acid decarboxylase (GAD: enzyme changing glutamate into GABA) cause cerebellar deficits.[36] The antibodies impair motor learning and cause behavioral deficits.[37] GAD antibodies related ataxia is part of the group called immune-mediated cerebellar ataxias.[38] The antibodies induce a synaptopathy.[39] The cerebellum is particularly vulnerable to autoimmune disorders. [40] Cerebellar circuitry has capacities to compensate and restore function thanks to cerebellar reserve, gathering multiple forms of plasticity. LTDpathies gather immune disorders targetting long-term depression (LTD), a form of plasticity.
## Diagnosis[edit]
* Imaging studies - A CT scan or MRI of the brain might help determine potential causes. An MRI can sometimes show shrinkage of the cerebellum and other brain structures in people with ataxia. It may also show other treatable findings, such as a blood clot or benign tumour, that could be pressing on the cerebellum.
* Lumbar puncture (spinal tap) - A needle is inserted into the lower back (lumbar region) between two lumbar vertebrae to obtain a sample of cerebrospinal fluid for testing.
* Genetic testing - Determines whether the mutation that causes one of the hereditary ataxic conditions is present. Tests are available for many but not all of the hereditary ataxias.
## Treatment[edit]
The treatment of ataxia and its effectiveness depend on the underlying cause. Treatment may limit or reduce the effects of ataxia, but it is unlikely to eliminate them entirely. Recovery tends to be better in individuals with a single focal injury (such as stroke or a benign tumour), compared to those who have a neurological degenerative condition.[41] A review of the management of degenerative ataxia was published in 2009.[42] A small number of rare conditions presenting with prominent cerebellar ataxia are amenable to specific treatment and recognition of these disorders is critical. Diseases include vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann–Pick type C disease, Refsum's disease, glucose transporter type 1 deficiency, episodic ataxia type 2, gluten ataxia, glutamic acid decarboxylase ataxia.[43] Novel therapies target the RNA defects associated with cerebellar disorders, using in particular anti-sense oligonucleotides.[44]
The movement disorders associated with ataxia can be managed by pharmacological treatments and through physical therapy and occupational therapy to reduce disability.[45] Some drug treatments that have been used to control ataxia include: 5-hydroxytryptophan (5-HTP), idebenone, amantadine, physostigmine, L-carnitine or derivatives, trimethoprim/sulfamethoxazole, vigabatrin, phosphatidylcholine, acetazolamide, 4-aminopyridine, buspirone, and a combination of coenzyme Q10 and vitamin E.[42]
Physical therapy requires a focus on adapting activity and facilitating motor learning for retraining specific functional motor patterns.[46] A recent systematic review suggested that physical therapy is effective, but there is only moderate evidence to support this conclusion.[47] The most commonly used physical therapy interventions for cerebellar ataxia are vestibular habituation, Frenkel exercises, proprioceptive neuromuscular facilitation (PNF), and balance training; however, therapy is often highly individualized and gait and coordination training are large components of therapy.
Current research suggests that, if a person is able to walk with or without a mobility aid, physical therapy should include an exercise program addressing five components: static balance, dynamic balance, trunk-limb coordination, stairs, and contracture prevention. Once the physical therapist determines that the individual is able to safely perform parts of the program independently, it is important that the individual be prescribed and regularly engage in a supplementary home exercise program that incorporates these components to further improve long term outcomes. These outcomes include balance tasks, gait, and individual activities of daily living. While the improvements are attributed primarily to changes in the brain and not just the hip or ankle joints, it is still unknown whether the improvements are due to adaptations in the cerebellum or compensation by other areas of the brain.[46]
Decomposition, simplification, or slowing of multijoint movement may also be an effective strategy that therapists may use to improve function in patients with ataxia.[48] Training likely needs to be intense and focused—as indicated by one study performed with stroke patients experiencing limb ataxia who underwent intensive upper limb retraining.[49] Their therapy consisted of constraint-induced movement therapy which resulted in improvements of their arm function.[49] Treatment should likely include strategies to manage difficulties with everyday activities such as walking. Gait aids (such as a cane or walker) can be provided to decrease the risk of falls associated with impairment of balance or poor coordination. Severe ataxia may eventually lead to the need for a wheelchair. To obtain better results, possible coexisting motor deficits need to be addressed in addition to those induced by ataxia. For example, muscle weakness and decreased endurance could lead to increasing fatigue and poorer movement patterns.
There are several assessment tools available to therapists and health care professionals working with patients with ataxia. The International Cooperative Ataxia Rating Scale (ICARS) is one of the most widely used and has been proven to have very high reliability and validity.[50] Other tools that assess motor function, balance and coordination are also highly valuable to help the therapist track the progress of their patient, as well as to quantify the patient's functionality. These tests include, but are not limited to:
* The Berg Balance Scale
* Tandem Walking (to test for Tandem gaitability)
* Scale for the Assessment and Rating of Ataxia (SARA)[51]
* tapping tests – The person must quickly and repeatedly tap their arm or leg while the therapist monitors the amount of dysdiadochokinesia.[52]
* finger-nose testing[52] – This test has several variations including finger-to-therapist's finger, finger-to-finger, and alternate nose-to-finger.[53]
## Other uses[edit]
The term "ataxia" is sometimes used in a broader sense to indicate lack of coordination in some physiological process. Examples include optic ataxia (lack of coordination between visual inputs and hand movements, resulting in inability to reach and grab objects) and ataxic respiration (lack of coordination in respiratory movements, usually due to dysfunction of the respiratory centres in the medulla oblongata). Optic ataxia may be caused by lesions to the posterior parietal cortex, which is responsible for combining and expressing positional information and relating it to movement. Outputs of the posterior parietal cortex include the spinal cord, brain stem motor pathways, pre-motor and pre-frontal cortex, basal ganglia and the cerebellum. Some neurons in the posterior parietal cortex are modulated by intention. Optic ataxia is usually part of Balint's syndrome, but can be seen in isolation with injuries to the superior parietal lobule, as it represents a disconnection between visual-association cortex and the frontal premotor and motor cortex.[54]
## See also[edit]
* Ataxic cerebral palsy
* Spinocerebellar ataxia
* Bruns apraxia
## References[edit]
1. ^ dystaxia. (n.d.). The American Heritage Stedman's Medical Dictionary. Retrieved 9 March 2014, from Dictionary.com website: http://dictionary.reference.com/browse/dystaxia
2. ^ "Ataxia - Symptoms & Causes". Mayo Clinic. 3 June 2020. Retrieved 10 August 2020.
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## Further reading[edit]
* Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, Bird TD (1998). "Hereditary Ataxia Overview". Hereditary Ataxia Overview (last revision 2012). All GeneReview. University of Washington, Seattle. PMID 20301317.
* Manto M, Gruol D, Schmahmann J, Koibuchi N, Rossi F (2013). Handbook of the Cerebellum and Cerebellar Disorders. Springer. ISBN 9789400713321.
* Esmail S (2018). "Cerebellar ataxia but normal neuroimaging: now what?". Scivision.
## External links[edit]
Classification
D
* ICD-10: R27.0
* MeSH: D001259
* DiseasesDB: 15409
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
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* Magnetic gait
* Truncal ataxia
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Coordination
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Abnormal movement
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* Category
*[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
|
Ataxia
|
c0751837
| 25,548 |
wikipedia
|
https://en.wikipedia.org/wiki/Ataxia
| 2021-01-18T18:53:16 |
{"mesh": ["D001259", "D020234"], "umls": ["C0751837"], "icd-9": ["781.3"], "icd-10": ["R27.0"], "wikidata": ["Q213373"]}
|
A number sign (#) is used with this entry because amelogenesis imperfecta type IB (AI1B) is caused by heterozygous mutation in the enamelin gene (ENAM; 606585) on chromosome 4q13.
Clinical Features
Weinmann et al. (1945) made the useful division of enamel defects into 2 classes: (1) hereditary enamel hypoplasia, in which the enamel is hard but deficient in quantity, and (2) hereditary enamel hypocalcification, in which the enamel is soft and undercalcified but normal in quantity and histology (see 130900).
In autosomal dominant local hypoplastic amelogenesis imperfecta, the hypoplastic defect is a horizontal row of pits, linear depressions, or one large hypoplastic area in the enamel with hypocalcification of the enamel adjacent to and below the hypoplastic area. These defects appear most prominent on the buccal surfaces of the teeth involving the middle third of the enamel. The incisal edge or occlusal surface is usually not involved (Witkop, 1957; Witkop and Sauk, 1976).
Chaudhry et al. (1959) reported 5 families with an autosomal dominant enamel dysplasia. The authors found it difficult to classify the families as either hypoplastic or hypocalcified.
Mardh et al. (2002) described 6 families from Vasterbotten county in northern Sweden with hypoplastic amelogenesis imperfecta. The enamel defects included horizontal rows of pits, grooves, or a large hypoplastic area in the enamel. Apart from the variations in number and localization of defect, the phenotype was consistent within the families and also between families.
Pavlic et al. (2007) described a father and son (family 1) with hypoplastic AI. The son presented with chalky whitish enamel with localized hypoplastic alteration. The father had open-bite malocclusion and yellowish enamel with horizontal grooves in the cervical half of the crowns of the teeth. Panoramic tomograms of the father and son showed poor differentiation between the dental enamel and dentin translucency. Scanning electron microscopy of one of the son's deciduous molars (tooth 85) showed defective mineralization of the enamel without a 'prismless' outer layer on most of the enamel surface. The enamel prisms were deformed, and the borders of the enamel prisms were undulated. The dentin-enamel junction contained the least structured and the most porous enamel.
Inheritance
Backman and Holmgren (1988) studied 51 families with amelogenesis imperfecta from the county of Vasterbotten in northern Sweden. Autosomal dominant inheritance was the likely mode of inheritance in 33 families, although X-linked dominant inheritance was a possible alternative in 1 of these. Autosomal recessive inheritance was found likely in 6 families (see 204650 and 204700) and X-linked recessive inheritance in 2 families. Ten probands were sporadic cases. AI was of the hypoplastic form in 72% and of the hypomineralization form in 28% of the individuals. Autosomal dominant inheritance was found in 89% of the cases with the hypoplastic form and in 44% of the cases with the hypomineralization form. In most families the type was consistent within the family; in 3 families, however, both hypoplastic and hypomineralization forms were seen. In the families with X-linked inheritance, clinical manifestations were more severe in males.
Seymen et al. (2014) reported autosomal dominant inheritance of AI1B with incomplete penetrance in 2 unrelated Turkish families. Segregation analysis within each family revealed that individuals with normal enamel or with an extremely mild enamel phenotype had the same mutation as affected family members.
Mapping
In 3 families from northern Sweden segregating an autosomal dominant form of amelogenesis imperfecta, Forsman et al. (1994) found linkage of the disorder to a 17.6-cM region between markers D4S392 and D4S395 on chromosome 4q. This region also contains the albumin gene (ALB; 103600) which was hypothesized to be a candidate gene for the disorder. Karrman et al. (1997) constructed a detailed marker map of the region and refined the localization of the locus, which they designated AIH2, to a 4-Mb YAC contig corresponding to chromosome 4q11-q21. Studies by Karrman et al. (1997) excluded ALB as the disease-causing gene. Affected members in all 6 families studied shared the same allele haplotype, indicating a common ancestral mutation in all families.
Molecular Genetics
In a 3-generation family with autosomal dominant hypoplastic local amelogenesis imperfecta, Rajpar et al. (2001) identified a G-to-A transition in the splice donor site following exon 7 of the enamelin gene (606585.0001).
In affected members of 6 families from northern Sweden with AI1B, Mardh et al. (2002) identified a heterozygous nonsense mutation (606585.0002) in the ENAM gene.
In a Turkish family (family 1) with autosomal dominant amelogenesis imperfecta, Pavlic et al. (2007) identified a heterozygous 2-bp insertion in the ENAM gene (606585.0003).
INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Amelogenesis imperfecta, hypoplastic \- Enamel has horizontal row of pits or linear depressions \- Incisal edge or occlusal surface not usually involved MOLECULAR BASIS \- Caused by mutation in the enamelin gene (ENAM, 606585.0001 ) ▲ Close
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*[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
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*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
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*[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
|
AMELOGENESIS IMPERFECTA, TYPE IB
|
c0002452
| 25,549 |
omim
|
https://www.omim.org/entry/104500
| 2019-09-22T16:45:15 |
{"doid": ["0110052"], "mesh": ["D000567"], "omim": ["104500"], "orphanet": ["88661", "100031"], "synonyms": ["Alternative titles", "AMELOGENESIS IMPERFECTA, HYPOPLASTIC LOCAL, AUTOSOMAL DOMINANT", "AIH2", "ENAMEL HYPOPLASIA, HEREDITARY LOCALIZED"]}
|
Disease of the lungs
Bronchiectasis
Figure A shows a cross-section of the lungs with normal airways and widened airways. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway with bronchiectasis.
Pronunciation
* /ˌbrɒŋkɪˈɛktəsɪs/[1]
SpecialtyPulmonology
SymptomsProductive cough, shortness of breath, chest pain[2][3]
Usual onsetGradual[4]
DurationLong term[5]
CausesInfections, cystic fibrosis, other genetic conditions, unknown[3][6]
Diagnostic methodBased on symptoms, CT scan[7]
Differential diagnosisChronic obstructive pulmonary disease, Asbestosis, Tracheobronchomalacia
TreatmentAntibiotics, bronchodilators, lung transplant[3][8][9]
Frequency1–250 per 250,000 adults[10]
Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung.[5] Symptoms typically include a chronic cough with mucus production.[3] Other symptoms include shortness of breath, coughing up blood, and chest pain.[2] Wheezing and nail clubbing may also occur.[2] Those with the disease often get frequent lung infections.[8]
Bronchiectasis may result from a number of infectious and acquired causes, including pneumonia, tuberculosis, immune system problems, as well as the genetic disorder cystic fibrosis.[11][3][12] Cystic fibrosis eventually results in severe bronchiectasis in nearly all cases.[13] The cause in 10–50% of those without cystic fibrosis is unknown.[3] The mechanism of disease is breakdown of the airways due to an excessive inflammatory response.[3] Involved airways (bronchi) become enlarged and thus less able to clear secretions.[3] These secretions increase the amount of bacteria in the lungs, resulting in airway blockage and further breakdown of the airways.[3] It is classified as an obstructive lung disease, along with chronic obstructive pulmonary disease and asthma.[14] The diagnosis is suspected based on symptoms and confirmed using computed tomography.[7] Cultures of the mucus produced may be useful to determine treatment in those who have acute worsening and at least once a year.[7]
Periods of worsening may occur due to infection.[8] In these cases, antibiotics are recommended.[8] Common antibiotics used include amoxicillin, erythromycin, or doxycycline.[15] Antibiotics, such as erythromycin, may also be used to prevent worsening of disease.[3][16] Airway clearance techniques, a type of physical therapy, are also recommended.[17] Medications to dilate the airways and inhaled steroids may be used during sudden worsening, but there are no studies to determine effectiveness.[3][18] There are also no studies on the use of inhaled steroids in children.[18] Surgery, while commonly done, has not been well studied.[19][3] Lung transplantation may be an option in those with very severe disease.[9]
The disease affects between 1 per 1000 and 1 per 250,000 adults.[10] The disease is more common in women and increases as people age.[3] It became less common since the 1950s with the introduction of antibiotics.[10] It is more common among certain ethnic groups such as indigenous people.[10] It was first described by René Laennec in 1819.[3] The economic costs in the United States are estimated at $630 million per year.[3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Cystic fibrosis
* 2.2 Airway obstruction
* 2.3 Lung infections
* 2.4 Impaired host defenses
* 2.5 Aspergillosis
* 2.6 Autoimmune diseases
* 2.7 Lung injury
* 2.8 Congenital
* 2.9 Cigarette smoking
* 3 Pathophysiology
* 4 Diagnosis
* 5 Prevention
* 6 Management
* 6.1 Airway clearance
* 6.2 Anti-inflammatories
* 6.3 Antibiotics
* 6.4 Bronchodilators
* 6.5 Surgery
* 6.6 Clinical trials
* 7 Epidemiology
* 8 History
* 9 References
* 10 External links
## Signs and symptoms[edit]
The typical symptoms of bronchiectasis are shown. Also, the change in bronchi under bronchiectasis are illustrated.
Symptoms of bronchiectasis commonly include a cough productive of frequent green or yellow sputum lasting months to years.[3] Other common symptoms include difficulty breathing, wheezing (a whistling sound when you breath), and chest pain. Bronchiectasis may also present with coughing up blood in the absence of sputum, which has been called "dry bronchiectasis."
People often report frequent bouts of "bronchitis" requiring therapy with repeated courses of antibiotics. People with bronchiectasis may have bad breath from active infection. On examination, crepitations and expiratory rhonchi may be heard with auscultation. Nail clubbing is a rare symptom.[3]
The complications of bronchiectasis include serious health conditions, such as respiratory failure and atelectasis. Respiratory failure occurs when not enough oxygen passes from the lungs into the blood.[20] Atelectasis occur when one or more segments of the lungs collapse or do not inflate properly. Other pulmonary complications include lung abscess and empyema. Cardiovascular complications include cor pulmonale, in which there is enlargement and failure of the right side of the heart as a result of disease of the lungs.[21]
## Causes[edit]
Category Causes
Autoimmune disease Rheumatoid arthritis
Sjögren syndrome
Impaired host defenses Cystic fibrosis
Primary ciliary dyskinesia
Primary immunodeficiency
HIV/AIDS
Job's syndrome
Post-infective Bacterial pneumonia
Mycobacterium infection
Viral infection
Congenital Tracheobronchomegaly
Marfan syndrome
Williams–Campbell syndrome
Young's syndrome
Alpha-1 antitrypsin deficiency
Hypersensitivity Allergic bronchopulmonary aspergillosis
Inflammatory bowel disease Ulcerative colitis
Crohn's disease
Malignancy Chronic lymphocytic leukemia
Graft-versus-host disease
Obstruction Tumor
Foreign body aspiration
Lymphadenopathy
Other Pneumonia
Chronic aspiration
Ammonia inhalation
Smoke inhalation
Radiation-induced lung disease
Yellow nail syndrome
There are many causes that can induce or contribute to the development of bronchiectasis. The frequency of these different causes varies with geographic location.[22] Cystic fibrosis is identified as a cause in up to half of cases.[3] Bronchiectasis without CF is known as non-CF bronchiectasis. Historically, about half of all case of non-CF bronchiectasis were found to be idiopathic, or without a known cause.[23] However, more recent studies with a more thorough diagnostic work-up have found an etiology in 60 to 90% of patients.[22][24][25]
### Cystic fibrosis[edit]
Cystic fibrosis is the most common life-threatening autosomal recessive disease in the United States and Europe.[26] It is a genetic disorder that affects the lungs, but also the pancreas, liver, kidneys, and intestine.[27] It is caused by mutations in the CFTR protein, a chloride channel expressed in epithelial cells.[26] Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation.[28] In later stages, changes to the structure of the lung, such as bronchiectasis, occur. Around 5 to 10% of all patients with cystic fibrosis develop bronchiectasis.[29]
### Airway obstruction[edit]
An airway obstruction can be caused by either an intraluminal mass such as a tumor or a foreign body.[30] The presence of an airway obstruction leads to a cycle of inflammation.[3] It is important to identify the presence of an obstruction because surgical resection is often curative if obstruction is the cause.[31] In adults, foreign body aspiration is often associated with an altered state of consciousness. The foreign body is often unchewed food, or part of a tooth or crown.[32] Bronchiectasis that results from foreign body aspiration generally occurs in the right lung in the lower lobe or posterior segments of the upper lobe.[33]
### Lung infections[edit]
A range of bacterial, mycobacterial, and viral lung infections are associated with the development of bronchiectasis. Bacterial infections commonly associated with bronchiectasis include P. aeruginosa, H. influenzae, and S. pneumoniae.[3] Gram-negative bacteria are more commonly implicated than gram-positive bacteria.[3] A history of mycobacterial infections such as tuberculosis can lead to damage of the airways that predisposes to bacterial colonization.[34] Severe viral infections in childhood can also lead to bronchiectasis through a similar mechanism.[35] Nontuberculous mycobacteria infections such as Mycobacterium avium complex are found to be a cause in some patients.[36] Recent studies have also shown Nocardia infections to been implicated in bronchiectasis.[37]
### Impaired host defenses[edit]
Impairments in host defenses that lead to bronchiectasis may be congenital, such as with primary ciliary dyskinesia, or acquired, such as with the prolonged use of immunosuppressive drugs.[38] Additionally, these impairments may be localized to the lungs, or systemic throughout the body. In these states of immunodeficiency, there is a weakened or absent immune system response to severe infections that repeatedly affect the lung and eventually result in bronchial wall injury.[39] HIV/AIDS is an example of an acquired immunodeficiency that can lead to the development of bronchiectasis.[40]
### Aspergillosis[edit]
Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by hypersensitivity to the fungus Aspergillus fumigatus.[41] It is suspected in patients with a long history of asthma and symptoms of bronchiectasis such as a productive, mucopurulent cough.[42] Imaging often shows peripheral and central airway bronchiectasis, which is unusual in patients with bronchiectasis caused by other disorders.[43]
### Autoimmune diseases[edit]
Several autoimmune diseases have been associated with bronchiectasis. Specifically, individuals with rheumatoid arthritis and Sjögren syndrome have increased rates of bronchiectasis.[44][45] In these diseases, the symptoms of bronchiectasis usually presents later in the disease course.[46] Other autoimmune diseases such as ulcerative colitis and Crohn's disease also have an association with bronchiectasis.[47] Additionally, graft-versus-host disease in patients who have underwent stem cell transplantation can lead to bronchiectasis as well.[38]
### Lung injury[edit]
Bronchiectasis could be caused by: inhalation of ammonia and other toxic gases,[48] chronic pulmonary aspiration of stomach acid from esophageal reflux,[49] or a hiatal hernia.[49]
### Congenital[edit]
Bronchiectasis may result from congenital disorders that affect cilia motility or ion transport.[50] A common genetic cause is cystic fibrosis, which affects chloride ion transport.[26] Another genetic cause is primary ciliary dyskinesia, a rare disorder that leads to immotility of cilia and can lead to situs inversus.[51] When situs inversus is accompanied by chronic sinusitis and bronchiectasis, this is known as Kartagener's syndrome.[52] Other rare genetic causes include Young's syndrome[53] and Williams-Campbell syndrome.[54] Tracheobronchomegaly, or Mournier-Kuhn syndrome is a rare condition characterized by significant tracheobronchial dilation and recurrent lower respiratory tract infections.[55] Individuals with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of inhibition to enzyme elastase which cleaves elastin.[56] This decreases the ability of the alveoli to return to normal shape during expiration.[57]
### Cigarette smoking[edit]
A causal role for tobacco smoke in bronchiectasis has not been demonstrated.[38] Nonetheless, tobacco smoking can worsen pulmonary function and accelerate the progression of disease that is already present.[58][59]
## Pathophysiology[edit]
"Vicious cycle" theory of the pathogenesis of bronchiectasis.
The development of bronchiectasis requires two factors: an infectious insult and impaired drainage, obstruction, or a defect in host defense.[3] This triggers a host immune response from neutrophils (elastases), reactive oxygen species, and inflammatory cytokines that results in progressive destruction of normal lung architecture. In particular, the elastic fibers of bronchi are affected.[12] The result is permanent abnormal dilation and destruction of the major bronchi and bronchiole walls.[citation needed]
The "vicious cycle" theory is the generally accepted explanation for the pathogenesis of bronchiectasis.[60] In this model, a predisposed individual develops an excessive inflammatory response to pulmonary infection or tissue injury. The inflammation that results is partially responsible for the structural damage to the airways. The structural abnormalities allow for the stasis of mucus, which favors continued chronic infection and the persistence of the vicious cycle.[3]
Endobronchial tuberculosis commonly leads to bronchiectasis, either from bronchial stenosis or secondary traction from fibrosis.[61] Traction bronchiectasis characteristically affects peripheral bronchi (which lack cartilage support) in areas of end-stage fibrosis.[62]
## Diagnosis[edit]
CT scan of the lungs showing findings diagnostic of bronchiectasis. White and black arrows point to dilated bronchi characteristic of the disease.
The goals of a diagnostic evaluation for bronchiectasis are radiographic confirmation of the diagnosis, identification of potential treatable causes, and functional assessment of the patient. A comprehensive evaluation consists of radiographic imaging, laboratory testing, and lung function testing.[63]
A chest x-ray is abnormal in most patients with bronchiectasis. Computed tomography is recommended to confirm the diagnosis and is also used to describe the distribution and grade the severity of the disease. Radiographic findings include airway dilation, bronchial wall thickening, and atelectasis.[3]
Laboratory tests that are commonly part of the initial evaluation include a complete blood count, sputum cultures for bacteria, mycobacteria, and fungi, testing for cystic fibrosis, and immunoglobulin levels.[64] Additional tests that are sometimes indicated include testing for specific genetic disorders.[citation needed]
Lung function testing is used for the assessment and monitoring of functional impairment due to bronchiectasis. These tests may include spirometry and walking tests.[60] Obstructive lung impairment is the most common finding but restrictive lung impairment can be seen in advanced disease. Flexible bronchoscopy may be performed when sputum studies are negative and a focal obstructing lesion is suspected.[30]
* Bronchiectasis primarily in the middle lobe of the right lung.
* Bronchiectasis secondary to a large carcinoid tumor (not shown) that was completely obstructing the bronchus proximally. Dilation of the airways is present.
## Prevention[edit]
In preventing bronchiectasis, it is necessary to prevent the lung infections and lung damage that can cause it.[20] Children should be immunized against measles, pertussis, pneumonia, and other acute respiratory infections of childhood. Additionally, parents should stay alert to keep children from inhaling objects such as pieces of food or small toys that may get stuck in small airways.[20] Smoking and other toxic fumes and gases should be avoided by all patients with bronchiectasis to decrease the development of infections (such as bronchitis) and further complications.[65]
Treatments to slow down the progression of this chronic disease include keeping bronchial airways clear and secretions weakened through various forms of airway clearance. Aggressively treating bronchial infections with antibiotics to prevent the destructive cycle of infection, damage to bronchi and bronchioles, and more infection is also standard treatment. Regular vaccination against pneumonia, influenza, and pertussis are generally advised. A healthy body mass index and regular doctor visits may have beneficial effects on the prevention of progressing bronchiectasis. The presence of hypoxemia, hypercapnia, dyspnea level and radiographic extent can greatly affect the mortality rate from this disease.[66]
## Management[edit]
A comprehensive approach to the management of bronchiectasis is recommended.[67] It is important to establish whether an underlying modifiable cause, such as immunoglobulin deficiency or alpha-1 antitrypsin deficiency is present.[67] The next steps include controlling infections and bronchial secretions, relieving airway obstructions, removing affected portions of lung by surgery, and preventing complications.[68]
### Airway clearance[edit]
The goal of airway clearance therapy is to loosen secretions and interrupt the cycle of inflammation and infection.[69] Airway clearance techniques improve difficulty breathing, cough, and help patients cough up phlegm and mucus plugs.[70] Airway clearance usually uses an inhaled agent (hypertonic saline) with chest physiotherapy, such as high-frequency chest wall oscillation.[3] Many airway clearance techniques and devices exist. The choice of a technique or device is based on the frequency and tenacity of phlegm, patient comfort, cost, and the patient's ability to use the technique or device with minimal interference to their lifestyle.[71] Mucolytic agents such as dornase alfa are not recommended for individuals with non-CF bronchiectasis.[3] Mannitol is a hyperosmolar agent that is thought to hydrate airway secretions, however, clinical trials with it have not demonstrated efficacy.[71]
### Anti-inflammatories[edit]
The two most commonly used classes of anti-inflammatory therapies are macrolides and corticosteroids.[3]
Despite also being antibiotics, macrolides exert immunomodulatory effects on the host inflammatory response without systemic suppression of the immune system.[3] These effects include modifying mucus production, inhibition of biofilm production, and suppression of inflammatory mediators.[38] Three large multicenter, randomized trials have shown reduced rates of exacerbations and improved cough and dyspnea with use of macrolide therapy.[72] The impact of adverse effects of macrolides such as gastrointestinal symptoms, hepatotoxicity, and increased antimicrobial resistance needs ongoing review and study.[16]
Inhaled corticosteroid therapy can reduce sputum production and decrease airway constriction over a period of time, helping prevent progression of bronchiectasis.[73] Long term use of high-dose inhaled corticosteroids can lead to adverse consequences such as cataracts and osteoporosis.[3] It is not recommended for routine use in children.[74] One commonly used therapy is beclometasone dipropionate.[75]
### Antibiotics[edit]
Azithromycin is a macrolide commonly used in bronchiectasis.
Antibiotics are used in bronchiectasis to eradicate P. aeruginosa or MRSA, to suppress the burden of chronic bacterial colonization, and to treat exacerbations.[3] The use of daily oral non-macrolide antibiotic treatment has been studied in small case series, but not in randomized trials.[72] The role of inhaled antibiotics in non-CF bronchiectasis has recently evolved with two society guidelines and a systematic review suggesting a therapeutic trial of inhaled antibiotics in patients with three or more exacerbations per year and P. aeruginosa in their sputum.[76][77] Options for inhaled antibiotics include aerosolized tobramycin, inhaled ciprofloxacin, aerosolized aztreonam, and aerosolized colistin.[38]
### Bronchodilators[edit]
Some clinical trials have shown a benefit with inhaled bronchodilators in certain people with bronchiectasis.[3] In people with demonstrated bronchodilator reversibility on spirometry, the use of inhaled bronchodilators resulted in improved dyspnea, cough, and quality of life without any increase in adverse events.[63] However, overall there is a lack of data to recommend use of bronchodilators in all patients with bronchiectasis.[78]
### Surgery[edit]
The primary role of surgery in the management of bronchiectasis is in localized disease to remove segments of the lung or to control massive hemoptysis.[38] Additionally, surgery is used to remove an airway obstruction that is contributing to bronchiectasis. The goals are conservative, aiming to control specific disease manifestations rather than cure or eliminate all areas of bronchiectasis.[79] Surgical case series have shown low operative mortality rate (less than 2%) and improvement of symptoms in the majority of patients selected to receive surgery.[80] However, no randomized clinical trials have been performed evaluating the efficacy of surgery in bronchiectasis.[79]
### Clinical trials[edit]
Results from a phase 2 clinical trial have recently been published.[81] In a placebo-controlled, double-blind study conducted in 256 patients worldwide, patients who received Brensocatib reported prolonged time to the first exacerbation and also reduced rate of yearly exacerbation.
## Epidemiology[edit]
The disease affects between 1 per 1000 and 1 per 250,000 adults.[10] The disease is more common in women and increases as people age.[3] It became less common since the 1950s, with the introduction of antibiotics.[10] It is more common among certain ethnic groups such as indigenous people.[10]
An estimated 350,000 to 500,000 adults have bronchiectasis in the United States.[82] The disease is more common in women and in elderly individuals over the age of 65.[3] Specifically, children of the indigenous populations of Australia, Alaska, Canada and New Zealand have significantly higher rates than other populations.[83] Overall, a shortage of data exists concerning the epidemiology of bronchiectasis in Asia, Africa, and South America.[83]
The exact rates of bronchiectasis are often unclear as the symptoms are variable.[84] Rates of disease appeared to have increased in the United States between 2000 and 2007.[3]
## History[edit]
René Laennec, the man who invented the stethoscope, used his invention to first discover bronchiectasis in 1819.[85]
The disease was researched in greater detail by Sir William Osler, one of the four founding professors of Johns Hopkins Hospital, in the late 1800s. It is suspected that Osler himself died of complications from undiagnosed bronchiectasis. His biographies mention that he suffered frequent severe chest infections for many years.[86]
The term "bronchiectasis" comes from the Greek words bronkhia (meaning "airway") and ektasis (meaning "widening").[87]
## References[edit]
1. ^ "Bronchiectasis | Definition of Bronchiectasis by Lexico". Lexico Dictionaries | English.
2. ^ a b c "What Are the Signs and Symptoms of Bronchiectasis?". NHLBI. June 2, 2014. Archived from the original on 23 August 2016. Retrieved 10 August 2016.
3. ^ 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 McShane, PJ; Naureckas, ET; Tino, G; Strek, ME (Sep 15, 2013). "Non-cystic fibrosis bronchiectasis". American Journal of Respiratory and Critical Care Medicine. 188 (6): 647–56. doi:10.1164/rccm.201303-0411CI. PMID 23898922.
4. ^ Maguire, G (November 2012). "Bronchiectasis – a guide for primary care". Australian Family Physician. 41 (11): 842–50. PMID 23145413.
5. ^ a b "What Is Bronchiectasis?". NHLBI. June 2, 2014. Archived from the original on 10 August 2016. Retrieved 10 August 2016.
6. ^ Bird, K; Memon, J (January 2019). "Bronchiectasis". PMID 28613561. Cite journal requires `|journal=` (help)
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## External links[edit]
Wikimedia Commons has media related to Bronchiectasis.
Wikisource has the text of the 1911 Encyclopædia Britannica article Bronchiectasis.
Classification
D
* ICD-10: J47, Q33.4
* ICD-9-CM: 494, 748.61
* MeSH: D001987
* DiseasesDB: 1684
External resources
* MedlinePlus: 000144
* eMedicine: article/296961
* Patient UK: Bronchiectasis
* 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
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* v
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Authority control
* NDL: 01148045
*[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
|
Bronchiectasis
|
c0006267
| 25,550 |
wikipedia
|
https://en.wikipedia.org/wiki/Bronchiectasis
| 2021-01-18T18:43:13 |
{"mesh": ["D001987"], "umls": ["C0006267"], "orphanet": ["60033"], "wikidata": ["Q32778"]}
|
A rare inflammatory multisystem disorder characterized clinically by four cardinal signs: fever of unknown origin, arthralgia or arthritis, hyperleucocytosis, and typical skin rash.
## Epidemiology
Prevalence and incidence data are difficult to determine given the broad, non-specific clinical presentation of adult-onset Still disease (AOSD). The estimated prevalence of AOSD is more than 1/100,000 population. There is a slightly higher number of affected women than affected men.
## Clinical description
AOSD primarily affects young adults, although older patients have been reported. The presenting features are variable and may include high fever (>39°C) with daily spikes, sore throat or pharyngitis, arthralgia or arthritis (>65% of patients), transient maculopapular rash, and more rarely myalgia, lymphadenopathy, hepatosplenomegaly, and serositis. Arthritis may involve any joint and can migrate in early disease and then stabilize with time. Arthralgia is usually correlated with fever spikes. Rash mostly consists of transient, small, discrete, salmon-pink, non-pruritic macules or maculopapules that often occur concomitantly with fever and generally spare the face, palms and soles of the feet. Pleuritis or pericarditis are commonly found. Patients may lose weight and have a generally poor overall health status. Three different disease courses have been described: self-limited, systemic course with a single flare and complete remission within 2 to 4 weeks, intermittent course with recurrence of systemic or articular flares after remission of 2 weeks to 2years, and a primarily articular chronic course (with erosions in a 1/3 patients). Some affected individuals have a history of systemic juvenile idiopathic arthritis.
## Etiology
The etiology of AOSD and its underlying pathogenetic mechanisms are not known. No risk factors for the disease have been identified so far, but environmental factors are suspected. Several infectious conditions have been reported to be associated with onset of the disease (e.g. Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, Coxsackie virus, hepatitis A, B, and C viruses, and Mycoplasma pneumoniae).
## Diagnostic methods
The non-specific clinical features of AOSD make diagnosis difficult. No serological marker is currently available. AOSD is a diagnosis of exclusion. Two sets of classification criteria, Yamaguchi and Fautrel, exist. Major diagnostic criteria include arthralgia for more than 2 weeks, intermittent high fever for more than 1 week, characteristic rash, and white blood cell count above 10,000. Minor criteria include sore throat, lymphadenopathy and/or splenomegaly, abnormal liver function tests, and negative rheumatoid factor and ANA. Elevated ferritin is often found and may assist in diagnosis, especially if it is associated with a low level of glycosylated ferritin.
## Differential diagnosis
Many other inflammatory, neoplastic, and infectious conditions with a similar presentation must be ruled out in order to diagnose AOSD. Differential diagnoses include infections (endocarditis, occult infections, secondary syphilis, viral rash), malignancies (lymphoma) or autoimmune diseases (such as polyarteritis nodosa, vasculitis, or polymyositis). Genetic counseling (if relevant) AOSD is a sporadic non-inheritable disease and genetic counseling is therefore not needed.
## Management and treatment
The aim is to achieve complete remission and prevent joint damage through treatment. Treatment-free remission is possible but the risk of relapse remains present throughout life Multidisciplinary rounds in contact with a reference center are highly recommended. The mainstay of first-line treatment is prednisone, and most guidelines tend to recommend an early association with biologic therapies (anti-IL1 agents (anakinra, canakinumab), and anti-IL-6 agents (tocilizumab)), in order to allow a rapid tapering of prednisone and hence prevent steroid-induced complications. Methotrexate and tumor necrosis factor blockers may be used in chronic articular forms, but have limited efficacy in systemic forms. Regular clinical and biological monitoring (initially tight) is necessary.
## Prognosis
The overall prognosis is generally good, but acute life-threatening manifestations may occur in rare cases. The most classical complication is macrophage activation syndrome but blood coagulation disorders, fulminant hepatitis, cardiac and pulmonary complications may occur. Some patients with chronic disease and major joint involvement may have significantly altered quality of life, but this tends to disappear thanks to a better and earlier management with biologics.
*[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
|
Adult-onset Still disease
|
c0043195
| 25,551 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=829
| 2021-01-23T18:11:54 |
{"gard": ["436"], "mesh": ["D014924", "D016706"], "umls": ["C0043195", "C0085253"], "icd-10": ["M06.1"], "synonyms": ["AOSD", "Wissler-Fanconi syndrome"]}
|
Inflammation of the skin
Dermatitis
Other namesEczema
A moderate case of dermatitis of the hands
SpecialtyDermatology
SymptomsItchiness, red skin, rash[1]
ComplicationsSkin infection[2]
Usual onsetChildhood[1][2]
CausesAtopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, stasis dermatitis[1][2]
Diagnostic methodBased on symptom[1]
Differential diagnosisScabies, psoriasis, dermatitis herpetiformis, lichen simplex chronicus[3]
TreatmentMoisturizers, steroid creams, antihistamines[2][4]
Frequency245 million in 2015[5] (3.34% of world population)
Dermatitis (also known as eczema) is inflammation of the skin, typically characterized by itchiness, redness and a rash.[1] In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened.[1] The area of skin involved can vary from small to covering the entire body.[1][2]
Dermatitis includes atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis and stasis dermatitis.[1][2] The exact cause of the condition is often unclear.[2] Cases may involve a combination of allergy and poor venous return.[1] The type of dermatitis is generally determined by the person's history and the location of the rash.[1] For example, irritant dermatitis often occurs on the hands of those who frequently get them wet.[1] Allergic contact dermatitis occurs upon exposure to an allergen, causing a hypersensitivity reaction in the skin.[1]
Treatment of atopic dermatitis is typically with moisturizers and steroid creams.[4] The steroid creams should generally be of mid- to high strength and used for less than two weeks at a time, as side effects can occur.[6] Antibiotics may be required if there are signs of skin infection.[2] Contact dermatitis is typically treated by avoiding the allergen or irritant.[7][8] Antihistamines may help with sleep and decrease nighttime scratching.[2]
Dermatitis was estimated to affect 245 million people globally in 2015,[5] or 3.34% of the world population. Atopic dermatitis is the most common type and generally starts in childhood.[1][2] In the United States, it affects about 10–30% of people.[2] Contact dermatitis is twice as common in females as males.[9] Allergic contact dermatitis affects about 7% of people at some point in their lives.[10] Irritant contact dermatitis is common, especially among people with certain occupations; exact rates are unclear.[11]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Environmental
* 2.2 Genetic
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Classification
* 4.1.1 Histopathologic classification
* 4.2 Terminology
* 4.3 Common types
* 4.3.1 Atopic
* 4.3.2 Contact
* 4.3.3 Seborrhoeic
* 4.4 Less common types
* 4.4.1 Dyshidrosis
* 4.4.2 Discoid
* 4.4.3 Venous
* 4.4.4 Herpetiformis
* 4.4.5 Neurodermatitis
* 4.4.6 Autoeczematization
* 4.4.7 Viral
* 5 Prevention
* 6 Management
* 6.1 Lifestyle
* 6.2 Moisturizers
* 6.3 Medications
* 6.3.1 Corticosteroids
* 6.3.2 Antihistamines
* 6.3.3 Immunosuppressants
* 6.4 Light therapy
* 6.5 Alternative medicine
* 7 Prognosis
* 8 Epidemiology
* 9 History
* 10 Society and culture
* 11 Research
* 12 References
* 13 External links
## Signs and symptoms[edit]
Dermatitis of the hand
Dermatitis symptoms vary with all different forms of the condition. They range from skin rashes to bumpy rashes or including blisters.[12] Although every type of dermatitis has different symptoms, there are certain signs that are common for all of them, including redness of the skin, swelling, itching and skin lesions with sometimes oozing and scarring. Also, the area of the skin on which the symptoms appear tends to be different with every type of dermatitis, whether on the neck, wrist, forearm, thigh or ankle. Although the location may vary, the primary symptom of this condition is itchy skin. More rarely, it may appear on the genital area, such as the vulva or scrotum.[13][14] Symptoms of this type of dermatitis may be very intense and may come and go. Irritant contact dermatitis is usually more painful than itchy.
Although the symptoms of atopic dermatitis vary from person to person, the most common symptoms are dry, itchy, red skin. Typical affected skin areas include the folds of the arms, the back of the knees, wrists, face and hands. Perioral dermatitis refers to a red bumpy rash around the mouth.[15]
Dermatitis herpetiformis symptoms include itching, stinging and a burning sensation. Papules and vesicles are commonly present.[16] The small red bumps experienced in this type of dermatitis are usually about 1 cm in size, red in color and may be found symmetrically grouped or distributed on the upper or lower back, buttocks, elbows, knees, neck, shoulders, and scalp. Less frequently, the rash may appear inside the mouth or near the hairline.
The symptoms of seborrheic dermatitis, on the other hand, tend to appear gradually, from dry or greasy scaling of the scalp (dandruff) to scaling of facial areas, sometimes with itching, but without hair loss.[17] In newborns, the condition causes a thick and yellowish scalp rash, often accompanied by a diaper rash. In severe cases, symptoms may appear along the hairline, behind the ears, on the eyebrows, on the bridge of the nose, around the nose, on the chest, and on the upper back.[18]
* Dermatitis
* More severe dermatitis
* A patch of dermatitis that has been scratched
* Complex dermatitis
## Cause[edit]
The cause of dermatitis is unknown but is presumed to be a combination of genetic and environmental factors.[2]
### Environmental[edit]
The hygiene hypothesis postulates that the cause of asthma, eczema, and other allergic diseases is an unusually clean environment in childhood which leads to an insufficient human microbiota. It is supported by epidemiologic studies for asthma.[19] The hypothesis states that exposure to bacteria and other immune system modulators is important during development, and missing out on this exposure increases the risk for asthma and allergy.
While it has been suggested that eczema may sometimes be an allergic reaction to the excrement from house dust mites,[20] with up to 5% of people showing antibodies to the mites,[21] the overall role this plays awaits further corroboration.[22]
### Genetic[edit]
A number of genes have been associated with eczema, one of which is filaggrin.[4] Genome-wide studies found three new genetic variants associated with eczema: OVOL1, ACTL9 and IL4-KIF3A.[23]
Eczema occurs about three times more frequently in individuals with celiac disease and about two times more frequently in relatives of those with celiac disease, potentially indicating a genetic link between the conditions.[24][25]
## Pathophysiology[edit]
Eczema can be characterized by spongiosis which allows inflammatory mediators to accumulate. Different dendritic cells sub types, such as Langerhans cells, inflammatory dendritic epidermal cells and plasmacytoid dendritic cells have a role to play.[26][27]
## Diagnosis[edit]
Diagnosis of eczema is based mostly on the history and physical examination.[4] In uncertain cases, skin biopsy may be taken for a histopathologic diagnosis of dermatitis.[28] Those with eczema may be especially prone to misdiagnosis of food allergies.[29]
Patch tests are used in the diagnosis of allergic contact dermatitis.[30][31]
### Classification[edit]
The term eczema refers to a set of clinical characteristics. Classification of the underlying diseases has been haphazard with numerous different classification systems, and many synonyms being used to describe the same condition.
A type of dermatitis may be described by location (e.g., hand eczema), by specific appearance (eczema craquele or discoid) or by possible cause (varicose eczema). Further adding to the confusion, many sources use the term eczema interchangeably for the most common type: atopic dermatitis.
The European Academy of Allergology and Clinical Immunology (EAACI) published a position paper in 2001, which simplifies the nomenclature of allergy-related diseases, including atopic and allergic contact eczemas.[32] Non-allergic eczemas are not affected by this proposal.
#### Histopathologic classification[edit]
Main article: Histopathologic diagnosis of dermatitis
By histopathology, superficial dermatitis (in the epidermis, papillary dermis, and superficial vascular plexus) can basically be classified into either of the following groups:[33]
* Vesiculobullous lesions
* Pustular dermatosis
* Non vesicullobullous, non-pustular
* With epidermal changes
* Without epidermal changes. These characteristically have a superficial perivascular inflammatory infiltrate and can be classified by type of cell infiltrate:[33]
* Lymphocytic (most common)
* Lymphoeosinophilic
* Lymphoplasmacytic
* Mast cell
* Lymphohistiocytic
* Neutrophilic
### Terminology[edit]
There are several types of dermatitis including atopic dermatitis, contact dermatitis, stasis dermatitis and seborrheic eczema.[2] Many use the term dermatitis and eczema synonymously.[1]
Others use the term eczema to specifically mean atopic dermatitis.[34][35][36] Atopic dermatitis is also known as atopic eczema.[4] In some languages, dermatitis and eczema mean the same thing, while in other languages dermatitis implies an acute condition and eczema a chronic one.[37]
### Common types[edit]
Diagnosis of types may be indicated by codes defined according to International Statistical Classification of Diseases and Related Health Problems (ICD).
#### Atopic[edit]
Atopic dermatitis is an allergic disease believed to have a hereditary component and often runs in families whose members have asthma. Itchy rash is particularly noticeable on head and scalp, neck, inside of elbows, behind knees, and buttocks. It is very common in developed countries and rising. Irritant contact dermatitis is sometimes misdiagnosed as atopic dermatitis. Stress can cause atopic dermatitis to worsen.[38]
#### Contact[edit]
Contact dermatitis is of two types: allergic (resulting from a delayed reaction to an allergen, such as poison ivy, nickel, or Balsam of Peru),[39] and irritant (resulting from direct reaction to a detergent, such as sodium lauryl sulfate, for example).
Some substances act both as allergen and irritant (wet cement, for example). Other substances cause a problem after sunlight exposure, bringing on phototoxic dermatitis. About three quarters of cases of contact eczema are of the irritant type, which is the most common occupational skin disease. Contact eczema is curable, provided the offending substance can be avoided and its traces removed from one's environment. (ICD-10 L23; L24; L56.1; L56.0)
#### Seborrhoeic[edit]
Seborrhoeic dermatitis or seborrheic dermatitis ("cradle cap" in infants) is a condition sometimes classified as a form of eczema that is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk. In newborns, it causes a thick, yellow, crusty scalp rash called cradle cap, which seems related to lack of biotin and is often curable. (ICD-10 L21; L21.0)
### Less common types[edit]
#### Dyshidrosis[edit]
Dyshidrosis (dyshidrotic eczema, pompholyx, vesicular palmoplantar dermatitis) only occurs on palms, soles, and sides of fingers and toes. Tiny opaque bumps called vesicles, thickening, and cracks are accompanied by itching, which gets worse at night. A common type of hand eczema, it worsens in warm weather. (ICD-10 L30.1)
#### Discoid[edit]
Discoid eczema (nummular eczema, exudative eczema, microbial eczema) is characterized by round spots of oozing or dry rash, with clear boundaries, often on lower legs. It is usually worse in winter. Cause is unknown, and the condition tends to come and go. (ICD-10 L30.0)
#### Venous[edit]
Venous eczema (gravitational eczema, stasis dermatitis, varicose eczema) occurs in people with impaired circulation, varicose veins, and edema, and is particularly common in the ankle area of people over 50. There is redness, scaling, darkening of the skin, and itching. The disorder predisposes to leg ulcers. (ICD-10 I83.1)
#### Herpetiformis[edit]
Dermatitis herpetiformis (Duhring's disease) causes an intensely itchy and typically symmetrical rash on arms, thighs, knees, and back. It is directly related to celiac disease, can often be put into remission with an appropriate diet, and tends to get worse at night. (ICD-10 L13.0)
#### Neurodermatitis[edit]
Neurodermatitis (lichen simplex chronicus, localized scratch dermatitis) is an itchy area of thickened, pigmented eczema patch that results from habitual rubbing and scratching. Usually, there is only one spot. Often curable through behaviour modification and anti-inflammatory medication. Prurigo nodularis is a related disorder showing multiple lumps. (ICD-10 L28.0; L28.1)
#### Autoeczematization[edit]
Autoeczematization (id reaction, auto sensitization) is an eczematous reaction to an infection with parasites, fungi, bacteria, or viruses. It is completely curable with the clearance of the original infection that caused it. The appearance varies depending on the cause. It always occurs some distance away from the original infection. (ICD-10 L30.2)
#### Viral[edit]
There are eczemas overlaid by viral infections (eczema herpeticum or vaccinatum), and eczemas resulting from underlying disease (e.g., lymphoma). Eczemas originating from ingestion of medications, foods, and chemicals, have not yet been clearly systematized. Other rare eczematous disorders exist in addition to those listed here.
## Prevention[edit]
Exclusive breastfeeding of infants during at least the first few months may decrease the risk.[40] There is no good evidence that a mother's diet during pregnancy or breastfeeding affects the risk,[40] nor is there evidence that delayed introduction of certain foods is useful.[40] There is tentative evidence that probiotics in infancy may reduce rates but it is insufficient to recommend its use.[41]
Certain military and healthcare personnel who might come into contact with the smallpox are still vaccinated against the virus.[42] Those who also have eczema should not receive the smallpox vaccination due to risk of developing eczema vaccinatum, a potentially severe and sometimes fatal complication.[43]
## Management[edit]
There is no known cure for some types of dermatitis, with treatment aiming to control symptoms by reducing inflammation and relieving itching. Contact dermatitis is treated by avoiding what is causing it.
### Lifestyle[edit]
Bathing once or more a day is recommended, usually for five to ten minutes in warm water.[4][44] Soaps should be avoided, as they tend to strip the skin of natural oils and lead to excessive dryness.[45] The American Academy of Dermatology suggests using a controlled amount of bleach diluted in a bath to help with atopic dermatitis.[46]
There has not been adequate evaluation of changing the diet to reduce eczema.[47][48] There is some evidence that infants with an established egg allergy may have a reduction in symptoms if eggs are eliminated from their diets.[47] Benefits have not been shown for other elimination diets, though the studies are small and poorly executed.[47][48] Establishing that there is a food allergy before dietary change could avoid unnecessary lifestyle changes.[47]
People can wear clothing designed to manage the itching, scratching and peeling.[49]
House dust mite reduction and avoidance measures have been studied in low quality trials and have not shown evidence of improving eczema.[50]
### Moisturizers[edit]
Low-quality evidence indicates that moisturizing agents (emollients) may reduce eczema severity and lead to fewer flares.[51] In children, oil–based formulations appear to be better, and water–based formulations are not recommended.[4] It is unclear if moisturizers that contain ceramides are more or less effective than others.[52] Products that contain dyes, perfumes, or peanuts should not be used.[4] Occlusive dressings at night may be useful.[4]
Some moisturizers or barrier creams may reduce irritation in occupational irritant hand dermatitis,[53] a skin disease that can affect people in jobs that regularly come into contact with water, detergents, chemicals or other irritants.[53] Some emollients may reduce the number of flares in people with dermatitis.[54]
### Medications[edit]
#### Corticosteroids[edit]
If symptoms are well controlled with moisturizers, steroids may only be required when flares occur.[4] Corticosteroids are effective in controlling and suppressing symptoms in most cases.[55] Once daily use is generally enough.[4] For mild-moderate eczema a weak steroid may be used (e.g., hydrocortisone), while in more severe cases a higher-potency steroid (e.g., clobetasol propionate) may be used. In severe cases, oral or injectable corticosteroids may be used. While these usually bring about rapid improvements, they have greater side effects.
Long term use of topical steroids may result in skin atrophy, stria, telangiectasia.[4] Their use on delicate skin (face or groin) is therefore typically with caution.[4] They are, however, generally well tolerated.[56] Red burning skin, where the skin turns red upon stopping steroid use, has been reported among adults who use topical steroids at least daily for more than a year.[57]
#### Antihistamines[edit]
There is little evidence supporting the use of antihistamine medications for the relief of dermatitis.[4][58] Sedative antihistamines, such as diphenhydramine, may be useful in those who are unable to sleep due to eczema.[4] Second generation antihistamines have minimal evidence of benefit.[59] Of the second generation antihistamines studied, fexofenadine is the only one to show evidence of improvement in itching with minimal side effects.[59]
#### Immunosuppressants[edit]
Tacrolimus 0.1%
Topical immunosuppressants like pimecrolimus and tacrolimus may be better in the short term and appear equal to steroids after a year of use.[60] Their use is reasonable in those who do not respond to or are not tolerant of steroids.[61][62] Treatments are typically recommended for short or fixed periods of time rather than indefinitely.[4][63] Tacrolimus 0.1% has generally proved more effective than pimecrolimus, and equal in effect to mid-potency topical steroids.[64] There is no link to increased risk of cancer from topical use of 1% pimecrolimus cream.[63]
When eczema is severe and does not respond to other forms of treatment, systemic immunosuppressants are sometimes used. Immunosuppressants can cause significant side effects and some require regular blood tests. The most commonly used are ciclosporin, azathioprine, and methotrexate.
Dupilumab is a new medication that improves eczema lesions, especially moderate to severe eczema.[65] Dupilumab, a monoclonal antibody, suppresses inflammation by targeting the interleukin-4 receptor.
### Light therapy[edit]
Light therapy using ultraviolet light has tentative support but the quality of the evidence is not very good.[66] A number of different types of light may be used including UVA and UVB;[67] in some forms of treatment, light sensitive chemicals such as psoralen are also used. Overexposure to ultraviolet light carries its own risks, particularly that of skin cancer.[68]
### Alternative medicine[edit]
Limited evidence suggests that acupuncture may reduce itching in those affected by atopic dermatitis.[69] There is currently no scientific evidence for the claim that sulfur treatment relieves eczema.[70] It is unclear whether Chinese herbs help or harm.[71] Dietary supplements are commonly used by people with eczema.[72] Neither evening primrose oil nor borage seed oil taken orally have been shown to be effective.[73] Both are associated with gastrointestinal upset.[73] Probiotics are likely to make little to no difference in symptoms.[74] There is insufficient evidence to support the use of zinc, selenium, vitamin D, vitamin E, pyridoxine (vitamin B6), sea buckthorn oil, hempseed oil, sunflower oil, or fish oil as dietary supplements.[72]
Chiropractic spinal manipulation lacks evidence to support its use for dermatitis.[75] There is little evidence supporting the use of psychological treatments.[76] While dilute bleach baths have been used for infected dermatitis there is little evidence for this practice.[77]
## Prognosis[edit]
Most cases are well managed with topical treatments and ultraviolet light.[4] About 2% of cases are not.[4] In more than 60% of young children, the condition subsides by adolescence.[4]
## Epidemiology[edit]
Globally dermatitis affected approximately 230 million people as of 2010 (3.5% of the population).[78] Dermatitis is most commonly seen in infancy, with female predominance of eczema presentations occurring during the reproductive period of 15–49 years.[79] In the UK about 20% of children have the condition, while in the United States about 10% are affected.[4]
Although little data on the rates of eczema over time exists prior to the 1940s, the rate of eczema has been found to have increased substantially in the latter half of the 20th century, with eczema in school-aged children being found to increase between the late 1940s and 2000.[80] In the developed world there has been rise in the rate of eczema over time. The incidence and lifetime prevalence of eczema in England has been seen to increase in recent times.[4][81]
Dermatitis affected about 10% of U.S. workers in 2010, representing over 15 million workers with dermatitis. Prevalence rates were higher among females than among males, and among those with some college education or a college degree compared to those with a high school diploma or less. Workers employed in healthcare and social assistance industries and life, physical, and social science occupations had the highest rates of reported dermatitis. About 6% of dermatitis cases among U.S. workers were attributed to work by a healthcare professional, indicating that the prevalence rate of work-related dermatitis among workers was at least 0.6%.[82]
## History[edit]
from Ancient Greek ἔκζεμα ékzema,[83]
from ἐκζέ-ειν ekzé-ein,
from ἐκ ek "out" + ζέ-ειν zé-ein "to boil"
(OED)
The term "atopic dermatitis" was coined in 1933 by Wise and Sulzberger.[84] Sulfur as a topical treatment for eczema was fashionable in the Victorian and Edwardian eras.[70]
The word dermatitis is from the Greek δέρμα derma "skin" and -ῖτις -itis "inflammation" and eczema is from Greek: ἔκζεμα ekzema "eruption".[85]
## Society and culture[edit]
Some cosmetics are marketed as hypoallergenic to imply that their use is less likely to lead to an allergic reaction than other products.[86] However, the term "hypoallergenic" is not regulated,[87] and no research has been done showing that products labeled "hypoallergenic" are less problematic than any others. In 1977, courts overruled the U.S. Food and Drug Administration's regulation of the use of the term hypoallergenic.[86] In 2019, the European Union on released a document about claims made concerning cosmetics,[88] but this was issued as "guidance" not a regulation.[89]
## Research[edit]
Monoclonal antibodies are under preliminary research to determine their potential as treatments for atopic dermatitis, with only dupilumab showing evidence of efficacy, as of 2018.[90][91]
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77. ^ Barnes TM, Greive KA (November 2013). "Use of bleach baths for the treatment of infected atopic eczema". The Australasian Journal of Dermatology. 54 (4): 251–8. doi:10.1111/ajd.12015. PMID 23330843. S2CID 19644659.
78. ^ Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. (December 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607.
79. ^ Osman M, Hansell AL, Simpson CR, Hollowell J, Helms PJ (February 2007). "Gender-specific presentations for asthma, allergic rhinitis and eczema in primary care". Primary Care Respiratory Journal. 16 (1): 28–35. doi:10.3132/pcrj.2007.00006. PMC 6634172. PMID 17297524.
80. ^ Taylor B, Wadsworth J, Wadsworth M, Peckham C (December 1984). "Changes in the reported prevalence of childhood eczema since the 1939-45 war". Lancet. 2 (8414): 1255–7. doi:10.1016/S0140-6736(84)92805-8. PMID 6150286. S2CID 2842761.
81. ^ Simpson CR, Newton J, Hippisley-Cox J, Sheikh A (March 2009). "Trends in the epidemiology and prescribing of medication for eczema in England". Journal of the Royal Society of Medicine. 102 (3): 108–17. doi:10.1258/jrsm.2009.080211. PMC 2746851. PMID 19297652.
82. ^ Luckhaupt SE, Dahlhamer JM, Ward BW, Sussell AL, Sweeney MH, Sestito JP, Calvert GM (June 2013). "Prevalence of dermatitis in the working population, United States, 2010 National Health Interview Survey". American Journal of Industrial Medicine. 56 (6): 625–34. doi:10.1002/ajim.22080. PMID 22674651.
83. ^ Liddell HG, Scott R. "Ekzema". A Greek-English Lexicon. Tufts University: Perseus.
84. ^ Textbook of Atopic Dermatitis. Taylor & Francis. 1 May 2008. p. 1. ISBN 9780203091449. Archived from the original on 28 May 2016.
85. ^ "Definition of ECZEMA". www.merriam-webster.com. Archived from the original on 22 February 2016. Retrieved 15 February 2016.
86. ^ a b Center for Food Safety and Applied Nutrition (1 September 2020). ""Hypoallergenic" Cosmetics". FDA.
87. ^ Murphy LA, White IR, Rastogi SC (May 2004). "Is hypoallergenic a credible term?". Clinical and Experimental Dermatology. 29 (3): 325–7. doi:10.1111/j.1365-2230.2004.01521.x. PMID 15115531. S2CID 41482522.
88. ^ "Technical document on cosmetic claims". ec.europa.eu. European Commission. Retrieved 7 December 2020.
89. ^ Kulliney, Kacey (6 September 2019). "EU 'free from' cosmetics claims technical document is guidance, not regulation: Expert". cosmeticsdesign-europe.com. Retrieved 7 December 2020.
90. ^ Snast I, Reiter O, Hodak E, Friedland R, Mimouni D, Leshem YA (April 2018). "Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and Meta-Analysis". American Journal of Clinical Dermatology. 19 (2): 145–165. doi:10.1007/s40257-017-0324-7. PMID 29098604. S2CID 4220890.
91. ^ Lauffer F, Ring J (2016). "Target-oriented therapy: Emerging drugs for atopic dermatitis". Expert Opinion on Emerging Drugs. 21 (1): 81–9. doi:10.1517/14728214.2016.1146681. PMID 26808004. S2CID 207484890.
## External links[edit]
Classification
D
* ICD-10: L20-L30
* ICD-9-CM: 692
* OMIM: 603165
* MeSH: D004485
External resources
* MedlinePlus: 000853
* eMedicine: Derm/38 Ped/2567
Look up dermatitis in Wiktionary, the free dictionary.
Wikimedia Commons has media related to Dermatitis.
* Dermatitis at Curlie
* v
* t
* e
Dermatitis and eczema
Atopic dermatitis
* Besnier's prurigo
Seborrheic dermatitis
* Pityriasis simplex capillitii
* Cradle cap
Contact dermatitis
(allergic, irritant)
* plants: Urushiol-induced contact dermatitis
* African blackwood dermatitis
* Tulip fingers
* other: Abietic acid dermatitis
* Diaper rash
* Airbag dermatitis
* Baboon syndrome
* Contact stomatitis
* Protein contact dermatitis
Eczema
* Autoimmune estrogen dermatitis
* Autoimmune progesterone dermatitis
* Breast eczema
* Ear eczema
* Eyelid dermatitis
* Topical steroid addiction
* Hand eczema
* Chronic vesiculobullous hand eczema
* Hyperkeratotic hand dermatitis
* Autosensitization dermatitis/Id reaction
* Candidid
* Dermatophytid
* Molluscum dermatitis
* Circumostomy eczema
* Dyshidrosis
* Juvenile plantar dermatosis
* Nummular eczema
* Nutritional deficiency eczema
* Sulzberger–Garbe syndrome
* Xerotic eczema
Pruritus/Itch/
Prurigo
* Lichen simplex chronicus/Prurigo nodularis
* by location: Pruritus ani
* Pruritus scroti
* Pruritus vulvae
* Scalp pruritus
* Drug-induced pruritus
* Hydroxyethyl starch-induced pruritus
* Senile pruritus
* Aquagenic pruritus
* Aquadynia
* Adult blaschkitis
* due to liver disease
* Biliary pruritus
* Cholestatic pruritus
* Prion pruritus
* Prurigo pigmentosa
* Prurigo simplex
* Puncta pruritica
* Uremic pruritus
Other
* substances taken internally: Bromoderma
* Fixed drug reaction
* Nummular dermatitis
* Pityriasis alba
* Papuloerythroderma of Ofuji
Authority control
* GND: 4140644-8
* NDL: 00563155
*[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
|
Dermatitis
|
c0011603
| 25,552 |
wikipedia
|
https://en.wikipedia.org/wiki/Dermatitis
| 2021-01-18T18:28:18 |
{"mesh": ["D003872"], "umls": ["C0011603", "C3875321"], "icd-9": ["692.9"], "wikidata": ["Q229256"]}
|
A rare subtype of Griscelli syndrome characterized by pigmentary dilution in skin and hair with irregular clumps of pigment in hair shafts resulting in silvery hair, in association with increased susceptibility to recurrent infections and immunological abnormalities, in particular impairment of T-cell and natural killer cytotoxic activity eventually leading to hemophagocytic lymphohistiocytosis. Patients may present neurological manifestations related to infiltration of the central nervous system in the context of the hemophagocytic syndrome. The disease is mostly fatal in the first decade of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Griscelli syndrome type 2
|
c1868679
| 25,553 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79477
| 2021-01-23T18:00:27 |
{"gard": ["4483"], "mesh": ["C537302"], "omim": ["607624"], "umls": ["C1868679"], "icd-10": ["E70.3"], "synonyms": ["Griscelli-Pruniéras syndrome type 2", "Hypopigmentation-immunodeficiency with or without neurologic impairment syndrome"]}
|
Levator syndrome is characterized by sporadic pain in the rectum caused by spasm of a muscle near the anus (the levator ani muscle). The muscle spasm causes pain that typically is not related to defecation. The pain usually lasts less than 20 minutes. Pain may be brief and intense or a vague ache high in the rectum. It may occur spontaneously or with sitting and can waken a person from sleep. The pain may feel as if it would be relieved by the passage of gas or a bowel movement. In severe cases, the pain can persist for many hours and can recur frequently. A person may have undergone various unsuccessful rectal operations to relieve these symptoms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Levator syndrome
|
c0423738
| 25,554 |
gard
|
https://rarediseases.info.nih.gov/diseases/6899/levator-syndrome
| 2021-01-18T17:59:25 |
{"mesh": ["C535890"], "umls": ["C0423738"], "synonyms": ["Levator ani syndrome", "Levator ani spasm syndrome"]}
|
Ablepharon macrostomia syndrome is genetic disorder characterized by absent eyelids (ablepharon) and very large mouth (macrostomia). Other common signs and symptoms include abnormal external ears, fusion (syndactyly) of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations, and developmental delay. Other reported findings include underdeveloped cheeks (malar hypoplasia), absent or very small (hypoplastic) nipples, umbilical abnormalities and growth retardation. It belongs to a group of diseases called ectodermal dysplasias (genetic disorders that involve defects in the skin, hair, nails, sweat glands, and/or teeth). Ablepharon macrostomia syndrome is caused by mutations in the TWIST2 gene. Inheritance is autosomal dominant, but most cases are sporadic (when there are no other cases in the family). Treatment is aimed toward correcting the problems that are present.
Mutations in TWIST2 gene also cause the Barber Say syndrome and Setleis syndrome, other ectodermal dysplasia syndromes which have very similar features.
*[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
|
Ablepharon macrostomia syndrome
|
c1860224
| 25,555 |
gard
|
https://rarediseases.info.nih.gov/diseases/3/ablepharon-macrostomia-syndrome
| 2021-01-18T18:02:23 |
{"mesh": ["C535557"], "omim": ["200110"], "umls": ["C1860224"], "orphanet": ["920"], "synonyms": ["AMS", "Congenital ablepharon, absent eyelashes/eyebrows, macrostomia, auricular, nasal, genital and other systemic anomalies"]}
|
Reactive neutrophilic dermatoses
SpecialtyDermatology
Reactive neutrophilic dermatoses are a spectrum of conditions mediated by neutrophils, and typically associated with underlying diseases, such as inflammatory bowel disease and hematologic malignancy.[1]:144
Conditions considered to be reactive neutrophilic dermatoses include:[1]:144–9
* Erythema nodosum
* Marshall syndrome
* Sweet syndrome (Acute febrile neutrophilic dermatosis)
* Neutrophilic dermatosis of the dorsal hands (Pustular vasculitis of the dorsal hands)
* Neutrophilic eccrine hidradenitis
* Pyoderma gangrenosum
* PAPA syndrome
## References[edit]
1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
* v
* t
* e
Neutrophilic and eosinophilic dermatoses
Eosinophilic dermatosis
With vasculitis
* Eosinophilic vasculitis
* Eosinophilic granulomatosis with polyangiitis
Without vasculitis
* Arthropod assault
* Eosinophilic cellulitis
* Hypereosinophilic syndrome
* Papuloerythroderma of Ofuji
* Granuloma faciale
* Eosinophilic folliculitis
Ungrouped
* Angiolymphoid hyperplasia with eosinophilia/Kimura's disease
* Annular erythema of infancy
* Eosinophilic fasciitis
* Eosinophilic granuloma
* Eosinophilic ulcer of the oral mucosa
* Erythema toxicum neonatorum
* Incontinentia pigmenti
* Itchy red bump disease
* Juvenile xanthogranuloma
* Pachydermatous eosinophilic dermatitis
* Papular eruption of blacks
* Pruritic papular eruption of HIV disease
Reactive neutrophilic dermatoses
Epidermis
* Keratoderma blennorrhagicum
* Subcorneal pustular dermatosis
Dermis
without vasculitis:
* Sweet's syndrome
* Pyoderma gangrenosum
* Bowel-associated dermatosis–arthritis syndrome
with vasculitis:
* Neutrophilic dermatosis of the dorsal hands
Ungrouped
* Acute erythema nodosum
* Marshall syndrome
* Neutrophilic eccrine hidradenitis
* Pyogenic arthritis–pyoderma gangrenosum–acne syndrome
* Rheumatoid neutrophilic dermatitis
* Superficial granulomatous pyoderma
* Sweet's syndrome-like dermatosis
* Vesicopustular dermatosis
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Reactive neutrophilic dermatoses
|
None
| 25,556 |
wikipedia
|
https://en.wikipedia.org/wiki/Reactive_neutrophilic_dermatoses
| 2021-01-18T18:35:03 |
{"wikidata": ["Q7300315"]}
|
Onychauxis
SpecialtyMedical genetics
Onychauxis presents with thickened nails without deformity, and this simple thickening may be the result of trauma, acromegaly, Darier's disease, psoriasis, or pityriasis rubra pilaris, or, in some cases, hereditary.[1]:783[2]
## See also[edit]
* Onycholysis
* 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.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
## External links[edit]
Classification
D
* ICD-10: L60.2, Q84.5
* ICD-9-CM: 703.8, 757.5
* DiseasesDB: 32084
* v
* t
* e
Disorders of skin appendages
Nail
* thickness: Onychogryphosis
* Onychauxis
* color: Beau's lines
* Yellow nail syndrome
* Leukonychia
* Azure lunula
* shape: Koilonychia
* Nail clubbing
* behavior: Onychotillomania
* Onychophagia
* other: Ingrown nail
* Anonychia
* ungrouped: Paronychia
* Acute
* Chronic
* Chevron nail
* Congenital onychodysplasia of the index fingers
* Green nails
* Half and half nails
* Hangnail
* Hapalonychia
* Hook nail
* Ingrown nail
* Lichen planus of the nails
* Longitudinal erythronychia
* Malalignment of the nail plate
* Median nail dystrophy
* Mees' lines
* Melanonychia
* Muehrcke's lines
* Nail–patella syndrome
* Onychoatrophy
* Onycholysis
* Onychomadesis
* Onychomatricoma
* Onychomycosis
* Onychophosis
* Onychoptosis defluvium
* Onychorrhexis
* Onychoschizia
* Platonychia
* Pincer nails
* Plummer's nail
* Psoriatic nails
* Pterygium inversum unguis
* Pterygium unguis
* Purpura of the nail bed
* Racquet nail
* Red lunulae
* Shell nail syndrome
* Splinter hemorrhage
* Spotted lunulae
* Staining of the nail plate
* Stippled nails
* Subungual hematoma
* Terry's nails
* Twenty-nail dystrophy
Hair
Hair loss/
Baldness
* noncicatricial alopecia: Alopecia
* areata
* totalis
* universalis
* Ophiasis
* Androgenic alopecia (male-pattern baldness)
* Hypotrichosis
* Telogen effluvium
* Traction alopecia
* Lichen planopilaris
* Trichorrhexis nodosa
* Alopecia neoplastica
* Anagen effluvium
* Alopecia mucinosa
* cicatricial alopecia: Pseudopelade of Brocq
* Central centrifugal cicatricial alopecia
* Pressure alopecia
* Traumatic alopecia
* Tumor alopecia
* Hot comb alopecia
* Perifolliculitis capitis abscedens et suffodiens
* Graham-Little syndrome
* Folliculitis decalvans
* ungrouped: Triangular alopecia
* Frontal fibrosing alopecia
* Marie Unna hereditary hypotrichosis
Hypertrichosis
* Hirsutism
* Acquired
* localised
* generalised
* patterned
* Congenital
* generalised
* localised
* X-linked
* Prepubertal
Acneiform
eruption
Acne
* Acne vulgaris
* Acne conglobata
* Acne miliaris necrotica
* Tropical acne
* Infantile acne/Neonatal acne
* Excoriated acne
* Acne fulminans
* Acne medicamentosa (e.g., steroid acne)
* Halogen acne
* Iododerma
* Bromoderma
* Chloracne
* Oil acne
* Tar acne
* Acne cosmetica
* Occupational acne
* Acne aestivalis
* Acne keloidalis nuchae
* Acne mechanica
* Acne with facial edema
* Pomade acne
* Acne necrotica
* Blackhead
* Lupus miliaris disseminatus faciei
Rosacea
* Perioral dermatitis
* Granulomatous perioral dermatitis
* Phymatous rosacea
* Rhinophyma
* Blepharophyma
* Gnathophyma
* Metophyma
* Otophyma
* Papulopustular rosacea
* Lupoid rosacea
* Erythrotelangiectatic rosacea
* Glandular rosacea
* Gram-negative rosacea
* Steroid rosacea
* Ocular rosacea
* Persistent edema of rosacea
* Rosacea conglobata
* variants
* Periorificial dermatitis
* Pyoderma faciale
Ungrouped
* Granulomatous facial dermatitis
* Idiopathic facial aseptic granuloma
* Periorbital dermatitis
* SAPHO syndrome
Follicular cysts
* "Sebaceous cyst"
* Epidermoid cyst
* Trichilemmal cyst
* Steatocystoma
* simplex
* multiplex
* Milia
Inflammation
* Folliculitis
* Folliculitis nares perforans
* Tufted folliculitis
* Pseudofolliculitis barbae
* Hidradenitis
* Hidradenitis suppurativa
* Recurrent palmoplantar hidradenitis
* Neutrophilic eccrine hidradenitis
Ungrouped
* Acrokeratosis paraneoplastica of Bazex
* Acroosteolysis
* Bubble hair deformity
* Disseminate and recurrent infundibulofolliculitis
* Erosive pustular dermatitis of the scalp
* Erythromelanosis follicularis faciei et colli
* Hair casts
* Hair follicle nevus
* Intermittent hair–follicle dystrophy
* Keratosis pilaris atropicans
* Kinking hair
* Koenen's tumor
* Lichen planopilaris
* Lichen spinulosus
* Loose anagen syndrome
* Menkes kinky hair syndrome
* Monilethrix
* Parakeratosis pustulosa
* Pili (Pili annulati
* Pili bifurcati
* Pili multigemini
* Pili pseudoannulati
* Pili torti)
* Pityriasis amiantacea
* Plica neuropathica
* Poliosis
* Rubinstein–Taybi syndrome
* Setleis syndrome
* Traumatic anserine folliculosis
* Trichomegaly
* Trichomycosis axillaris
* Trichorrhexis (Trichorrhexis invaginata
* Trichorrhexis nodosa)
* Trichostasis spinulosa
* Uncombable hair syndrome
* Wooly hair nevus
Sweat
glands
Eccrine
* Miliaria
* Colloid milium
* Miliaria crystalline
* Miliaria profunda
* Miliaria pustulosa
* Miliaria rubra
* Occlusion miliaria
* Postmiliarial hypohidrosis
* Granulosis rubra nasi
* Ross’ syndrome
* Anhidrosis
* Hyperhidrosis
* Generalized
* Gustatory
* Palmoplantar
Apocrine
* Body odor
* Chromhidrosis
* Fox–Fordyce disease
Sebaceous
* Sebaceous hyperplasia
* v
* t
* e
Congenital malformations and deformations of skin appendages
Nail disease
* Anonychia
* Leukonychia
* Pachyonychia congenita/Onychauxis
* Koilonychia
Hair disease
* hypotrichosis/abnormalities: keratin disease
* Monilethrix
* IBIDS syndrome
* Sabinas brittle hair syndrome
* Pili annulati
* Pili torti
* Uncombable hair syndrome
* Björnstad syndrome
* Giant axonal neuropathy with curly hair
* hypertrichosis: Zimmermann–Laband syndrome
This condition of the skin appendages 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
|
Onychauxis
|
c0266002
| 25,557 |
wikipedia
|
https://en.wikipedia.org/wiki/Onychauxis
| 2021-01-18T19:02:20 |
{"umls": ["C0266002"], "icd-9": ["757.5", "703.8"], "icd-10": ["L60.2", "Q84.5"], "wikidata": ["Q7095142"]}
|
Osteomyelitis is the medical term for an infection in a bone. Signs and symptoms vary but may include bone pain, fever, chills, excessive sweating, malaise, or an open wound. People with the condition may also experience local swelling, redness, and warmth at the site of the infection. Although any bone in the body can be affected, the long bones of the arms and legs are most commonly infected in children, while the feet, spine bones, and hips are primarily affected in adults. Osteomyelitis is most often caused by a bacterial infection, although it can also be caused by a fungal infection. Risk factors for the condition include diabetes, poor blood supply, recent injury, intravenous drug abuse, surgery involving the bones, and a weakened immune system. The goal of treatment is to cure the infection and reduce damage to the bone and surrounding tissues. This may include medications to treat the infection and surgery to drain, clean and/or remove dead bone tissue.
*[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
|
Osteomyelitis
|
c0029443
| 25,558 |
gard
|
https://rarediseases.info.nih.gov/diseases/7286/osteomyelitis
| 2021-01-18T17:58:32 |
{"mesh": ["D010019"], "umls": ["C0029443"], "synonyms": []}
|
Well-differentiated liposarcoma (WDLS), the most common type of liposarcoma (LS; see this term), is a slow growing, painless tumor usually located in the retroperitoneum or the limbs. It is composed of proliferating mature adipocytes.
## Epidemiology
The incidence is approximately 1/200,000 per year and it accounts for 30-50% of all liposarcomas.
## Clinical description
WDLS occurs in adulthood, most often between the ages of 50 to 60 years, and it is seen more frequently in males. A slow growing, painless mass presents most often in the retroperitoneum or the limbs but occasionally in the spermatic cord and the mediastinum. The mass can be soft and fleshy or firm. Symptoms of urinary or bowel obstruction may be experienced if the tumor is large and compresses these organs.
## Etiology
WDLS is characterized by extensive chromosomal aberrations, which in 90% of cases include amplification of the chromosomal region 12q13-15. This amplification causes the overexpression of three genes that promote cell growth: MDM2 (that blocks p53 tumor suppressor function), CDK4 (involved in cell cycle regulation) and HMGA2.
## Diagnostic methods
When a mass is detected, computed tomography (CT) or magnetic resonance imaging (MRI) is performed. Chest and abdominal lesions do not require pretreatment biopsy unless resection is likely to be incomplete or highly morbid. Extremity lesions are generally removed completely without prior biopsy. WDLS resembles large, cohesive groups of adipocytes of varying cell size. Fluorescent in situ hybridization (FISH) and immunohistochemistry show the overexpression of MDM2 and CDK4. The four morphological subtypes of WDLS are adipocytic (lipoma-like), sclerosing, inflammatory and spindle cell.
## Differential diagnosis
Differential diagnoses include benign lipomas and other types of sarcomas, inflammatory myofibroblastic tumor and Castleman disease (see these terms).
## Management and treatment
Surgery is the mainstay of treatment for WDLS. If tumor excision is complete, then no further therapy is recommended, although the patient should be monitored for recurrence. Complete excision is often curative if the tumor is located in an extremity. Lesions in the retroperitoneum and inguinal areas are more difficult to treat and are more likely to recur locally and transform into dedifferentiated liposarcoma (DDLS; see this term). If the tumor is unresectable (or if the excision was incomplete), systemic therapies and radiation can be proposed but have shown little efficacy. Clinical trials are ongoing to assess new therapies in patients with advanced unresectable disease (CDK4 and MDM2 inhibitor trials).
## Prognosis
WDLS prognosis depends on the tumor location. Extremity WDLS usually has a good prognosis after the tumor has been removed, with low rates of recurrence and essentially no mortality. Retroperitoneal WDLS, however, has a 5-year probability of freedom from recurrence of only 54% and a 5-year disease-specific survival of 80 to 90%.
*[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
|
Well-differentiated liposarcoma
|
c1370889
| 25,559 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99971
| 2021-01-23T17:47:32 |
{"mesh": ["D008080"], "umls": ["C1370889"], "icd-10": ["C49.9"], "synonyms": ["ALT", "Atypical lipoma", "Atypical lipomatous tumor", "WDLS"]}
|
Frequent and recurrent binge eating episodes with associated negative psychological and social problems
Binge eating disorder
SpecialtyPsychiatry, clinical psychology
SymptomsEating much faster than normal, eating until feeling uncomfortably full, eating a large amount when not hungry
ComplicationsObesity, tooth decay
CausesUnclear
Risk factorsLow self-esteem, family history of eating disorders, childhood abuse or trauma, anxiety, depression, drug and alcohol use
Diagnostic methodPsychiatry, psychology
Differential diagnosisBulimia nervosa
TreatmentPsychiatry, psychology
Binge eating disorder (BED) is an eating disorder characterized by frequent and recurrent binge eating episodes with associated negative psychological and social problems, but without subsequent purging episodes, such as vomiting.[1]
BED is a recently described condition,[2] which was required to distinguish binge eating similar to that seen in bulimia nervosa but without characteristic purging. Individuals who are diagnosed with bulimia nervosa and binge eating disorder exhibit similar patterns of compulsive overeating, neurobiological features of dysfunctional cognitive control and food addiction, and biological and environmental risk factors.[3] Some professionals consider BED to be a milder form of bulimia with the two conditions on the same spectrum.[4]
Binge eating is one of the most prevalent eating disorders among adults,[5] though there tends to be less media coverage and research about the disorder in comparison to anorexia nervosa and bulimia nervosa.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 International Classification of Diseases
* 3.2 Diagnostic and Statistical Manual
* 4 Treatment
* 4.1 Counselling
* 4.2 Medication
* 4.3 Surgery
* 4.4 Lifestyle Interventions
* 5 Prognosis
* 6 Epidemiology
* 6.1 General
* 6.2 Worldwide Prevalences
* 6.3 Co-morbidities
* 6.4 Underreporting in Men
* 7 History
* 8 See also
* 9 References
* 9.1 Bibliography
* 10 External links
## Signs and symptoms[edit]
Binge eating is the core symptom of BED; however, not everyone who binge eats has BED.[6] An individual may occasionally binge eat without experiencing many of the negative physical, psychological, or social effects of BED. This example may be considered an eating problem (or not), rather than a disorder. Precisely defining binge eating can be problematic,[2] however binge eating episodes in BED are generally described as having the following potential features:
* Eating much faster than normal,[7] perhaps in a short space of time[8]
* Eating until feeling uncomfortably full[7]
* Eating a large amount when not hungry[7]
* Subjective loss of control over how much or what is eaten[9]
* Binges may be planned in advance,[7] involving the purchase of special binge foods,[7] and the allocation of specific time for binging, sometimes at night
* Eating alone or secretly due to embarrassment over the amount of food consumed[7]
* There may be a dazed mental state during the binge[7]
* Not being able to remember what was eaten after the binge[7]
* Feelings of guilt, shame or disgust following a food binge[7][9]
In contrast to bulimia nervosa, binge eating episodes are not regularly followed by activities intended to prevent weight gain,[2] such as self-induced vomiting, laxative or enema misuse, or strenuous exercise.[9] BED is characterized more by overeating than dietary restriction and over concern about body shape.[2] Obesity is common in persons with BED,[2] as are depressive features,[2] low self-esteem, stress and boredom.[8]
## Causes[edit]
As with other eating disorders, binge eating is an "expressive disorder"—a disorder that is an expression of deeper psychological problems.[3] People who have binge eating disorder have been found to have higher weight bias internalization, which includes low self-esteem, unhealthy eating patterns, and general body dissatisfaction.[10] Binge eating disorder commonly develops as a result or side effect of depression, as it is common for people to turn to comfort foods when they are feeling down.[11]
There was resistance to give binge eating disorder the status of a fully fledged eating disorder because many perceived binge eating disorder to be caused by individual choices.[5] Previous research has focused on the relationship between body image and eating disorders, and concludes that disordered eating might be linked to rigid dieting practices.[12] In the majority of cases of anorexia, extreme and inflexible restriction of dietary intake leads at some point to the development of binge eating, weight regain, bulimia nervosa, or a mixed form of eating disorder not otherwise specified. Binge eating may begin when individuals recover from an adoption of rigid eating habits. When under a strict diet that mimics the effects of starvation, the body may be preparing for a new type of behavior pattern, one that consumes a large amount of food in a relatively short period of time.[13][14][15][citation needed]
Some studies show that BED aggregates in families and could be genetic. However, very few published studies around the genetics exist.[16]
However, other research suggests that binge eating disorder can also be caused by environmental factors and the impact of traumatic events. One study showed that women with binge eating disorder experienced more adverse life events in the year prior to the onset of the development of the disorder, and that binge eating disorder was positively associated with how frequently negative events occur.[17] Additionally, the research found that individuals who had binge eating disorder were more likely to have experienced physical abuse, perceived risk of physical abuse, stress, and body criticism.[17] Other risk factors may include childhood obesity, critical comments about weight, low self-esteem, depression, and physical or sexual abuse in childhood.[18] A systematic review concluded that bulimia nervosa and binge eating disorder are more impacted by family separations, a loss in their lives and negative parent-child interactions compared to those with anorexia nervosa.[19] A few studies have suggested that there could be a genetic component to binge eating disorder,[5] though other studies have shown more ambiguous results. Studies have shown that binge eating tends to run in families and a twin study by Bulik, Sullivan, and Kendler has shown a, "moderate heritability for binge eating" at 41 percent.[20] More research must be done before any firm conclusions can be drawn regarding the heritability of binge eating disorder. Studies have also shown that eating disorders such as anorexia and bulimia reduce coping abilities, which makes it more likely for those suffering to turn to binge eating as a coping strategy.[21]
A correlation between dietary restraint and the occurrence of binge eating has been shown in some research.[6] While binge eaters are often believed to be lacking in self-control, the root of such behavior might instead be linked to rigid dieting practices. The relationship between strict dieting and binge eating is characterized by a vicious circle. Binge eating is more likely to occur after dieting, and vice versa. Several forms of dieting include delay in eating (e.g., not eating during the day), restriction of overall calorie intake (e.g., setting calorie limit to 1,000 calories per day), and avoidance of certain types of food (e.g., "forbidden" food, such as sugar, carbohydrates, etc.) [22] Strict and extreme dieting differs from ordinary dieting. Some evidence suggests the effectiveness of moderate calorie restriction in decreasing binge eating episodes among overweight individuals with binge eating disorder, at least in the short-term.[23][24]
“In the U.S, it is estimated that 3.5% of young women and 30% to 40% of people who seek weight loss treatments, can be clinically diagnosed with binge eating disorder.”[25]
## Diagnosis[edit]
### International Classification of Diseases[edit]
BED was first included in the Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1994 simply as a feature of eating disorder. In 2013 it gained formal recognition as a psychiatric condition in the DSM-5.[26]
The 2017 update to the American version of the ICD-10 includes BED under F50.81.[27] ICD-11 may contain a dedicated entry (6B62), defining BED as frequent, recurrent episodes of binge eating (once a week or more over a period of several months) which are not regularly followed by inappropriate compensatory behaviors aimed at preventing weight gain.[9]
### Diagnostic and Statistical Manual[edit]
Previously considered a topic for further research exploration, binge eating disorder was included in the Diagnostic and Statistical Manual of Mental Disorders in 2013.[28] Until 2013, binge eating disorder was categorized as an Eating Disorder Not Otherwise Specified, an umbrella category for eating disorders that don't fall under the categories for anorexia nervosa or bulimia nervosa. Because it was not a recognized psychiatric disorder in the DSM-IV until 2013, it has been difficult to obtain insurance reimbursement for treatments.[29] The disorder now has its own category under DSM-5, which outlines the signs and symptoms that must be present to classify a person's behavior as binge eating disorder. Studies have confirmed the high predictive value of these criteria for diagnosing BED.[30]
According to the World Health Organization's ICD-11 classification of BED, the severity of the disorder can be classified as mild (1-3 episodes/week), moderate (4-7 episodes/week), severe (8-13 episodes/week) and extreme (>14 episodes/week).[26]
One study claims that the method for diagnosing BED is for a clinician to conduct a structured interview using the DSM-5 criteria or taking the Eating Disorder Examination.[26] The Structured Clinical Interview takes no more than 75 minutes to complete and has a systematic approach which follows the DSM-5 criteria. The Eating Disorder Examination is a semi-structured interview which identifies the frequency of binges and associated eating disorder features.[26]
## Treatment[edit]
Counselling and certain medication, such as lisdexamfetamine and selective serotonin reuptake inhibitor (SSRIs), may help.[31] Some recommend a multidisciplinary approach in the treatment of the disorder.[8]
### Counselling[edit]
Cognitive behavioral therapy (CBT) treatment has been demonstrated as a more effective form of treatment for BED than behavioral weight loss programs. 50 percent of BED individuals achieve complete remission from binge eating[32] and 68-90% will reduce the amount of binge eating episodes they have.[26] CBT has also been shown to be an effective method to address self-image issues and psychiatric comorbidities (e.g., depression) associated with the disorder.[32] The goal of CBT is to interrupt binge-eating behaviour, learn to create a normal eating schedule, change the perception around weight and shape and develop positive attitudes about one's body.[26] Although this treatment is successful in eliminating binge eating episodes, it does not lead to losing any weight.[33] Recent reviews have concluded that psychological interventions such as psychotherapy and behavioral interventions are more effective than pharmacological interventions for the treatment of binge eating disorder.[34] A meta-analysis concluded that psychotherapy based on CBT not only significantly improved binge-eating symptomatology but also reduced a client's BMI significantly at posttreatment and longer than 6 and 12 months after treatment.[35] There is the 12-step Overeaters Anonymous or Food Addicts in Recovery Anonymous. Behavioral weight loss treatment has been proven to be effective as a means to achieve weight loss amongst patients.[36]
### Medication[edit]
Lisdexamfetamine is a USFDA-approved drug that is used for the treatment of moderate to severe binge eating disorder in adults.[37]
Three other classes of medications are also used in the treatment of binge eating disorder: antidepressants, anticonvulsants, and anti-obesity medications.[38] Antidepressant medications of the selective serotonin reuptake inhibitor (SSRI) have been found to effectively reduce episodes of binge eating and reduce weight.[38] Similarly, anticonvulsant medications such as topiramate and zonisamide may be able to effectively suppress appetite.[38] The long-term effectiveness of medication for binge eating disorder is currently unknown.[34] For BED patients with manic episodes, risperidone is recommended. If BED patients have bipolar depression, lamotrigine is appropriate to use.[39]
Trials of antidepressants, anticonvulsants, and anti-obesity medications suggest that these medications are superior to placebo in reducing binge eating.[40] Medications are not considered the treatment of choice because psychotherapeutic approaches, such as CBT, are more effective than medications for binge eating disorder. A meta-analysis concluded that using medications did not reduce binge-eating episodes and BMI posttreatment at 6–12 months. This indicates a potential possibility of relapse after withdrawal from the medications.[35] Medications also do not increase the effectiveness of psychotherapy, though some patients may benefit from anticonvulsant and anti-obesity medications, such as phentermine/topiramate, for weight loss.[40]
Blocking opioid receptors leads to less food intake. Additionally, bupropion and naltrexone used together may cause weight loss. Combining these alongside psychotherapies like CBT may lead to better outcomes for BED.[41]
### Surgery[edit]
Bariatric surgery has also been proposed as another approach to treat BED and a recent meta-analysis showed that approximately two-thirds of individuals who seek this type of surgery for weight loss purposes have BED. Bariatric surgery recipients who had BED prior to receiving the surgery tend to have poorer weight-loss outcomes and are more likely to continue to exhibit eating behaviors characteristic of BED.[32]
### Lifestyle Interventions[edit]
Other treatments for BED include lifestyle interventions like weight training, peer support groups, and investigation of hormonal abnormalities.
## Prognosis[edit]
Individuals suffering from BED often have a lower overall quality of life and commonly experience social difficulties.[34] Early behavior change is an accurate prediction of remission of symptoms later.[42]
Individuals who have BED commonly have other comorbidities such as major depressive disorder, personality disorder, bipolar disorder, substance abuse, body dysmorphic disorder, kleptomania, irritable bowel syndrome, fibromyalgia, or an anxiety disorder.[32][38] Individuals may also exhibit varying degrees of panic attacks and a history of attempted suicide.[8]
While people of a healthy weight may overeat occasionally, an ongoing habit of consuming large amounts of food in a short period of time may ultimately lead to weight gain and obesity. Bingeing episodes usually include foods that are high in fat, sugar, and/or salt, but low in vitamins and minerals, as these types of foods tend to trigger the greatest chemical and emotional rewards.[citation needed] The main physical health consequences of this type of eating disorder are brought on by the weight gain resulting from calorie-laden bingeing episodes. Mental and emotional consequences of binge eating disorder include social weight stigma and emotional loss of control.[43] Up to 70% of individuals with BED may also be obese,[8] and therefore obesity-associated morbidities such as high blood pressure[8] and coronary artery disease[8] type 2 diabetes mellitus gastrointestinal issues (e.g., gallbladder disease), high cholesterol levels, musculoskeletal problems and obstructive sleep apnea[32][34][44] may also be present.
## Epidemiology[edit]
### General[edit]
The prevalence of BED in the general population is approximately 1-3%.[45]
BED cases usually occur between the ages of 12.4 and 24.7, but prevalence rates increase until the age of 40.[46]
Binge eating disorder is the most common eating disorder in adults.[34]
The limited amount of research that has been done on BED shows that rates of binge eating disorder are fairly comparable among men and women.[47] The lifetime prevalence of binge eating disorder has been observed in studies to be 2.0 percent for men and 3.5 percent for women, higher than that of the commonly recognized eating disorders anorexia nervosa and bulimia nervosa.[32] However another systematic literature review found the prevalence average to be about 2.3% in women and about 0.3% in men.[26] Lifetime prevalence rates for BED in women can range anywhere from 1.5 to 6 times higher than in men.[46] One literature review found that point prevalence rates for BED vary from 0.1 percent to 24.1 percent depending on the sample.[46] This same review also found that the 12-month prevalence rates vary between 0.1 percent to 8.8 percent.[46]
Recent studies found that eating disorders which included anorexia nervosa, bulimia nervosa and binge-eating disorder are common among sexual and gender minority populations, including gay, lesbian, bisexual and transgender people. This could be due to the minority stress and discrimination this population experiences.[48]
Due to limited and inconsistent information and research on ethnic and racial differences, prevalence rates are hard to determine for BED.[46] Rates of binge eating disorder have been found to be similar among black women, white women, and white men,[49] while some studies have shown that binge eating disorder is more common among black women than among white women.[5] However, majority of the research done around BED is focused on White women.[50] One literature review found information citing no difference between BED prevalence among Hispanic, African American, and White women while other information found that BED prevalence was highest among Hispanics followed by Black individuals and finally White people.[46]
### Worldwide Prevalences[edit]
Eating disorders have usually been considered something that was specific to Western countries. However, the prevalence of eating disorders is increasing in other non-Western countries.[51] Though the research on binge eating disorders tends to be concentrated in North America, the disorder occurs across cultures.[52] In the USA, BED is present in 0.8% of male adults and 1.6% of female adults in a given year.[28]
The prevalence of BED is lower in Nordic countries compared to Europe in a study that included Finland, Sweden, Norway, and Iceland.[51] The point prevalence ranged from 0.4 to 1.5 percent and the lifetime prevalence ranged from 0.7 to 5.8 percent for BED in women.[51]
In a study that included Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela, the point prevalence for BED was 3.53 percent.[53] Therefore, this particular study found that the prevalence for BED is higher in these Latin American countries compared to Western countries.[53]
The prevalence of BED in Europe ranges from <1 to 4 percent.[54]
### Co-morbidities[edit]
BED is co-morbid with diabetes, hypertension, previous stroke, and heart disease in some individuals.[46]
In people who have obsessive-compulsive disorder or bipolar I or II disorders, BED lifetime prevalence was found to be higher.[46]
Additionally, 30 to 40 percent of individuals seeking treatment for weight-loss can be diagnosed with binge eating disorder.[32]
### Underreporting in Men[edit]
Eating disorders are oftentimes underreported in men.[51] Underreporting could be a result of measurement bias due to how eating disorders are defined.[51] The current definition for eating disorders focuses on thinness.[51] However, eating disorders in men tend to center on muscularity and would therefore warrant a need for a different measurement definition.[51] Further research should focus on including more men in samples since previous research has focused primarily on women.[51]
## History[edit]
The disorder was first described in 1959 by psychiatrist and researcher Albert Stunkard as "night eating syndrome" (NES).[55] The term "binge eating" was coined to describe the same bingeing-type eating behavior but without the exclusive nocturnal component.[56]
There is generally less research on binge eating disorder in comparison to anorexia nervosa and bulimia nervosa.[5]
## See also[edit]
* Prader–Willi syndrome
## References[edit]
1. ^ Agüera, Zaida; Lozano-Madrid, María; Mallorquí-Bagué, Núria; Jiménez-Murcia, Susana; Menchón, José M.; Fernández-Aranda, Fernando (28 April 2020). "A review of binge eating disorder and obesity". neuropsychiatrie. doi:10.1007/s40211-020-00346-w. ISSN 0948-6259.
2. ^ a b c d e f Eating disorders: core interventions in the treatment and management of anorexia nervosa, bulimia nervosa, and related eating disorders; National Clinical Practice Guideline No. CG9. Leicester [u.a.]: The British Psychological Society and Gaskell. 2004. ISBN 978-1854333988.
3. ^ a b Wu M, Brockmeyer T, Hartmann M, Skunde M, Herzog W, Friederich HC (December 2014). "Set-shifting ability across the spectrum of eating disorders and in overweight and obesity: a systematic review and meta-analysis". Psychological Medicine. 44 (16): 3365–85. doi:10.1017/S0033291714000294. PMID 25066267.
4. ^ Hay PP, Bacaltchuk J, Stefano S, Kashyap P (October 2009). "Psychological treatments for bulimia nervosa and binging". The Cochrane Database of Systematic Reviews (4): CD000562. doi:10.1002/14651858.CD000562.pub3. PMC 7034415. PMID 19821271.
5. ^ a b c d e Saguy A, Gruys K. "Morality and Health: News Media Constructions of Overweight and Eating Disorders" (PDF). UCLA. Retrieved 23 November 2014.
6. ^ a b Fairburn C (2013). Overcoming binge eating: the proven program to learn why you binge and how you can stop (Second ed.). New York: Guilford Publications. ISBN 978-1572305618.
7. ^ a b c d e f g h i "Binge eating disorder - NHS Choices". www.nhs.uk. Nation Health Service. Retrieved 19 January 2017.
8. ^ a b c d e f g Michalska A, Szejko N, Jakubczyk A, Wojnar M (2016). "Nonspecific eating disorders - a subjective review" (PDF). Psychiatria Polska. 50 (3): 497–507. doi:10.12740/PP/59217. PMID 27556109.
9. ^ a b c d "ICD-11 Beta Draft - Mortality and Morbidity Statistics". apps.who.int. Retrieved 19 January 2017.
10. ^ Pearl RL, White MA, Grilo CM (April 2014). "Overvaluation of shape and weight as a mediator between self-esteem and weight bias internalization among patients with binge eating disorder". Eating Behaviors. 15 (2): 259–61. doi:10.1016/j.eatbeh.2014.03.005. PMC 4053161. PMID 24854815.
11. ^ "USATODAY.com - Women like sugar, men like meat". usatoday30.usatoday.com. Retrieved 21 April 2016.
12. ^ Herbozo S, Schaefer LM, Thompson JK (April 2015). "A comparison of eating disorder psychopathology, appearance satisfaction, and self-esteem in overweight and obese women with and without binge eating". Eating Behaviors. 17: 86–9. doi:10.1016/j.eatbeh.2015.01.007. PMID 25668799.
13. ^ "Binge Eating Disorder". HelpGuide. Retrieved 10 May 2020.
14. ^ "Where next after anorexia: death, recovery, or another eating disorder?". Psychology Today. Retrieved 21 April 2016.
15. ^ Veenstra EM, de Jong PJ (August 2010). "Restrained eaters show enhanced automatic approach tendencies towards food". Appetite. 55 (1): 30–6. doi:10.1016/j.appet.2010.03.007. PMID 20298730.
16. ^ "Genetics of Eating Disorders: What the Clinician Needs to Know". Psychiatric Clinics of North America. 42 (1): 59–73. 1 March 2019. doi:10.1016/j.psc.2018.10.007. ISSN 0193-953X.
17. ^ a b Mazzeo SE, Bulik CM (January 2009). "Environmental and genetic risk factors for eating disorders: what the clinician needs to know". Child and Adolescent Psychiatric Clinics of North America. 18 (1): 67–82. doi:10.1016/j.chc.2008.07.003. PMC 2719561. PMID 19014858.
18. ^ Rayworth BB, Wise LA, Harlow BL (May 2004). "Childhood abuse and risk of eating disorders in women". Epidemiology. 15 (3): 271–8. doi:10.1097/01.ede.0000120047.07140.9d. JSTOR 20485891. PMID 15097006.
19. ^ Grogan, Katie; MacGarry, Diarmuid; Bramham, Jessica; Scriven, Mary; Maher, Caroline; Fitzgerald, Amanda (December 2020). "Family-related non-abuse adverse life experiences occurring for adults diagnosed with eating disorders: a systematic review". Journal of Eating Disorders. 8 (1): 36. doi:10.1186/s40337-020-00311-6. ISSN 2050-2974. PMC 7374817. PMID 32704372.
20. ^ Bulik CM, Sullivan PF, Kendler KS (April 2003). "Genetic and environmental contributions to obesity and binge eating". The International Journal of Eating Disorders. 33 (3): 293–8. doi:10.1002/eat.10140. PMID 12655626.
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22. ^ Tuschl RJ (April 1990). "From dietary restraint to binge eating: some theoretical considerations". Appetite. 14 (2): 105–9. doi:10.1016/0195-6663(90)90004-R. PMID 2186700.
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25. ^ "Eating Disorder Statistics".
26. ^ a b c d e f g Chevinsky, Jonathan D.; Wadden, Thomas A.; Chao, Ariana M. (14 April 2020). "Binge Eating Disorder in Patients with Type 2 Diabetes: Diagnostic and Management Challenges". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. doi:10.2147/dmso.s213379. PMC 7166070. PMID 32341661. Retrieved 26 October 2020.
27. ^ "2017 ICD-10-CM Diagnosis Code F50.81 : Binge eating disorder". www.icd10data.com. Retrieved 8 May 2017.
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33. ^ Citrome, Leslie (August 2019). "Binge eating disorder revisited: what's new, what's different, what's next". CNS Spectrums. 24 (S1): 4–13. doi:10.1017/S1092852919001032. ISSN 1092-8529.
34. ^ a b c d e Iacovino JM, Gredysa DM, Altman M, Wilfley DE (August 2012). "Psychological treatments for binge eating disorder". Current Psychiatry Reports. 14 (4): 432–46. doi:10.1007/s11920-012-0277-8. PMC 3433807. PMID 22707016.
35. ^ a b Hilbert, Anja; Petroff, David; Herpertz, Stephan; Pietrowsky, Reinhard; Tuschen‐Caffier, Brunna; Vocks, Silja; Schmidt, Ricarda (September 2020). "Meta‐analysis on the long‐term effectiveness of psychological and medical treatments for binge‐eating disorder". International Journal of Eating Disorders. 53 (9): 1353–1376. doi:10.1002/eat.23297. ISSN 0276-3478.
36. ^ Wilson GT, Wilfley DE, Agras WS, Bryson SW (January 2010). "Psychological treatments of binge eating disorder". Archives of General Psychiatry. 67 (1): 94–101. doi:10.1001/archgenpsychiatry.2009.170. PMC 3757519. PMID 20048227.
37. ^ "Vyvanse Prescribing Information" (PDF). United States Food and Drug Administration. Shire US Inc. May 2017. pp. 1–3. Retrieved 10 July 2017.
38. ^ a b c d Marazziti D, Corsi M, Baroni S, Consoli G, Catena-Dell'Osso M (December 2012). "Latest advancements in the pharmacological treatment of binge eating disorder" (PDF). European Review for Medical and Pharmacological Sciences. 16 (15): 2102–7. PMID 23280026.
39. ^ Himmerich, Hubertus; Kan, Carol; Au, Katie; Treasure, Janet (25 August 2020). "Pharmacological treatment of eating disorders, comorbid mental health problems, malnutrition and physical health consequences". Pharmacology & Therapeutics: 107667. doi:10.1016/j.pharmthera.2020.107667. ISSN 0163-7258.
40. ^ a b Lindsay Bodell, Michael Devlin (2011). "Pharmacotherapy for binge-eating disorder". In Grilo C, Mitchell J (eds.). The treatment of eating disorders: a clinical handbook. New York: Guilford. ISBN 978-1609184957.
41. ^ Valbrun, Leon P.; Zvonarev, Valeriy (2020). "The Opioid System and Food Intake: Use of Opiate Antagonists in Treatment of Binge Eating Disorder and Abnormal Eating Behavior". Journal of Clinical Medicine Research. 12 (2): 41–63. doi:10.14740/jocmr4066. ISSN 1918-3003. PMC 7011935. PMID 32095174.
42. ^ Nazar BP, Gregor LK, Albano G, Marchica A, Coco GL, Cardi V, Treasure J (March 2017). "Early Response to treatment in Eating Disorders: A Systematic Review and a Diagnostic Test Accuracy Meta-Analysis". European Eating Disorders Review. 25 (2): 67–79. doi:10.1002/erv.2495. PMID 27928853.
43. ^ "Binge Eating Disorder". National Eating Disorders Association. 26 February 2017. Retrieved 18 February 2019.
44. ^ "Binge Eating Disorder". National Eating Disorders Association. Retrieved 18 April 2014.
45. ^ Perkins SJ, Murphy R, Schmidt U, Williams C (July 2006). "Self-help and guided self-help for eating disorders". The Cochrane Database of Systematic Reviews (3): CD004191. doi:10.1002/14651858.CD004191.pub2. PMID 16856036.
46. ^ a b c d e f g h Ágh, Tamás; Kovács, Gábor; Pawaskar, Manjiri; Supina, Dylan; Inotai, András; Vokó, Zoltán (March 2015). "Epidemiology, health-related quality of life and economic burden of binge eating disorder: a systematic literature review". Eating and weight disorders: EWD. 20 (1): 1–12. doi:10.1007/s40519-014-0173-9. ISSN 1590-1262. PMC 4349998. PMID 25571885.
47. ^ Striegel-Moore RH, Rosselli F, Perrin N, DeBar L, Wilson GT, May A, Kraemer HC (July 2009). "Gender difference in the prevalence of eating disorder symptoms". The International Journal of Eating Disorders. 42 (5): 471–4. doi:10.1002/eat.20625. PMC 2696560. PMID 19107833.
48. ^ Nagata, Jason M.; Ganson, Kyle T.; Austin, S. Bryn (November 2020). "Emerging trends in eating disorders among sexual and gender minorities". Current Opinion in Psychiatry. 33 (6): 562–567. doi:10.1097/YCO.0000000000000645. ISSN 0951-7367.
49. ^ Mitchison D, Mond J, Slewa-Younan S, Hay P (May 2013). "Sex differences in health-related quality of life impairment associated with eating disorder features: a general population study". The International Journal of Eating Disorders. 46 (4): 375–80. doi:10.1002/eat.22097. PMID 23355018.
50. ^ Goode, Rachel W.; Cowell, Mariah M.; Mazzeo, Suzanne E.; Cooper‐Lewter, Courtney; Forte, Alexandria; Olayia, Oona‐Ifé; Bulik, Cynthia M. (April 2020). "Binge eating and binge‐eating disorder in Black women: A systematic review". International Journal of Eating Disorders. 53 (4): 491–507. doi:10.1002/eat.23217. ISSN 0276-3478.
51. ^ a b c d e f g h Dahlgren, Camilla Lindvall; Stedal, Kristin; Wisting, Line (3 July 2018). "A systematic review of eating disorder prevalence in the Nordic countries: 1994–2016". Nordic Psychology. 70 (3): 209–227. doi:10.1080/19012276.2017.1410071. ISSN 1901-2276.
52. ^ Pike KM, Hoek HW, Dunne PE (November 2014). "Cultural trends and eating disorders". Current Opinion in Psychiatry. 27 (6): 436–42. doi:10.1097/YCO.0000000000000100. PMID 25211499.
53. ^ a b Kolar, David R.; Rodriguez, Dania L. Mejía; Chams, Moises Mebarak; Hoek, Hans W. (November 2016). "Epidemiology of eating disorders in Latin America: a systematic review and meta-analysis". Current Opinion in Psychiatry. 29 (6): 363–371. doi:10.1097/YCO.0000000000000279. ISSN 0951-7367.
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55. ^ Stunkard AJ (April 1959). "Eating patterns and obesity". The Psychiatric Quarterly. 33 (2): 284–95. doi:10.1007/BF01575455. PMID 13835451.
56. ^ Brewerton T. "Binge Eating: Recognition, Diagnosis, and Treatment". Medscape Health eJournal. Retrieved 15 December 2014.
### Bibliography[edit]
* Fairburn CG (1995). "Overcoming Binge Eating". New York: Guilford Press. ISBN 0-89862-961-6. Cite journal requires `|journal=` (help)
* Grilo CM (1998). "The Assessment and Treatment of Binge Eating Disorder". Journal of Practical Psychiatry and Behavioral Health. 4 (4): 191–201. doi:10.1097/00131746-199807000-00001.
* Siegel M, Brisman J, Weinshel M (1988). Surviving an Eating Disorder: New Perspectives and Strategies for Family and Friends. New York: Harper & Row. ISBN 0-06-015859-X.
* Yanovski SZ (July 1993). "Binge eating disorder: current knowledge and future directions". Obesity Research. 1 (4): 306–24. doi:10.1002/j.1550-8528.1993.tb00626.x. PMID 16350580.
## External links[edit]
* Binge Eating Disorder on Medscape
* Binge Eating Disorder on National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Classification
D
* ICD-10: F50.81
* ICD-9-CM: 307.59
* MeSH: D056912
External resources
* MedlinePlus: 003265
*[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
|
Binge eating disorder
|
c0596170
| 25,560 |
wikipedia
|
https://en.wikipedia.org/wiki/Binge_eating_disorder
| 2021-01-18T18:32:00 |
{"mesh": ["D056912"], "icd-10": ["F50.8"], "wikidata": ["Q209522"]}
|
Visual field loss on the left or right side of the vertical midline
Homonymous hemianopsia
Paris as seen with left homonymous hemianopsia
SpecialtyOphthalmology
Hemianopsia, or hemianopia, is a visual field loss on the left or right side of the vertical midline. It can affect one eye but usually affects both eyes.
Homonymous hemianopsia (or homonymous hemianopia) is hemianopic visual field loss on the same side of both eyes. Homonymous hemianopsia occurs because the right half of the brain has visual pathways for the left hemifield of both eyes, and the left half of the brain has visual pathways for the right hemifield of both eyes. When one of these pathways is damaged, the corresponding visual field is lost.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Management
* 5 Etymology
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Paris as seen with right homonymous hemianopsia
Mobility can be difficult for people with homonymous hemianopsia. "Patients frequently complain of bumping into obstacles on the side of the field loss, thereby bruising their arms and legs."[1]
People with homonymous hemianopsia often experience discomfort in crowds. "A patient with this condition may be unaware of what he or she cannot see and frequently bumps into walls, trips over objects or walks into people on the side where the visual field is missing."[2]
A related phenomenon is hemispatial neglect, the possible neglect of the right or left. The patient is not conscious of its existence. The right side of the face is not shaven, make up is applied to one side of the face only and only half of a plate of food is eaten.[3] This, however, is not necessarily due to a sensory abnormality, and is therefore distinct from hemianopsia.[4]
## Causes[edit]
Homonymous hemianopsia can be congenital, but is usually caused by brain injury such as from stroke, trauma,[5] tumors, infection, or following surgery.
Vascular and neoplastic (malignant or benign tumours) lesions from the optic tract, to visual cortex can cause a contralateral homonymous hemianopsia. Injury to the right side of the brain will affect the left visual fields of each eye. The more posterior the cerebral lesion, the more symmetric (congruous) the homonymous hemianopsia will be. For example, a person who has a lesion of the right optic tract will no longer see objects on his left side. Similarly, a person who has a stroke to the right occipital lobe will have the same visual field defect, usually more congruent between the two eyes, and there may be macular sparing. A stroke on the right side of the brain (especially parietal lobe), in addition to producing a homonymous hemianopsia, may also lead to the syndrome of hemispatial neglect.
Transient homonymous hemianopsia does not necessarily mean stroke. For instance, it can constitute the aura phase of migraine. Concomitant presence of a moving scintillating scotoma is suggestive of migraine,[6] but has been seen in cerebral cancer as well.[7] Computed tomography (CT scan) or MRI can be used to investigate if stroke, tumor, structural lesion, or demyelination is the cause of homonymous hemianopsia.[6]
## Diagnosis[edit]
Homonymous hemianopsia secondary to posterior cerebral artery occlusion – may result in syndromes of memory impairment, opposite visual field loss (homonymous hemianopsia), and sometimes hemisensory deficits. The PCA supplies the occipital lobe and the medial portion of the temporal lobe.
Infarction of occipital cortex typically causes macular sparing hemianopias due to dual blood supply from both posterior cerebral artery and middle cerebral artery.
Occlusion of the calcarine artery that results in infarction of the superior part of the occipital lobe causes a lower peripheral visual field defect.
Posterior cerebral artery penetrating branch occlusion may result in infarction of the posterior capsule, causing hemisensory loss, and (if low enough) a transient hemianopia may also occur.
## Management[edit]
Prisms or "field expanders" that bend light have been prescribed for decades in patients with hemianopsia. Higher power Fresnel ("stick-on") prisms are commonly employed because they are thin and lightweight, and can be cut and placed in different positions on a spectacle lens.
Peripheral prism spectacles expand the visual field of patients with hemifield visual defects and have the potential to improve visual function and mobility.[8] Prism spectacles incorporate higher power prisms, with variable shapes and designs. The Gottlieb button prism, and the Peli superior and inferior horizontal bands are some proprietary examples of prism glasses. These high power prisms "create" artificial peripheral vision into the non-blind field for obstacle avoidance and motion detection.
Certain counterbalancing brain lesions have also been shown to improve visual deficits in a phenomenon known as the Sprague effect.
## Etymology[edit]
Homonymous hemianopsia can be broken down as follows:
* Homonymous: (Greek >ομόνυμος = όμοιος + όνομα (same + name) (having the same name or designation) or standing in the same relation
* hemi: ημι-, half
* anopsia: α(ν)+όψις = without + sight; blindness
Homonymous hemianopsia is also called homonymous hemianopia.
## See also[edit]
* Binasal hemianopsia
* Bitemporal hemianopsia
* Blindsight
* Vision restoration therapy
## References[edit]
1. ^ Peli E. Field expansion for homonymous hemianopia by optically induced peripheral exotropia. Optom Vis Sci 2000; 77:453-464.
2. ^ Prism Glasses Expand The View For Patients With Hemianopia, Medical News today, 14 May 2008, www.medicalnewstoday.com/articles/107160.php
3. ^ Oliver Sacks, The Man Who Mistook His Wife for a Hat
4. ^ Parton, A; Malhotra, P; Husain, M (2004). "Hemispatial neglect". Journal of Neurology, Neurosurgery, and Psychiatry. 75 (1): 13–21. PMC 1757480. PMID 14707298.
5. ^ Zhang X, Kedar S, Lynn MJ, Newman NJ, Biousse V (March 2006). "Homonymous hemianopias: clinical-anatomic correlations in 904 cases". Neurology. 66 (6): 906–10. doi:10.1212/01.wnl.0000203913.12088.93. PMID 16567710.
6. ^ a b eMedicine > Posterior Cerebral Artery Stroke Authors: Christopher Luzzio and Consuelo T Lorenzo. Updated: Jul 15, 2009
7. ^ Weinstein, J. M.; Appen, R. E.; Houston, L.; Zurhein, G. (1987). "Recurrent scintillating scotoma and homonymous hemianopia due to metastatic melanoma". Journal of clinical neuro-ophthalmology. 7 (3): 155–160. PMID 2958508.
8. ^ Bowers AR, Keeney K, Peli E. Community-based trial of a peripheral prism visual field expansion device for hemianopia. Arch Ophthalmol 2008;126:657-664
* Schofield TM, Leff, AP, Rehabilitation of Hemianopia, Current Opinion in Neurology, 2009, 22:36-40
## External links[edit]
Classification
D
* ICD-10: H53.4
* ICD-9-CM: 368.46
* 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
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* Chorioretinitis
Lens
* Cataract
* Congenital cataract
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* Aphakia
* Ectopia lentis
Retina
* Retinitis
* Chorioretinitis
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* Ocular ischemic syndrome / Central retinal vein occlusion
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* Branch retinal artery occlusion
* Retinopathy
* diabetic
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* of prematurity
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* 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
|
Homonymous hemianopsia
|
c0271202
| 25,561 |
wikipedia
|
https://en.wikipedia.org/wiki/Homonymous_hemianopsia
| 2021-01-18T18:54:03 |
{"mesh": ["D006423"], "umls": ["C0271202"], "icd-9": ["368.46"], "icd-10": ["H53.46"], "wikidata": ["Q2624988"]}
|
Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Complications resulting from these clots can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.
Blood clots normally form to stop blood loss at the sites of blood vessel injury. In people with thrombotic thrombocytopenic purpura, clots develop even in the absence of apparent injury. Blood clots are formed from clumps of cells called platelets that circulate in the blood and assist with clotting. Because a large number of platelets are used to make clots in people with thrombotic thrombocytopenic purpura, fewer platelets are available in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura.
This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.
There are two major forms of thrombotic thrombocytopenic purpura, an acquired (noninherited) form and a familial (inherited) form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or, more commonly, they may experience multiple recurrences over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood, although it can appear later in life. In people with the familial form, signs and symptoms often recur on a regular basis and may return during times of stress, such as during illness or pregnancy.
## Frequency
The precise incidence of thrombotic thrombocytopenic purpura is unknown. Researchers estimate that, depending on geographic location, the condition affects 1.7 to 14.5 per million people each year in the United States. For unknown reasons, the disorder occurs more frequently in women than in men. The acquired form of thrombotic thrombocytopenic purpura is much more common than the familial form.
## Causes
Mutations in the ADAMTS13 gene cause the familial form of thrombotic thrombocytopenic purpura. The ADAMTS13 gene provides instructions for making an enzyme that is involved in the normal process of blood clotting. Mutations in this gene lead to a severe reduction in the activity of this enzyme. The acquired form of thrombotic thrombocytopenic purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not have mutations in the ADAMTS13 gene. Instead, their immune systems make specific proteins called autoantibodies that block the activity of the enzyme.
A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. Normally, blood clots form at the site of an injury to seal off damaged blood vessels and prevent excess blood loss. In people with thrombotic thrombocytopenic purpura, clots form throughout the body as platelets bind together abnormally and stick to the walls of blood vessels. These clots can block small blood vessels, causing organ damage and the other features of thrombotic thrombocytopenic purpura.
Researchers believe that other genetic or environmental factors may contribute to the onset of signs and symptoms of thrombotic thrombocytopenic purpura. In people with reduced ADAMTS13 enzyme activity, factors such as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications.
### Learn more about the gene associated with Thrombotic thrombocytopenic purpura
* ADAMTS13
## Inheritance Pattern
The familial form of thrombotic thrombocytopenic purpura 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.
The acquired form of thrombotic thrombocytopenic purpura is not inherited.
*[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
|
Thrombotic thrombocytopenic purpura
|
c1268935
| 25,562 |
medlineplus
|
https://medlineplus.gov/genetics/condition/thrombotic-thrombocytopenic-purpura/
| 2021-01-27T08:24:56 |
{"gard": ["9430", "4607"], "mesh": ["D011697"], "omim": ["274150"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that methylmalonic aciduria and homocystinuria of the cblF type (MAHCF) is caused by homozygous or compound heterozygous mutation in the LMBRD1 gene (612625) on chromosome 6q13.
Description
Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism. The defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase (MUT; 609058) and methyltetrahydrofolate:homocysteine methyltransferase, also known as methionine synthase (MTR; 156570). Different forms of the disorder have been classified according to complementation groups of cells in vitro: cblC (MAHCC; 277400), cblD (MAHCD; 277410), cblF, and cblJ (MAHCJ; 614857).
Clinical Features
Rosenblatt et al. (1985, 1986) reported an infant girl with developmental delay, stomatitis, glossitis, seizures, and minimal methylmalonic aciduria responsive to vitamin B12. There was no megaloblastic anemia or homocystinuria. Like control cells, the patient's fibroblasts accumulated the transcobalamin II-B12 complex within lysosomes and released B12 from the binding protein. However, the patient's cells were defective in the release of cobalamin from the lysosome into the cytoplasm. The cells also showed indirect evidence of methylmalonyl-CoA mutase and methionine synthase activity, as well as inability to synthesize AdoCbl and MeCbl. No abnormality of lysosomal structure was detected by electron microscopy. After incubation in labeled vitamin B12, accumulation was found in lysosomes (Vassiliadis et al., 1991). Like Salla disease (604369) and cystinosis (219800), this disorder appeared to result from impeded egress (efflux) from lysosomes. Rosenblatt et al. (1986) suggested that the disorder be called cblF, cobalamin F disease. In vitro studies showed that the patient's fibroblasts complemented the other known groups of methylmalonic aciduria (Watkins and Rosenblatt, 1986).
Shih et al. (1987, 1989) reported a female infant with failure to thrive, developmental delay, minor facial anomalies, stomatitis, skin rashes, macrocytosis, homocystinuria, and methylmalonic acidemia. In vitro studies showed decreased synthesis of AdoCbl and MeCbl, and accumulation of unmetabolized free cobalamin. Treatment with hydroxocobalamin resulted in clinical and biochemical improvement, but sudden death occurred at 5 months of age.
MacDonald et al. (1992) reported 2 unrelated males with cblF. The older patient had recurrent stomatitis during infancy, juvenile rheumatoid arthritis at age 4 years, and a reticulate pigmented skin abnormality at age 10.
Rutsch et al. (2009) reported 12 unrelated patients with cblF. Frequent clinical findings included being small for gestational age, poor feeding, failure to thrive, developmental delay and persistent stomatitis. Two individuals had minor facial abnormalities, including pegged teeth and bifid incisors, and 4 had congenital heart defects. Other common features included macrocytic anemia, neutropenia, thrombocytopenia, and pancytopenia. Affected individuals were identified by elevated homocysteine and methylmalonic acid concentrations in blood or urine samples, although 3 patients were identified by increased propionylcarnitine concentrations detected by newborn screening. The diagnosis of the cblF defect was established by complementation analysis on fibroblasts.
Clinical Management
Alfadhel et al. (2011) reported an 18-year follow-up of a girl with cblF disease, confirmed by genetic analysis, who started treatment with intramuscular hydroxycobalamin (vitamin B12) beginning at age 6 months. She presented at that time with failure to thrive, delayed development, recurrent infections, skin rash, megaloblastic anemia, borderline neutropenia, and impaired T-cell response. Laboratory studies showed decreased serum B12, increased plasma homocysteine, methylmalonic aciduria, and decreased AdoCbl and MeCbl. Treatment resulted in normalization of hematologic and immunologic parameters and growth parameters. She showed progress in psychomotor development, with speech acquisition, but remained mildly intellectually disabled. Physical examination at age 18 years showed no abnormalities of the major organ systems, although she had delayed cognitive skills. Alfadhel et al. (2011) noted that cblF disease is a treatable condition and that the disorder should be suspected in patients with failure to thrive, developmental delay, recurrent infections, and megaloblastic anemia.
Mapping
By linkage analysis of several families with cblF, Rutsch et al. (2009) identified a locus on chromosome 6q12-q13 (maximum lod score of 4.7).
Molecular Genetics
In 12 unrelated patients with MAHCF, Rutsch et al. (2009) identified 5 different homozygous or compound heterozygous mutations in the LMBRD1 gene (612625.0001-612625.0003). A 1-bp deletion (612625.0001) was present in 18 of the 24 disease chromosomes, consistent with a common founder of European ancestry. All mutations were truncating, but the phenotype was variable, ranging from developmental delay to asymptomatic long-term survival; thus there were no genotype/phenotype correlations.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Ears \- Low-set ears \- Small ears Eyes \- Epicanthal folds Mouth \- Stomatitis \- Glossitis \- Thin upper lip \- High-arched palate ABDOMEN Gastrointestinal \- Poor feeding SKIN, NAILS, & HAIR Skin \- Reticulate pigmented skin abnormalities \- Skin rashes NEUROLOGIC Central Nervous System \- Hypotonia \- Lethargy \- Developmental delay \- Impaired coordination HEMATOLOGY \- Pancytopenia \- Neutropenia \- Thrombocytopenia \- Megaloblastic anemia LABORATORY ABNORMALITIES \- Methylmalonic acidemia \- Methylmalonic aciduria \- Homocystinemia \- Homocystinuria \- Cystathioninemia \- Cystathioninuria \- Decreased adenosylcobalamin (AdoCbl) \- Decreased methylcobalamin (MeCbl) \- Decreased activity of methylmalonyl-CoA mutase (MUT, 609058 ) \- Decreased activity of methionine synthase (MTR, 156570 ) \- Increased free cyanocobalamin in fibroblasts MISCELLANEOUS \- Onset in infancy \- Responsive to vitamin B12 therapy \- See also CblC ( 277400 ) MOLECULAR BASIS \- Caused by mutation in the LMBR1 domain-containing protein 1 gene (LMBRD1, 612625.0001 ). ▲ 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
|
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblF TYPE
|
c1848561
| 25,563 |
omim
|
https://www.omim.org/entry/277380
| 2019-09-22T16:21:21 |
{"doid": ["0050717"], "mesh": ["C537359"], "omim": ["277380"], "orphanet": ["26", "79284"], "synonyms": ["Alternative titles", "METHYLMALONIC ACIDEMIA AND HOMOCYSTINURIA, cblF TYPE", "METHYLMALONIC ACIDURIA DUE TO VITAMIN B12-RELEASE DEFECT", "VITAMIN B12 LYSOSOMAL RELEASE DEFECT", "COBALAMIN, DEFECT IN LYSOSOMAL RELEASE OF", "VITAMIN B12 STORAGE DISEASE", "COBALAMIN F DISEASE"], "genereviews": ["NBK1328"]}
|
Elastoderma is a rare condition that affects the skin. People affected by elastoderma generally have increased laxity of skin covering a specific area of the body. Decreased recoil of the skin has also been reported. Although any part of the body can be affected, the skin of the neck and extremities (arms and legs, especially at the elbows and/or knees) are most commonly involved. The exact underlying cause is currently unknown; however, it generally occurs sporadically in people with no family history of the condition. There is no standard therapy available for elastoderma. Some cases have been treated with surgical excision (removal of affected skin), but hyperlaxity of skin often returns following the surgery.
*[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
|
Elastoderma
|
c0406555
| 25,564 |
gard
|
https://rarediseases.info.nih.gov/diseases/12716/elastoderma
| 2021-01-18T18:00:43 |
{"orphanet": ["228240"], "synonyms": []}
|
A number sign (#) is used with this entry because the Lan(-) blood group phenotype is caused by homozygous or compound heterozygous mutation in the ABCB6 gene (605452) on chromosome 2q36.
Description
Individuals with Lan(-) blood group lack the Lan antigen on their red blood cells. These individuals may have anti-Lan antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. The Lan(-) blood group is only clinically significant in transfusion settings or during pregnancy; otherwise Lan(-) individuals have no clinical features (summary by Helias et al., 2012).
Clinical Features
Smith et al. (1969) reported a 26-year-old Caucasian woman with 1 child and a history of blood transfusion who developed anti-Lan IgG antibodies that were detected during a second pregnancy. She was found to have the Lan(-) blood group. Due to low hemoglobin, she was transfused with her brother's blood, which also lacked the Lan antigen. The infant developed mild hemolytic anemia of the newborn due to the presence of maternal anti-Lan antibodies, but recovered with time.
Page (1983) reported a 29-year-old Caucasian woman of Italian descent who was transfused during her first pregnancy and developed anti-Lan antibodies, which were detected during her second pregnancy. She and her sister were found to have the Lan(-) blood group. A Lan(+) girl was born to the proband, and the direct antiglobin test was weakly positive. The daughter developed mild anemia, increased serum bilirubin, and jaundice, but recovered well. There was a history of consanguinity in the family, indicating autosomal recessive inheritance of the blood group Lan(-).
Okubo et al. (1984) reported 3 unrelated Japanese individuals with the Lan(-) blood group phenotype who had anti-Lan antibodies. One was a man with ulcerative colitis who had a history of being transfused; 1 was a woman who had been pregnant 4 times; and the third was a woman with a history of being transfused. All had anti IgG anti-Lan antibodies in their serum, and their red cells were found to lack the Lan antigen.
Inheritance
The Lan(-) blood group is transmitted as an autosomal recessive trait (Helias et al., 2012).
Molecular Genetics
In 12 individuals with the Langereis(-) blood group phenotype, Helias et al. (2012) identified 10 different truncating mutations in the ABCB6 gene (see, e.g., 605452.0001-605452.0005). All mutations were present in the homozygous or compound heterozygous state, indicating autosomal recessive inheritance of the trait. None of the individuals had anemia, abnormal erythropoiesis, or signs of porphyria, but some of the women developed anti-Lan antibodies during pregnancy and/or in response to transfusion with Lan(+) blood. Helias et al. (2012) suggested that Lan(-) individuals may have altered pharmacokinetics with regard to certain drugs potentially transported by ABCB6.
In 3 members of a Moroccan family with the Lan(-) phenotype, Saison et al. (2013) identified homozygosity for a missense mutation in the ABCB6 gene (R192W; 605452.0012); Lan(+) members of the family were heterozygous for the mutation. Saison et al. (2013) identified 5 unrelated individuals with the Lan(-) phenotype who were homozygous for the same mutation.
*[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
|
BLOOD GROUP, LANGEREIS SYSTEM
|
None
| 25,565 |
omim
|
https://www.omim.org/entry/111600
| 2019-09-22T16:44:12 |
{"omim": ["111600"]}
|
Uterine septum
SpecialtyGynaecology
A uterine septum is a form of a congenital malformation where the uterine cavity is partitioned by a longitudinal septum; the outside of the uterus has a normal typical shape. The wedge-like partition may involve only the superior part of the cavity resulting in an incomplete septum or a subseptate uterus, or less frequently the total length of the cavity (complete septum) and the cervix resulting in a double cervix. The septation may also continue caudally into the vagina resulting in a "double vagina".[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Management
* 5 Epidemiology
* 6 References
* 7 External links
## Signs and symptoms[edit]
The condition may not be known to the affected individual and not result in any reproductive problems; thus normal pregnancies may occur. In more serious cases have reported high infertility rates.[2] However, it is associated with a higher risk for miscarriage, premature birth, and malpresentation. According to the classical study by Buttram there is a 60% risk of a spontaneous abortion, this being more common in the second than in the first trimester.[3] However, there is no agreement on this number and other studies show a lower risk. Woelfer found that the miscarriage risk is more pronounced in the first trimester.[4]
The condition is also associated with abnormalities of the renal system. Further, skeletal abnormalities have been linked to the condition.[5]
## Cause[edit]
The uterus is formed during embryogenesis by the fusion of the two Müllerian ducts. During this fusion a resorption process eliminates the partition between the two ducts to create a single cavity. This process begins caudally and advances cranially, thus a complete septum formation represents an earlier disturbance of this absorption than the incomplete form. Causes for incomplete absorption are not known.[citation needed]
## Diagnosis[edit]
A pelvic examination may reveal a double vagina or double cervix that should be further investigated and may lead to the discovery of a uterine septum. In most patients, however, the pelvic examination is normal. Investigations are usually prompted on the basis of reproductive problems.{{
Helpful techniques to investigate a septum are transvaginal ultrasonography and sonohysterography, [citation needed}}[MRI]], and hysteroscopy. More recently 3-D ultrasonography has been advocated as an excellent non-invasive method to delineate the condition.[4] Prior to modern imaging hysterosalpingography was used to help diagnose the uterine septum, however, a bicornuate uterus may deliver a similar image. An important category of septate uterus is the hybrid type a variant that may be misdiagnosed as bicornuate uterus when seen by laparoscopy[6] Professor El Saman From Egypt was the first to describe this anomaly and warned gynecologist about this common misdiagnosis, whenever there is a uterine fundus depression on laparoscopy gynecologists should compare the depth of this depression with the depth of the dividing internal interface. Hybrid septate uterus benefit from hysteroscopic metroplasty under laparoscopic control.[7]
### Differential diagnosis[edit]
Other forms of uterine malformation need to be considered in the work-up for uterine septum. An arcuate uterus contains a residual cranial septum that is smaller than an incomplete septum but definitions between the two conditions are not standardized, - a cause for discrepancies in the literature. A bicornuate uterus is sometimes confused with a septate uterus as in each situation the cavity is partitioned, however, in the former case the uterine body is cranially doubled (two uterine horns) while in the latter a single uterine body is present. The former represents a malformation of incomplete fusion of the Müllerian systems, and the latter of incomplete absorption. A hysterosalpingogram may not be able to distinguish between the two conditions. The differentiation, however, is important as a septum can be corrected by hysteroscopy, while a bicornuate uterus would be corrected by a metroplasty via laparotomy if necessary.[citation needed]
## Management[edit]
A septum can be resected with surgery. Hysteroscopic removal of a uterine septum is generally the preferred method, as the intervention is relatively minor and safe in experienced hands. A follow-up imaging study should demonstrate the removal of the septum. Tactile cold scissor metroplasty was described as a back technique for hysteroscopic challenges that interfere with proper visualization[8] or uterine distention
It is not considered necessary to remove a septum that has not caused problems, especially in women who are not considering pregnancy. There is controversy over whether a septum should be removed prophylactically to reduce the risk of pregnancy loss prior to a pregnancy or infertility treatment.[9]
## Epidemiology[edit]
Most studies are based on populations of women who have experienced a pregnancy loss and thus do not address the issue of the prevalence in the general population. A screening study by Woelfer et al. of women without a history of reproductive problems found that about 3% of women had a uterine septation; the most common anomaly in their study was an arcuate uterus (5%), while 0.5% were found to have a bicornuate uterus.[4] In contrast, in about 15% of patients with recurrent pregnancy loss anatomical problems are thought to be causative with the septate uterus as the most common finding.[10]
## References[edit]
1. ^ Heinonen PK (March 2006). "Complete septate uterus with longitudinal vaginal septum". Fertil. Steril. 85 (3): 700–5. doi:10.1016/j.fertnstert.2005.08.039. PMID 16500341.
2. ^ Creasy RK, Resnik R (1994). Maternal-Fetal Medicine: Principles and Practice. Philadelphia: W.B.Saunders. p. 447. ISBN 0-7216-6590-X.
3. ^ Buttram VC, Gibbons WE (July 1979). "Müllerian anomalies: a proposed classification. (An analysis of 144 cases)". Fertil. Steril. 32 (1): 40–6. doi:10.1016/s0015-0282(16)44114-2. PMID 456629.
4. ^ a b c Woelfer B, Salim R, Banerjee S, Elson J, Regan L, Jurkovic D (December 2001). "Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening". Obstet Gynecol. 98 (6): 1099–103. doi:10.1016/S0029-7844(01)01599-X. PMID 11755560.
5. ^ Li S, Qayyum A, Coakley FV, Hricak H (2000). "Association of renal agenesis and Müllerian duct anomalies". J Comput Assist Tomogr. 24 (6): 829–34. doi:10.1097/00004728-200011000-00001. PMID 11105695.
6. ^ El Saman, AM; Nasr, A; Tawfik, RM; Saadeldeen, HS (Aug 2011). "Müllerian duct anomalies: successful endoscopic management of a hybrid bicornuate/septate variety". J Pediatr Adolesc Gynecol. 24 (4): e89–92. doi:10.1016/j.jpag.2011.02.013. PMID 21514191.
7. ^ El Saman, AM; Shahin, AY; Nasr, A; Tawfik, RM; Saadeldeen, HS; Othman, ER; Habib, DM; Abdel-Aleem, MA (Nov 2012). "Hybrid septate uterus, coexistence of bicornuate and septate varieties: a genuine report". J Obstet Gynaecol Res. 38 (11): 1308–14. doi:10.1111/j.1447-0756.2012.01866.x. PMID 22612567.
8. ^ El Saman, AM; Darwish, AM; Zakherah, MS; Hamed, HO; Bedaiwy, MA; Nasr, AM (Aug 2010). "Tactile cold scissor metroplasty as a novel backup method for hysteroscopic metroplasty". Fertil Steril. 94 (3): 1086–9. doi:10.1016/j.fertnstert.2009.05.018. PMID 19591982.
9. ^ Ozgur K, Isikoglu M, Donmez L, Oehninger S (March 2007). "Is hysteroscopic correction of an incomplete uterine septum justified prior to IVF?". Reprod Biomed Online. 14 (3): 335–40. doi:10.1016/S1472-6483(10)60876-0. PMID 17359587.[permanent dead link]
10. ^ Propst AM, Hill JA (2000). "Anatomic factors associated with recurrent pregnancy loss". Semin. Reprod. Med. 18 (4): 341–50. doi:10.1055/s-2000-13723. PMID 11355792.
## External links[edit]
Classification
D
* ICD-10: Q51
* ICD-9-CM: 752.35
*[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
|
Uterine septum
|
c0152240
| 25,566 |
wikipedia
|
https://en.wikipedia.org/wiki/Uterine_septum
| 2021-01-18T18:33:59 |
{"umls": ["C0152240"], "icd-9": ["752.2"], "icd-10": ["Q51"], "orphanet": ["180122"], "wikidata": ["Q7902656"]}
|
Torsade-de-pointes (TdP) syndrome with short coupling interval is a very rare variant of Torsade de pointes, a polymorphic ventricular tachycardia, which is characterized by a short coupling interval of the first TdP beat on electrocardiogram in the absence of any structural heart disease. It manifests in early adulthood with syncope, often results in ventricular fibrillation and shows a high risk of sudden cardiac death.
*[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
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Torsade-de-pointes syndrome with short coupling interval
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c3150851
| 25,567 |
orphanet
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https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=51084
| 2021-01-23T17:32:10 |
{"omim": ["613600"], "icd-10": ["I49.8"]}
|
A number sign (#) is used with this entry because phenylketonuria (PKU) and non-PKU mild hyperphenylalaninemia (HPA) result from mutations in the PAH gene (612349).
Description
Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of phenylalanine hydroxylase (PAH; 612349), an enzyme that catalyzes the hydroxylation of phenylalanine to tyrosine, the rate-limiting step in phenylalanine catabolism. If undiagnosed and untreated, phenylketonuria can result in impaired postnatal cognitive development resulting from a neurotoxic effect of hyperphenylalaninemia (Zurfluh et al., 2008).
See Scriver (2007) and Blau et al. (2010) for detailed reviews of PKU.
Clinical Features
Early diagnosis of phenylketonuria, a cause of mental retardation, is important because it is treatable by dietary means. Features other than mental retardation in untreated patients include a 'mousy' odor; light pigmentation; peculiarities of gait, stance, and sitting posture; eczema; and epilepsy (Paine, 1957). Kawashima et al. (1988) suggested that cataracts and brain calcification may be frequently overlooked manifestations of classic untreated PKU. Brain calcification has been reported in dihydropteridine reductase (DHPR) deficiency (261630). Pitt and O'Day (1991) found only 3 persons with cataracts among 46 adults, aged 28 to 71 years, with untreated PKU. They concluded that PKU is not a cause of cataracts. Levy et al. (1970) screened the serum of 280,919 'normal' teenagers and adults whose blood had been submitted for syphilis testing. Only 3 adults with the biochemical findings of PKU were found. Each was mentally subnormal. Normal mentality is very rare among patients with phenylketonuria who have not received dietary therapy.
Evidence of heterogeneity in phenylketonuria was presented by Auerbach et al. (1967) and by Woolf et al. (1968).
Coskun et al. (1990) observed scleroderma in 2 infants with PKU. Improvement in the skin lesions after commencement of a low phenylalanine diet supported the possibility of a causal relationship.
Widespread screening of neonates for phenylketonuria brought to light a class of patients with a disorder of phenylalanine metabolism milder than that in PKU. These patients show serum phenylalanine concentrations well below those in PKU, but still several times the normal. PKU and hyperphenylalaninemia breed true in families (Kaufman et al., 1975), each behaving as an autosomal recessive. Kaufman et al. (1975) studied liver biopsies from patients with HPA and their parents. The patients with HPA had levels of phenylalanine hydroxylase about 5% of normal.
Burgard et al. (1996) found that all patients but one who had predicted in vitro residual enzyme activity greater than 20% had mild PKU, while those with predicted in vitro residual enzyme activity less than 20% were identified as having classical PKU. The authors stated that 'the difficulties of some patients to adjust their blood Phe level according to their target value although they comply with the dietary recommendations might be caused by low residual enzyme activity.' In addition, when considering the R261Q (612349.0006) mutation (a mutation with a considerable amount of residual enzyme activity, which produced higher Phe levels than expected), they hypothesized a negative intraallelic complementation effect as an explanation for higher than expected diagnostic Phe values.
Mildly depressed IQ is common in treated PKU. Griffiths et al. (2000) analyzed IQ scores collected from 57 British children with early-treated classic PKU using variants of the Wechsler intelligence scale for children (WISC) in relation to indicators of dietary control such as serum phenylalanine levels and socioeconomic factors. The authors found that, after correcting for socioeconomic status, phenylalanine control at age 2 was predictive of overall IQ, although early and continuous treatment did not necessarily lead to normalization of overall IQ. Subscale analysis revealed normalized verbal IQ in those children with phenylalanine levels of less than 360 micromol/l during infancy (the recommended UK upper limit), but performance IQ remained depressed.
Weglage et al. (2000) compared 42 PKU patients, aged 10 to 18 years, with 42 diabetic patients matched for sex, age, and socioeconomic status. Patients' groups were compared with a control sample of healthy controls (2,900 individuals) from an epidemiologic study. The Child Behavior Check List, IQ tests, and monitoring of blood phenylalanine concentrations and HBA1 concentrations were used. Weglage et al. (2000) found that internalizing problems such as depressive mood, anxiety, physical complaints, or social isolation were significantly elevated in both PKU and diabetic patients, whereas externalizing problems were not. The 2 patient groups did not differ significantly either in the degree or in the pattern of their psychologic profile.
In a retrospective study from birth in 13 patients with classic PKU, Barat et al. (2002) found greater variation of phenylalanine levels and a higher mean of cumulative variations in the 8 osteopenic patients than in 5 nonosteopenic patients. Barat et al. (2002) suggested that serum phenylalanine variations may contribute to osteopenia in patients with classic PKU.
Crujeiras et al. (2015) conducted a cross-sectional observational multicenter study that included 156 patients with hyperphenylalaninemia. Prealbumin was reduced in 34.6% of patients (74% with PKU phenotype and 94% below 18 years old), showing an adequate adherence to diet in nearly all patients (96.3%). Selenium was diminished in 25% of patients (95% with PKU phenotype), and 25-OHD in 14%. Surprisingly, folic acid levels were increased in 39% of patients, 66% with classic PKU. Phosphorus and B12 levels were diminished only in patients with low adherence to diet.
### Maternal Phenylketonuria
The occurrence of mental retardation in the offspring of homozygous mothers is an example of a genetic disease based on the genotype of the mother. Kerr et al. (1968) demonstrated 'fetal PKU' by administering large amounts of phenylalanine to mother monkeys. The offspring had reduced learning ability. They pointed out that the damage is aggravated by the normal placental process which functions to maintain higher levels of amino acids in the fetus than in the mother. Huntley and Stevenson (1969) and Hanley et al. (1987) reviewed the subject of PKU embryofetopathy, also known as the maternal PKU syndrome.
Huntley and Stevenson (1969) described 2 sisters with PKU who had a total of 28 pregnancies. Sixteen ended in spontaneous first-trimester abortion. The fetus in each of the 12 pregnancies carried to term had intrauterine growth retardation and microcephaly and 9 of the 12 term infants had cardiac malformations as well.
Superti-Furga et al. (1991) reported the maternal PKU syndrome in cousins, caused by mild unrecognized PKU in their mothers, who were homozygous for the arg261-to-gln mutation (612349.0006).
Usha et al. (1992) found 3 children with PKU embryofetopathy among the offspring of a Bedouin woman who was not recognized to have PKU until the birth of the third affected child. She had an apparently normal phenotype except for pigment dilution of the hair, which was more lightly colored than expected for the family and ethnic norms. She was not mentally retarded. One of the affected offspring had died of congenital heart disease at the age of 4 months.
Fisch et al. (1993) suggested that surrogate motherhood should be recommended as alternative management of PKU in women who wish to have children, i.e., in vitro fertilization using the parental gametes, followed by implantation of the pre-embryo in a surrogate mother.
Levy et al. (1996) compared MRI results of 5 children (age range: 8 months to 17 years) whose mothers had classic PKU and were not under metabolic control (plasma phenylalanine = 1,260 micromoles per liter) during at least the first 2 trimesters of pregnancy to MRI results of 2 sibs aged 9 and 11 years whose mother had classic PKU but whose plasma phenylalanine levels were generally below 360 micromoles per liter during both pregnancies. The MRI results showed a tendency for corpus callosum hypoplasia in those children whose mothers were not in metabolic control during their pregnancies. All children studied (even those with mothers in metabolic control) displayed some residual developmental/behavioral effects such as hyperactivity.
Rouse et al. (1997) reported a collaborative study of maternal PKU offspring. The cohort of offspring were examined for malformations, including congenital heart disease, craniofacial abnormalities, microcephaly, intrauterine and postnatal growth retardation, other major and minor defects, and early abnormal urologic signs. The mothers were grouped according to their mean phenylalanine levels during critical gestational weeks and average for phenylalanine exposure throughout the pregnancy. The frequency of congenital abnormalities increased with increasing maternal phenylalanine levels. Significant relationships included average phenylalanine levels at weeks 0 to 8 with congenital heart disease (P = 0.001); average phenylalanine at weeks 8 to 12 with brain, fetal, and postnatal growth retardation, wide nasal bridge, and anteverted nares; and average phenylalanine exposure during the entire pregnancy with neurologic signs. Although 14% of infants had congenital heart disease, none of the congenital heart disease occurred at the lower range of the maternal phenylalanine levels. At the lowest levels of phenylalanine, there were 3 infants (6%) with microcephaly, 2 (4%) with postnatal growth, and none with intrauterine growth retardation, in contrast to 85%, 51%, and 26%, respectively, with phenylalanine levels in the highest range. These data supported the concept that women with PKU should begin a low phenylalanine diet to achieve phenylalanine levels of less than 360 micromole/liter prior to conception and maintain this throughout the pregnancy.
Waisbren et al. (2000) studied 149 children of women with PKU and 33 children of women with mild hyperphenylalaninemia at 4 years of age. Children were stratified by the timing of maternal metabolic control at 0 to 10 weeks', 10 to 20 weeks', or after 20 weeks' gestation. Scores of a General Cognitive Index decreased as weeks to maternal metabolic control increased. Offspring of women who had metabolic control prior to pregnancy had a mean score of 99. Forty-seven percent of offspring whose mothers did not have metabolic control by 20 weeks' gestation had a General Cognitive Index score 2 standard deviations below the norm. Overall, 30% of children born to mothers with PKU had social and behavioral problems.
Rouse et al. (2000) studied a cohort of 354 women with PKU, followed up weekly with diet records, blood phenylalanine levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring were examined; they were followed up at 3 months, 6 months, and then annually. Bayley Mental Developmental Index and Psychomotor Developmental Index tests were given at 1 and 2 years. Congenital heart defects were found in 31 offspring; of these, 17 also had microcephaly. Mean phenylalanine levels at 4 to 8 weeks' gestation predicted congenital heart defects (P less than 0.0001). An infant with a congenital heart defect had a 3-fold risk of having microcephaly when the mother had higher phenylalanine levels. No direct relationship to the specific PAH mutation was found. None of the women whose offspring had congenital heart defects had blood phenylalanine levels in control during the first 8 weeks of gestation. Rouse et al. (2000) concluded that women with PKU need to be well controlled on a low phenylalanine diet before conception and throughout pregnancy.
Levy et al. (2001) reported on 416 offspring from 412 maternal PKU pregnancies that produced live births and compared them to 100 offspring from 99 control pregnancies. Thirty-four of the 235 offspring (14%; 95% confidence interval, 10.2 to 19.6%) from pregnancies in maternal PKU patients with a basal phenylalanine level of greater than 900 micromolar and not in metabolic control (defined as phenylalanine level less than or equal to 600 micromolar) by the eighth gestational week had congenital heart disease compared with 1 control offspring with congenital heart disease. One of the children among 50 from mothers with non-PKU mild hyperphenylalaninemia also had congenital heart disease. Coarctation of the aorta and hypoplastic left heart syndrome were overrepresented.
Other Features
Brumm et al. (2010) reviewed studies of psychiatric symptoms and disorders in patients with PKU. Those with untreated PKU tended to have severe behavioral disturbances, including psychotic disorders, autistic features, hyperactivity, and aggression, as well as self-mutilation. Among early-treated children and adolescents, discontinuation of treatment was associated with attention-deficit disorder and decreased social competence. Children who continued treatment had fewer behavioral problems. However, most tended to be less happy and confident. Even adults who had early treatment had higher rates of depression, anxiety-related disorders, and social introversion compared to the normal population. In general, the severity of problems correlated with the timing and degree of exposure to increased blood levels of phenylalanine. Brumm et al. (2010) stated that mechanisms of psychiatric disorders in PKU most likely result from a combination of neurotransmitter imbalance, myelination defects, and the stress of living with a chronic illness.
Gentile et al. (2010) reviewed studies of psychosocial aspects of PKU and concluded that even treated individuals have hidden disabilities resulting from poor executive function, decreased mental processing speed, and psychosocial problems. These included difficulties in forming interpersonal relationships, achieving autonomy, attending educational goals, and having healthy emotional development. The most important way to reduce these problems is strict metabolic control throughout life, with particular importance on the first year of life.
Biochemical Features
Normal blood phenylalanine levels are 58 +/- 15 micromoles/liter in adults, 60 +/- 13 micromoles/liter in teenagers, and 62 +/- 18 micromoles/liter (mean +/- SD) in childhood. In the newborn, the upper limit of normal is 120 micromoles/liter (2 mg/dl) (Scriver et al., 1985; Gregory et al., 1986). In untreated classical PKU, blood levels as high as 2.4 mM/liter can be found.
Bowden and McArthur (1972) found that phenylpyruvic acid inhibits pyruvate decarboxylase in brain but not in liver. They suggested that this accounts for the defect in formation of myelin and mental retardation in this disease.
In the liver of a fetus aborted after prenatal DNA diagnosis of PKU, Ledley et al. (1988) found no detectable phenylalanine hydroxylase enzymatic activity or immunoreactive protein, although both were found in control specimens of similar gestational age. Both the size and the amount of phenylalanine hydroxylase mRNA were normal. The findings confirmed the genetic diagnosis of PKU in the fetus and indicated that the mutations affected translation or stability of the protein.
Tolerance to dietary phenylalanine and therefore the clinical severity of PKU have been presumed to be the consequence of the rate of conversion of phenylalanine into tyrosine. However, in a study of 7 classic PKU patients, van Spronsen et al. (1998) found that although the in vivo hydroxylation of phenylalanine into tyrosine was decreased, there was no significant correlation between the in vivo hydroxylation rates and the tolerances.
Kaufman (1999) described the derivation of a quantitative model of phenylalanine metabolism in humans. The model was based on the kinetic properties of pure recombinant human PAH and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine from the blood after an oral load of the amino acid, and dietary tolerance of phenylalanine all agreed with data from normal as well as from phenylketonuric patients and obligate heterozygotes. Kaufman (1999) suggested that these calculated values may help in the decision about the degree of restriction of phenylalanine intake that is necessary to achieve a satisfactory clinical outcome in patients with classic PKU and in those with milder forms of the disease.
It has been postulated that the significant incidence of learning disabilities in treated patients with PKU may be due, in part, to reduced production of neurotransmitters as a result of deficient tyrosine transport across the neuronal cell membrane. In a study of hypotyrosinemia in a PKU population, Hanley et al. (2000) found that the mean nonfasting plasma tyrosine was 41.1 micromol/L in 99 classic PKU patients, 53.3 micromol/L in 26 mild (atypical) PKU patients, and 66.6 micromol/L in 35 non-PKU mild hyperphenylalaninemia patients. This compared to nonfasting plasma tyrosine levels of 64.0 micromol/L in 102 non-PKU subjects in their hospital biochemistry database, 69.1 micromol/L in 58 volunteers in private office practice, and 64 to 78.8 micromol/L in infants, children, and adolescents in a literature review. The data supported previous findings that plasma tyrosine levels are low in PKU.
Leuzzi et al. (2000) assessed brain Phe concentration by in vivo proton magnetic resonance spectroscopy in 10 off-diet PKU patients, aged 15.5 to 30.5 years. An abnormal concentration of brain Phe was detected in all patients, but there was wide interindividual variability of concurrent plasma Phe. In late-detected subjects, brain Phe concentration correlated with clinical phenotype better than did plasma Phe. White-matter alterations were found in all patients.
Koch et al. (2000) referred to preliminary reports suggesting that the occasional untreated person with PKU with normal intellect has elevated blood phenylalanine but low brain phenylalanine levels, They measured blood phenylalanine levels and used MRI/MRS to measure brain phenylalanine content in 29 individuals with PKU, 4 carriers of phenylalanine hydroxylase mutations, and 5 controls. For each individual with PKU, the authors also noted IQ, mutations, whether or not a restricted diet was followed, and age at diagnosis. Koch et al. (2000) concluded that MRI/MRS measurements of brain phenylalanine content may be of value in recommending appropriate blood phenylalanine concentrations for treatment of adults.
Weglage et al. (2002) investigated 4 pairs of sibs with classical PKU using in vivo NMR spectroscopy in the course of an oral phenylalanine load (100 mg/kg body weight). Patients' brain phenylalanine concentrations were different in spite of similar blood levels. Interindividual variations of the apparent transport Michaelis constant ranged from 0.10 to 0.84 mmol/L. Sibs with lower values for the apparent transport constant, higher values for the ratio of the maximal transport velocity over the intracerebral consumption rate, and higher concurrent brain phenylalanine levels showed a lower IQ and a higher degree of cerebral white matter abnormalities. Weglage et al. (2002) concluded that blood-brain barrier transport characteristics and the resultant brain phenylalanine levels are causative factors for the individual clinical outcome in PKU.
To determine whether impairments of cerebral metabolism may play a role in acute phenylalanine neurotoxicity, Pietz et al. (2003) studied 11 adult early-treated PKU patients and 10 healthy controls for changes in concentrations of cerebral metabolites using noninvasive quantitative phosphorus-31 MRS. In adult patients, derived ADP concentration and phosphorylation potential were increased by 11% and 22%, respectively; peak areas of inorganic phosphate and phospholipids were decreased by 22% and 8%, respectively. ADP correlated with concurrent plasma (r = 0.65) and brain (r = 0.55) phenylalanine levels. PKU patients showed slowing of EEG background activity, a sign of impaired brain function, 24 hours after oral phenylalanine challenge. Pietz et al. (2003) concluded that there were subtle abnormalities of cerebral energy metabolism and encouraged more clinical studies on the relationship of imbalances of high energy phosphates and cerebral energy metabolism to acute phenylalanine neurotoxicity.
Inheritance
Classical PKU is inherited in a strictly autosomal recessive manner and is the result of mutations in the PAH gene. Most variation in classical PKU is due to heterogeneity in the mutant alleles with many patients being compound heterozygotes rather than homozygotes for one particular mutant allele. Bartholome et al. (1984) concluded that examples of parent (usually mother)-to-child transmission of hyperphenylalaninemia are likely to be due to compound heterozygosity for PKU and HPA in either the parent or the child or both.
Mapping
Using a cDNA probe for human phenylalanine hydroxylase to analyze human-mouse hybrid cells by Southern hybridization, Lidsky et al. (1984) showed that the PAH locus is on chromosome 12 and presumably on the distal part of 12q because in hybrids containing translocated chromosome 12, it segregated with PEPB (12q21) and not with TPI (12p13). Since in family studies concordance of segregation between a mutant PAH gene and PKU was found (Woo et al., 1983), one can state that the 'PKU locus' is on chromosome 12. By in situ hybridization, the assignment of the PAH locus was narrowed to chromosome 12q22-q24.1 (Woo et al., 1984).
For information on early mapping studies, see HISTORY.
Molecular Genetics
The first PKU mutation identified in the PAH gene was a single base change (GT-to-AT) in the canonical 5-prime splice donor site of intron 12 (612349.0001). Gene transfer and expression experiments demonstrated that the splice donor site mutation resulted in abnormal PAH mRNA processing and loss of PAH activity (DiLella et al., 1986).
Eisensmith and Woo (1992) reviewed mutations and polymorphisms in the human PAH gene. About 50 of the mutations were single-base substitutions, including 6 nonsense mutations and 8 splicing mutations, with the remainder being missense mutations. Of the missense mutations, 12 apparently resulted from the methylation and subsequent deamination of highly mutagenic CpG dinucleotides. Recurrent mutations had been observed at several sites, producing associations with different haplotypes in different populations. Studies of in vitro expression showed significant correlations between residual PAH activity and severity of the disease phenotype.
For more detailed information on the molecular genetics of PKU and non-PKU hyperphenylalaninemia, see 612349.
Genotype/Phenotype Correlations
For information on genotype/phenotype correlations in PKU and non-PKU hyperphenylalaninemia, see 612349.
Pathogenesis
Waters et al. (2000) characterized 4 PKU-associated PAH mutations that change an amino acid distant from the enzyme active site. Using 3 complementary in vitro protein expression systems and 3D structural localization, Waters et al. (2000) demonstrated a common mechanism, i.e., PAH protein folding is affected, causing altered oligomerization and accelerated proteolytic degradation, leading to reduced cellular levels of this cytosolic protein. Enzyme-specific activity and kinetic properties are not adversely affected, implying that the only way these mutations reduce enzyme activity within cells in vivo is by producing structural changes which provoke the cell to destroy the aberrant protein. The mutations were chosen because of their associations with a spectrum of in vivo hyperphenylalaninemia among patients. Waters et al. (2000) concluded that their in vitro data suggests that interindividual differences in cellular handling of the mutant but active PAH proteins contributes to the observed variability of phenotypic severity.
Most PAH missense mutations impair enzyme activity by causing increased protein instability and aggregation. Gjetting et al. (2001) described an alternative mechanism by which some PAH mutations may render phenylalanine hydroxylase defective. They used database searches to identify regions in the N-terminal domain of PAH with homology to the regulatory domain of prephenate dehydratase (PDH), the rate-limiting enzyme in the bacterial phenylalanine biosynthesis pathway. Naturally occurring N-terminal PAH mutations are distributed in a nonrandom pattern and cluster within residues 46-48 (amino acids GAL) and 65-69 (amino acids IESRP), 2 motifs highly conserved in PDH. To examine whether N-terminal PAH mutations affect the ability of PAH to bind phenylalanine at the regulatory domain, wildtype and 5 mutant forms (including G46S, 612349.0055; A47V, 612349.0056; and I65T, 612349.0063) of the N-terminal domain (residues 2-120) of human PAH were expressed as fusion proteins in E. coli. Binding studies showed that the wildtype form of this domain specifically binds phenylalanine, whereas all mutations abolished or significantly reduced this phenylalanine-binding capacity. The data suggested that impairment of phenylalanine-mediated activation of PAH may be an important disease-causing mechanism of some N-terminal PAH mutations.
Most missense mutations found in PKU result in misfolding of the phenylalanine hydroxylase protein, increased protein turnover, and loss of enzymatic function. Pey et al. (2007) studied the prediction of the energetic impact on PAH native-state stability of 318 PKU-associated missense mutations, using the protein-design algorithm FoldX. For the 80 mutations for which expression analyses had been performed in eukaryotes, in most cases they found substantial overall correlation between the mutational energetic impact and both in vitro residual activities and patient metabolic phenotype. This finding confirmed that the decrease in protein stability is the main molecular pathogenic mechanism in PKU and the determinant for phenotypic outcome. Metabolic phenotypes had been shown to be better predicted than in vitro residual activities, probably because of greater stringency in the phenotyping process. All the remaining 238 PKU missense mutations compiled in the PAH locus knowledgebase (PAHdb) were analyzed, and their phenotypic outcomes were predicted on the basis of the energetic impact provided by FoldX. Residues in exons 7-9 and in interdomain regions within the subunit appeared to play an important structural role and constitute hotspots for destabilization.
Using recombinant proteins expressed in E. coli, Gersting et al. (2008) characterized 10 BH4-responsive PAH mutations, including arg408 to trp (R408W; 612349.0002) and tyr414 to cys (Y414C; 612349.0017). Residual activity was generally high, but allostery was disturbed in almost all variants, suggesting altered protein conformation. This hypothesis was confirmed by reduced proteolytic stability, impaired tetramer assembly or aggregation, increased hydrophobicity, and accelerated thermal unfolding, which primarily affected the regulatory domain, in most variants. Three-dimensional modeling revealed that the misfolding was communicated throughout the protein. Gersting et al. (2008) concluded that global conformational changes in PAH hinder the molecular motions essential for enzyme function.
Diagnosis
Matalon et al. (1977) reported high levels of phenylalanine hydroxylase in placenta and suggested use of placental biopsy in prenatal diagnosis.
Woo (1983) identified a DNA restriction polymorphism detected by a phenylalanine hydroxylase cDNA probe and tentatively demonstrated the feasibility of carrier detection and prenatal diagnosis, using the haplotypes defined by the DNA polymorphism.
By the use of RFLPs related to the phenylalanine hydroxylase gene, Lidsky et al. (1985) achieved prenatal diagnosis of a PKU homozygote and a PKU heterozygote. Riess et al. (1987) described experience with prenatal diagnosis of PKU by RFLP analysis. They pointed out that in those cases in which the affected child had died but a phenotypically normal brother or sister is available for investigation, full genetic predictability could be obtained only if this child proved to be homozygously healthy in the phenylalanine-loading heterozygote test.
DiLella et al. (1988) showed that the 2 mutant alleles of PAH common among Caucasians of northern European ancestry can be detected by direct analysis of genomic DNA after specific amplification of a DNA fragment by PCR. The results suggested that it is technically feasible to develop a program for carrier detection of the genetic trait in a population of individuals without a family history of PKU.
Ramus et al. (1992) used PCR amplification of the low levels of mRNA resulting from illegitimate transcription of the PAH gene in fibroblasts and Epstein-Barr virus-transformed lymphocytes to detect mutations in patients with PKU.
Taking advantage of the 'illegitimate' transcription of the PAH gene in circulating lymphocytes, Abadie et al. (1993) succeeded in making the DNA diagnosis of phenylketonuria. Furthermore, they identified 3 novel mutations in 2 patients.
Kalaydjieva et al. (1991) identified 3 silent mutations in the PAH gene, in codons 232, 245, and 385, linked to specific RFLP haplotypes in several Caucasian populations. All 3 mutations created a new restriction site and were easily detected on PCR-amplified DNA. The combined analysis of these markers and 1 or 2 PKU mutations formed a simple panel of diagnostic tests with full informativeness in a large proportion of PKU families.
Forrest et al. (1991) used a modification of the chemical cleavage of mismatch (CCM) method to identify mutations in PAH in PKU. They stated that 'judicious choice of probes gives the CCM method the potential to detect close to 100% of single-base mutations.'
Clinical Management
### Dietary Treatment
Phenylketonuria is treatable by a low phenylalanine diet. In treated patients, severe white matter abnormalities are predominantly associated with blood phenylalanine levels above 15 mg per deciliter (Thompson et al., 1993). Ullrich et al. (1994) performed MRI on 15 adolescents with good dietary control (phenylalanine levels below 10 mg per deciliter). Ten of these patients had a normal cranial MRI whereas 4 showed mild changes of the signal intensity of the white matter on T2-weighted images confined to the parietooccipital region. The affected and unaffected patients could not be distinguished by age, sex, or mean blood phenylalanine concentrations.
From studies in 4 women, Rohr et al. (1987) concluded that fetal damage from maternal PKU can be largely and perhaps entirely prevented by dietary therapy, but that therapy must begin before conception for the best chance of a normal infant. Drogari et al. (1987) presented evidence suggesting that only a diet restricting phenylalanine intake started before conception is likely to prevent fetal damage.
In a report of preliminary results from the North American Maternal PKU Study, Hanley et al. (1996) suggested that early and adequate dietary treatment during pregnancy may provide some protection to the fetus for later intellectual development. The German Maternal PKU Study had followed 43 pregnancies (Cipcic-Schmidt et al., 1996). For minimizing risks of ill effects, preconceptional dietary control was strongly recommended.
Brenton and Lilburn (1996) reported that by November 1994, 39 pregnancies had been completed in PKU mothers. Dietary control was post-conception in 6; 2 of these offspring died of congenital heart disease and another needed surgery for coarctation. There were no heart defects in the 34 offspring of the 33 pregnancies following preconception diet controlled by Guthrie assays of maternal Phe 3 times weekly. Excessively high and low values occurred intermittently in many pregnancies, both of which may adversely affect the fetus.
A multicenter follow-up study (Holtzman et al., 1986) presented evidence that treatment of PKU should be continued beyond age 8 years.
Weglage et al. (1999) reported results of testing of IQ, fine motor abilities, and sustained and selective attention in 10 boys and 10 girls with early-treated phenylketonuria and 20 healthy controls matched for age, sex, and IQ; the individuals were tested twice, at mean ages of 11 and 14 years. At the first test, examination showed significant blood phenylalanine-correlated neuropsychologic deficits in PKU patients. In spite of raised blood phenylalanine concentrations during the following 3 years, the repeated measurements revealed a significant decrease in patients' deficits compared to controls. Clinical-neurologic status of patients and controls was normal at both test times. The results indicated decreased vulnerability of PKU patients with respect to their neuropsychologic functioning against elevated phenylalanine levels on aging.
Greeves et al. (2000) examined the effect of diet relaxation after the age of 8 years in 125 Northern Irish children with PKU or non-PKU hyperphenylalaninemia, correlating verbal, performance, and overall IQ at ages 8, 14, and 18 with the predicted residual enzyme activity conferred by their genotype. Multiple regression analysis demonstrated a significant reduction in verbal and overall IQ between the ages of 8 and 14 or 18, with a greater reduction in those with a lower predicted residual enzyme activity. This study also showed that patients with residual enzyme activities of 25% or more were more likely to maintain or gain IQ points after dietary relaxation than those patients with lower enzyme activities. These data suggested that continued dietary control in this latter group, as defined by genotype, may prove beneficial.
Recognizing that a low phenylalanine diet is also low in the long-chain polyunsaturated fatty acids (LCPUFA) necessary for cell membrane formation and normal brain and visual development, Agostoni et al. (2000) examined the effects of a 12-month supplementation of LCPUFA on fatty acid composition of erythrocyte lipids and visual evoked potentials in children with well-controlled PKU. The children who received supplementation showed a significant increase in docosahexaenoic acid (DHA) levels of erythrocyte lipids and improved visual function, as measured by a decreased P100 wave latency.
Huijbregts et al. (2002) sought to answer whether there is an effect of dietary interventions that induce relatively small changes in phenylalanine concentration on neuropsychologic outcome of early and continuously treated PKU patients and whether there are differences in effect for PKU children versus adolescents. Huijbregts et al. (2002) sought short-term dietary intervention of 1 to 2 weeks and compared this for patients whose phenylalanine concentrations increased versus those whose phenylalanine concentrations decreased. Huijbregts et al. (2002) found that relatively small fluctuations in phenylalanine concentration influenced neuropsychologic task performance of PKU patients. Patients whose phenylalanine concentrations had decreased by the second assessment showed generally more improvement than controls. Patients whose phenylalanine concentrations had increased showed minimal improvement or deterioration of task performance. The strongest effects were observed when sustained attention and manipulation of working memory content were required.
Koch et al. (2002) reported the follow-up studies of 125 children who were a part of the original cohort for short-term versus long-term treatment of PKU with diet. Seventy of the 125 children were located and evaluated in adulthood. Mental problems, including phobias and depression, were reported in 41% of those off diet and 22% of continuers. The 'on diet' group had only 2 reported episodes of transient depression not requiring psychiatric care. The neurologic signs related primarily to increased or decreased muscle tone and deep tendon reflex changes. The group who remained on a phenylalanine-restricted diet had fewer problems overall than the discontinued group (P = 0.02).
Singh et al. (2014) reported updated recommendations for the nutritional management of phenylalanine hydroxylase deficiency. Their paper was accompanied by an American College of Medical Genetics practice guideline authored by Vockley et al. (2014), which updated phenylalanine hydroxylase deficiency diagnosis and management, including the use of sapropterin dihydrochloride to achieve improved metabolic control and/or increased protein tolerance in patients who respond.
### Sapropterin (Tetrahydrobiopterin)-Responsive PKU
At least half of patients with phenylketonuria have a mild clinical phenotype. Muntau et al. (2002) explored the therapeutic efficacy of tetrahydrobiopterin for the treatment of mild phenylketonuria. Tetrahydrobiopterin significantly lowered blood phenylalanine levels in 27 of 31 patients with mild hyperphenylalaninemia (10 patients) or mild phenylketonuria (21 patients). Phenylalanine oxidation was significantly enhanced in 23 of these 31 patients. Conversely, none of the 7 patients with classic phenylketonuria had a response to tetrahydrobiopterin. Long-term treatment with tetrahydrobiopterin in 5 children increased daily phenylalanine tolerance, allowing them to discontinue their restricted diets. Mutations connected to tetrahydrobiopterin responsiveness were predominantly in the catalytic domain of the PAH protein and were not directly involved in cofactor binding. Muntau et al. (2002) concluded that responsiveness could not consistently be predicted on the basis of genotype, particularly in compound heterozygotes.
Lassker et al. (2002) reported 2 new patients with tetrahydrobiopterin-responsive PKU who carried missense mutations in the PAH gene. Both patients showed no effect of tetrahydrobiopterin at 7.5 mg/kg/day on plasma phenylalanine levels in the newborn period, and the authors suggested that a normal neonatal tetrahydrobiopterin test does not necessarily exclude tetrahydrobiopterin responsiveness in all such patients.
Matalon et al. (2004) found that 21 of 36 (58.3%) PKU patients responded favorably to oral tetrahydrobiopterin (BH4) supplementation. A single dose of 10 mg/kg resulted in a mean decrease of greater than 30% in blood phenylalanine levels. Patients who responded were found to have mutations in the PAH gene within the catalytic, regulatory, oligomerization, and BH4-binding domains.
Steinfeld et al. (2004) reported 2 unrelated infants with PKU who responded favorably to daily BH4 supplementation. They no longer needed dietary restriction and showed normal development after 2 years. One of the patients was homozygous for a mild PAH mutation (Y414C; 612349.0017). No side effects were observed.
Keil et al. (2013) reported the follow-up of 147 patients treated with sapropterin dihydrochloride for up to 12 years: 41.9% had mild hyperphenylalaninemia, 50.7% mild PKU, and 7.4% classic PKU. Median phenylalanine (Phe) tolerance increased 3.9 times with BH4/sapropterin therapy, compared with dietary treatment, and median Phe blood concentrations were within the therapeutic range in all patients. Compared with diet alone, improvement in quality of life was reported in 49.6% of patients, improvement in adherence to diet in 47% of patients, and improvement in adherence to treatment in 63.3% of patients. No severe adverse events were reported. Keil et al. (2013) concluded that their data documented a long-term beneficial effect of orally administered BH4/sapropterin in responsive PKU patients by improving metabolic control, increasing daily tolerance for dietary Phe intake, and for some, by improving dietary adherence and quality of life.
For more detailed information on genotype/phenotype correlations in tetrahydrobiopterin-responsive PKU, see 612349
### Other Treatments
Hoskins et al. (1980) showed that the plant enzyme phenylalanine ammonia lyase (PAL; EC 4.3.1.5) will survive in the gut long enough to deplete the phenylalanine derived from food protein and so reduce the rise in blood phenylalanine that otherwise occurs after a protein meal. Preliminary studies suggested that it may have a place in the treatment of PKU.
Sarkissian et al. (1999) described experiments on a mouse model using a different modality for treatment of PKU compatible with better compliance using ancillary PAL to degrade phenylalanine, the harmful nutrient of PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase, which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. Sarkissian et al. (1999) described (i) an efficient recombinant approach to produce large quantities of PAL enzyme using a construct of the PAL gene from Rhodosporidium toruloides and expressing it in a strain of E. coli; (ii) testing of PAL in orthologous mouse with hyperphenylalaninemia induced by N-ethyl-N-nitrosourea (ENU) mutation; and (iii) proofs of principle (PAL reduces hyperphenylalaninemia), both pharmacologic (with a clear dose-response effect) and physiologic (protected enteral PAL is significantly effective against hyperphenylalaninemia). They concluded that the appropriate dosage of orally administered PAL, perhaps in combination with a controlled and modestly low protein diet, should effectively control the phenylalanine pool size through its effect on the gastrointestinal tract. These findings opened a new avenue to the treatment of this classic genetic disorder.
Stegink et al. (1989) tested the effect of aspartame (N-L-alpha-aspartyl-L-phenylalanine methyl ester--a widely used dipeptide sweetener) on phenylalanine concentrations in persons heterozygous for PKU. They found moderate elevations in phenylalanine levels above baseline for heterozygotes for PKU (2.3-4.7 micromoles, 30-45 minutes after ingestion of a 12-ounce beverage).
Liver transplantation is not a usual therapy for PKU because of the usually good results achieved with early dietary restriction and because liver disease is not part of the clinical picture of PKU. Vajro et al. (1993) reported that orthotopic liver transplantation in a 10-year-old boy with PKU and concomitant, unrelated end-stage liver disease cured the PKU.
Eisensmith and Woo (1996) reviewed the current state of gene therapy for phenylketonuria. Of the 3 basic steps required, 2 have been accomplished: a cDNA clone expressing human phenylalanine hydroxylase and a phenylalanine hydroxylase-deficient animal model have been developed, while vectors for efficient gene transfer in vivo have yet to be developed. Retroviral vectors, while effective in vitro, have a low transduction efficiency in vivo. Similarly, DNA/protein complexes have not been efficiently transduced in vivo. Recombinant adenoviral vectors, although completely successful in the short term, did not persist beyond a few weeks due to an immune response against the adenoviral vector.
Population Genetics
PKU occurs in about 1 in 10,000 births (Steinfeld et al., 2004).
Peculiarities in the distribution of phenylketonuria have been noted. The disorder is rare in Ashkenazi Jews (Cohen et al., 1961; Centerwall and Neff, 1961). Carter and Woolf (1961) noted that of the cases seen in London and presently living in southeast England, a disproportionately large number had parents and grandparents born in Ireland or West Scotland. The frequency at birth in northern Europeans may be about 1 per 10,000 (Guthrie and Susi, 1963).
In Kuwait, Teebi et al. (1987) found 7 cases of PKU among 451 institutionalized mentally retarded persons (1.9%).
Saugstad (1975) determined the frequency and distribution of PKU in Norway and concluded that the PKU gene was probably of Celtic origin, i.e., was brought from Ireland and Scotland (which have the highest frequency of PKU) with wives and slaves of the Vikings. Rh, Kell, and PGM-1 types support the suggestion. PKU was first discovered in Norway by Folling (1934).
From the increase in frequency of parental consanguinity, Romeo et al. (1983) estimated that the frequency of PKU in Italy is between 1 in 15,595 and 1 in 17,815 (according to 2 different formulas), values not greatly different from that derived from screening programs (about 1 in 12,000). Flatz et al. (1984) concluded that the PKU gene was 1.37 times more frequent in prewar northeastern Germany than northwestern Germany.
DiLella et al. (1986) cited an incidence of 1 per 4,500 in Ireland and 1 per 16,000 in Switzerland with an average incidence of about 1 per 8,000 in U.S. Caucasians. The PKU gene has been considered to be Celtic in origin. Perhaps surprisingly, DiLella et al. (1986) found the splice donor site mutation of intron 12 (612349.0001) in Denmark, England, Ireland, Scotland, Switzerland, and Italy. Furthermore, the association with RFLP haplotype 3 was preserved in these populations. This is a difficult finding to explain in population genetics terms that are compatible with demographic history.
Guttler and Woo (1986) identified 12 different haplotypes in Danish PKU families; however, of 132 chromosomes analyzed from 66 obligate heterozygotes, 59 of 66 PKU genes were associated with only 4 haplotypes. Mutant PAH alleles related to 2 of the 4 RFLP haplotypes seemed to be associated with a more severe clinical phenotype.
In Denmark, Guttler et al. (1987) found that 89% of families were accounted for by 4 RFLP haplotypes. Patients who were either homozygous or heterozygous for the mutant alleles of haplotypes 2 or 3 had a severe clinical course, whereas patients who had a mutant allele of haplotypes 1 or 4 usually had a less severe clinical phenotype.
Woo (1988) provided a collation of the 43 RFLP haplotypes at the PAH locus identified to date. Ninety percent of all mutant alleles in Danes are associated with only 4 haplotypes, of which 2 had been fully characterized at the molecular level. The haplotypes are based on the combined pattern of presence or absence of sites of cutting by 7 restriction enzymes (BglIII, PvuII, EcoRI, MspI, XmnI, HindIII, and EcoRV), of which one, PvuII, has 2 cut sites. The GT-to-AT transition at the canonical splice donor site of intron 12, causing skipping of the preceding exon during RNA splicing, is associated with a mutant haplotype 3. The missense mutation involving an arginine-to-tryptophan substitution at residue 408 (612349.0002) of the enzyme is associated with mutant haplotype 2. Both mutant alleles are in linkage disequilibrium with the corresponding RFLP haplotypes throughout Europe, suggesting that 2 mutational events occurred on background chromosomes of the 2 haplotypes, followed by spread and expansion in the Caucasian population.
In 37 French kindreds, Rey et al. (1988) found that two-thirds of all mutant alleles were confined within 4 haplotypes, whereas the remaining third were accounted for by 12 haplotypes, including 8 absent from Caucasian pedigrees reported up to that time. Several mutant haplotypes were present in typical PKU only, others were present in variants only, and some were present in both. Because of the relatively large number of different alleles and the expected consequences of compound heterozygosity, one can account for the broad spectrum of individual phenotypes observed in France.
Hertzberg et al. (1989) used 8 RFLPs to construct haplotypes for the PAH locus in 5 ethnic groups from Polynesia; 630 distinct haplotypes were observed. Three common haplotypes constituted more than 95% of alleles. The finding of the same major haplotypes in a control group of individuals from Southeast Asia, as well as the finding of these haplotypes in the Caucasian population, suggested that the origin of these alleles predates the divergence of the races. The absence of severe PKU in Polynesians and Southeast Asians is consistent with the absence of the PAH haplotypes in which the most severe PKU mutants have been found among Caucasians.
Chen et al. (1989) found no DNA rearrangement or deletion of the PAH locus among 7 Chinese classical PKU families. Five different haplotypes were found in the 7 families: haplotypes 4 and 11, and 3 previously unreported haplotypes.
In the highly consanguineous Welsh Gypsy population, Tyfield et al. (1989) demonstrated that PKU is associated with haplotype 4, which is identical to that found in the northern European population.
Among 17 Turkish PKU families, Stuhrmann et al. (1989) identified 27 mutated PAH alleles representing 19 different haplotypes, of which 5 had not previously been described. The haplotype distribution differed significantly from that of northern European populations, suggesting that mutant PAH alleles had multiple origins and spread through different populations probably because of a selective advantage to the heterozygote. No deletions were discovered.
In 2 reports, Daiger et al. (1989) analyzed polymorphic DNA haplotypes at the PAH locus in European and Asian families. Much less haplotypic variation was found in Asians than in Caucasians. In particular, in Chinese and Japanese, haplotype 4 accounted for more than 77% of non-PKU chromosomes and for more than 80% of PKU-bearing chromosomes. The next most common Asian haplotype was 10 times less frequent than haplotype 4. By contrast, in many Caucasian populations, several of the most common haplotypes are equally frequent. Within European populations, a parent carrying a PKU mutation has an average probability of greater than 86% of being heterozygous--and hence informative for linkage--at 1 or more PAH RFLP sites. In Asian families about 36% of carriers are expected to be heterozygous at one or more RFLP sites.
In a study of 29 patients in Bulgaria, Kalaydjieva et al. (1990) found that the arg408-to-trp mutation (R408W; 612349.0002) was the most frequent, representing 34% of PKU alleles on the haplotype 2 background. The splicing defect in intron 12, which was found to account for nearly 40% of PKU alleles in Denmark, was absent in Bulgaria as was also the haplotype 3 associated with it. The arg158-to-gln mutation (612349.0010), which had been found in about 40% of mutant haplotype 4 alleles in western Europeans, was detected in only 1 out of 58 PKU chromosomes in Bulgaria.
Judging from the distribution of haplotypes and a limited investigation of the molecular defects, Dianzani et al. (1990) concluded that the 2 mutations most frequent in northern Europe, the splicing mutation (612349.0001) and the missense mutation (612349.0002), are uncommon in Italy, where haplotypes 1 and 6 account for about 57% of the PKU chromosomes and haplotypes 2 and 3 are found in less than 9%.
Konecki and Lichter-Konecki (1991) reviewed the haplotypes associated with specific PAH mutations in PKU patients. Haplotypes 2 and 3 are associated with mutant alleles among European populations north of the Alps; the same haplotypes are of little significance in European populations south of the Alps. A different haplotype 2 mutation (met1-to-val) was observed among French-Canadian PKU patients (John et al., 1990).
On the basis of 10 years of Maryland newborn-screening data, Hofman et al. (1991) concluded that the frequency of PKU in U.S. blacks is about 1 in 50,000, or one-third that in whites. They performed haplotype analysis of the PAH gene of 36 U.S. blacks, of whom 16 had classic PKU and 20 were controls. In the control blacks, 20% of wildtype PAH alleles had a common Caucasian haplotype, namely, haplotype 1, whereas 80% had a variety of haplotypes, all rare in Caucasians and Asians. One of these, haplotype 15, accounted for 30%. Among black mutant PAH alleles, 20% had a haplotype, either 1 or 4, common in Caucasians; 40% had a haplotype rare in Caucasians and Asians, and 40% had 1 of 2 previously undescribed haplotypes. Both of the latter could be derived from known haplotypes by a single event.
Eisensmith and Woo (1992) gave an updated listing of haplotypes at the PAH locus. Most if not all PAH mutations appear to have occurred after the divergence of the races (Eisensmith et al., 1992). Eisensmith et al. (1992) studied the haplotype associations, relative frequencies, and distributions of 5 prevalent PAH mutations in European populations: IVS12nt1 (612349.0001), arg408-to-trp (612349.0002), arg261-to-gln (612349.0006), arg158-to-gln (612349.0010), and IVS10nt546 (612349.0033). Each of these 5 mutations was strongly associated with only 1 of the more than 70 chromosomal haplotypes defined by 8 RFLPs in or near the PAH gene. These findings suggested that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these 5 alleles throughout Europe, 4 of the putative founding events could be localized to specific ethnic subgroups: the IVS12nt1 mutation appears to have occurred on a normal haplotype 3 chromosome in a Danish founding population. The arg408-to-trp mutation probably originated on a haplotype 2 chromosome in a Czechoslovakian population, although the absence of haplotype and frequency data from the more eastern regions of the Russian and other republics of the former Soviet Union precluded precise localization of a putative founding population. The absence of this mutation from haplotype 2 chromosomes in Chinese and Japanese populations suggested that the founding event was unique to Caucasoid peoples. Furthermore, the strong association still present between this mutation and haplotype 2 suggested that the founding event occurred within the past few millennia. The IVS10nt546 mutation was thought to be of Turkish origin but further study of its distribution within the Italian population showed that the allele was present primarily in regions that had been settled by Italian peoples prior to 1000 B.C., not in regions settled by Turks or other Middle Eastern groups. The arg261-to-gln mutation was relatively frequent in both Switzerland and Turkey where it occurred on haplotype 1. A putative founding population could not be identified for the arg158-to-gln mutation. Since only 2 of the 20 or so PAH mutations that account for more than 70% of all mutant alleles in Orientals are present in both Caucasians and Orientals, and since the 2 exceptions occur on different haplotype backgrounds suggesting that they result from recurrent mutation, most if not all PAH mutations appear to have occurred after the divergence of the races.
PKU has a very low incidence in Finland (Palo, 1967). Guldberg et al. (1995) studied all 4 known patients in Finland. The R408W mutation (612349.0002) was found on 4 mutant chromosomes (all haplotype 2), and IVS7nt1 (612349.0025), R261Q (612349.0006), and IVS2nt1 were each found on a single chromosome. No mutation was found on the remaining chromosome. The authors stated that the findings supported a pronounced negative founder effect as the cause of the low incidence of PKU in Finland. Eisensmith et al. (1992) demonstrated that the R408W mutation clusters in 2 regions: in northwest Europe, with the highest frequency reported in Ireland, and eastern Europe, with the highest frequency reported in Lithuania. In these 2 sites, the mutation is associated with haplotype 1 and haplotype 2, respectively, leading to the suggestion that R408W had 2 independent origins in Europe: 1 Celtic, and 1 Slavic. It is the Slavic mutation that has found its way to Finland in a small number of cases.
In an analysis of 236 Norwegian PKU alleles, Eiken et al. (1996) identified 33 different mutations constituting 99.6% of all mutant alleles; only 1 allele remained unidentified. Twenty-three of these mutations had been identified also in other European countries. There were 20 missense mutations, 6 splice mutations, 4 nonsense mutations, and 2 deletions, and 1 mutation disrupted the start codon. The 8 most common mutations represented 83.5% of the PKU alleles, with single allele frequencies ranging from 5.9% to 15.7%. Nineteen mutations were encountered only once. Most of the PKU mutations were found in the same RFLP/VNTR haplotype backgrounds in Norway as in other European populations, suggesting that only a few of the mutations may represent recurrent mutations (less than 3.4%). Among 10 mutations reported only in Norway, Eiken et al. (1996) detected 2 de novo mutations. From the birth places of the proband's grandparents, each mutation seemed to have an individual geographic distribution within Norway, with patterns of local mutation clustering. The observations were compatible with multiple founder effects and genetic drift for the distribution of PKU mutations within Norway.
Using mutation and haplotype analysis, Tyfield et al. (1997) examined the PAH gene in the PKU populations of 4 geographic areas of the British Isles: the west of Scotland, southern Wales, and southwestern and southeastern England. An enormous genetic diversity within the British Isles was demonstrated in the large number of different mutations characterized and in the variety of genetic backgrounds on which individual mutations were found. Allele frequencies of the more common mutations exhibited significant nonrandom distribution in a north/south differentiation.
In Quebec, Carter et al. (1998) analyzed 135 of 141 chromosomes from PKU probands and 8 additional chromosomes from a small number of probands with non-PKU hyperphenylalaninemia. The full set of chromosomes harbored 45 different PAH mutations: 7 polymorphisms, 4 mutations causing non-PKU HPA, and 34 mutations causing PKU. Only 6 mutations occurred in the whole province at relative frequencies greater than 5%; most of the mutations were rare and probably identical by descent. The PAH mutations stratified by geographic region and population, their distributions validating hypotheses about the European expansion to North America during 3 separate phases of immigration and demographic expansion in the Quebec region over the past 4 centuries.
Hutchesson et al. (1996) screened for tyrosinemia in the West Midlands region of the U.K., which includes the city of Birmingham, and demonstrated an increased frequency of tyrosinemia I in infants of 'non-oriental Asian ethnicity,' presumably mostly Pakistani. The incidence in this group was estimated to be 3.7 per million as compared with 0.04 per million in the rest of the population. Of the 12 patients with tyrosinemia I in the West Midlands, 10 were of non-Oriental Asian origin.
Zschocke et al. (1997) suggested that analysis of PKU mutations in Northern Ireland shows that most major episodes of immigration have left a record in the modern gene pool. The mutation ile65 to thr (612349.0063) could be traced to the Paleolithic people of western Europe who, in the Mesolithic period, first colonized Ireland. In contrast, arg408 to trp (612349.0002) on haplotype 1, the most common Irish PKU mutation, may have been prevalent in the Neolithic families who settled in Ireland after 4500 B.C. No mutation was identified that could represent European Celtic populations, supporting the view that the adoption of Celtic culture and language in Ireland did not involve major migration from the continent. Several less common mutations could be traced to the Norwegian Atlantic coast and were probably introduced into Ireland by Vikings. This indicated that PKU was not brought to Norway from the British Isles, as had been previously argued. The rarity in Northern Ireland of the IVS12nt1 mutation (612349.0001), the most common mutation in Denmark and England, indicated that the English colonization of Ireland did not alter the local gene pool in a direction that could be described as Anglo-Saxon.
Iceland was settled during the late ninth and early tenth centuries A.D. by Vikings who arrived from Norway and the British Isles. Although it is generally acknowledged that the Vikings brought with them Celtic slaves, the relative contribution of these peoples to the modern Icelandic gene pool is uncertain. Most population genetics studies using classical markers indicated a large Irish genetic contribution. Guldberg et al. (1997) investigated the molecular basis of PKU in 17 Icelandic patients and found 9 different mutations in the PAH gene. One novel mutation accounted for 40% of the mutant chromosomes: deletion of 1 of 2 successive thymidine residues in codons 376 and 377 in exon 11, resulting in a frameshift and the introduction of a termination codon at residue 399 (612349.0061). Haplotype data supported a common ancestral origin of the mutation, and genealogic examination extending back more than 5 generations showed that this mutation probably arose in an isolated part of southern Iceland and was enriched by founder effect. At least 7 PKU mutations had originated outside Iceland. The almost exclusively Scandinavian background of these mutations and the complete absence of common Irish PKU mutations strongly supported historic and linguistic evidence of a predominant Scandinavian heritage of the Icelandic people.
Khoury et al. (2003) discussed population screening in the age of genomic medicine using PKU as a classic example and extending the discussion to population screening for genetic susceptibility to common disorders such as hereditary hemochromatosis (235200) and factor V Leiden (see 612309.0001). They also discussed ethical, legal, and social issues such as testing children for adult-onset disorders, and the finding of unanticipated information such as misattribution of paternity and the discovery of a disorder other than the one for which the screening was undertaken in the first place.
Among 34 unrelated patients with PKU from Serbia and Montenegro. Stojiljkovic et al. (2006) found that the 2 most common mutations were L48S and R408W, accounting for 21% and 18% of mutant alleles, respectively. Overall, 5 mutations accounted for 60% of all mutant alleles. The results suggested that PKU in this population is heterogeneous and reflects numerous migrations over the Balkan peninsula.
Wang et al. (2007) reported unexpected PAH allelic heterogeneity between 2 groups of Old Order Amish: the Lancaster County, Pennsylvania settlement, and the Geauga County, Ohio settlement. Individuals with PKU from the Geauga County settlement were homozygous for a splice site mutation (612349.0033), and the incidence of PKU in this group was estimated to be 1 in 1,000, much higher than in other populations. In contrast, those with PKU from Lancaster County were compound heterozygous for 2 PAH mutations: R261Q (612349.0006) and a 3-bp deletion (612349.0030). The incidence of PKU in the Lancaster County Amish was 1 in 10,000, similar to that in other populations. Wang et al. (2007) commented that the findings highlighted important points in population genetics: rare genetic diseases in isolated populations are not uniformly caused by a single mutation and genetic drift is random, thus sampling effects are as likely to decrease as they are to increase mutation frequency within a given population.
Evolution
Woolf (1986) suggested that there may be a heterozygous advantage in PKU which operates through protection against the toxic effects of ochratoxin A. This mycotoxin is produced by several species of Aspergillus and Penicillium infesting stored grains and other foods. The mild, wet climate of Ireland and West Scotland tends to encourage the growth of molds. Furthermore, these areas have suffered repeated famines during which moldy food was eaten. Heterozygous women appear to have a lower spontaneous abortion rate.
Animal Model
McDonald et al. (1990) isolated mutant mice exhibiting hereditary hyperphenylalaninemia after ethylnitrosourea mutagenesis of the germ line. By linkage mapping, they demonstrated that the disorder, which had other characteristics close to those of phenylketonuria, mapped to mouse chromosome 10 at or near the Pah locus.
McDonald and Charlton (1997) identified a mutation within the protein coding sequence of the Pah gene in each of 2 genetic mouse models for human phenylketonuria. A genotype/phenotype relationship that was strikingly similar to the human disease emerged, underscoring the similarity of PKU in mouse and man. The enu1 mutation, induced by the chemical mutagen N-ethyl-N-nitrosourea (ENU), predicts a conservative valine-to-alanine amino acid substitution and is located in exon 3, a gene region where serious mutations are rare in humans. The phenotype in mice is mild. The second ENU-induced mutation, enu2, predicts a radical phenylalanine-serine substitution and is located in exon 7, a gene region where serious mutations are common in humans. The phenotype of the second mutation is severe.
Martynyuk et al. (2010) reviewed the findings from animal studies on the mechanism of phenylalanine action in the PKU brain, including defects in myelin and protein synthesis, blood-brain barrier transport, direct neurotoxic effects of phenylalanine, neurotransmitter imbalances, activity of glutamate receptors, and animal behavior.
Gersting et al. (2010) found that loss of function in Pah-enu1 mice was a consequence of misfolding, aggregation, and accelerated degradation of the enzyme. Tetrahydrobiopterin (BH4) attenuated this triad by conformational stabilization augmenting the effective PAH concentration, which led to rescue of the biochemical phenotype and enzyme function in vivo. Combined in vitro and in vivo analyses revealed a selective pharmaceutical action of BH4 confined to the pathologic metabolic state.
History
Folling (1934) in Norway first described PKU under the designation oligophrenica phenylpyruvica. Jervis (1947) localized the metabolic error as an inability to oxidize phenylalanine to tyrosine, and Jervis (1953) demonstrated deficiency of phenylalanine hydroxylase in the liver of a patient.
Guthrie (1996) gave a history of his introduction of newborn screening for PKU. A shift in his research from cancer research to the study of mental retardation had been prompted by the birth of his second child with mental retardation. He learned that the phenylalanine-restricted diet introduced for treatment of PKU required close monitoring of blood Phe levels for which the methods were then laborious. He conceived of modifying the bacterial test he was using to screen for different substances in the blood of patients who were being treated for cancer. These tests relied on 'competitive inhibition;' a compound that normally prevented growth of bacteria in culture plates no longer inhibited the growth when large amounts of Phe was present in a blood spot that was added to the plate. The birth of a niece who was found to have PKU at the age of 15 months also had an influence on his research. Since a positive ferric chloride urine test came too late to prevent her mental retardation, he became interested in developing a blood test for neonates. He had been using filter paper discs soaked in serum from the patient to be studied. He found, however, that whole blood worked equally well and facilitated newborn screening. Newborn screening with the heel stick began in 1961 and was reported by Guthrie and Susi (1963). In the first 2 years, 400,000 infants were tested in 29 states and 39 cases of PKU were found--an incidence of about 1 per 10,000. None was missed by screening. Guthrie (1996) noted that the National Association for Retarded Children through its state chapters lobbied vigorously for laws for PKU screening despite much opposition by organized medical groups; 37 states had such laws by 1967.
Bickel (1996) described his first introduction to the disease PKU in 1949 at the University Children's Hospital Zurich where Professor G. Fanconi instructed Bickel to perform the ferric chloride test in every retarded patient. Later, on moving to the University Children's Hospital in Birmingham, he introduced the ferric chloride test there and found a patient whose mother urged him to find a way to help the daughter. Under the pressure of this mother, Bickel, Gerrard, and Hickmans (Bickel et al., 1953) speculated that there might be a causal relation between the Phe excess in the biologic fluids and the girl's brain damage and that it might be possible to improve her condition by reducing Phe intake. The use of a Phe-restricted casein hydrolysate as the main protein source of the diet was considered. Early results were dramatic.
### Early Mapping Studies
Berg and Saugstad (1974) found low positive lod scores for linkage between PKU and PGM-1, Rh, Hp, and Kell. A previous suggestion of linkage between PKU and ABO could not be confirmed.
Kamaryt et al. (1978) studied linkage of the chromosome 1 amylase loci with PKU. Combined data for linkage with the two amylase loci yielded a lod score of 4.214 at a recombination fraction of 0.00. Paul et al. (1979) were unable to confirm linkage of PKU to chromosome 1 markers. Linkage with theta less than 0.10 was excluded for AMY2. They expressed reservations about the data of Kamaryt et al. (1978) because of the questionable accuracy of scoring AMY1 in urine and because data were used twice from a family with a parent heterozygous at both amylase loci. In this study done in Indiana, no evidence of linkage heterogeneity between Amish and non-Amish families was found.
Rao et al. (1979) derived a maximum likelihood map of chromosome 1, using data on 13 loci. They concluded that assignment of the PKU locus to chromosome 1 could be confirmed, but left as uncertain its location in the PGM1-AMY segment. Cabalska (1980) was unable, however, to confirm the linkage of chromosome 1 markers. Knapp et al. (1982) excluded close linkage between the amylase and PKU loci. They considered loose linkage unlikely. Genetic heterogeneity was considered a possible but unlikely explanation.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly Eyes \- Blue eyes \- Cataracts SKIN, NAILS, & HAIR Skin \- Pale pigmentation \- Dry skin \- Eczema \- Scleroderma Hair \- Blond hair NEUROLOGIC Central Nervous System \- Decreased mental processing speed \- Mental retardation (if left untreated) \- Infantile irritability (if left untreated) \- Peculiar gait (if left untreated) \- Peculiar stance and sitting posture (if left untreated) \- Limb posturing (if left untreated) \- Purposeless movements (if left untreated) \- Increased deep tendon reflexes (if left untreated) \- Seizures (if left untreated) \- Brain calcification (if left untreated) Peripheral Nervous System \- Defective myelin formation (if left untreated) Behavioral Psychiatric Manifestations \- Psychosis (if left untreated) \- Hyperactivity (if left untreated) \- Autistic features (if left untreated) \- Aggression (if left untreated) \- Self-mutilation (if left untreated) \- Attention deficit disorder (in those who stop treatment) \- Social sensitivity \- Obsessive-compulsive disorder \- Depression \- Anxiety disorders \- Defects in executive function METABOLIC FEATURES \- Phenylalanine hydroxylase deficiency \- Hyperphenylalaninemia \- Phenylpyruvic acidemia PRENATAL MANIFESTATIONS Maternal \- Maternal hyperphenylalaninemia teratogenic LABORATORY ABNORMALITIES \- Increased urinary o-hydroxyphenylacetic acid, phenylpyruvic acid, phenylacetic acid and phenylacetylglutamine MISCELLANEOUS \- Occurs in about 1 in 10,000 births \- Mousy odor MOLECULAR BASIS \- Caused by mutation in the phenylalanine hydroxylase gene (PAH, 261600.0001 ) ▲ 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
|
PHENYLKETONURIA
|
c0085547
| 25,568 |
omim
|
https://www.omim.org/entry/261600
| 2019-09-22T16:23:33 |
{"doid": ["9281"], "mesh": ["D017042"], "omim": ["261600"], "icd-10": ["E70.0"], "orphanet": ["2209", "716"], "synonyms": ["Alternative titles", "PHENYLALANINE HYDROXYLASE DEFICIENCY", "PAH DEFICIENCY", "OLIGOPHRENIA PHENYLPYRUVICA", "FOLLING DISEASE"], "genereviews": ["NBK1504"]}
|
Venous stasis
Other namesVenostasis
Skin changes as a result of long term venous stasis
Venostasis, or venous stasis, is a condition of slow blood flow in the veins, usually of the legs.
## Contents
* 1 Causes
* 2 Complications
* 3 See also
* 4 References
## Causes[edit]
Causes of venous stasis include:
* Chronic venous insufficiency.[1]
* Congestive heart failure.[2]
* Long periods of immobility that can be encountered from driving,[3] flying, bed rest/hospitalization, or having an orthopedic cast. Recommendations by clinicians to reduce venous stasis and DVT/PE often encourage increasing walking, calf exercises, and intermittent pneumatic compression when possible.[4][5][6]
## Complications[edit]
Potential complications of venous stasis are:
* Venous ulcers
* Blood clot formation in veins (venous thrombosis), as with the deep veins of the legs (deep vein thrombosis or DVT), potentially indicating thrombosis prophylaxis.[7]
## See also[edit]
* Virchow's triad
## References[edit]
1. ^ "Chronic Venous Insufficiency (CVI)". Cleveland Clinic. Last reviewed by a Cleveland Clinic medical professional on 05/14/2019.
2. ^ Zhu, Ruiqi; Hu, Yu; Tang, Liang (2017). "Reduced cardiac function and risk of venous thromboembolism in Asian countries". Thrombosis Journal. 15 (1). doi:10.1186/s12959-017-0135-3. ISSN 1477-9560.
3. ^ Barbara G. Wells; Joseph T. DiPiro; Terry L. Schwinghammer; Gary R. Matzke; Gary C. Yee; Robert L. Talbert; L. Michael Posey (2008). Pharmacotherapy Handbook. McGraw-Hill Professional. p. 163. ISBN 9780071485012.
4. ^ "New DVT guidelines: no evidence to support "economy class syndrome"; oral contraceptives, sitting in a window seat, advanced age, and pregnancy increase DVT risk in long-distance travelers". American College of Chest Physicians. 7 February 2012. Retrieved 10 February 2012.
5. ^ Hecht, M. E. (2010). A practical guide to hip surgery: from pre-op to recovery. Sunrise River Press. ISBN 978-1-934716-12-0.CS1 maint: ref=harv (link)
6. ^ Gould MK, Garcia DA, Wren SM, et al. (2012). "Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines". Chest. 141 (suppl 2): e227S–e277S. doi:10.1378/chest.11-2297. PMC 3278061. PMID 22315263.
7. ^ Martinelli I, Bucciarelli P, Mannucci PM (2010). "Thrombotic risk factors: basic pathophysiology". Crit Care Med. 38 (2 Suppl): S3-9. doi:10.1097/CCM.0b013e3181c9cbd9. PMID 20083911.
*[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
|
Venous stasis
|
c0042344
| 25,569 |
wikipedia
|
https://en.wikipedia.org/wiki/Venous_stasis
| 2021-01-18T18:34:14 |
{"mesh": ["D014647"], "wikidata": ["Q4107209"]}
|
Paroxysmal dyskinesia (PD) is a rare heterogenous group of movement disorders manifesting as abnormal involuntary movements that recur episodically and last only a brief time. PD includes paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia (PED) and a variant form of PKD, infantile convulsion and choreoathetosis (ICCA syndrome) (see these terms).
## Epidemiology
The prevalence of PD is still unknown. The worldwide prevalence of PKD and PNKD is estimated to be 1/150,000 and 1/1,000,000 respectively.
## Clinical description
The age of onset is typically in childhood. The paroxysmal movements are mainly dystonic and choreic but can be ballistic or a mixture of these. There is no alteration in consciousness. PD can be classified according to duration and precipitating factors and is thus divided into: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD) and paroxysmal exertion-induced dyskinesia (PED). Between attacks, patients are generally completely normal and neurological examination is typically normal. Infantile convulsion and choreoathetosis (ICCA syndrome) is considered a variant form of PKD.
## Etiology
The exact etiology of PD is still elusive and the causes multifactorial. A number of genes have been associated with different forms of PD, namely: PNKD (2q35) mutations have been found to cause PNKD in families whose attacks can be triggered by caffeine and alcohol, PRRT2 (16p11.2) mutations account for some families with PKD or ICCA syndrome, and SLC2A1 (solute carrier family 2 (facilitated glucose transporter), member 1) (1p34.2 ) mutations have been identified to cause PED.
## Diagnostic methods
Diagnosis of PD is essentially based on medical history and clinical examination which includes recordings of dystonia, abnormal postures and tremor, electroencephalogram, brain imaging (computed tomography or magnetic resonance imaging) and blood chemistry. Diagnosis is confirmed by the detection of known pathogenic mutations.
## Differential diagnosis
PD can occur secondary to other disorders such as multiple sclerosis, Aicardi-Goutières syndrome (see these terms), myelopathy, cerebral palsy, cerebral infarcts and hemorrhages, focal seizures, encephalitis, radiculopathy, hypoparathyroidism, hypoglycemia and reflex sympathetic dystrophy.
## Antenatal diagnosis
Prenatal diagnosis for pregnancies at increased risk for PRRT2, PNKD, and SLC2A1 mutations associated with familial PKD or ICCA syndrome, PNKD, and PED respectively is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at 15-18 weeks' gestation) or chorionic villus sampling (usually performed at 10-12 weeks' gestation). The disease-causing mutation of an affected family member must be identified in the family before prenatal testing can be performed.
## Genetic counseling
PD can be sporadic or familial with autosomal dominant inheritance. Genetic counseling should be offered to all patients and families.
## Management and treatment
Treatment is different for each of the 4 subtypes. Attacks may be controlled with anticonvulsant drugs such as carbamazepine and phenytoin. Deep brain stimulation may act as a potential therapeutic option in medically refractory PD.
## Prognosis
The frequency of attacks typically diminishes with age in the familial cases and the disease often completely remits. There are no long term implications for life expectancy.
*[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
|
Paroxysmal dyskinesia
|
c0752210
| 25,570 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1431
| 2021-01-23T17:55:01 |
{"mesh": ["D002819"], "umls": ["C0752210"], "icd-10": ["G24.8"], "synonyms": ["Paroxysmal choreoathetosis", "Paroxysmal dystonic choreoathetosis"]}
|
Choristomas, a form of heterotopia, are masses of normal tissues found in abnormal locations.[1][2][3][4] In contrast to a neoplasm or tumor, the growth of a choristoma is normally regulated.[5]
It is different from a hamartoma. The two can be differentiated as follows: a hamartoma is disorganized overgrowth of tissues in their normal location (e.g., Peutz–Jeghers polyps), while a choristoma is normal tissue growth in an abnormal location (e.g., osseous choristoma,[6] gastric tissue located in distal ileum in Meckel diverticulum).
## References[edit]
1. ^ "Choristoma" at Dorland's Medical Dictionary
2. ^ Lee, Kenneth H.; Roland, Peter S. (2013). Heterotopias, Teratoma, and Choristoma. Encyclopedia of Otolaryngology, Head and Neck Surgery. pp. 1179–1183. doi:10.1007/978-3-642-23499-6_642. ISBN 978-3-642-23498-9.
3. ^ Jorquera, JessicaPatricia Correa; Rubio-Palau, Josep; Cazalla, AsteriaAlbert; Rodríguez-Carunchio, Leonardo (2016). "Choristoma: A rare congenital tumor of the tongue". Annals of Maxillofacial Surgery. 6 (2): 311–313. doi:10.4103/2231-0746.200342. PMC 5343649. PMID 28299279.
4. ^ Goswamy, Monika; Tabasum, Syeda; Kudva, Praveen; Gupta, Shikha (2012). "Osseous choristoma of the periodontium". Journal of Indian Society of Periodontology. 16 (1): 120–2. doi:10.4103/0972-124X.94619. PMC 3357020. PMID 22628977.
5. ^ Birbrair, Alexander; Zhang, Tan; Wang, Zhong-Min; Messi, Maria Laura; Olson, John D.; Mintz, Akiva; Delbono, Osvaldo (2014-07-01). "Type-2 pericytes participate in normal and tumoral angiogenesis". American Journal of Physiology. Cell Physiology. 307 (1): C25–C38. doi:10.1152/ajpcell.00084.2014. ISSN 0363-6143. PMC 4080181. PMID 24788248.
6. ^ Adhikari, Bhoj Raj (2016). "Osseous choristoma of the tongue: two case reports". Journal of Medical Case Reports. 2016: 59. doi:10.1186/s13256-016-0840-8. PMC 4794853. PMID 26983573.
## External links[edit]
* MeSH C23.300.250 – Choristoma
* v
* t
* e
Overview of tumors, cancer and oncology
Conditions
Benign tumors
* Hyperplasia
* Cyst
* Pseudocyst
* Hamartoma
Malignant progression
* Dysplasia
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*[AA]: Adrenergic agonist
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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
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|
Choristoma
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c0008519
| 25,571 |
wikipedia
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https://en.wikipedia.org/wiki/Choristoma
| 2021-01-18T18:58:25 |
{"mesh": ["D002828"], "umls": ["C0008519"], "wikidata": ["Q40649915"]}
|
Human disease
Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) because the unknown etiology of some of them, and sometimes known as borderline forms of multiple sclerosis,[1] is a collection of multiple sclerosis variants, sometimes considered different diseases,[2][3] but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.[4][5]
Multiple sclerosis for some people is a syndrome more than a single disease.[6] As of 2019 three auto-antibodies have been found in atypical MS giving birth to separate diseases: Anti-AQP4 diseases, Anti-MOG and Anti-NF spectrums.[7] Also a LHON-associated MS[8] has been reported, as well as the medication-induced anti-TNF spectrum (which cannot be distinguished from natural MS with the current knowledge) can be included here.[9][10][11][12][13][14][15]
The subject is under intense research and the list of MS autoantibodies is expected to grow in the near future[16][17][18]
## Contents
* 1 Separated variants
* 1.1 Anti-AQP4 spectrum
* 1.2 Anti-MOG spectrum
* 1.3 Anti-neurofascin spectrum
* 1.4 Anti-TNF spectrum
* 1.5 LHON-associated MS
* 2 Variants still idiopathic
* 2.1 Pseudotumefactive variants
* 2.2 Atypical location variants
* 2.3 Atypical OCB variants
* 2.4 Radiologically atypical variants
* 2.5 Atypical clinical courses
* 2.5.1 Highly Active MS
* 2.5.2 Malignant MS
* 2.5.3 Aggressive MS
* 2.5.4 Rapidly progressive multiple sclerosis
* 3 Under research
* 4 Genetic types
* 4.1 HLA DRB3*02:02 patients
* 4.2 Rapidly progressive multiple sclerosis
* 5 Primary progressive variants
* 6 Clinical situations inside standard MS
* 6.1 Preclinical MS: CIS and CDMS
* 6.2 RIS, subclinical and silent MS
* 6.3 Aggressive multiple sclerosis
* 6.4 Pediatric and pubertal MS
* 7 Controversy for the definition
* 7.1 Pathological and clinical definitions
* 7.2 Other meanings of MS
* 7.3 Handling several clinical definitions
* 7.4 CIS and conversion to MS
* 8 See also
* 9 References
## Separated variants[edit]
Several previous MS variants have been recently separated from MS after the discovery of a specific auto-antibody. Those autoantibodies are currently anti-AQP4, anti-MOG and some anti-Neurofascins.[19]
The pathogenic mechanism is usually not related to the clinical course. Therefore, one given pathogenic underlying condition can yield several clinical diseases, and one disease can be produced by several pathogenic conditions.
These conditions can appear as Neuromyelitis optica (NMO), and its associated "spectrum of disorders" (NMOSD), currently considered a common syndrome for several separated diseases[20] but with some still idiopathic subtypes. Some researchers think that there could exist an overlapping between Anti-NMDA receptor encephalitis cases and neuromyelitis optica or acute disseminated encephalomyelitis.[21]
### Anti-AQP4 spectrum[edit]
See Anti-AQP4 diseases
Originally found in neuromyelitis optica, this autoantibody has been associated with other conditions. Its current spectrum is as following:
* Seropositive Devic's disease, according to the diagnostic criteria described above
* Limited forms of Devic's disease, such as single or recurrent events of longitudinally extensive myelitis, and bilateral simultaneous or recurrent optic neuritis
* Asian optic-spinal MS - this variant can present brain lesions like MS.[22]
* Longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease
* Optic neuritis or myelitis associated with lesions in specific brain areas such as the hypothalamus, periventricular nucleus, and brainstem[23]
* Some cases of tumefactive multiple sclerosis[24]
### Anti-MOG spectrum[edit]
See Anti-MOG associated encephalomyelitis
Anti-MOG associated spectrum, often clinically presented as an anti-MOG autoimmune encephalomyelitis,[25][26] but can also appear as negative NMO or atypical multiple sclerosis.[27]
The presence of anti-MOG autoantibodies has been associated with the following conditions[28]
* Some cases of aquaporin-4-seronegative neuromyelitis optica: NMO derived from an antiMOG associated encephalomyelitis,[29]
* Some cases of acute disseminated encephalomyelitis, specially the recurrent ones (MDEM)[30]
* Some cases of McDonalds-positive multiple sclerosis[28][31][27][32]
* isolated optic neuritis or transverse myelitis[28]
* Recurrent optic neuritis. The repetition of an idiopatic optic neuritis is considered a distinct clinical condition, and it has been found to be associated with anti-MOG autoantibodies[33]
* CRION (Chronic relapsing inflammatory optic neuritis): A distinct clinical entity from other inflammatory demyelinating diseases.[34] Some reports consider it a form of Anti-MOG encephalomyelitis[35] and the most recent ones consider it the main phenotype of the anti-MOG spectrum[36]
The anti-mog spectrum in children is equally variated: Out of a sample of 41 children with MOG-antibodies 29 had clinical NMOSD (17 relapsing), 8 had ADEM (4 relapsing with ADEM-ON), 3 had a single clinical event CIS, and 1 had a relapsing tumefactive disorder. Longitudinal myelitis was evident on MRI in 76[percent]. It has also been noted that percentage of children with anti-mog antibodies respect a demyelinating sample is higher than for adults[37]
Some NMO patients present double positive for autoantibodies to AQP4 and MOG. These patients have MS-like brain lesions, multifocal spine lesions and retinal and optic nerves atrophy.[38]
### Anti-neurofascin spectrum[edit]
See Anti-neurofascin demyelinating diseases
Some anti-neurofascin demyelinating diseases were previously considered a subtype of Multiple Sclerosis but now they are considered a separate entity, as it happened before to anti-MOG and anti-AQP4 cases. Around 10% of MS cases are now thought to be anti-Neurofascin disease in reality.[39]
Anti-neurofascin autoantibodies have been reported in atypical cases of MS and CIDP, and a whole spectrum of Anti-neurofascin demyelinating diseases has been proposed.[40]
Some cases of CIDP are reported to be produced by auto-antibodies against several neurofascin proteins. These proteins are present in the neurons and four of them have been reported to produce disease: NF186, NF180, NF166 and NF155.[40]
Antibodies against Neurofascins NF-155 can also appear in MS[41] and NF-186 could be involved in subtypes of MS[42] yielding an intersection between both conditions.
Summarising, autoantibodies against several neurofascins can produce MS: neurofascin186 (NF186), neurofascin155 (NF155), contactin 1 (CNTN1), contactin associated protein 1 (CASPR1) and gliomedin. All of them nodal and paranodal proteins.[40]
### Anti-TNF spectrum[edit]
Main article: TNF inhibitor
Several anti-TNF drugs like adalimumab[9][10] are commonly prescribed by a number of autoimmune conditions. Some of them have been reported to produce a CNS-demyelination compatible with, and by current knowledge indistinguishable from, standard MS.[11][12] Several other monoclonal antibodies like pembrolizumab,[13] nivolumab [14] and infliximab[15] have been also reported to produce MS artificially. Nevertheless, it is not so similar as reported in the previous references.[43]
This has given birth to the Anti-TNF-α therapy-associated demyelinating disorders. The reactions have been diverse according to the source of the disease.[11][12][14] Some of these cases can be classify as ADEM, using the confluent demyelination as barrier between both conditions.[44]
In most cases, the damage fulfills all pathological diagnostic criteria of MS and can therefore be classified as MS in its own right. The lesions were classified as pattern II in the Lassman/Lucchinetti system. Some lesions also showed Dawson fingers,[12] which is supposed to be a MS-only feature.
These recent problems with artificial anti-TNF-α autoimmunity also point to the possibility of tumor necrosis factor alpha involvement in some multiple sclerosis variants.
### LHON-associated MS[edit]
Also a previous subtype of MS associated to LHON has been described (LHON-MS)[8] It is a presentation of LHON with MS-like CNS damage.
It used to satisfy McDonalds definition for MS, but after demonstration that LHON can produce this kind of lesions, the "no better explanation" requirement does not hold anymore. It is not due to auto-antibodies, but to defective mitochondria instead.[45]
The symptoms of this higher form of the disease include loss of the brain's ability to control the movement of muscles, tremors, and cardiac arrhythmia.[46] and the lack of muscular control[47]
## Variants still idiopathic[edit]
Apart of the previously cited spectrums (Anti-AQP4 diseases, Anti-MOG, Anti-NF and anti-TNF spectrums) there is a long list of MS variants, with possibly different pathogenesis, which are still idiopathic and considered inside the MS-spectrum.
### Pseudotumefactive variants[edit]
Most atypical variants appear as tumefactive or pseudotumefactive variants (lesions whose size is more than 2 cm (0.79 in), with mass effect, oedema and/or ring enhancement)[48][49] Some cases of the following have shown anti-MOG auto-antibodies and therefore they represent MS cases only partially.
* Acute disseminated encephalomyelitis or ADEM, a closely related disorder in which a known virus or vaccine triggers autoimmunity against myelin. Around 40% of the ADEM cases are due to an "anti-MOG associated encephalomyelitis".[50] It includes Acute hemorrhagic leukoencephalitis, possibly a variant of Acute disseminated encephalomyelitis
* Marburg multiple sclerosis, an aggressive form, also known as malignant, fulminant or acute MS, currently reported to be closer to anti-MOG associated ADEM than to standard MS.[51] and is sometimes considered a synonym for Tumefactive multiple sclerosis[52]
* Balo concentric sclerosis, an unusual presentation of plaques forming concentrenic circles, which can sometimes get better spontaneously.
* Schilder disease or diffuse myelinoclastic sclerosis: is a rare disease that presents clinically as a pseudotumoural demyelinating lesion; and is more common in children.[53][54]
* Solitary sclerosis: This variant has been recently proposed (2012) by Mayo Clinic researchers.[55] though it was also reported by other groups more or less at the same time.[56][57] It is defined as isolated demyelinating lesions which produce a progressive myelopathy similar to primary progressive MS.
### Atypical location variants[edit]
Also the location of the lesions can be used to classify variants:
* Myelocortical multiple sclerosis (MCMS), proposed variant with demyelination of spinal cord and cerebral cortex but not of cerebral white matter [58] Several atypical cases could belong here. See the early reports of MCMS<[59][60]
* Opticospinal MS or Optic-spinal MS (OSMS): Old OSMS cases are now considered inside the NMO spectrum, but this does not apply to anti-AQP4 negative cases.[61] After the discovery of anti-AQP4 autoantibodies it was found that some cases of OSMS were AQP4-negative, and therefore, they are considered real MS cases. OSMS has its own specific immunological biomarkers[62] The whole picture is under construction and several reports exists about overlapping conditions.
* Pure spinal multiple sclerosis: Patients with clinical and paraclinical features suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the McDonald criteria[63] Some inflammatory conditions are associated with the presence of scleroses in the CNS.[64] Optic neuritis (monophasic and recurrent) and Transverse myelitis (monophasic and recurrent)
* LHON associated MS (LHON-MS), a presentation of LHON with MS-like CNS damage, and therefore a subtype of MS according to McDonalds definition.[8]
### Atypical OCB variants[edit]
Also different classifications by body fluid biomarkers is possible:
* Oligoclonal negative MS: Some reports point to the possibility of a different pathogenesis[65] They represent around 5% of the cases[66] which is suspected to be immunogenetically different.[67] Their evolution is better than standard MS patients,[68]
* Oligoclonal IgM positive MS, with immunoglobulin-M Bands (IgM-Bands), which accounts for a 30-40% of the MS population and has been identified as a predictor of MS severity.[69] It has been reported to have a poor response to interferon-beta but a better response to glatimer acetate instead[70]
* OCB's types: OCBs are made up of activated B-cells. It seems that the molecular targets for the OCB's are patient-specific.[71]
### Radiologically atypical variants[edit]
Inside well defined MS (Lesions disseminated in time and space with no other explanation) there are atypical cases based in radiological or metabolic criteria. A four-groups classification has been proposed:[72]
* Tumefactive demyelinating lesion (TDL)-onset MS
* Acute disseminated encephalomyelitis (ADEM)-like MS
* Multiple sclerosis with cavitary lesions: Atypical multiple sclerosis cases similar to vanishing white matter disease but etiologically different from both.[73] Lesions similar to vanishing white matter disease[73]
* Leukodystrophy-like MS.
Other radiological classification of atypical lesions proposes the following four subtypes:[74]
* infiltrative
* megacystic
* Baló-like
* ring-like lesions
### Atypical clinical courses[edit]
In 1996, the US National Multiple Sclerosis Society (NMSS) Advisory Committee on Clinical Trials in Multiple Sclerosis (ACCTMS) standardized four clinical courses for MS (Remitent-Recidivant, Secondary Progressive, Progressive-Relapsing and Primary progressive). Later,[75]
Some reports state that those "types" were artificially made up trying to classify RRMS as a separate disease so that the number of patients was low enough to get the interferon approved by the FDA under the orphan drugs act.[75] Revisions in 2013 and 2017 removed the Progressive-Relapsing course and introduced CIS as a variety/course/status of MS, establishing the actual classification (CIS, RRMS, SPMS and PPMS). Nevertheless, these types are not enough to predict the responses to medications and several regulatory agencies use additional types in their recommendations lide Highly active MS, Malignant MS, Aggressive MS or Rapidly progressive MS.[76]
#### Highly Active MS[edit]
As of 2019, HAMS is defined as an RRMS phenotype with one or more of the following characteristics:[76]
1. DSS scale of 4 points at 5 years of onset of the disease
2. Multiple relapses (two or more) with incomplete recovery in the ongoing year
3. More than 2 brain magnetic resonance imaging (MRI) studies demonstrating new lesions or increase in the size of the lesions in T2, or lesions that enhance with gadolinium despite treatment (Clinical case 1 and 2).
4. No response to treatment with one or more DMTs for at least one year.
There is a group of patients who have defined clinical and radiological risk factors that predict a behavior of greater risk of conversion to HAMS, without having the diagnostic criteria of HAMS in a first clinical attack have predictors of high risk.
Some other previous authors have used other definitions like:
* High activity according to 2017 definition of activity
* Rapid accumulation of physical and cognitive deficit, despite treatment with DMT's.
* Being eligible for immunoablative therapy followed by autologous haematopoietic stem cell transplantation (aHSCT) because of a) the failure of conventional treatment, b) frequent and severe (disabling) relapses, or c) MRI activity (new T2 or gadolinium-enhancing lesions).
#### Malignant MS[edit]
See malignant multiple sclerosis
Occasionally, the term ‘malignant’ MS (MMS) has been used to describe aggressive phenotypes of MS, but this is another ambiguous term that—despite wide usage—means different things to different people.
In 1996, the US National MS Society (NMSS) Advisory Committee on Clinical Trials in Multiple Sclerosis, “malignant MS” was also included, namely, “disease with a rapid progressive course, leading to significant disability in multiple neurologic systems or death in a relatively short time after disease onset.”
Many authors reserve the term malignant for fulminant forms of MS that deteriorate so rapidly from the outset as to be almost monophasic, and result in death within months to a few years. One such example is the Marburg variant of MS, which is classically characterized by extensive necrotic and/or tumefactive lesions with mass effect.
Interestingly, despite recent (and increasing) emphasis on early detection of patients with aggressive MS, the original definition of MMS was not modified by the NMSS Advisory Committee in its latest publication in 2013 (Lublin et al., 2014).
#### Aggressive MS[edit]
Common to all definitions is the early, unexpected acquisition of disability followed by frequent relapses and highly active disease seen on MRI.
One definition can be based on EDSS score and the time to develop secondary progressive MS (SPMS) (Menon et al., 2013).
No consensus exists on the speed of progression or degree of disability sufficient for aggressive MS, but we can assume that reaching an EDSS score of 6 points probably represents an upper limit beyond which the risk-benefit ratio for an aggressive treatment is unfavourable.
Pragmatically, AMS has been defined as any type of MS that is associated with repeated severe attacks and accelerated accrual of disability—put more simply, ‘rapidly progressive’ MS (See below)
#### Rapidly progressive multiple sclerosis[edit]
This kind of MS was previously reported to behave different that the standard progressive course,[77] being linked to Connexin 43 autoantibodies with pattern III lesions (distal oligodendrogliopathy)[78] and being responsive to plasma exchange[79]
In very rapidly progressive multiple sclerosis the use of immunosuppressive therapy (mitoxantrone/cyclophosphamide), rituximab, autologous haematopoietic stem cell therapy or combination therapy should be considered carefully.[80]
## Under research[edit]
Some auto-antibodies have been found consistently across different MS cases but there is still no agreement on their relevance:
* Anti-kir4.1: A KIR4.1 multiple sclerosis variant was reported in 2012[81] and later reported again,[82] which could be considered a different disease (as Devic's disease did before), and can represent up to a 47% of the MS cases
* Anoctamin 2: Auto-antibodies against anoctamin-2 (ANO-2), one of the ion-channel proteins, have been reported consistently since 2013[83]
* This finding is not universal. Most of the MS patients do not show auto-antibodies against ANO-2. Therefore, this points toward an ANO2 autoimmune sub-phenotype in MS.[84]
* Later reports point towards a mimicry between ANO-2 and EBV-EBNA-1 protein[85]
* Anti-NMDAR autoantibodies: There is an overlap between cases of Anti-NMDA receptor encephalitis and MS, NMO and ADEM.[21] It also could be a confusion with Anti-NMDA receptor encephalitis in the early stages[86] but there are also anti-NMDAR reported cases that evolve to McDonalds MS[87]
* Anti-Flotilin spectrum: The proteins Flotillin 1 and flotillin 2 have been recently identified as target antigens in some patients with multiple sclerosis. First 14 cases were reported together in the first report, and 3 new cases were reported later inside a cohort of 43 patients.[88]
* Mutations in GJB1 coding for connexin 32, a gap junction protein expressed in Schwann cells and oligodendrocytes, that usually produce Charcot-Marie-Tooth disease. In some cases also MS (as defined by McDonalds criteria) can appear in these patients.[89]
* Also an OPA1 variant [90] exists.
* There exist some reports by Drs. Aristo Vojdani, Partha Sarathi Mukherjee, Joshua Berookhim, and Datis Kharrazian of an aquaporin-related multiple sclerosis, related to vegetal aquaporin proteins.[91]
* Auto-antibodies against histones have been reported to be involved.[92]
* Anti-AQP1 could be involved in atypical MS and NMO[93]
* N-type calcium channel antibodies can produce cognitive relapses mimicking MS related cognitive decline, and may coexist with MS.[94]
* MLKL-MS: Mixed lineage kinase domain like pseudokinase (MLKL) related MS - A preliminary report has pointed out evidence of a novel neurodegenerative spectrum disorder related to it.[95]
Other auto-antibodies can be used to stablish a differential diagnosis from very different diseases like Sjögren syndrome which can be separated by Anti–Calponin-3 autoantibodies.[96]
The correlation between this genetic mutation and MS was challenged but in 2018 has been replicated by an independent team.[97] Notice that this results do not refer to general MS.
In general, NMO-like spectrum without known auto-antibodies is considered MS. Principal component analysis of these cases show 3 different kinds of antibody-negative patients. The metabolite discriminators of RRMS and Ab-NMOSD suggest that these groupings have some pathogenic meaning.[98]
As MS is an active field for research, the list of auto-antibodies is not closed nor definitive. For example, some diseases like Autoimmune GFAP Astrocytopathy or variants of CIDP that affects the CNS (CIDP is the chronic counterpart of Guillain–Barré syndrome) could be included. Autoimmune variants peripheral neuropathies or progressive inflammatory neuropathy could be in the list assuming the autoimmune model for MS, together with a rare demyelinating lesional variant of trigeminal neuralgia[99] and some NMDAR Anti-NMDA receptor encephalitis[51]
Venous induced demyelination has also been proposed as a hypothetical MS variant produced by CCSVI, Susac's syndrome and Neuro-Behçet’s disease(MS has an important vascular component[100]), myalgic encephalomyelitis (aka chronic fatigue syndrome).[101] Also leukoaraiosis can produce lesions disseminated in time and space. Maybe two sub-conditions of Leukodystrophy: Adrenoleukodystrophy and Adrenomyeloneuropathy could be in the list.
## Genetic types[edit]
Different behaviour has been reported according to the presence of different HLA genes.
### HLA DRB3*02:02 patients[edit]
In HLA DRB3 cases, autoimmune reactions against the enzyme GDP-L-fucose synthase has been reported[102][103] The same report points that the autoimmune problem could derive from the gut microbiota.
HLA-DRB1*15:01 has the strongest association with MS.[104]
HLA-DRB1*04:05, HLA-B*39:01, and HLA-B*15:01 are associated with independent MS susceptibility and HLA-DQβ1 position 9 with phenylalanine had the strongest effect on MS susceptibility.[104]
Another possible type is one with auto-antibodies against GDP-L-fucose synthase. In HLA-DRB3*02:02 patients, autoimmune reactions against the enzyme GDP-L-fucose synthase has been reported[102][103] The same report points that the autoimmune problem could derive from the gut microbiota.
### Rapidly progressive multiple sclerosis[edit]
See malignant multiple sclerosis
This is a specially aggressive clinical course of progressive MS[105] that has been found to be caused by a special genetic variant. It is due to a mutation inside the gene NR1H3, an arginine to glutamine mutation in the position p.Arg415Gln, in an area that codifies the protein LXRA.[106]
## Primary progressive variants[edit]
Some researchers propose to separate primary progressive MS from other clinical courses. PPMS, after recent findings seem to point that it is pathologically a very different disease.[107][108][109][110]
Some authors think since long ago that primary progressive MS should be considered a disease different from standard MS,[111][112] and it was also proposed that PPMS could be heterogeneous[113]
Clinical variants have been described. For example, Late Onset MS.[114] Since 2016, a special clinical variant of "rapidly progressive" MS has been found to be different from RRMS and other kinds of PPMS.[105] It is due to a mutation inside the gene NR1H3, an arginine to glutamine mutation in the position p.Arg415Gln, in an area that codifies the protein LXRA.
For the rest of the progressive cases, it has been found that the lesions are diffuse instead of the normal focal ones,[115] and are different under MR spectroscopy.[116] RRMS and PPMS patients also show differences on the retinal layers yields examined under OCT.[117]
Some authors have proposed a dual classification of PPMS, according to the shape of edges of the scars, in MS-like and ADEM-like[118] Proteomic analysis have shown that two proteins, Secretogranin II and Protein 7B2, in CSF can be used to separate RRMS from PPMS[119]
Recently, the hypothesis of PPMS being apart from RRMS/SPMS is taken further credibility due that it was shown that CSF from PPMS patients can carry the disease to other animals, producing neurodegeneration in mice[107] and that Normal Appearing White Matter (NAWM) structure is also different[120]
The predominant lesions in PPMS are slowly expanding lesions with T cells, microglial, and macrophage-associated demyelination in close similar to pattern I demyelination[121]
As of 2019 it has been found that the profile of T-cells is different in PPMS and SPMS[122]
## Clinical situations inside standard MS[edit]
MS can be considered among the acquired demyelinating syndromes with a multiphasic instead of monophasic behaviour.[123] Multiple sclerosis has a prodromal stage in which an unknown underlying condition, able to damage the brain, is present, but no lesion has still developed.
MS is usually classified in clinical types, though they are unrelated to the underlying pathology. Some critical reports say that the current "types" were artificially made up, just to treat RRMS as a separate disease. In this way the number of patients was low enough to enter the orphan drugs act, and get the interferon approved by the FDA under this schema.[124] Recent reviews state that all types are a mixture of inflammation and neurodegeneration, and that all types should be considered the same disease.[125]
Other possible clinical courses are:
### Preclinical MS: CIS and CDMS[edit]
The first manifestation of MS is the so-called Clinically isolated syndrome, or CIS, which is the first isolated attack. The current diagnosis criteria for MS do not allow doctors to give an MS diagnosis until a second attack takes place. Therefore, the concept of "clinical MS", for an MS that can be diagnosed, has been developed. Until MS diagnosis has been established, nobody can tell whether the disease one is dealing with is MS.
Cases of MS before the CIS are sometimes found during other neurological inspections and are referred to as subclinical MS.[126] Preclinical MS refers to cases after the CIS but before the confirming second attack.[127] After the second confirming attack the situation is referred to as CDMS (clinically defined multiple sclerosis).[128]
CIS itself is sometimes considered itself as a disease entity, different from MS. Even if they share the same underlying condition CIS is not MS given that it lacks the presence of lesions.[129] Approximately 84% of the subjects with CIS experience a second clinical demyelinating event and are diagnosed with clinically definite MS (CDMS) within 20 years.
### RIS, subclinical and silent MS[edit]
See also Radiologically isolated syndrome
Silent MS has been found in autopsies before the existence of MRI[130] showing that the so-called "clinical definitions" cannot be applied to around 25% of the MS cases.[131] Currently a distinction is made between "silent" and subclinical.
In absence of attacks, sometimes a radiological finding suggestive of demyelination (T2 hyperintensities[132]) can be used to establish a pre-diagnosis of MS. This is often named "Radiologically Isolated Syndrome" (RIS). Cases before the first attack or CIS are subclinical in the sense that they do not produce clinical situations.
If a second radiological event appears without clinical consequences, the clinical situation is named "Silent MS" (Okuda criteria).[133] Anyway, it is reported that all MS cases have an active subclinical phase before the CIS[134]
It has been noted that some aspects of the MS underlying condition are present in otherwise healthy MS patients' relatives,[135] suggesting a wider scope for the "silent MS" term.
In these cases Interleukin-8 is a risk for clinical conversion.[136] It has also been proposed that always exists a subclinical phase in the beginning of every MS case, during which the permeability of the BBB can be used for diagnosis[137]
It is also under investigation whether MS has a prodrome, i.e., a preliminary stage in which the disease exists with non-specific symptoms. Some reports point to a prodrome of several years for RRMS and decades for PPMS.[138]
### Aggressive multiple sclerosis[edit]
Relapsing-Remitting MS is considered aggressive when the frequency of exacerbations is not less than 3 during 2 years. Special treatment is often considered for this subtype.[139] According to these definition aggressive MS would be a subtype of RRMS. (See above)
Other authors disagree and define aggressive MS by the accumulation of disability, considering it as a rapidly disabling disease course[140] and therefore inside PPMS.
The aggressive course is associated to grey matter damage and meningeal inflammation, and presents a special intrathecal (meninges and CSF) inflammatory profile.[141]
After the 2016 revision of the MS phenotypes, it is called Highly active multiple sclerosis[142]
Mitoxantrone was approved for this special clinical course. Some reports point to Alemtuzumal being beneficial[143]
### Pediatric and pubertal MS[edit]
MS cases are rare before puberty, but they can happen. Whether they constitute a separate disease is still an open subject. Anyway, even this pubertal MS could be more than one disease, because early-onset and late-onset have different demyelination patterns[144]
Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset. Due to efficient repair mechanisms at early life, pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age.[145]
An iron-responsive variant of MS has been reported in children.[146]
## Controversy for the definition[edit]
Given that the etiology of MS is unknown, the current definitions of MS are all based on its appearance. The most commonly used definition, the McDonald criteria, requires just the presence of demyelinating lesions separated in space and time, together with the exclusion of every known demyelinating condition.
This unspecific definition has been criticized. For some people this has turned MS into a heterogeneous condition with several underlying problems.[147] Besides, the complementary problem also exists. Given that McDonalds-MS is based just in the distribution of the lesions, even twins with the same underlying condition can be classified different[148]
Finally, the "exclusion of every other known disease" condition also creates problems. Rightfully classified MS patients can be rightfully classified out of the spectrum when their particular underlying problem is discovered. For example, neuromyelitis optica was previously considered MS and currently is not, even if it appears that the MS definition has not changed.
Currently there is no single diagnosis test for MS that is 100% sensitive and specific.[149][150]
### Pathological and clinical definitions[edit]
McDonald criteria propose a clinical diagnosis based on a pathological definition, saying that the focus for diagnosis "remains on the objective demonstration of dissemination of lesions in both time and space" (DIT and DIS). But given that other diseases produce similar lesions, it is also required that those lesions cannot be explained by any other known disease.
This open definition present problems.[151] For example, before the discovery of anti-AQP4 in 2006, most optic-spinal MS patients were classified rightfully as MS. Currently they are classified as NMO. Both diagnosis are correct even though the definition has not (apparently) changed.
According to some pathologists, a pathological definition is required because clinical definitions have problems with differential diagnosis[152] and they always use a pathological definition on articles about post-mortem retrospective diagnosis, but for practitioners that need a diagnosis as soon as possible MS is often regarded as a pure clinical entity, defined simply by a positive result in the standard clinical case definition being then named "clinically definite MS" (CDMS, Poser) or simply "MS" (McDonald).[153]
Both definitions lead to different results. For example, confluent subpial cortical lesions are the most specific finding for MS, being exclusively present in MS patients.[154] but can only be detected post-mortem by an autopsy[155] Therefore, any other diagnosis method will have false positives.
### Other meanings of MS[edit]
There is no known etiology for MS and therefore no etiology-based definition is possible. Comparison to a post-mortem retrospective diagnosis is possible, but useless to practitioners and short-term researchers, and it is not usually done. Therefore, all meanings for the words "Multiple Sclerosis" are somehow diffuse.
The pathological definition based on proven dissemination in time and space has problems. For example, it leaves situations like RIS (radiologically isolated syndrome) outside the MS spectrum because the lack of proof, even in the case that this condition later could shown the same pathogenic conditions than MS cases.[156]
Besides, usually the term "multiple sclerosis" is used to refer to the presence of the unknown underlying condition that produces the MS lesions instead to the mere presence of the lesions. The term MS is also used to refers to the process of developing the lesions.[157]
Some authors instead speak about the biological disease vs. its clinical presentation.[158]
Anyway, the precise meaning in each case can be normally deduced from the context.
### Handling several clinical definitions[edit]
Given that several definitions of MS coexist, some authors are referring to them using whether CDMS for Poser positives, or McDonalds-MS with a prefix for McDonalds positives, including the release year in the prefix.[159]
### CIS and conversion to MS[edit]
The 2010 revision of the McDonald criteria[160] allows the diagnosis of MS with only one proved lesion (CIS). Consistently, the later revision for the MS phenotypes in 2013 was forced to consider CIS as one of the MS phenotypes.[161]
Therefore, the former concept of "Conversion from CIS to MS", that was declared when a patient had a second MS attack, does not apply anymore. More accurate is now to speak about conversions from the CIS phenotype to other MS phenotype.[162]
## See also[edit]
* Demyelinating disease
* Pathophysiology of multiple sclerosis
* The Myelin Project
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161. ^ Lublin, F. D.; Reingold, S. C.; Cohen, J. A.; Cutter, G. R.; Sorensen, P. S.; Thompson, A. J.; Wolinsky, J. S.; Balcer, L. J.; Banwell, B.; Barkhof, F.; Bebo, B.; Calabresi, P. A.; Clanet, M.; Comi, G.; Fox, R. J.; Freedman, M. S.; Goodman, A. D.; Inglese, M.; Kappos, L.; Kieseier, B. C.; Lincoln, J. A.; Lubetzki, C.; Miller, A. E.; Montalban, X.; O'Connor, P. W.; Petkau, J.; Pozzilli, C.; Rudick, R. A.; Sormani, M. P.; et al. (2014). "Defining the clinical course of multiple sclerosis: The 2013 revisions". Neurology. 83 (3): 278–286. doi:10.1212/WNL.0000000000000560. PMC 4117366. PMID 24871874.
162. ^ Dalton CM, Brex PA, Miszkiel KA, Hickman SJ, MacManus DG, Plant GT, Thompson AJ, Miller DH (July 2002). "Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis". Annals of Neurology. 52 (1): 47–53. doi:10.1002/ana.10240. PMID 12112046. S2CID 24039151.
* v
* t
* e
Multiple sclerosis and other demyelinating diseases of the central nervous system
Signs and symptoms
* Ataxia
* Depression
* Diplopia
* Dysarthria
* Dysphagia
* Fatigue
* Incontinence
* Nystagmus
* Optic neuritis
* Pain
* Uhthoff's phenomenon
Investigations and diagnosis
* Multiple sclerosis diagnosis
* McDonald criteria
* Poser criteria
* Clinical
* Clinically isolated syndrome
* Expanded Disability Status Scale
* Serological and CSF
* Oligoclonal bands
* Radiological
* Radiologically isolated syndrome
* Lesional demyelinations of the central nervous system
* Dawson's fingers
Approved[by whom?] treatment
* Management of multiple sclerosis
* Alemtuzumab
* Cladribine
* Dimethyl fumarate
* Fingolimod
* Glatiramer acetate
* Interferon beta-1a
* Interferon beta-1b
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Hereditary
* Adrenoleukodystrophy
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* Central pontine myelinolysis
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Other
* List of multiple sclerosis organizations
* List of people with multiple sclerosis
* Multiple sclerosis drug pipeline
* Pathophysiology
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
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* Cavernous sinus thrombosis
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* Encephalomyelitis
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* Meningoencephalitis
Brain/
encephalopathy
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Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
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* NMS
* PKAN
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* Striatonigral degeneration
* Hemiballismus
* HD
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* Meige's
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Dementia
* Tauopathy
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* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
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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
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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
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* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
*[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
|
Inflammatory demyelinating diseases of the central nervous system
|
None
| 25,572 |
wikipedia
|
https://en.wikipedia.org/wiki/Inflammatory_demyelinating_diseases_of_the_central_nervous_system
| 2021-01-18T18:35:24 |
{"orphanet": ["228145"], "synonyms": [], "wikidata": ["Q5988897"]}
|
A number sign (#) is used with this entry because the serum level of interleukin-6 soluble receptor (IL6R; 147880) is associated with a polymorphism in the IL6R gene (147880) on chromosome 1q21.3.
Mapping
Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, Reich et al. (2007) genotyped 1,343 SNPs in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, they found a significant association of interleukin-6 soluble receptor (IL6SR) with European ancestry on chromosome 1 (lod 4.59), in a region (1q21.3) that includes the IL6R gene. Genotyping 19 SNPs showed that the effect was largely explained by an allele of a nonsynonymous SNP in IL6R, rs8192284 (147880.0001), at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL6SR in a Japanese cohort (Galicia et al., 2004). Reich et al. (2007) replicated this association (P much less than 1.0 x 10(-12)) and also demonstrated a new association with circulating levels of a different molecule, interleukin-6 (IL6; 147620) (P less than 3.4 x 10(-5)) (see 614752). After replication in 1,674 European Americans from Health ABC, the combined result was even more significant: P much less than 1.0 x 10(-12) for IL6SR, and P less than 2.0 x 10(-9) for IL6. After correction for covariates, there was a 1.09- to 1.13-fold increase in IL6SR levels with 1 copy of the C allele of rs8192284 and a 1.24- to 1.43-fold increase with 2 copies, and there was a 1.06- to 1.15-fold increase in IL6 levels with 1 copy of the C allele and a 1.22- to 1.43-fold increase with 2 copies. Surveying cell lines from several different ethnic groups showed no evidence of an association of surface IL6R with rs8192284. This finding supported the hypothesis of Galicia et al. (2004) that the mechanism of action of rs8192284 is to affect cleavage efficiency, because the SNP occurs at the proteolytic cleavage site of IL6R.
*[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
|
SOLUBLE INTERLEUKIN-6 RECEPTOR, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS
|
c3553493
| 25,573 |
omim
|
https://www.omim.org/entry/614689
| 2019-09-22T15:54:30 |
{"omim": ["614689"], "synonyms": ["Alternative titles", "SOLUBLE IL6R, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS"]}
|
Chvostek sign
Differential diagnosishypocalcemia
The Chvostek sign (/ˈkvɒstɪk/) is a clinical sign of hypocalcemia. It is evidenced by the twitching of muscles innervated by the facial nerve (CNVII).[1] It refers to an abnormal reaction to stimulation of the facial nerve. When the facial nerve is tapped in front of the tragus, the facial muscles on the same side of the face (ipsilateral) will contract momentarily (typically a twitch of the nose or lips), because of hypocalcemia (i.e. from hypoparathyroidism, pseudohypoparathyroidism, hypovitaminosis D), with resultant hyperexcitability of nerves. Though classically described in hypocalcemia, this sign may also be encountered in respiratory alkalosis, such as that seen in hyperventilation, which causes decreased serum calcium with a normal calcium level due to a shift of Ca2+ from the blood to albumin which has become more negative in the alkalotic state.
The Trousseau sign of latent tetany is also often used to detect early tetany.[1]
## Contents
* 1 Etymology
* 2 Features
* 2.1 Chvostek sign – type I
* 2.2 Chvostek sign – type II
* 3 Causes
* 4 Clinical significance
* 5 References
* 6 External links
## Etymology[edit]
The sign is named after František Chvostek, an Austrian-born surgeon who lived in Moravia, in the Czech Republic. In his professional life, Chvostek devoted himself to the study of etiopathogenesis and to the treatment of neurological disorders, including by means of electrotherapy. In 1876, he first described the sign that bears his name.[2] Later it was independently described by another Austrian physician, Nathan Weiss (1851–1883), in 1883.[3]
## Features[edit]
### Chvostek sign – type I[edit]
It is obtained by striking with a finger or a hammer a point that is approximately 2 cm in front of the lobe of the ear and about 1 cm below the zygomatic process. Response occurs in the form of ipsilateral contraction of some or all of the muscles innervated by the facial nerve.[4] The effect is the lateral deviation of the labial and nasal fold toward the stimulated side.
### Chvostek sign – type II[edit]
Hitting a point between the middle third and upper third of the line joining the angle of the mouth to the zygomatic process gives rise to only a contraction of the muscles of the mouth and nose.
## Causes[edit]
Chvostek's sign is found in tetany. However, it may also be present in hypomagnesemia.[5][6] Magnesium is a cofactor for adenylate cyclase, which catalyzes the conversion of ATP to 3',5'-cyclic AMP. The 3',5'-cyclic AMP (cAMP) is required for parathyroid hormone activation.[7] It is frequently seen in alcoholics, persons with diarrhea, patients taking aminoglycosides or diuretics, because hypomagnesemia can cause hypocalcemia. It is also seen in measles, tetanus and myxedema.
It can also be found in subjects with respiratory alkalosis, for example as a result of hyperventilation syndrome, which can lead to a drastic reduction of the concentration in serum of calcium ions while at normal levels, for the binding of a significant proportion of ionized calcium (Ca2+) with albumin and globulins.
## Clinical significance[edit]
Chvostek's sign is not a very specific sign of tetany as it may be seen in 10% to 25% of healthy adults.[8] It is therefore not a reliable clinical sign for diagnosing latent tetany.[9][10] The sensitivity is lower than that in the corresponding Trousseau sign as it is negative in 30% of patients with hypocalcemia.[11] Due to the combination of poor sensitivity and specificity the clinical utility of this sign is reduced.[8]
## References[edit]
1. ^ a b Jesus, JE; Landry, A (Sep 13, 2012). "Images in clinical medicine. Chvostek's and Trousseau's signs". The New England Journal of Medicine. 367 (11): e15. doi:10.1056/NEJMicm1110569. PMID 22970971.
2. ^ Chvostek F. Beitrag zur Tetanie. Wien Med Press 1876;17:1201-3, 1225–27, 1253–58, 1313–16.
3. ^ Weiss N. Centralbl Gesammt Ther 1883;1:9.
4. ^ Krogh, L; Wynne, JM; Cywes, S (Aug 17, 1968). "The value of Chvostek's sign in tetany". South African Medical. 42 (32): 846–7. PMID 5680230.
5. ^ Weisinger, JR; Bellorín-Font, E (Aug 1, 1998). "Magnesium and phosphorus". Lancet. 352 (9125): 391–6. doi:10.1016/S0140-6736(97)10535-9. PMID 9717944.
6. ^ Flink, EB (1981). "Magnesium deficiency. Etiology and clinical spectrum". Acta Medica Scandinavica. Supplementum. 647: 125–37. PMID 7020347.
7. ^ Goljan, EF. Rapid Review Pathology. Mosby, Elsevier, 2007; pp. 504.
8. ^ a b Méneret, A; Guey, S; Degos, B (Mar 12, 2013). "Chvostek sign, frequently found in healthy subjects, is not a useful clinical sign". Neurology. 80 (11): 1067. doi:10.1212/WNL.0b013e31828728bc. PMID 23479466.
9. ^ Hoffman, E (Jul 1958). "The Chvostek sign; a clinical study". American Journal of Surgery. 96 (1): 33–7. doi:10.1016/0002-9610(58)90868-7. PMID 13545482.
10. ^ Garrad, P; Perks, AM (Aug 1990). "The effects of temperature change on lung liquid production by in vitro lungs from fetal guinea pigs". Journal of Developmental Physiology. 14 (2): 109–14. PMID 2092052.
11. ^ Fonseca, OA; Calverley, JR (Aug 1967). "Neurological manifestations of hypoparathyroidism". Archives of Internal Medicine. 120 (2): 202–6. doi:10.1001/archinte.1967.00300020074009. PMID 4952674.
## External links[edit]
* František Chvostek
* Nathan Weiss
* v
* t
* e
Electrolyte imbalances
Sodium
* High
* Salt poisoning
* Low
* Hypotonic
* Isotonic
* Cerebral salt-wasting syndrome
Potassium
* High
* Low
Chloride
* High
* Low
Calcium
* High
* Low
* Symptoms and signs
* Chvostek sign
* Trousseau sign
* Milk-alkali syndrome
* Disorders of calcium metabolism
* Calcinosis (Calciphylaxis, Calcinosis cutis)
* Calcification (Metastatic calcification, Dystrophic calcification)
* Familial hypocalciuric hypercalcemia
Phosphate
* High
* Low
Magnesium
* High
* Low
*[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
|
Chvostek sign
|
c0234180
| 25,574 |
wikipedia
|
https://en.wikipedia.org/wiki/Chvostek_sign
| 2021-01-18T18:42:39 |
{"umls": ["C0234180"], "wikidata": ["Q1090174"]}
|
Hereditary angioedema type 2 (HAE 2) is a form of hereditary angioedema (see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.
## Epidemiology
Prevalence is unknown. HAE 2 is the less common form of HAE, accounting for 15% of HAE cases and is seen equally in men and women.
## Clinical description
Like HAE 1 and 3 (see these terms) it occurs generally in childhood with symptoms becoming more severe in adolescence. Precipitating factors of HAE 2 thought to trigger attacks include: trauma, anxiety, puberty, infection, alcohol consumption, exercise and stress.
## Etiology
It is caused by deletions, frameshift or splice mutations in the SERPING1 gene encoding the C1 inhibitor (C1-INH). These mutations cause a decrease in C1-INH activity (while C1 inhibitor serum levels remain normal) leading to an increase in bradykinin formation.
## Management and treatment
Treatment usually consists of intravenous C1 inhibitor concentrate or subcutaneous administration of the orphan drug icatibant (bradykinin receptor antagonist). Prophylaxis with danazol is often given before surgical procedures.
*[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
|
Hereditary angioedema type 2
|
c1862892
| 25,575 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100051
| 2021-01-23T18:35:28 |
{"mesh": ["D056829"], "omim": ["106100"], "umls": ["C0398776", "C1862892"], "icd-10": ["D84.1"], "synonyms": ["HAE 2", "HAE-II", "Hereditary angioneurotic edema type 2"]}
|
This article needs attention from an expert in Medicine. The specific problem is: see talk page. WikiProject Medicine may be able to help recruit an expert. (February 2018)
Subcortical dementia
SpecialtyNeurology
Subcortical dementias includes those diseases which predominantly affects the basal ganglia along with features of cognitive decline.
Diseases such as, progressive supranuclear palsy, Huntington's chorea and Parkinson's disease are different in many features from the other cortical dementias like Alzheimer’s disease.Yet these patients do present clinically with mild forgetfulness and slowed thought process along with abnormal movements and problems with motility.
## Contents
* 1 Clinical Features
* 2 Pathophysiology
* 3 Controversy
* 4 History
* 5 Examples
* 6 References
## Clinical Features[edit]
Clinically sub cortical dementia usually is seen with features like slowness of mental processing, forgetfulness, impaired cognition, lack of initiative-apathy, depressive symptoms (such as anhedonia, negative thoughts, loss of self-esteem and dysphoria), loss of social skills along with extrapyramidal features like tremors and abnormal movements .[1]
In most of the patients with Huntington's diseases the first clinical feature to appear is the change in personality.The dementia is more severe in patients with early onset of Huntington's disease.
Parkinson's disease is characterised by features of dementia in older age.[2][3] The adult type “leukodystrophy” also causes subcortical dementia with prominent frontal lobe features.
As a general rule the earliest symptoms in "cortical" dementia include difficulty with high-level behaviors such as memory, language, problem-solving and reasoning, mathematics and abstract thoughts – functions associated with the cerebral cortex.Such patients have prominent apraxia and agnosia.
However, in "subcortical" dementia these high-level behaviours are less affected.[4]
## Pathophysiology[edit]
In most common types of dementias there is widespread degeneration in the cerebral cortex – such as the plaques and neuro fibrillation tangles which are the hallmark of Alzheimer's disease. In subcortical dementia, there is targeted damage to regions lying under the cortex.
The pathological process that result in subcortical dementia shows neuronal changes that involve primarily the thalamus, basal ganglia, and rostral brain-stem nuclei and mostly, some projections in the white matter from these regions to the cortex, with relative sparing of the cerebral cortex.
It affects arousal, attention, mood, motivation, language, memory, abstraction, social skills (especially empathy), extrapyramidal functions, and visuospatial skills. Additionally, damage to the basal forebrain can cause amnesia and psychotic disorders.[1]
## Controversy[edit]
One of the problems with the concept of sub cortical dementia is the fact that name implies that it is due to lesions confined to sub cortical structures.Anatomically none of the neurodegenerative dementias are strictly cortical or subcortical. In fact, there's invariably an overlap of both cortical and subcortical neuronal changes in both types.[5]
## History[edit]
Charcot described dementia as a feature in Parkinson's disease.McHugh introduced the concept of subcortical dementia.[6][7]
Mayeux and Stern and their colleagues and Tierney and coworkers have been critical of the concept of subcortical dementia.[8][9]
## Examples[edit]
* Chronic acetogenin poisoning
* Atypical parkinsonism
* Binswanger disease (and other forms of vascular dementia)
* Corticobasal degeneration
* Huntington disease
* Multiple system atrophy
* Progressive supranuclear palsy
## References[edit]
1. ^ a b Cummings, Jeffrey L.; Benson, D. Frank (1984). "Subcortical Dementia: Review of an Emerging Concept". Arch Neurol. 41 (8): 874–879. doi:10.1001/archneur.1984.04050190080019. PMID 6235797.
2. ^ Hirani A,Malamud M,Kurland LT (1961). "Parkinsonism - dementia complex on the island of Guam". Brain. 84: 662–79. doi:10.1093/brain/84.4.662. PMID 13907610.CS1 maint: multiple names: authors list (link)
3. ^ Hoehn Mm, Yahr MD (1967). "Parkinsonism: onset, progression and mortality". Neurology. 17 (5): 427–42. doi:10.1212/WNL.17.5.427. PMID 6067254.
4. ^ Subcortical Dementias – Memory loss and the brain
5. ^ Mayeux R,Stern Y (1987). "Subcortical dementia". Arch Neurol. 44 (2): 129–31. doi:10.1001/archneur.1987.00520140005006. PMID 3813928.
6. ^ Ropper, Allan H. (2014-05-16). Adams and Victor's principles of neurology. Samuels, Martin A.,, Klein, Joshua (Tenth ed.). New York. ISBN 978-0-07-179479-4. OCLC 857402060.
7. ^ McHugh PR (1990). The basal ganglia: The region, the integration of its symptoms and implications for psychiatry and neurology. New York: Manchester Press. pp. 259–268.
8. ^ Tierney MC,Snow WG, Reid DE (1987). "Psychometric differentiation of dementia". Arch Neurol. 44 (7): 720–2. doi:10.1001/archneur.1987.00520190032013. PMID 3593061.CS1 maint: multiple names: authors list (link)
9. ^ Mayeux R,Foster NL, Rossor MN, Whitehouse PJ (1993). The clinical evaluation of patients with dementia. Philadelphia: Davis. pp. 92–129.CS1 maint: multiple names: authors list (link)
This article about a medical condition affecting the nervous system 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
|
Subcortical dementia
|
c4024935
| 25,576 |
wikipedia
|
https://en.wikipedia.org/wiki/Subcortical_dementia
| 2021-01-18T18:59:34 |
{"umls": ["C4024935"], "wikidata": ["Q2802231"]}
|
Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch to the brain. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic neurons, which control involuntary body functions such as heart rate, digestion, and breathing. The sensory and autonomic neurons are part of the body's peripheral nervous system, which comprises the nerves outside the brain and spinal cord. HSAN2 is considered a form of peripheral neuropathy.
The signs and symptoms of HSAN2 typically begin in infancy or early childhood. The first sign of the condition is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. In people with HSAN2, unnoticed injuries often lead to open sores (ulcers) on the hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the affected area. People with HSAN2 often injure themselves unintentionally, typically by biting the tongue, lips, or fingers. These injuries may lead to loss of the affected areas, such as the tip of the tongue. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are damaged.
The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux) or slow eye-blink or gag reflexes. Affected individuals may also have weak deep-tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.
Some people with HSAN2 lose a type of taste bud on the tip of the tongue called lingual fungiform papillae and have a diminished sense of taste.
## Frequency
HSAN2 is a rare disease; however, the prevalence is unknown.
## Causes
There are several types of HSAN2, each caused by mutations in a different gene. HSAN2A is caused by mutations in the WNK1 gene, and HSAN2B is caused by mutations in the RETREG1 gene. Additional types caused by mutations in other genes are rare. Although different genes are involved, all types of HSAN2 have similar signs and symptoms.
The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including sensory neurons. The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is not well understood, it is likely that the abnormally short version cannot function properly or is broken down. People with HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 protein changes play in that loss is unclear.
HSAN2B is caused by mutations in the RETREG1 gene. These mutations lead to an abnormally short and nonfunctional protein. The RETREG1 protein is normally found in sensory and autonomic neurons. It is involved in the recycling of worn-out cell parts (autophagy), specifically a cell structure called the endoplasmic reticulum. When the RETREG1 protein is nonfunctional, recycling of the endoplasmic reticulum is impaired. The buildup of these structures likely results in death of the neurons.
The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2.
### Learn more about the genes associated with Hereditary sensory and autonomic neuropathy type II
* RETREG1
* SCN9A
* WNK1
Additional Information from NCBI Gene:
* KIF1A
## 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
|
Hereditary sensory and autonomic neuropathy type II
|
c2752089
| 25,577 |
medlineplus
|
https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii/
| 2021-01-27T08:24:54 |
{"gard": ["3976"], "mesh": ["C567738"], "omim": ["201300", "613115"], "synonyms": []}
|
## Summary
### Clinical characteristics.
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway. Clinical manifestations and age of onset vary among individuals even in the same family.
Neonatal onset (~8% of affected individuals). Manifestations of hyperammonemia usually begin 24-48 hours after feeding begins and can include lethargy, somnolence, refusal to feed, vomiting, tachypnea with respiratory alkalosis, and/or seizures.
Infantile, childhood, and adult onset (~92%). Affected individuals may present with:
* Chronic neurocognitive deficits (including developmental delay, ataxia, spasticity, learning disabilities, cognitive deficits, and/or unexplained seizures);
* Acute encephalopathy secondary to hyperammonemic crisis precipitated by a variety of factors; and
* Chronic liver dysfunction (unexplained elevation of liver transaminases with or without mild coagulopathy, with or without mild hyperammonemia and protein intolerance).
Neurologic findings and cognitive abilities can continue to deteriorate despite early metabolic control that prevents hyperammonemia.
### Diagnosis/testing.
The biochemical diagnosis of HHH syndrome is established in a proband with the classic metabolic triad of episodic or postprandial hyperammonemia, persistent hyperornithinemia, and urinary excretion of homocitrulline. The molecular diagnosis of HHH syndrome is established in a symptomatic individual with or without suggestive metabolic/biochemical findings by identification of biallelic pathogenic variants in SLC25A15.
### Management.
Treatment of manifestations: Acute and long-term management is best performed in conjunction with a metabolic specialist. Of primary importance is the use of established protocols to rapidly control hyperammonemic episodes by discontinuation of protein intake, intravenous infusion of glucose and, as needed, infusion of supplemental arginine and the ammonia removal drugs sodium benzoate and sodium phenylacetate. Hemodialysis is performed if hyperammonemia persists and/or the neurologic status deteriorates.
Prevention of primary manifestations: Individuals with HHH syndrome should be maintained on an age-appropriate protein-restricted diet, citrulline supplementation, and sodium phenylbutyrate to maintain plasma concentrations of ammonia, glutamine, arginine, and essential amino acids within normal range. Note: Liver transplantation is not indicated when metabolic control can be achieved with this regimen as liver transplantation may correct the hyperammonemia but will not correct tissue-specific metabolic abnormalities that also contribute to the neuropathology.
Surveillance: Routine assessment of height, weight, and head circumference from the time of diagnosis to adolescence. Routine assessment of plasma ammonia concentration, plasma and urine amino acid concentrations, urine organic acids, and urine orotic acid based on age and history of compliance and metabolic control. Routine developmental and educational assessment to assure optional interventions. Attention to subtle changes in mood, behavior, and eating and/or the onset of vomiting, which may suggest that plasma concentrations of glutamine and ammonia are increasing. Periodic neurologic evaluation to monitor for neurologic deterioration even when metabolic control is optimal.
Agents/circumstances to avoid: Excess dietary protein intake; nonprescribed protein supplements such as those used during exercise regimens; prolonged fasting during an illness or weight loss; oral and intravenous steroids; and valproic acid, which exacerbates hyperammonemia in urea cycle disorders.
Evaluation of relatives at risk: Once the pathogenic variants in a family are known, use molecular genetic testing to clarify the genetic status of at-risk relatives to allow early diagnosis and treatment, perhaps even before symptoms occur.
Pregnancy management: In general, pregnant women should continue dietary protein restriction and supplementation with citrulline and ammonia-scavenging medications based on their clinical course before pregnancy. Due to increased protein and energy requirements in pregnancy and, oftentimes, difficulty with patient compliance, weekly to every two-week monitoring of plasma amino acids and ammonia is recommended, especially in the first and third trimester, and close monitoring immediately after delivery.
### Genetic counseling.
HHH syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SLC25A15 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible. However, the identification of familial SLC25A15 pathogenic variants cannot predict clinical outcome because of significant intrafamilial phenotypic variability.
## Diagnosis
### Suggestive Findings
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome should be suspected in symptomatic individuals with the following age-related clinical, laboratory, and neuroimaging findings.
#### Clinical Findings
Neonatal presentation (~8% of individuals). Manifestations of hyperammonemia usually begin 24-48 hours after the start of feeding and can include lethargy, somnolence, refusal to feed, vomiting, tachypnea with respiratory alkalosis, and/or seizures.
Infantile, childhood, and adolescent/adult presentation (~92% of individuals) may exhibit any of the following:
* Chronic neurocognitive deficits including developmental and speech delay, ataxia, spasticity, learning disabilities, cognitive deficits, and/or unexplained seizures
* Acute encephalopathy secondary to hyperammonemic crisis, which can be precipitated by infection, fasting, or injury (or occur for no apparent reason) and can manifest as lethargy, decreased appetite, nausea, vomiting, increased respiratory rate, and seizures
* Chronic liver dysfunction characterized by unexplained elevation of liver enzymes (AST and ALT) with or without mild coagulopathy and with or without mild hyperammonemia.
* Mild encephalopathy manifesting as disorientation, irritability, and episodic confusion with mild hyperammonemia, which is difficult to detect as it may resolve spontaneously without treatment or quickly normalize with IV solutions that include glucose [Qadri et al 2016].
#### Laboratory Findings
Episodic or postprandial mild to moderate hyperammonemia. Plasma ammonia concentrations at the time of diagnosis are summarized in Table 1. Note that neonates have a higher median plasma ammonia level than older affected individuals.
Note: (1) In HHH syndrome the degree of hyperammonemia is usually significantly less than in other urea cycle disorders such as OTC, ASS, or CPS-I deficiency (see Urea Cycle Disorders). (2) Once an affected individual is placed on a protein-restricted diet and treated with sodium phenylbutyrate (see Management), plasma ammonia concentrations return to normal.
### Table 1.
Plasma Ammonia Concentrations Observed in HHH Syndrome by Age of Diagnosis
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Plasma Ammonia Concentration in µmol/L by Age of Diagnosis 1
Neonatal (birth – 1 mo) (n=6)Infantile (>1 mo – 1 yr) (n=5)Childhood (>1 yr – 12 yrs) (n=36)Adolescence to Adulthood (>12 yrs) (n=17)Total (n=64)
Median300173120117136
Mean560577160119219
SD50796512169339
Range111-130049-230025-53218-25018-2300
Based on 64 of 120 individuals with HHH syndrome [Kumar et al 2015, Martinelli et al 2015, Qadri et al 2016, Guan et al 2017, Ono et al 2018, Silfverberg et al 2018, Ho et al 2019, Wild et al 2019]
SD = standard deviation
1\.
The upper limit of normal plasma ammonia can vary among laboratories. Values of 40 μmol/L or less are usually considered normal for most infants, children, and adults; however, the upper limit of normal in neonates is 100 μmol/L (see Argininosuccinate Lyase Deficiency).
Hyperornithinemia (increased plasma concentration of ornithine). At the time of initial diagnosis, plasma concentration of ornithine can range from 200 to 1915 μmol/L (normal: 30-110 μmol/L).
Note: While plasma concentration of ornithine decreases significantly with a protein-restricted diet, it very rarely normalizes.
Homocitrullinuria (urinary excretion of homocitrulline) is a key feature of HHH syndrome; however, exceptions exist: some infants with neonatal-onset HHH syndrome do not excrete homocitrulline in significant amounts and individuals with HHH syndrome who self-restrict protein intake may excrete minimal or no homocitrulline in the urine [Valle & Simell 2001]. In controls, homocitrulline is not detected in the urine.
Note: Homocitrulline may be found in infant formulas due to the carbamylation of lysine during manufacture and, thus, may cause a false positive result.
Of note, in neonates, the classic metabolic triad of hyperammonemia, hyperornithinemia, and homocitrullinuria may be absent or subtle; alternatively, it may be obscured by the abnormal plasma amino acid profile and aminoaciduria characteristic of hepatic dysfunction and prematurity [Wild et al 2019].
Neuroimaging findings include evidence of cortical or subtentorial atrophy, abnormal white matter signal, demyelination, stroke-like lesions, and/or calcifications/lesions of the basal ganglia [Al-Hassnan et al 2008, Martinelli et al 2015, Guan et al 2017]. For example:
* At initial presentation brain MRI of a previously undiagnosed male age 36 years demonstrated multiple foci of subcortical white matter gliosis and moderate atrophy of the frontoparietal opercula and cerebellar hemispheres [Filosto et al 2013].
* The initial brain MRI findings (pre-diagnosis of HHH syndrome) in a male age 48 years were normal; seven months after extended treatment for hyperammonemic coma requiring dialysis, brain MRI showed evidence of severe hyperammonemic encephalopathy: brain gliosis, widespread hemorrhagic necrosis in the tips of the temporal lobes, and widened horns of the lateral ventricles [Silfverberg et al 2018].
### Establishing the Diagnosis
#### Biochemical Diagnosis
The biochemical diagnosis of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is established in a proband with the classic metabolic triad of episodic or postprandial hyperammonemia, persistent hyperornithinemia, and urinary excretion of homocitrulline. Note: An incomplete metabolic triad may be observed because of the following: (a) individuals whose protein intake was restricted during early childhood may never have experienced hyperammonemia; (b) affected individuals who come to medical attention because of learning disabilities or school difficulties may only have isolated persistent hyperornithinemia at the time of evaluation; or (c) a low-protein diet can be associated with little to no homocitrulline in the urine.
#### Molecular Diagnosis
The molecular diagnosis of HHH syndrome is established in a symptomatic individual with or without suggestive metabolic/biochemical findings by identification of biallelic pathogenic variants in SLC25A15 (Table 2).
Molecular genetic testing approaches that depend on the clinical and biochemical findings can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (typically exome sequencing and exome array).
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive laboratory findings of HHH syndrome described in Suggestive Findings are likely to be diagnosed using gene-targeted testing, whereas symptomatic individuals with nonspecific but suggestive clinical, laboratory, and neuroimaging findings in whom the diagnosis of HHH syndrome has not been considered are more likely to be diagnosed using either a multigene panel or comprehensive genomic testing.
Single-gene testing. Sequence analysis of SLC25A15 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no SLC25A15 variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications (see Table 2).
Targeted analysis for the following pathogenic variants (see Table 8) may be considered.
* c.562_564delTTC (p.Phe188del):
* French-Canadian founder variant
* Accounts for 28% of individuals with HHH syndrome [Debray et al 2008, Martinelli et al 2015]
* c.535C>T (p.Arg179Ter):
* Japanese and Middle Eastern founder variant
* Accounts for 16% of individuals with HHH syndrome [Debray et al 2008, Martinelli et al 2015]
A hyperammonemia or urea cycle disorder multigene panel that includes SLC25A15 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 2).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Comprehensive genomic testing. When the diagnosis of HHH syndrome has not been considered because an individual has nonspecific clinical and laboratory findings, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is an option. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 2.
Molecular Genetic Testing Used in Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
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Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
SLC25A15Sequence analysis 399.3% 4
Gene-targeted deletion/duplication analysis 5See footnote 6.
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Martinelli et al [2015]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
One exon-intron deletion (~4.5 kb) has been reported [Camacho et al 1999].
## Clinical Characteristics
### Genotype-Phenotype Correlations
The SLC25A15 genotype does not correlate with the clinical or biochemical phenotype of HHH syndrome [Fiermonte et al 2003, Camacho et al 2006, Tessa et al 2009].
### Nomenclature
The name "hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome" was coined by Vivian Shih, MD in 1969 for the disorder in which a "block in the ornithine metabolic pathway" has biochemical findings "not concordant with those in patients with proven hepatic ornithine transcarbamylase deficiency" [Shih et al 1969].
In 1999 after ORNT1 (now known as SLC25A15), the gene encoding ORNT1, was identified, the term ORNT1 deficiency was introduced and used interchangeably with HHH syndrome [Camacho et al 1999].
HHH syndrome may also be referred to as "ornithine transporter deficiency" or "ornithine translocase deficiency."
### Clinical Description
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is characterized by variable clinical presentation and age of onset ranging from the neonatal period to adulthood. Those with neonatal onset are normal for the first 24-48 hours, followed by onset of symptoms related to hyperammonemia (poor feeding, vomiting, lethargy, low temperature, rapid breathing). Those with later onset may present with chronic neurocognitive deficits and/or unexplained seizures, spasticity, acute encephalopathy secondary to hyperammonemic crisis, or chronic liver dysfunction. Neurologic findings and cognitive abilities can continue to deteriorate despite early metabolic control that prevents hyperammonemia.
Unless otherwise indicated, the data used in this chapter are from a total of 122 individuals with HHH syndrome: Martinelli et al 2015 (n=111), six subsequent case reports [Qadri et al 2016, Guan et al 2017, Ono et al 2018, Silfverberg et al 2018, Ho et al 2019, Wild et al 2019] and three unpublished affected individuals [Author, personal observation].
### Table 3.
Selected Clinical Findings in Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome
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Findings% of Persons w/Feature
Findings that resolve quickly w/protein-restricted dietLethargy62% (52/84)
Significant ↑ of liver enzymes AST & ALT52% (44/84)
Coagulopathy49% (34/69)
Coma33% (33/101)
Long-term neurodevelopmental outcomePyramidal signs75% (71/95)
Intellectual disability66% (63/96)
Myoclonic seizures34% (31/91)
The overall survival rate in individuals with HHH syndrome is 94% (109/116). Of the 21% (13/62) of individuals with HHH syndrome who manifested in the neonatal period, the mortality rate is 15% (2/13). Treatment with a protein-restricted diet resolves hepatic dysfunction (elevated transaminases and coagulopathy). Since hyperammonemia in HHH syndrome responds quickly to treatment, early diagnosis leads to an overall improved long-term outcome regardless of the age of onset.
The long-term neurodevelopmental outcome usually (but not always) correlates with the severity and duration of the hyperammonemic insult.
Pyramidal tract findings and intellectual disability, which range from mild to severe, are generally evident by childhood since almost 70% of HHH syndrome manifests in infancy and childhood [Martinelli et al 2015]. While treatment with a protein-restricted diet prevents postprandial and acute hyperammonemia, outcomes vary. For example, individuals with HHH syndrome with limited clinical manifestations throughout life have been reported [Filosto et al 2013; Silfverberg et al 2018; L Merritt, MD & E Font-Montgomery, MD, personal communication (see Outcomes and Presentation; pdf). Conversely, three of four adults with HHH syndrome who maintained normal levels of plasma ammonia for 11 to 38 years exhibited progressive neurologic and cognitive deterioration with serious outcomes [Kim et al 2012].
Neonatal diagnosis (birth – 1 month). About 8% (9/116) of affected individuals were diagnosed during the neonatal period, usually following an uncomplicated pregnancy and delivery. The clinical course is indistinguishable from that of other neonatal-onset urea cycle disorders: the infant is asymptomatic for the first 24-48 hours and, thereafter, has episodes of poor feeding, vomiting, lethargy, low temperature, and/or rapid breathing related to hyperammonemia (see Table 1). If left untreated seizures, coma, and even death may ensue. Hepatic dysfunction and coagulopathy in the neonatal period are common [Martinelli et al 2015, Wild et al 2019].
Given the small number of case studies published to date, little is known about the long-term outcome of individuals with neonatal onset of HHH syndrome. One child died from hyperammonemic encephalopathy at birth and another at age two months. Survivors ranged in age from one to 23 years – one demonstrated normal development at age six years, four had progressive pyramidal signs, and one with significant neuromotor impairment underwent liver transplantation at age seven years. In eight survivors with neonatal onset, cognitive abilities in four ranged from normal to mild deficiency, three exhibited severe cognitive impairment, and one was a recently reported premature infant [Martinelli et al 2015, Wild et al 2019].
Click here (pdf) for more details about outcomes in the neonatal-onset cases described above.
Infantile (>1 month – 1 year) age at diagnosis. Approximately 10% (12/116) of individuals with HHH syndrome present in this timeframe. Highly variable manifestations in infancy can include hypotonia, lethargy, failure to thrive, seizures, psychomotor delay, hepatomegaly, hepatic dysfunction (coagulopathy and elevated transaminases), hyperammonemia, feeding difficulties, and recurrent vomiting. Some children come to medical attention only after experiencing environmental stressors, most commonly infection.
Unique case studies include an affected individual who presented with fulminant hepatic failure and a recent example of the clinical progression of symptoms in an undiagnosed infant.
Click here (pdf) for more details about the presentation of infantile-onset HHHS described above.
Childhood (>1 year to 12 years) presentation accounts for almost half (56/116) of all HHH syndrome. Children in this group come to medical attention either for findings related to mild hyperammonemia with or without liver dysfunction or for evaluation of developmental and speech delay, dysarthria, intellectual disability, learning disabilities, hyperactivity, recurring vomiting, academic difficulties, spasticity, ataxia, and/or unexplained seizure activity. Environmental triggers (i.e., surgery, infection, medication) may also induce manifestations in previously healthy children.
A salient characteristic of affected individuals diagnosed in childhood who harbor the same SLC25A15 pathogenic variants is marked phenotypic variability.
Click here (pdf) for more details about outcomes in childhood-onset HHHS.
Liver dysfunction, a predominant feature at time of diagnosis, generally manifests as mild coagulopathy and elevated liver enzymes (AST and ALT) with or without hyperammonemia. In a few reports acute liver failure prompted consideration of liver transplantation [Fecarotta et al 2006, Mhanni et al 2008]. However, the liver dysfunction that may occur during the initial clinical presentation does not appear to cause long-term complications. Once the hyperammonemia is treated in a standard manner (see Treatment of Manifestations), the liver dysfunction subsides [Martinelli et al 2015, Ono et al 2018].
Despite early detection and adequate metabolic control (i.e., absence of hyperammonemia), some individuals with HHH syndrome continue to worsen neurologically with pyramidal tract involvement and cognitive decline [Camacho et al 2006, Debray et al 2008, Tessa et al 2009, Martinelli et al 2015]. Subclinical hyperammonemia is thought to be a major factor in neurocognitive decline, but not in the cause or progression of pyramidal syndrome. In some individuals with early-childhood onset, gait abnormalities and spasticity are the predominant findings.
The Urea Cycle Disorders Consortium reported developmental quotients (DQ) in four preschool children (age 4-5 years) with HHH syndrome: two were in the normal range and two were <71\. Two also exhibited anxiety and acting out behaviors [Waisbren et al 2016].
Adolescence/adulthood (>12 years) accounts for about one third (39/116) of persons with HHH syndrome. After infancy, these individuals quickly learn to self-restrict their protein intake to avoid the malaise and vomiting that accompanies protein-rich meals. The milder form of the disease and self-adherence to a low-protein diet allow these individuals to lead a relatively symptom-free life and remain undetected until they inadvertently overwhelm their compromised ability to detoxify harmful elevations of plasma ammonia. Ammonia overload may result from catabolic events (i.e., surgery, infection, prolonged fasting, pregnancy, internal bleeding), deviation from a protein-restricted diet, or certain medications (e.g., valproate, steroids).
Individuals diagnosed in adolescence/adulthood may present with recurrent encephalopathy secondary to hyperammonemia (lethargy, disorientation, episodic confusion, unexplained seizures), intellectual disabilities, recurrent vomiting, chronic behavioral problems, cerebellar signs (dizziness, loss of balance, poor coordination, abnormal gait/posture), and pyramidal tract dysfunction (inability to perform fine movements, positive Babinski reflex, muscle weakness, ataxia, hyperreflexia, and spasticity).
Click here (pdf) for more details about outcomes in adolescent/adult-onset HHHS.
Cognitive development in persons with HHH syndrome ranges from normal (34%) to severe impairment (34%), with the majority having normal to mild neurocognitive deficit (59%). In some reports, affected individuals have significant neurologic findings such as spasticity and ataxia without cognitive impairment [Martinelli et al 2015]. Of note, pyramidal signs of the lower extremities (hyperreflexia, clonus, tip-toe gait, and/or spastic ataxia) may develop years after the initial diagnosis [Salvi et al 2001b, Debray et al 2008, Tessa et al 2009].
The Urea Cycle Disorder Consortium reported findings of two successive neurocognitive evaluations given to one adult with HHH syndrome: full scale IQ was 100 and 84 at ages 21 years and 26 years, respectively; performance was significantly diminished across all neuropsychological tests. No cognitive or behavioral issues were noted [Waisbren et al 2016].
Additional clinical biochemical abnormalities in HHHS can include the following:
* Mildly elevated plasma glutamine concentration (1.5- to 2-fold the upper limits of control values)
* Plasma lysine can range from normal to moderately decreased
* Increased urinary excretion of:
* Orotic acid (2.5- to 12-fold the upper limit of control values)
* Organic acids. An increase in the urinary excretion of components of the Krebs cycle (succinate, citrate, fumaric, α-ketoglutaric), methylcitrate, and lactate has been documented in a few reports [Korman et al 2004, Fecarotta et al 2006].
* Statistically significant elevation of AFP and pronounced liver ultrasound abnormalities at follow up [Ranucci et al 2019]
### Prevalence
Since the description of the first individual with HHH syndrome by Shih et al [1969], approximately 122 individuals with HHH syndrome have been reported [Martinelli et al 2015, Qadri et al 2016, Guan et al 2017, Ono et al 2018, Silfverberg et al 2018, Ho et al 2019, Wild et al 2019].
Summar et al [2013], using two large longitudinal registries in the US (NIH-sponsored Urea Cycle Disorders (UCD) Consortium and The National UCD Foundation) and one in Europe (European Registry and Network for Intoxication-Type Metabolic Diseases), calculated an incidence for HHH syndrome of 1% and 3% of all UCDs in the US and Europe, respectively. In the US, the frequency of HHH syndrome is less than 1:2,000,000 live births [Summar et al 2013].
The incidence of HHH syndrome is highest in individuals of French-Canadian ancestry because of the SLC25A15 founder variant c.562_564delTTC (p.Phe188del) in this population (see Table 8) [Camacho et al 1999, Debray et al 2008]. A study of this founder variant in an isolated northern Saskatchewan population of mixed French-Canadian and Aboriginal descent suggested that the incidence of HHH syndrome in this population is 1:1,550 live births [Sokoro et al 2010].
Another common pathogenic variant, c.535C>T (p.Arg179Ter) (see Table 8), seen in 14% of individuals with HHH syndrome, is frequent in persons with HHH syndrome of Japanese and Middle Eastern descent [Tsujino et al 2000, Salvi et al 2001a].
## Differential Diagnosis
### Hyperammonemia
Most commonly, neonates with hyperammonemia and neonatal-onset HHH syndrome are initially suspected of having sepsis. See Häberle et al [2019] for a comprehensive algorithm for the differential diagnosis of neonatal hyperammonemia based on plasma and urine metabolites.
Like other urea cycle disorders (UCDs), HHH syndrome should be included in the differential diagnosis of any individual with hyperammonemia, including women who experience hyperammonemia during or following pregnancy. The onset and severity of findings in HHH syndrome are more variable and less severe when compared to UCDs like ornithine transcarbamylase (OTC) deficiency or carbamyl phosphate synthase (CPS-I) deficiency (OMIM 237300). UCDs usually present with isolated elevation in plasma ammonia concentration and metabolic alkalosis. Plasma amino acid analysis and acylcarnitine profile, urine amino acid analysis, urine organic acid analysis, and urine orotic acid measurements allow diagnosis of the specific UCD (see Urea Cycle Disorders) or HHH syndrome. Neonates with a UCD may have hypoglycemia.
A complete chemistry panel (CMP), CBC and differential, lactate determination, arterial blood gases, serum creatine kinase (CK), and urinalysis (to check for ketonuria) should always be included in the evaluation of any person with an elevated plasma ammonia concentration to evaluate for conditions including the following:
* Organic acidemias (present with acidosis)
* Lysinuric protein intolerance (associated with low plasma ornithine, lysine, and arginine)
* Fatty-acid oxidation defects (associated with nonketotic hypoglycemia and liver dysfunction). See MCAD Deficiency.
* Pyruvate carboxylase deficiency (presents with lactic acidosis and hypoglycemia)
* Mitochondrial disease. Given that the neurologic nonacute presentation for HHH syndrome may be indistinguishable from primary mitochondrial disease, urine organic acid analysis should also be ordered. In some cases of HHH syndrome, urinary excretion of Krebs cycle components (succinate, fumarate, citrate, and α-ketoglutarate) and lactate have been reported [Korman et al 2004]. This pattern of excretion of organic acids, which is commonly seen in children and adults with defects in mitochondrial complex I or III, may create the impression that persons with HHH syndrome have a primary rather than a secondary mitochondrial defect.
### Hyperornithinemia
The only other condition that causes chronic elevations in plasma ornithine concentration is deficiency of ornithine amino transferase (OAT) (OMIM 258870), a mitochondrial matrix enzyme involved in the ornithine degradation pathway. However, OAT deficiency never presents with the neurologic and clinical biochemical features of HHH syndrome (e.g., elevation in plasma ammonia concentration and glutamine, urinary excretion of homocitrulline and/or orotic acid). OAT deficiency presents mostly with ophthalmologic findings known as hyperornithinemia with gyrate atrophy of the choroid and retina that manifest as chorioretinal degeneration with loss of peripheral vision, night blindness, and often posterior subcapsular cataracts [Kim et al 2013].
### Homocitrullinuria
Homocitrulline is a by-product of canned milk production that arises from the reaction of cyanate and the terminal ε-amino group of lysine. In canned formulas, cyanate is produced from heat-induced urea breakdown. When homocitrulline is consumed in the diet from sources such as these, it is absorbed in the small intestine via a transport system similar to that of cationic amino acids and excreted in the urine. In contrast, homocitrullinuria detected in neonates given IV glucose only (and no dietary source of protein) indicates the presence of a metabolic disorder.
Some individuals with lysinuric protein intolerance (LPI) have been shown to excrete homocitrulline [Habib et al 2013]. Although these individuals may also have hyperammonemia, their clinical biochemical profile demonstrates low concentrations of plasma ornithine, lysine, and arginine and persistent urinary excretion of lysine, ornithine, and arginine.
### Neurologic Findings
In those individuals with early-childhood onset HHH syndrome in whom gait abnormalities and spasticity predominate, the differential diagnosis should also include early-onset inherited spastic paraplegia (see Hereditary Spastic Paraplegia Overview).
Arginase I deficiency is the only other urea cycle disorder (UCD) in which a prominent manifestation is progressive pyramidal tract involvement leading to spastic paraparesis. In general, spastic paraparesis in arginase I deficiency manifests earlier in childhood.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs of an individual diagnosed with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to diagnosis) are recommended.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome
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System/ConcernEvaluationComment
ConstitutionalMeasurement of HT, WT, & HCAlways consider ethnic/geographic origin as it may influence baseline HT & WT.
NeurologicAssess cerebellar motor function (gait & postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades & smooth pursuit)Use standardized scale to establish baseline for ataxia (SARA, ICARS, or BARS) 1
Assess spasticityCan range from lower-limb hyperreflexia w/Babinski sign ± gait abnormalities to spastic paraparesis
Refer to neuromuscular clinic (OT/PT/ rehabilitation specialist)To assess gross motor & fine motor skills, ambulation, & need for adaptive devices & PT.
EEG if seizures are suspectedMainly myoclonic seizures
MRI/MRS
* Baseline evaluation of patients w/significant neurologic impairment
* Evaluation of patient who develops hyperammonemic coma
Development/IDTo incl motor, speech/language evaluation, general cognitive, & vocational skills
MusculoskeletalAssess for skeletal involvement related to spasticity.
SpeechFor those w/dysarthria: speech/language evaluationImproving speech can ↓ secondary behavior problems & contribute to dietary compliance.
FeedingFor those w/recurrent vomiting or severe dysphagia: assess nutritional status, aspiration risk.Consider involving a gastroenterology / nutrition / feeding team.
PsychiatricNeuropsychiatric evaluationIn individuals age >12 mos: screen for behavioral problems incl sleep disturbances, ADHD, &/or anxiety.
LiverEvaluate for evidence of hepatic dysfunction - biochemical profile & US.↑ transaminases & coagulopathy resolve after implementation of protein-restricted diet.
Miscellaneous/
OtherFamily support/resources
* Community or online resources such as Parent to Parent
* Social work involvement for parental support
Consultation w/clinical or metabolic geneticist, genetic counselor, metabolic dietician, &/or social worker
* Consultation w/genetic counselor to address genetic counseling issues
* Social worker can help w/school IEP, access to low-protein foods, & social services assistance.
ADHD = attention-deficit/hyperactivity disorder; BARS = Brief Ataxia Rating Scale; HC = head circumference; HT = height; ICARS= International Co-operative Ataxia Rating Scale; ID = intellectual disability; IEP = individualized educational plan; OT = occupational therapist; PT = physical therapist; SARA= Scale for the Assessment and Rating of Ataxia; US = ultrasound; WT = weight
1\.
Bürk & Sival [2018]
### Treatment of Manifestations
It is critical that the acute and long-term management of individuals with HHH syndrome be performed in conjunction with a metabolic specialist. Of primary importance is the rapid control of acute hyperammonemic episodes that may result from changes in diet (e.g., protein intake), infection, dehydration, fasting, injury, or unknown cause. Long-term management focuses on prevention of postprandial hyperammonemia and acute hyperammonemic episodes and efforts to lower the plasma ornithine concentration.
Acute hyperammonemic episodes are treated like hyperammonemic episodes in other UCDs: assessment of plasma ammonia concentration, complete chemistry panel, arterial blood gases, CBC and differential (to evaluate for an infectious process), urinalysis, urine and plasma amino acids, and urine orotic acid. Urine organic acids should also be included to determine possible secondary mitochondrial dysfunction. Viral studies are indicated to evaluate infection as a possible cause of catabolism.
Plasma ammonia concentrations ≥80 μmol/L (~2x control value) should be treated immediately.
Discontinue all oral intake until the patient is stabilized to stop all protein intake (a cornerstone of acute treatment) and to reduce the risk of vomiting from hyperammonemia and/or nitrogen-scavenging medications. Of note, use of the recently approved ammonia-scavenging medication glycerol phenylbutyrate (RAVICTI®) should be stopped as it relies on pancreatic lipases and, thus, only works when administered with food [Berry et al 2017].
Provide intravenous fluid with dextrose and intralipids to reverse catabolism while optimizing caloric intake:
* Initial intravenous infusion should be 10% dextrose (with 1/4 normal saline and 20 mEq/L KCl) at twice maintenance; ammonia and glucose/Na/K/Cl/CO2 concentrations should be monitored every two hours or when neurologic status changes.
* It is important to maintain an approximate glucose infusion rate (GIR) between 10 to 15 mg/kg/min in order to prevent catabolism (protein sparring effect) and maintain adequate blood glucose levels between 100 and 150 mg/dL. The concentration of glucose may need to be increased (12.5% to 15%) to prevent fluid overload, particularly when secondary brain edema is present. As the patient's metabolic condition stabilizes, it is important to keep a stable GIR and not decrease or stop infusion rate in response to hyperglycemia (>150 mg/dL). An insulin drip should be used to maintain blood glucose at ~150-160 mg/dL during the critical phase of the hyperammonemic event and may be quickly withdrawn or reduced in rate if hypoglycemia develops.
* The use of IV intralipids (2-3 g/kg/day) is an additional source of energy used in patients with prolonged episodes of hyperammonemia common during periods of infection.
* An individual with HHH syndrome is more likely to respond to the initial IV infusion of dextrose and to normalize his/her plasma ammonia concentration when compared to an individual with a urea cycle disorder such as OTC deficiency or ASS deficiency. If clinical status does not improve, infusion of supplemental arginine and ammonia removal drugs is added to the regimen.
Of note, as clinical manifestations often do not correlate with rising plasma ammonia concentrations, treatment decisions should consider both plasma ammonia concentration and neurologic status.
Follow published protocols for treatment of acute hyperammonemic episodes similar to those instituted for OTC deficiency (see National Organization for Rare Diseases Physician Guide to the Urea Cycle Disorders) [Brusilow & Horwich 2001]. See also Häberle et al [2019] and Matsumoto et al [2019] for protocols specific to HHH syndrome. These protocols consist of arginine supplementation and use of intravenous bolus and maintenance infusions of the ammonia removal drugs sodium benzoate and sodium phenylacetate.
The New England Consortium of Metabolic Programs complete set of treatment protocols for neonatal hyperammonemia and OTC deficiency focusing on the use of Ammonul® (Ucyclyd Pharma) are freely available. Alfadhel et al [2016] provide an excellent online step-by-step resource for management of hyperammonemia.
It is important to note that unless the patient is transferred to a specialized metabolic center, treatment with scavenging agents to remove excess nitrogen and ammonia from the blood will depend on availability of medications.
An initial priming dose of arginine, benzoate, and phenylacetate is given (see Table 5).
### Table 5.
Initial Priming Dose of Arginine, Benzoate, and Phenylacetate by Age Group
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Infusion 1Infants and ChildrenAdolescents and Adults
10% arginine HCl210 mg/kg4.0 g/m2
Sodium benzoate250 mg/kg5.5 g/m2
Sodium phenylacetate250 mg/kg5.5 g/m2
1\.
Mix solutions of arginine, benzoate, and phenylacetate in a 10% dextrose solution at a dose of 25 mL of 10% dextrose/kg and infuse over 90 minutes. The solutions containing arginine, benzoate, and phenylacetate should be given in conjunction with 10% dextrose + 1/4 normal saline + 20 mEq/L KCL solution.
If ammonia levels stabilize, the same arginine, benzoate, and phenylacetate solution is infused over 24 hrs.
Note: All preparations of arginine and ammonia removal drugs should be double- or triple-checked given the potential for drug intoxication (if high doses are given) or for continued CNS ammonia toxicity (if low doses are given). If sodium benzoate or sodium phenylacetate solutions are not available, infusion of arginine should be started.
* Sodium phenylbutyrate (sodium phenylacetate prodrug) may be given either by mouth or by nasogastric tube (Buphenyl® powder) during acute episodes of hyperammonemia in hospitals that do not carry IV Ammonul® (sodium benzoate/phenylacetate). Moreover, in patients who use glycerol phenylbutyrate for maintenance at home, sodium phenylbutyrate should continue after formula and food are started until discharge to avoid double medication errors.
* Dose of sodium phenylbutyrate:
* ≤25 kg: 550-600 mg/kg/day
* >25 kg: 9.9-13.0 g/m2/day
Table 6 summarizes mechanisms of drug actions in the treatment of hyperammonemia.
### Table 6.
Mechanisms of Drug Action in Treatment of Hyperammonemia
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DrugAction
Glucose
* Raises insulin levels
* Induces anabolic state
* Causes protein sparing effect from skeletal muscle amino acids
Arginine 1
* Needs to be supplemented in those w/a urea cycle disorder
* Stimulates secretion of insulin
* Plays a role in 1st step of creatine synthesis 2
Sodium benzoate 3
* Forms benzoate-glycine (hippurate) via the benzoylCoA:glycine acyltransferase reaction 4
* Eliminates 1 amino group in the urine
Sodium phenylacetate 3
* Forms a phenylacetate-glutamine compound via the phenylacetateCoA:glutamine acetyl-transferase reaction 4
* Eliminates 2 amino groups in the urine
1\.
A nonessential amino acid in humans
2\.
Interruption in the synthesis of brain creatine secondary to hyperammonemia has been proposed as a contributing factor to the neurologic findings in affected individuals.
3\.
Initially esterified to its CoA-ester via the medium-chain fatty acid enzyme acyl-CoA ligase
4\.
Reaction takes place in the mitochondrial matrix (liver and kidney) [Brusilow & Horwich 2001].
Concurrent with the above, the trigger for the hyperammonemic event (most commonly infection or internal bleeding) should be identified and treated to prevent ongoing protein catabolism and allow for the metabolic stabilization of the patient.
Hemodialysis. If the patient fails to respond to the above treatment of hyperammonemia, if the plasma ammonia concentration increases, and/or if the neurologic status deteriorates, dialysis should be started promptly to remove ammonia from the circulation. Infusion of arginine, benzoate, and phenylacetate should continue during dialysis. The preferred method to remove increased levels of ammonia in neonates, infants, and children is continuous renal replacement therapy (CRRT), especially when there is hemodynamic instability [Häberle et al 2019, Matsumoto et al 2019].
Need for dialysis (CRRT) falls into one of the following three categories based on age and plasma ammonia level [Alfadhel et al 2016, Häberle et al 2019]:
* Neonates and children
* Unlikely: <200 µmol/L
* Possible: ≥200-300 µmol/L if no response within four hours
* Definitely: >400-500 µmol/L
* Adolescents and adults. Definitely if ammonia >200µmol/L
Dialysis may be prolonged if the catabolic state (e.g., infection) persists.
Nutrition. Twenty-four to 36 hours after initial admission oral intake should start, including daily doses of only essential amino acids, carnitine, vitamins, and lipids to help avoid a catabolic state, which will prolong hyperammonemia. Note: Nonessential amino acids (i.e., glutamine, proline, and glycine) should be avoided since they increase the nitrogen load to an already compromised urea cycle.
Long-term management includes maintenance on an age-appropriate protein-restricted diet that controls hyperammonemia, but also provides sufficient protein for normal growth and development, especially for infants and children.
The recommended amount of total protein, calories, and fluids consumed per day varies with age. The ratio of natural protein to essential amino acids is approximately 60:40. The Ross Manual [Acosta & Yannicelli 2001] can serve as a guide for the recommended daily nutrient intake for infants, children, and adults. For example, patients age 12 yrs or older usually need approximately 0.7-1.0 g/kg/day of total protein.
* Dietary supplementation with Cyclinex®-1 formula (infants and toddlers) or Cyclinex®-2 formula (children, adolescents, and adults) that provides only essential amino acids and other nutritional supplements has been helpful for some patients. Children older than age 10-12 years and adults with a urea cycle disorder use VITAFLO® essential amino acid supplement.
* Caloric supplements such as ProPhree® (4.5 calories per gram) are available for neonates, infants, and toddlers.
* UCD-Trio® provides isoleucine, leucine, and valine for toddlers and children whose branched-chain amino acid levels are consistently low, often due to ammonia-scavenging drugs.
* Citrulline supplementation at 0.17 g/kg/day or 3.8 g/m2/day is preferred to arginine because citrulline provides better metabolic control and avoids secondary creatine deficiency [Martinelli et al 2015]. Citrulline accepts an aspartate (via the arginosuccinate synthase reaction) and therefore eliminates two amino groups per cycle. Molema et al [2019] reported that in patients with OTC deficiency, CPS1 deficiency, or HHH syndrome, the relatively greater bioavailability of citrulline leads to higher plasma arginine levels than no supplementation or supplementation with arginine.
* Sodium phenylbutyrate (Buphenyl®) is given in three divided doses either as 450-600 mg/kg/day for patients ≤25 kg or as 9.9-13.0 g/m2/day for patients ≥25 kg when glycerol phenylbuyrate (RAVICTI®) is not available. Note that sodium phenylbutyrate initially is imported into the mitochondria where it undergoes β-oxidation to produce phenylacetate.
* Effective January 2019, the FDA approved the use of glycerol phenylbutyrate (RAVICTI®, Horizon Pharma) for patients of all ages (including neonates) for treatment of hyperammonemic episodes due to urea cycle disorders [Author, personal communication].
* Lysine supplementation is indicated when plasma lysine concentrations are low. Low plasma lysine concentrations have been associated with delayed growth and development.
* Creatine supplementation has also been recommended in HHH syndrome and urea cycle disorders such as OTC and ASS deficiencies [Boenzi et al 2012]. In HHH syndrome, the synthesis of creatine from arginine is decreased due to ornithine inhibition of the first step, which depends on glycine transaminidase.
* Carnitine supplementation may be necessary due to carnitine deficiency secondary to dietary restriction (e.g., meat) and/or conjugation of carnitine with ammonia removal drug metabolites (phenylacetate).
* Plasma concentrations of ammonia, glutamine, arginine, ornithine, and essential amino acids (in particular lysine, isoleucine, leucine, and valine) should be maintained within the normal range.
Note: (1) Although elevated plasma ornithine concentrations may decrease significantly if dietary management is followed, complete normalization of plasma ornithine concentration is rarely observed. (2) Even in the absence of hyperammonemic episodes, affected individuals may continue to develop neurologic complications such as spasticity or learning disabilities. Maintaining as low a level of plasma ornithine as possible by restricting protein intake could help prevent some of the progressive neurologic complications seen in these individuals [Valle & Simell 2001].
Three individuals with HHH syndrome who had acute fulminant hepatic failure and coagulopathy rapidly stabilized after protein restriction and arginine or citrulline supplementation [Fecarotta et al 2006, Mhanni et al 2008, Lee et al 2014].
Liver transplantation is not indicated when metabolic control can be achieved with diet, supplemental citrulline, and ammonia-scavenging medications. Because SLC25A15 and the ornithine degradation pathway are expressed in all tissues (e.g., brain, kidney) and most cell types (e.g., astrocytes, fibroblasts), liver transplantation may correct the hyperammonemia, but it will not correct tissue-specific metabolic abnormalities that also contribute to the neuropathology.
Two instances of liver transplantation for HHH syndrome were reported:
* A child age six years with a history of continued biochemical abnormalities, protein intolerance, developmental delay, and abnormal posture [Guan et al 2017];
* A child age seven years with poor metabolic control who had presented at age four weeks with hyperammonemic coma (plasma ammonia 2,300 µmol/L) [Verloo et al 2007].
#### Developmental Delay / Intellectual Disability Management Issues
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.
All ages. Consultation with a developmental pediatrician and social worker is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:
* Individualized education plan (IEP) services:
* An IEP provides specially designed instruction and related services to children who qualify.
* IEP services will be reviewed annually to determine if any changes are needed.
* As required by special education law, children should be in the least restricted environment feasible at school and included in general education as much as possible and when appropriate.
* Vision and hearing consultants should be a part of the child’s IEP team to support access to academic material.
* PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual’s needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
* As a child enters teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
* A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
* Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
* Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.
### Surveillance
All surveillance of patients with HHH syndrome (Table 7) should be a combined effort of the general pediatrician or adult practitioner and a metabolic team (metabolic geneticist, metabolic dietician, and social worker).
### Table 7.
Recommended Surveillance for Individuals with Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome
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System/ConcernEvaluationFrequency
ConstitutionalMeasure HT, WT, & HC. BMI should always be included.
* From time of diagnosis until adolescence
* During pre-school years: follow WT, HT & HC in conjunction w/PCP even when not seen in metabolic clinic.
Metabolic statusConcentration of:
* Plasma ammonia & amino acids 1, 2
* Urine amino acids, organic acids, & orotic acid
Phenylbutyrate & its metabolites (phenylacetate, phenylacetate-glutamine) to optimize management & check complianceRoutine monitoring based on:
* Age:
<1 yr: every mo
1-2 yrs: every 2-3 mos
>2 yrs: every 3-4 mos
* History of compliance
* History of metabolic decompensation
Mood, behavior,
eatingParents should be alert to subtle behavior changes which may suggest ↑ plasma concentrations of glutamine & ammonia.
* Incl changes in eating habits, motor skills, & behavior
* In children age ≤3 yrs, especially in flu season or hot/humid weather
DevelopmentEvaluation by developmental pediatrician to assess & manage emergence of behavior issues (ADD/ADHD)Prior to starting kindergarten; evaluate as needed.
Academic
performance 3Neurocognitive evaluation1x/yr if any academic regression or behavior changes occur
Neurologic
evaluationA detailed evaluation by neurologist especially in children w/neonatal, infantile, & early school-age onset to assess for slow, progressive neurologic involvementMonitor 1x/yr even when metabolic control is optimal, especially in children age <12 yrs.
Perform MRI/MRS in consultation w/neurologist.MRI/MRS every 2 yrs to correlate motor/cognitive/language development w/imaging findings (possible progressive cerebral atrophy, stroke-like lesions, &/or white matter disease)
ADD = attention-deficit disorder; ADHD = attention-deficit/hyperactivitry disorder; BMI = body mass index; HC = head circumference; HT = height; PCP = primary care provider; WT = weight
1\.
Low plasma concentrations of essential amino acids (isoleucine, leucine, valine, and arginine) could trigger a catabolic state, requiring readjustment of diet/formulas and/or supplements.
2\.
Low plasma concentrations of lysine may lead to delays in growth and development in infants.
3\.
Poor school performance may lead to low self-esteem and/or behavioral problems that could influence compliance with a protein-restricted diet.
### Agents/Circumstances to Avoid
Avoid the following:
* Excess dietary protein intake
* Nonprescribed protein supplements such as those used to increase size of skeletal muscle during exercise regimens
* Prolonged fasting during an illness or weight loss
* Use of oral and intravenous steroids
* Valproic acid, which induces and exacerbates hyperammonemia in urea cycle disorders
* Exposure to communicable diseases
### Evaluation of Relatives at Risk
Testing of at-risk sibs is warranted to allow for early diagnosis and treatment.
If the SLC25A15 pathogenic variants in the family are known and if prenatal testing has not been performed on an at-risk sib, test for the familial SLC25A15 pathogenic variants in the newborn period while restricting the diet (≤1.2 g/kg/day protein using breastfeeding and a zero-protein formula) and monitoring plasma ammonia, plasma amino acids, and urine orotic acid.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Ho et al [2019] reported pregnancy management and outcomes of four women with HHH syndrome: a patient of their own who had two pregnancies; and three women reported in the literature. They provide a systematic protocol for severe metabolic decompensation during pregnancy.
Management of the affected mother before and during pregnancy to achieve metabolic control to enable normal fetal growth and development. In general, pregnant women should continue dietary protein restriction and supplementation with citrulline and ammonia-scavenging medications (after an appropriate benefit/risk calculation) based on their clinical course before pregnancy. Protein restriction during pregnancy is challenging given the complications that commonly arise during pregnancy (i.e., nausea, vomiting, anorexia) plus the natural aversion to protein exhibited by individuals with HHH syndrome. Due to increased protein and energy requirements in pregnancy and, oftentimes, difficulty with patient compliance, weekly to every two-week monitoring of plasma amino acids and ammonia is recommended, especially in the first and third trimester, and close monitoring immediately after delivery. Plasma amino acid levels can help guide quick adjustments to diet in order to achieve normal plasma amino acid profiles that prevent catabolism and hyperammonemia while allowing for normal fetal growth and development. Protein intake during pregnancy varied from 0.8 g/kg/day to 1.3 g/kg/day (normal dietary reference intakes: 1.1 g/kg/day to 1.2-1.52 g/kg/day) [Ho et al 2019].
Delivery by cesarean section is recommended in order to optimize metabolic control.
Häberle et al [2019] provide a table detailing protein intake and extra energy requirements in pregnancy and lactation.
Management of metabolic complications during pregnancy in women with HHH syndrome. Complications related to HHH syndrome arose during pregnancy and delivery and in the immediate postpartum period in three of the four women reported by Ho et al [2019]. Mild hyperammonemic episodes and seizures during pregnancy were treated by adjustments to dietary protein intake (decrease) and anti-seizure medication (carbamazepine), respectively [Kim et al 2012, Ho et al 2019].
* One woman experienced mild hyperammonemia at the end of the first trimester of her first pregnancy. In her second pregnancy, she experienced metabolic decompensation (ammonia 295 µmol/L) prior to the second trimester and responded well to emergency treatment with Ammonul® and arginine [Ho et al 2019].
* A second woman experienced mild hyperammonemia at the end of the first trimester of her first pregnancy, and developed petit mal seizures in the second trimester and elevations in ammonia (21-103 µmol/L) post partum. In her second pregnancy, she experienced hyperammonemia ten hours post-C-section delivery that responded to treatment with oral sodium benzoate and IV arginine. During her third pregnancy, she had a seizure.
* A third woman experienced mild elevation of plasma ammonia (43-126 µmol/L) during labor.
Normal pregnancy and delivery were documented in two women with HHH syndrome.
* One, diagnosed with HHH syndrome at age 13 years in the course of evaluation of an affected sib, was clinically asymptomatic before pregnancy. During the pregnancy, she was maintained on citrulline and an appropriate protein-restricted diet [Rebecca Mardach, MD, Kaiser Permanente, personal communication].
* The other, a woman age 22 years with no neurologic findings, had learned to self-restrict protein intake after severe protein intolerance in infancy [Ho et al 2019].
Fetal outcomes. Ho et al [2019] summarized the outcome of five previously reported infants born to three women with HHH who were primarily on dietary management or older ammonia-scavenging medications (lactulose) during pregnancy. Three of the five pregnancies resulted in healthy newborns.
* One female had intrauterine growth restriction (IUGR); development at age two years was normal.
* One of the neonates who had normal development at birth experienced transient respiratory distress requiring mechanical ventilation.
There are no well-controlled epidemiologic studies of the fetal effects of sodium benzoate, phenylacetate, or phenylbutyrate during human pregnancy, although there are several case reports.
* Redonnet-Vernhet et al [2000] reported a woman with symptomatic ornithine transcarbamylase (OTC) deficiency who was treated with sodium benzoate during the first 11 weeks of gestation and was subsequently transitioned to sodium phenylbutyrate for the remainder of pregnancy. She delivered a healthy female who continued to do well at age two years.
* Lamb et al [2013] reported another woman with symptomatic OTC who was treated throughout pregnancy with sodium benzoate (4 g/4x/day), sodium phenylbutyrate (2 g/4x/day) and arginine (300 mg/4x/day) who delivered a healthy, unaffected male who was doing well at age six weeks.
* Ho et al [2019] are the first to document the use of sodium phenylbutyrate throughout two sequential pregnancies in a woman with HHH syndrome:
* In the first pregnancy sodium phenylbutyrate (5.5 g/4x/day) was used as maintenance therapy. This resulted in the delivery of a healthy female who was noted to have typical growth and development at age five years.
* In the second pregnancy, emergency treatment with Ammonul® (sodium phenylacetate/sodium benzoate) to manage hyperammonemic crisis (ammonia 295 µmol/L) was used in addition to maintenance therapy of sodium phenylbutyrate (5 g/4x/day).
Although the mother responded well to emergency treatment, the baby experienced IUGR and remained in the NICU due to prematurity and low birth weight. At age two years the child exhibited speech delay and autism.
How severe metabolic decompensation, elevated plasma ornithine, and/or side effects of sodium phenylbutyrate, phenylacetate, and/or benzoate may have contributed to the speech delay and/or autism is not known.
* Ho et al [2019] prefer and recommend the use of sodium benzoate if deemed medically necessary during pregnancy, but did not advise switching maintenance medications during pregnancy
Theoretic concerns. Sodium benzoate has been reported to lead to malformations and neurotoxicity/nephrotoxicity in zebrafish larvae [Tsay et al 2007]. As a known differentiating agent, sodium phenylbutyrate also functions as a histone deacetylase (HDAC) inhibitor with potential teratogenicity given its ability to alter gene expression in fetal mice [Di Renzo et al 2007]. Theoretically, the use of benzoate/phenylacetate and in particular sodium phenylbutyrate should be avoided during pregnancy, especially during the first trimester. The use of these medications should be carefully evaluated for each individual (benefit/risk ratio) in consultation with a metabolic genetics specialist.
See MotherToBaby for further information on medication use during pregnancy.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
|
c0268540
| 25,578 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK97260/
| 2021-01-18T21:19:09 |
{"mesh": ["C538380"], "synonyms": ["HHH Syndrome"]}
|
Johnson et al. (1971) described a family in which 11 persons in 4 generations had microspherophakia with upward dislocation of the lens, myopia, retinal detachment and inguinal hernias in various combinations. No other stigmata of either the Marfan (154700) or the Weill-Marchesani (277600) syndrome were detected. They suggested that this is a distinct connective tissue disorder. No male-to-male transmission occurred in their family. As an isolated trait, microspherophakia has been thought to be recessive (251750).
Eyes \- Microspherophakia \- Upward lens dislocation \- Myopia \- Retinal detachment Abdomen \- Inguinal hernia 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
|
MICROSPHEROPHAKIA WITH HERNIA
|
c1834881
| 25,579 |
omim
|
https://www.omim.org/entry/157150
| 2019-09-22T16:38:11 |
{"mesh": ["C537468"], "omim": ["157150"]}
|
A number sign (#) is used with this entry because medium-chain acyl-CoA dehydrogenase deficiency is caused by homozygous or compound heterozygous mutation in the medium-chain acyl-CoA dehydrogenase gene (ACADM; 607008) on chromosome 1p31.
Description
Inherited deficiency of medium-chain acyl-CoA dehydrogenase is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain dicarboxylic aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. The disorder may be severe, and even fatal, in young patients (Matsubara et al., 1986).
Clinical Features
Gregersen et al. (1976) first described MCADH deficiency in a patient who presented with unexplained episodes of lethargy and unconsciousness and C6-C10 dicarboxylic aciduria. Naylor et al. (1978) studied 2 early-adolescent sisters who suffered from intermittent hypoglycemia, lethargy, and coma associated with peripheral lobular fatty changes in the liver. During hypoglycemia, massive C6-C14 dicarboxylic aciduria was demonstrated by gas chromatography. Adipic and monounsaturated sebacic, seburic, ozeleic acids were among those elevated in urine and serum. The workers suggested that because of a defect in beta-oxidation of fatty acids of medium chain length, omega oxidation to dicarboxylic acids had occurred through an alternative pathway. Probably identical cases have been reported, although not in full detail.
Colle et al. (1983) reported 2 children with reversible episodes of hypoglycemia and 'Reye syndrome' who during the acute phases showed urinary excretion of dicarboxylic acids and psi-hydroxy fatty acids. Rhead et al. (1983) measured defective medium-chain acyl-CoA dehydrogenase in one of the patients of Colle et al. (1983), thus supporting the findings of Kolvraa et al. (1982) and Divry et al. (1983) that acyl-CoA dehydrogenase deficiency can be responsible for dicarboxylic aciduria.
In a Finnish family, Rasanen et al. (1971) reported 2 sibs with hepatic steatosis (228100). Studies of a subsequently born affected sib showed changes consistent with nonketotic C6-C10-dicarboxylic aciduria (Simila et al., 1984). Stanley et al. (1983) reported 3 children in 2 families who presented in early childhood with episodes of illness associated with fasting and resembling Reye syndrome: coma, hypoglycemia, hyperammonemia, and fatty liver. Deficiency of medium-chain acyl-CoA dehydrogenase was demonstrated. The authors concluded that the carnitine deficiency was a secondary phenomenon and suggested that other patients with 'systemic carnitine deficiency' (see 212140) who fail to respond to carnitine therapy may have defects in fatty acid oxidation of this type.
Roe et al. (1986) identified this defect in mitochondrial beta-oxidation in 2 asymptomatic sibs in a family in which 2 previous infant deaths had occurred: one attributed to sudden infant death syndrome and one to Reye syndrome. Recognition of MCAD deficiency in one of these infants and in a surviving sib was accomplished by detection of octanoylcarnitine.
Matsubara et al. (1986) stated that at least 24 cases of MCADH deficiency had been reported. Taubman et al. (1987) diagnosed MCADH deficiency in a 20-month-old girl with a history of 2 sibs who died of an encephalopathy diagnosed as Reye syndrome.
Biochemical Features
Amendt and Rhead (1985) studied the original patient described by Gregersen et al. (1976) and 7 others and found no biochemical heterogeneity. The patients showed elevated urinary excretion of straight-chain C6-C10-omega-dicarboxylic acids. These are formed by omega-oxidation of accumulated C10-C12-monocarboxylic acids, which are then shortened by beta-oxidation to medium-chain length. The isolated excretion of straight-chain C6-C10-dicarboxylic acids without associated ketosis is consistent with the defective mitochondrial beta-oxidation produced by MCADH deficiency.
Onkenhout et al. (2001) determined the fatty acid composition of liver, skeletal muscle, and heart obtained postmortem from patients with deficiency of 1 of 3 types of acyl-CoA dehydrogenase: medium-chain, multiple (MADD; 231680), and very long-chain (VLCADD; 201475). Increased amounts of multiple unsaturated fatty acids were found exclusively in the triglyceride fraction. They could not be detected in the free fatty acid or phospholipid fractions. Onkenhout et al. (2001) concluded that intermediates of unsaturated fatty acid oxidation that accumulate as a consequence of MCAD, MADD, and VLCADD are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation is characteristic for each disease, which makes fatty acid analysis of total lipid of postmortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who have died unexpectedly.
Diagnosis
Rinaldo et al. (1988) found that measurement of urinary hexanoylglycine and phenylpropionylglycine by a method of stable-isotope dilution is a fast and reliable method for diagnosis of MCAD deficiency. It can be applied to random urine specimens without pretreatment such as fasting.
Bennett et al. (1990) identified urinary metabolites useful in detecting MCAD deficiency in the newborn period. They suggested that this would be useful in the screening of later-born sibs of cases of the following: proven MCAD deficiency, Reye syndrome (deceased and not tested for MCAD deficiency), sudden infant death syndrome under 1 year of age, sudden unexpected death between ages 1 and 4, and hypoglycemia of unknown origin. Two of the 5 patients studied by von Dobeln et al. (1990) had elder sibs who had died unexpectedly in early infancy. In 3 of the 5 patients and in both deceased sibs, stored filter paper blood samples obtained from the patients and their deceased sibs for purposes of neonatal screening showed elevated levels of 3-hydroxy fatty acids.
Santer et al. (1990) suggested that there are distinctive mitochondrial abnormalities on electron microscopy that rule out Reye syndrome and are suggestive of a disorder of mitochondrial fatty acid oxidation: in addition to large-droplet steatosis, there are an electron-dense mitochondrial matrix and a widened space of inner mitochondrial membranes.
Van Hove et al. (1993) demonstrated that the diagnosis of MCAD deficiency, including presymptomatic neonatal recognition, can be made reliably through the analysis of acylcarnitines in blood. Tandem mass spectrometry is a convenient method for fast and accurate determination.
Iafolla et al. (1994) suggested that MCAD deficiency satisfies the criteria for newborn population screening. The authors collated medical data on 120 patients with MCAD deficiency referred to Duke University Medical Center for biochemical testing. They found that 88% were initially referred because of clinical illness or sudden death. Viral infections precipitated the illness in 85% of cases. Only 12% were initially suspected of having MCAD deficiency. Other initial diagnoses included Reye syndrome, SIDS, idiopathic hypoglycemia, and carnitine deficiency. There were 55 male and 65 female patients ranging from birth to 19 years of age; 118 were white. Twenty-three children died before the diagnosis was made, indicating that unidentified patients with this disorder have a risk of sudden death in early childhood. Furthermore, they found that survivors have a risk of developmental disability, chronic muscle weakness, failure to thrive, and 'cerebral palsy.' Among the sibs of the patients, 23 living sibs were found to be affected on screening and 14 had died. Five carrier parents had been symptomatic in childhood.
Ziadeh et al. (1995) reported the findings in a prospective neonatal screening program in Pennsylvania using tandem mass spectrometry. From the first 80,371 newborns screened, they found 9 babies with MCAD (1/8930), plus 2 additional newborns, screened because of a previously known family history. Molecular analysis showed that 56% of the patients were compound heterozygotes for the 985A-G mutation (K304E; 607008.0001), commonly referred to as G985, and a second mutation.
Clayton et al. (1998) reported their experience in diagnosing MCAD deficiency using the technique of electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of butylated carnitine species from dried blood spots. The authors concluded that if neonatal screening was undertaken at 7 to 10 days of age, this technique was both sensitive and specific and would therefore be suitable for a national neonatal screening program.
### Prenatal Diagnosis
Bennett et al. (1987) succeeded in prenatal diagnosis by demonstration of marked reduction in octanoate oxidation in cultured amniotic cells. The diagnosis was confirmed by enzyme assay of skin fibroblasts from the aborted fetus.
Clinical Management
In the family reported by Roe et al. (1986), early treatment with L-carnitine was important to the survivors. Breast feeding may be protective in MCAD deficiency. Treem et al. (1989) found that supplementation with carnitine was ineffective. They stressed that avoidance of fasting and prompt institution of glucose supplementation in situations when oral intake is interrupted remain the mainstays of therapy.
Molecular Genetics
In 9 patients with MCAD deficiency, Matsubara et al. (1990) found a 985A-G transition which resulted in a lys304-to-glu substitution (K304E; 607008.0001) in the mature protein. These patients were unrelated, suggesting a high incidence of this abnormality among Caucasian patients. The change was not found in 20 healthy Caucasian and 6 healthy Japanese subjects. Matsubara et al. (1990) found this point mutation in 31 of 34 (91%) mutant MCAD alleles. Yokota et al. (1992) estimated that 90% of MCAD cases involve the same mutation.
Andresen et al. (1997) determined the frequency of 14 known and 7 previously unknown non-G985 mutations in 52 families with MCAD deficiency not caused by homozygosity for the prevalent G985 mutation. They showed that none of the non-G985 mutations is prevalent. In 14 families in which they identified both disease-causing mutations, they correlated the mutations with clinical/biochemical data and found that a genotype/phenotype correlation in MCAD deficiency is not straightforward.
Zschocke et al. (2001) characterized the molecular defect in 4 patients with mild MCAD deficiency. In routine neonatal screening on the fifth day of life, they had been found to have abnormal acylcarnitine profiles indicative of MCAD deficiency. Two were of German origin and the other 2 were born to different consanguineous Turkish parents. In all 4, the clinical course and routine laboratory investigations up to the age of 6 months were unremarkable. Enzyme studies showed residual MCAD activities between those with classic MCAD deficiency and heterozygotes. In 2 cases, ACADM gene analysis revealed compound heterozygosity for the common K304E mutation (607008.0001) and the 199T-C mutation (Y42H; 607008.0011), which they designated Y67H. In the 2 children of consanguineous parents, homozygosity was found for the gly267-to-arg mutation (G267R; 607008.0003) and the S220L mutation (607008.0012), respectively. As in other metabolic disorders, the distinction between 'normal' and 'disease' in MCAD deficiency is blurred into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.
Genotype/Phenotype Correlations
Gregersen et al. (2001) reviewed the understanding of genotype-phenotype relationships in VLCAD, MCAD, and SCAD. They discussed both the structural implications of mutation type and the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. The realization that the effect of the monogene, such as disease-causing mutations in these 3 genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. They stated that the rapid development of mutation detection systems, such as chip technologies, made such profile analyses feasible.
Population Genetics
Pollitt and Leonard (1998) reported the findings of a prospective clinical study of MCAD deficiency in the UK. Between 1994 and 1996 there were 62 reported cases in 54 families, giving a minimum incidence of 4.5 in 100,000. In 46 cases, diagnosis followed an acute illness: 39 after a single episode, 6 after a second, and 1 after his third episode at the age of 12 years. The authors commented that the mortality and morbidity associated with MCAD deficiency remained high. Most patients have their first acute manifestation after the age of 3 months; this, the authors argued, supported the case for the introduction of a national neonatal screening program in the UK.
In a prospective tandem mass spectrometry screening of 930,078 blood spots from neonates in the U.S. population, Andresen et al. (2001) determined the frequency of MCAD deficiency to be 1 in 15,001. Mutation analysis showed that the MS/MS-based method is excellent for detection of MCAD deficiency. The frequency of the 985A-G (607008.0001) mutant allele in newborns with a positive acylcarnitine profile is much lower than that observed in clinically affected patients. They identified a new mutation, 199T-C (607008.0011), which had never been observed in patients with clinically manifest disease but was present in a large proportion of the acylcarnitine-positive samples. Overexpression experiments showed that 199T-C is a mild folding mutation that exhibits decreased levels of enzyme activity only under stringent conditions. A carrier frequency of 1 in 500 in the general population made the 199T-C mutation 1 of the 3 most prevalent mutations in the enzymes of fatty acid oxidation.
In a meta-regression analysis of 43 studies reporting the frequency of the c.985A-G mutation in over 10 million individuals, Leal et al. (2014) found significant variation in the frequency of the mutation across regions. The proportion of individuals homozygous for the mutation was highest in western Europe (4.1 per 100,000), followed by the New World, including the United States, Canada, and Australia (3.2), southern Europe (1.2), and eastern Europe (0.9). No cases with the mutation were identified in Asia or the Middle East. The findings were consistent with a founder effect originating in northern Europe.
INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Hepatomegaly \- Fatty infiltration of liver Gastrointestinal \- Vomiting NEUROLOGIC Central Nervous System \- Lethargy \- Seizures \- Coma \- Cerebral edema \- Developmental delay if undiagnosed or untreated \- Hypotonia METABOLIC FEATURES \- Absent to trace urine and plasma ketones \- Mild metabolic acidosis \- Hypoglycemia LABORATORY ABNORMALITIES \- Mildly elevated blood ammonia \- Increased liver enzymes \- Medium chain dicarboxylic aciduria \- Decreased plasma carnitine \- Acylglycinuria \- Deficiency of medium-chain acyl-CoA dehydrogenase MISCELLANEOUS \- Most common disorder of fatty acid oxidation (1/13,000 births) \- Clinical presentation varies from asymptomatic to fulminant course \- Onset precipitated by fasting or illness MOLECULAR BASIS \- Caused by mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene (ACADM, 607008.0001 ) ▲ 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
|
ACYL-CoA DEHYDROGENASE, MEDIUM-CHAIN, DEFICIENCY OF
|
c0220710
| 25,580 |
omim
|
https://www.omim.org/entry/201450
| 2019-09-22T16:31:28 |
{"doid": ["0080153"], "mesh": ["C536038"], "omim": ["201450"], "icd-10": ["E71.311"], "orphanet": ["42"], "synonyms": ["Alternative titles", "ACADM DEFICIENCY", "MCAD DEFICIENCY", "MCADH DEFICIENCY", "CARNITINE DEFICIENCY SECONDARY TO MEDIUM-CHAIN ACYL-CoA DEHYDROGENASE DEFICIENCY"], "genereviews": ["NBK1424"]}
|
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (commonly referred to as LBSL) is a progressive disorder that affects the brain and spinal cord. Leukoencephalopathy refers to abnormalities in the white matter of the brain, which is tissue containing nerve cell fibers (axons) that transmit nerve impulses.
Most affected individuals begin to develop movement problems during childhood or adolescence. However, in some individuals, these problems do not develop until adulthood. People with LBSL have abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). In addition, affected individuals lose the ability to sense the position of their limbs or vibrations with their limbs. These movement and sensation problems affect the legs more than the arms, making walking difficult. Most affected individuals eventually require wheelchair assistance, sometimes as early as their teens, although the age varies.
People with LBSL can have other signs and symptoms of the condition. Some affected individuals develop recurrent seizures (epilepsy), speech difficulties (dysarthria), learning problems, or mild deterioration of mental functioning. Some people with this disorder are particularly vulnerable to severe complications following minor head trauma, which may trigger a loss of consciousness, other reversible neurological problems, or fever.
Distinct changes in the brains of people with LBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve particular parts of the white matter of the brain and specific regions (called tracts) within the brainstem and spinal cord, especially the pyramidal tract and the dorsal column. In addition, most affected individuals have a high level of a substance called lactate in the white matter of the brain, which is identified using another test called magnetic resonance spectroscopy (MRS).
## Frequency
LBSL is a rare condition. Its exact prevalence is not known.
## Causes
LBSL is caused by mutations in the DARS2 gene, which provides instructions for making an enzyme called mitochondrial aspartyl-tRNA synthetase. This enzyme is important in the production (synthesis) of proteins in cellular structures called mitochondria, the energy-producing centers in cells. While most protein synthesis occurs in the fluid surrounding the nucleus (cytoplasm), some proteins are synthesized in the mitochondria.
During protein synthesis, in either the mitochondria or the cytoplasm, building blocks (amino acids) are connected together in a specific order, creating a chain of amino acids that forms the protein. Mitochondrial aspartyl-tRNA synthetase plays a role in adding the amino acid aspartic acid at the proper place in mitochondrial proteins.
Mutations in the DARS2 gene result in decreased mitochondrial aspartyl-tRNA synthetase enzyme activity, which hinders the addition of aspartic acid to mitochondrial proteins. It is unclear how the gene mutations lead to the signs and symptoms of LBSL. Researchers do not understand why reduced activity of mitochondrial aspartyl-tRNA synthetase specifically affects certain parts of the brain and spinal cord.
### Learn more about the gene associated with Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation
* DARS2
## Inheritance Pattern
LBSL is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In this condition, each copy of the gene carries a different mutation (compound heterozygous mutations). An affected individual never has the same mutation in both copies of the gene (a homozygous mutation). 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
|
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation
|
c1970180
| 25,581 |
medlineplus
|
https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation/
| 2021-01-27T08:25:08 |
{"gard": ["12652"], "mesh": ["C567009"], "omim": ["611105"], "synonyms": []}
|
Epiphyseal dysplasia-hearing loss-dysmorphism syndrome is a rare multiple congenital anomalies/dysmorphic syndrome characterized by developmental delay, intellectual disability, short stature, sensorineural hearing impairment, facial dysmorphism (incl. epicanthus, broad, depressed nasal bridge, broad, fleshy nasal tip, mildly anteverted nares, deep nasolabial folds, broad mouth with thin upper lip) and skeletal anomalies (incl. abnormally placed thumbs, brachydactyly, scoliosis, dysplastic carpal bones). Patients also present severe behavior disturbances (aggression, hyperactivity), as well as hypopigmented skin lesions and hypoplastic digital patterns. There have been no further descriptions in the literature since 1992.
*[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
|
Epiphyseal dysplasia-hearing loss-dysmorphism syndrome
|
None
| 25,582 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1825
| 2021-01-23T18:41:19 |
{"gard": ["2178"], "icd-10": ["Q87.0"], "synonyms": ["Epiphyseal dysplasia-deafness-dysmorphism syndrome", "Finucane-Kurtz-Scott syndrome"]}
|
A very rare congenital genetic neurological disorder characterized by agenesis/hypoplasia of corpus callosum with developmental abnormalities, ocular disorders, and variable craniofacial and skeletal abnormalities.
## Epidemiology
The syndrome is a rare and has been reported in more than 7 families to date, representing 56 affected individuals. While generally considered a rare disease, one large cohort of Arab patients (1000 individuals) suggested that start codon mutations in C12ORF57 alone accounts for 1.5% of all cases of intellectual disability, a contribution that rivals that of the much more familiar Fragile‐X syndrome and would make it the single most common cause of recessive intellectual disability/developmental delay in Saudi Arabia. Most affected families are of Middle-Eastern Arab descent, specifically Saudi Arabian. Most reported families have multiplex cases of Temtamy syndrome and almost all are from consanguineous unions. Male and female patients have been reported.
## Clinical description
.Age of onset is generally in the neonatal period and in infancy. The manifestations of Temtamy syndrome are variable. The main clinical findings are dysmorphic facies (including elongated face, hypertelorism, prominent nose, low-set ears, and micrognathia), hypotonia, moderate to severe intellectual disability, intractable seizures and autistic features such as absent language or stereotypy. Motor and cognitive delay usually manifests in early childhood. Skeletal anomalies may include brachydactyly of the hands and feet, genu vara, and pes planus. Visual abnormalities include microphthalmia, coloboma of iris, esotropia, and optic atrophy, sometimes leading to progressive loss of vision. Atrial septal defect was also found in some patients. Involvement of other systems was not reported.
## Etiology
The pathogenesis of Temtamy syndrome is not known. Various mutations (homozygous, missense, compound heterozygous) in the C12ORF57 gene (12p13.31) have been reported in affected patients. The gene is of unknown function but appears to be required for development of the corpus callosum and the eye. It is expressed primarily in the neurological, visual, and cardiovascular systems. In vitro cellular expression studies indicated that the mutation decreased protein synthesis suggesting the lost-of-function mechanism and phenotypic variability.
## Diagnostic methods
Diagnosis is based on the specific constellation of clinical signs and brain imaging. Brain magnetic resonance imaging (MRI) of affected patients has shown aplasia, thickening, or hypoplasia of the corpus callosum, thalamic hypoplasia, and rarely colpocephaly.
## Differential diagnosis
Differential diagnoses include muscle-eye-brain disease, Peters-plus, Walker-Warburg, Aicardi, Donnai-Barrow, and Baraitser-Winter syndromes.
## Genetic counseling
Temtamy syndrome follows an autosomal recessive pattern of inheritance. Genetic counseling should be offered to affected families.
## Management and treatment
Currently, management of the disease is symptomatic.
## Prognosis
Prognosis and quality of life depend on the severity of disease manifestations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
|
Temtamy syndrome
|
c1857512
| 25,583 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1777
| 2021-01-23T17:46:36 |
{"gard": ["5688"], "mesh": ["C536959"], "omim": ["218340"], "umls": ["C1857512"], "icd-10": ["Q87.8"], "synonyms": ["Craniofacial dysmorphism-coloboma-corpus callosum agenesis syndrome", "Temtamy-Shalash syndrome"]}
|
A number sign (#) is used with this entry because of evidence that one form of autosomal recessive spondyloepimetaphyseal dysplasia is caused by homozygous mutation in the matrilin-3 gene (MATN3; 602109) on chromosome 2p24. One such family has been reported.
Clinical Features
Borochowitz et al. (2004) described a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia. Affected individuals presented with disproportionate early-onset dwarfism, bowing of the lower limbs, lumbar lordosis, and normal hands. Skeletal findings included short, wide, and stocky long bones with severe epiphyseal and metaphyseal changes, hypoplastic iliac bones, and flat, ovoid vertebral bodies.
Molecular Genetics
In affected members of a consanguineous Arab family segregating SEMD, Borochowitz et al. (2004) identified homozygosity for a cys304-to-ser mutation in the MATN3 gene (602109.0005). Heterozygotes in the family had no clinical or radiographic abnormalities.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short-limb dwarfism CHEST External Features \- Small chest Ribs Sternum Clavicles & Scapulae \- Posterior rib cupping SKELETAL Spine \- Lumbar hyperlordosis \- Flat oval-shaped vertebral bodies Pelvis \- Flat acetabular roof \- Hypoplastic pubic bones \- Underossified ischia \- Dysplastic iliac wings \- Narrow iliac wings Limbs \- Bowed legs \- Short limbs \- Limited elbow extension \- Short, tubular bones \- Wide metaphyses with lateral spurs \- Irregular, small epiphyses MISCELLANEOUS \- Allelic to multiple epiphyseal dysplasia, type 5 ( 607078 ) and hand osteoarthritis ( 607850 ) \- Waddling gait MOLECULAR BASIS \- Caused by mutations in the matrilin 3 gene (MATN3, 602109.0005 ) ▲ 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
|
SPONDYLOEPIMETAPHYSEAL DYSPLASIA, MATRILIN-3 RELATED
|
c1837481
| 25,584 |
omim
|
https://www.omim.org/entry/608728
| 2019-09-22T16:07:19 |
{"mesh": ["C563869"], "omim": ["608728"], "orphanet": ["156728"], "synonyms": ["Alternative titles", "SEMD, MATN3-RELATED"]}
|
Lumbar disc disease
Lumbar disc
Lumbar disc disease is the drying out of the spongy interior matrix of an intervertebral disc in the spine. Many physicians and patients use the term lumbar disc disease to encompass several different causes of back pain or sciatica. In this article, the term is used to describe a lumbar herniated disc. It is thought that lumbar disc disease causes about one-third of all back pain.
## Contents
* 1 Symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Symptoms[edit]
Pain, loss of muscle strength and loss of touch sensation may occur if this herniation causes the compression of the most proximal part of the nerve closely neighbouring the intervertebral disc material. Pain is in the distribution of the nerve compressed, usually down the back of the leg, side of the calf and inside of the foot (sciatica). Most commonly, the nerve root between the fourth and fifth lumbar vertebrae or between the fifth lumbar vertebra and first sacral segment are impinged.[citation needed]
In symptomatic cases the diagnosis should be confirmed by an MRI scan. However, in cases with slight symptoms, a faster and cheaper CT scan (although it is inferior to MRI scan) may be recommended. While a CT scan can show the bony structures in more detail, an MRI scan can better portray soft tissue.[citation needed]
## Genetics[edit]
An inheritable gene variation may cause increased susceptibility. People with a variation in a gene that encodes the cartilage intermediate-layer protein (CILP) were 1.6 times more likely to have the disease than persons without the variation.[1] CILP is a normal component of disc tissue. The gene variant was hypothesized to disrupt normal building and maintenance of cartilage. However, this association was not replicated in a follow-up study of Finnish and Chinese individuals.[2]
## Diagnosis[edit]
Diagnosis can be made on clinical basis with MRI findings[citation needed]
## Treatment[edit]
Initial treatment in lumbar disc disease is one or two days of bedrest (although growing number of studies shows that it makes little difference) and pain relieving medications. In cases with ongoing pain despite conservative treatments, a surgical operation that will remove the compressing disc material, a microdiscectomy or discectomy may be recommended to treat a lumbar disc herniation.[citation needed]
## See also[edit]
* Degenerative disc disease
* Sciatica
* Spinal disc herniation
* Lumbar spinal stenosis
## References[edit]
1. ^ Seki, S; Kawaguchi, Y; Chiba, K; Mikami, Y; Kizawa, H; Oya, T; Mio, F; Mori, M; Miyamoto, Y; Masuda, I; Tsunoda, T; Kamata, M; Kubo, T; Toyama, Y; Kimura, T; Nakamura, Y; Ikegawa, S (2005). "A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease". Nature Genetics. 37 (6): 607–12. doi:10.1038/ng1557. PMID 15864306.
2. ^ Virtanen, I. M.; Song, Y. Q.; Cheung, K. M.; Ala-Kokko, L; Karppinen, J; Ho, D. W.; Luk, K. D.; Yip, S. P.; Leong, J. C.; Cheah, K. S.; Sham, P; Chan, D (2007). "Phenotypic and population differences in the association between CILP and lumbar disc disease". Journal of Medical Genetics. 44 (4): 285–8. doi:10.1136/jmg.2006.047076. PMC 2598035. PMID 17220213.
* Seki S, Andrews C, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S (2005). "A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease". Nature Genetics. 37 (6): 607–612. doi:10.1038/ng1557. PMID 15864306.
## External links[edit]
* E-medicine - Lumbar disc disease
Classification
D
* ICD-10: M51.9
*[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
|
Lumbar disc disease
|
c0221775
| 25,585 |
wikipedia
|
https://en.wikipedia.org/wiki/Lumbar_disc_disease
| 2021-01-18T18:47:02 |
{"mesh": ["C535531"], "wikidata": ["Q6703059"]}
|
A rare syndromic trigonocephaly characterized by marked malformations of the head and face (essentially acrocephaly), broad depressed nasal bridge, narrow maxillae, abnormalities of the hands and feet (polydactyly, brachydactyly, syndactyly, clinodactyly, camptodactyly, ulnar deviation), obesity and congenital heart disease. This disease is considered a variant of Carpenter syndrome without intellectual disabaility. There have been no further descriptions in the literature since 1992.
*[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
|
Summitt syndrome
|
c1802405
| 25,586 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3210
| 2021-01-23T16:55:16 |
{"gard": ["127"], "mesh": ["C538142"], "omim": ["272350"], "umls": ["C1802405"], "icd-10": ["Q82.0"]}
|
Chronic Somogyi rebound is a contested explanation of phenomena of elevated blood sugars in the morning. Also called the Somogyi effect and posthypoglycemic hyperglycemia, it is a rebounding high blood sugar that is a response to low blood sugar.[1] When managing the blood glucose level with insulin injections, this effect is counter-intuitive to people who experience high blood sugar in the morning as a result of an overabundance of insulin at night.
This theoretical phenomenon was named after Michael Somogyi, a Hungarian-born professor of biochemistry at the Washington University and Jewish Hospital of St. Louis, who prepared the first insulin treatment given to a child with diabetes in the USA in October 1922.[2] Somogyi showed that excessive insulin makes diabetes unstable and first published his findings in 1938.[3]
Compare with the dawn phenomenon, which is a morning rise in blood sugar in response to waning insulin and a growth hormone surge (that further antagonizes insulin).
## Contents
* 1 Background
* 2 Detection
* 3 Avoidance
* 4 Controversy
* 5 See also
* 6 References
## Background[edit]
The rebounding blood sugar following undetected diabetic hypoglycemia can easily become chronic when the high morning blood sugar data is misjudged to be due to insufficient nighttime insulin delivery.
A person with type 1 diabetes should balance insulin delivery to manage their blood glucose level. Occasionally, insufficient insulin can result in hyperglycemia. The appropriate response is to take a correction dose of insulin to reduce the blood sugar level and to consider adjusting the insulin regimen to deliver additional insulin in the future to prevent hyperglycemia. Conversely, excessive insulin delivery may result in hypoglycemia. The appropriate response is to treat the hypoglycemia and to consider adjusting the regimen to reduce insulin in the future.
Somogyi and others[4] have claimed that if prolonged hypoglycemia is untreated, then stress due to low blood sugar can result in a high blood glucose rebound. The physiological mechanisms driving the rebound are defensive. When the blood glucose level falls below normal, the body responds by releasing the endocrine hormone glucagon as well as the stress hormones epinephrine, cortisol and growth hormone. Glucagon facilitates release of glucose from the liver that raises the blood glucose immediately; the stress hormones cause insulin resistance for several hours, sustaining the elevated blood sugar.
## Detection[edit]
The first line of defense in preventing chronic Somogyi rebound is additional blood glucose testing. Continuous glucose monitoring is the preferred method to detect and prevent the Somogyi rebound, but this technology is far from universally used. Alternatively, testing blood sugar more often, 8 to 10 times daily with a traditional blood glucose meter, facilitates detecting the low blood sugar level before such a rebound occurs.
Testing occasionally during the middle of the night is also important, particularly when high waking blood sugars are found, to determine if more insulin is needed to prevent hyperglycemia or if less insulin is needed to prevent such a rebound.
Sometimes a person with diabetes will experience the Somogyi rebound when awake and notice symptoms of the initial low blood sugar or symptoms of the rebound. Waking with a night sweat (perhaps combined with a rapid heart rate) is a symptom of the adrenaline and rebound. Unfortunately, the evidence shows that patients with type 1 diabetes do not normally wake during nocturnal hypoglycemic episodes.[5]
While reviewing log data of blood glucose after the fact, signs of Somogyi rebound should be suspected when blood glucose numbers seem higher after the insulin dosage has been raised, particularly in the morning. One simple way to determine if nocturnal hypoglycemia may be causing morning hyperglycemia is to have the patient have a high protein snack with a small amount of carbohydrates at bedtime. This will help keep the blood sugar up overnight and prevent the Somogyi effect. If the morning blood sugar decreases, this is indicative of the Somogyi effect and the daily insulin should be decreased.
## Avoidance[edit]
In theory, avoidance is simply a matter of preventing hyperinsulinemia. In practice, the difficulty for a diabetic person to aggressively dose insulin to keep blood sugars levels close to normal — while adjusting the insulin regimen to the demands of exercise, stress, and wellness — can practically assure occasional hyperinsulinemia. The pharmacokinetic imperfections of all insulin replacement regimens is a severe limitation.
Some practical behaviors which are useful in avoiding chronic Somogyi rebound are:
* frequent blood glucose monitoring (8–10 times daily);
* continuous blood glucose monitoring;
* logging and review of blood glucose values, searching for patterns of low blood sugar values;
* conservative increases in insulin delivery;
* awareness to the signs of hypoglycemia;
* awareness to hyperglycemia in response to increased delivery of insulin;
* use of appropriate types of insulin (long-acting, short-acting, etc.) in appropriate amounts.
## Controversy[edit]
Although this hypothesis is well known among clinicians and individuals with diabetes, there is little scientific evidence to support it. Clinical studies indicate that a high fasting glucose in the morning is more likely because the insulin given on the previous evening fails to last long enough.[6] A study published in 2007 using continuous glucose monitoring showed that a low glucose during the night (nocturnal hypoglycemia) can be highly prevalent in type 1 diabetic treatments, but is associated rather with morning hypoglycemia, not hyperglycemia.[7] Furthermore, many individuals with hypoglycemic episodes during the night don't wake due to a failure of release of epinephrine during nocturnal hypoglycemia.[8] Thus, Somogyi's hypothesis is not assured and may be refuted.
## See also[edit]
* Idiopathic postprandial syndrome
* Reactive hypoglycemia
## References[edit]
1. ^ http://www.ucdenver.edu/academics/colleges/medicalschool/centers/BarbaraDavis/Documents/book-understandingdiabetes/ud06.pdf, Understanding Diabetes a.k.a. The Pink Panther Book by H. Peter Chase, chapter 6 page 47.
2. ^ Michael Somogyi (www.whonamedit.com)
3. ^ Somogyi, M; Kirstein, M (1938). "Insulin as a cause of extreme hyperglycemia and instability". Weekly Bulletin of the St Louis Medical Society. 32: 498–510. hdl:2027/uc1.$b721522. OCLC 11637296.
(As of 2011-05-28, the electronic text is not open access).
4. ^ Gerich, J. E. (1988). "Lilly lecture 1988. Glucose counterregulation and its impact on diabetes mellitus". Diabetes. 37 (12): 1608–17. doi:10.2337/diabetes.37.12.1608. PMID 3056759.
5. ^ Schultes, Bernd; Jauch-Chara, Kamila; Gais, Steffen; Hallschmid, Manfred; Reiprich, Eva; Kern, Werner; Oltmanns, Kerstin M.; Peters, Achim; Fehm, Horst L.; Born, Jan (2007). "Defective Awakening Response to Nocturnal Hypoglycemia in Patients with Type 1 Diabetes Mellitus". PLOS Medicine. 4 (2): e69. doi:10.1371/journal.pmed.0040069. PMC 1808097. PMID 17326710.
6. ^ Gale EA, Kurtz AB, Tattersall RB (August 1980). "In search of the Somogyi effect". Lancet. 2 (8189): 279–82. doi:10.1016/s0140-6736(80)90233-0. PMID 6105438. S2CID 9371847.CS1 maint: multiple names: authors list (link)
7. ^ Guillod L, Comte-Perret S, Monbaron D, Gaillard RC, Ruiz J (November 2007). "Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?" (PDF). Diabetes Metab. 33 (5): 360–5. doi:10.1016/j.diabet.2007.03.007. PMID 17652003.CS1 maint: multiple names: authors list (link)
8. ^ Matyka KA, Crowne EC, Havel PJ, Macdonald IA, Matthews D, Dunger DB (July 1999). "Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes". Diabetes Care. 22 (7): 1144–50. doi:10.2337/diacare.22.7.1144. PMID 10388980.CS1 maint: multiple names: authors list (link)
Michael Cooperman, MD; Chief Editor: George T Griffing, MD. Somogyi Phenomenon. Medscape Dec 15, 2011.
*[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
|
Chronic Somogyi rebound
|
None
| 25,587 |
wikipedia
|
https://en.wikipedia.org/wiki/Chronic_Somogyi_rebound
| 2021-01-18T18:29:24 |
{"wikidata": ["Q1467170"]}
|
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-20 (COXPD20) is caused by homozygous or compound heterozygous mutation in the VARS2 gene (612802) on chromosome 6p21.
For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Clinical Features
Taylor et al. (2014) reported a 10-year-old British boy who presented in the first year of life with muscle weakness and hypotonia and later developed central neurologic disease, including progressive external ophthalmoplegia, ptosis, and ataxia. Further clinical details were not provided. Biochemical studies on patient cells showed a deficiency of mitochondrial respiratory complexes I and IV. Muscle biopsy was mosaic for COX-positive fibers.
Diodato et al. (2014) reported a boy with delayed psychomotor development, facial dysmorphism, and microcephaly that became apparent soon after birth. He never achieved independent ambulation. At age 4 years, he developed seizures and myoclonic jerks. Brain MRI showed hyperintense lesions in the periventricular region, insulae, and right frontotemporal cortex. Muscle biopsy was histologically normal, but muscle homogenate showed isolated complex I deficiency (25% residual activity). Patient fibroblasts showed no enzymatic defects, but oxygen consumption was impaired, suggesting defective mitochondrial respiration.
Inheritance
The transmission pattern of COXPD20 in the family reported by Diodato et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a British boy with COXPD20, Taylor et al. (2014) identified compound heterozygous missense mutations in the VARS2 gene (612802.0001 and 612802.0002). The mutations were found by whole-exome sequencing. The patient was part of a larger study of 53 patients with mitochondrial respiratory chain complex deficiencies who underwent whole-exome sequencing. Functional studies of the variants were not performed.
In a boy with a mitochondrial encephalomyopathy, Diodato et al. (2014) identified a homozygous missense mutation in the VARS2 gene (612802.0003). Patient cells showed decreased amounts of tRNA-Val, and introduction of wildtype VARS2 rescued the mitochondrial biochemical defects. Studies in yeast also confirmed the deleterious effect of the mutation.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (1 patient) Face \- Facial dysmorphism (1 patient) Eyes \- Ptosis (1 patient) \- Progressive external ophthalmoplegia (1 patient) MUSCLE, SOFT TISSUES \- Hypotonia \- Mitochondrial complex I deficiency \- Muscle biopsy may show deficiency of multiple mitochondrial respiratory complexes NEUROLOGIC Central Nervous System \- Delayed psychomotor development (1 patient) \- Seizures (1 patient) \- Ataxia (1 patient) \- White matter abnormalities in the periventricular regions (1 patient) MISCELLANEOUS \- Onset in infancy \- Variable features \- Two unrelated patients have been reported (last curated July 2014) MOLECULAR BASIS \- Caused by mutation in the valyl-tRNA synthetase 2 gene (VARS2, 612802.0001 ) ▲ 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
|
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20
|
c4014660
| 25,588 |
omim
|
https://www.omim.org/entry/615917
| 2019-09-22T15:50:43 |
{"doid": ["0060286"], "omim": ["615917"], "orphanet": ["420728"], "synonyms": ["COXPD20"]}
|
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: "Acute decompensated heart failure" – news · newspapers · books · scholar · JSTOR (January 2016) (Learn how and when to remove this template message)
Heart failure
Acute interstitial pulmonary edema. Note enlarged heart size, apical vascular redistribution ( circle ), and small bilateral pleural effusions ( arrow ).
SpecialtyCardiology
Acute decompensated heart failure (ADHF) is a sudden worsening of the signs and symptoms of heart failure, which typically includes difficulty breathing (dyspnea), leg or feet swelling, and fatigue.[1] ADHF is a common and potentially serious cause of acute respiratory distress. The condition is caused by severe congestion of multiple organs by fluid that is inadequately circulated by the failing heart. An attack of decompensation can be caused by underlying medical illness, such as myocardial infarction, an abnormal heart rhythm, infection, or thyroid disease.
Treatment consists of reducing the fluid level with diuretics and improving heart function with nitrates, or levosimendan; other treatments such as aquapheresis ultra-filtration may also be required.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 4.1 Oxygen
* 4.2 Medication
* 4.2.1 Vasodilators
* 4.2.2 Diuretics
* 4.2.3 Others
* 4.3 Ventilation
* 4.4 Ultrafiltration
* 4.5 Surgery
* 5 References
* 6 External links
## Signs and symptoms[edit]
Difficulty breathing, a cardinal symptom of left ventricular failure, may manifest with progressively increasing severity as the following:
* Difficulty breathing with physical activity (exertional dyspnea)
* Difficulty breathing while lying flat (orthopnea)
* Episodes of waking up from sleep gasping for air (paroxysmal nocturnal dyspnea)
* Acute pulmonary edema
Other cardiac symptoms of heart failure include chest pain/pressure and palpitations. Common noncardiac signs and symptoms of heart failure include loss of appetite, nausea, weight loss, bloating, fatigue, weakness, low urine output, waking up at night to urinate, and cerebral symptoms of varying severity, ranging from anxiety to memory impairment and confusion.[2]
## Causes[edit]
Chronic stable heart failure may easily decompensate. This most commonly results from an intercurrent illness (such as pneumonia), myocardial infarction (a heart attack), abnormal heart rhythms (such as atrial fibrillation), uncontrolled high blood pressure, or the person's failure to maintain a fluid restriction, diet, or medication.[3] Other well recognized precipitating factors include anemia and hyperthyroidism which place additional strain on the heart muscle. Excessive fluid or salt intake, and medication that causes fluid retention such as NSAIDs and thiazolidinediones, may also precipitate decompensation.[4]
Acute myocardial infarction can precipitate acute decompensated heart failure and will necessitate emergent revascularization with thrombolytics, percutaneous coronary intervention, or coronary artery bypass graft.
## Diagnosis[edit]
A man with congestive heart failure and marked jugular venous distension. External jugular vein marked by an arrow.
Pedal edema during and after the application of pressure to the skin.
A jugular venous distension is the most sensitive clinical sign for acute decompensation.[5]
## Treatment[edit]
In acute decompensated heart failure, the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that airway, breathing, and circulation are adequate. Management consists of propping up the head of the patient, giving oxygen to correct hypoxemia, administering morphine, diuretics like furosemide, addition of an ACE inhibitor, use of nitrates and use of digoxin if indicated for the heart failure and if arrhythmic.[6]
### Oxygen[edit]
Supplemental oxygen may be administered if blood levels of oxygen are low; the Heart Failure Society of America, however, has recommended that it not be used routinely.[6]
### Medication[edit]
Initial therapy of acute decompensated heart failure usually includes some combination of a vasodilator such as nitroglycerin, a loop diuretic such as furosemide, and non-invasive positive pressure ventilation (NIPPV).
Even if symptoms of heart failure are not present, medications can be used to treat the symptoms that are being experienced. These medicines work to control these symptoms as well as treat other health problems that might be present. They can work to improve the quality of life, slow down the progression of heart failure and reduce the risk for other complications that can occur due to heart failure. It is very important to take proper medicines exactly as prescribed by the physician.
A number of different medications are required for people who are experiencing heart failure. Common types of medications that are prescribed for heart failure patients include ACE inhibitors, vasodilators, beta blockers, aspirin, calcium channel blockers, and cholesterol lowering medications such as statins. Depending on the type of damage a patient has suffered and the underlying cause of the heart failure, any of these drug classes or a combination of them can be prescribed. Patients with heart pumping problems will use a different medication combination than those who are experiencing problems with the heart's ability to fill properly during diastole. Potentially dangerous drug interactions can occur when different drugs mix together and work against each other.[7]
#### Vasodilators[edit]
Nitrates such as nitroglycerin are often used as part of the initial therapy for ADHF.
Another option is nesiritide, although it should only be considered if conventional therapy has been ineffective or contraindicated as it is much more expensive than nitroglycerine and has not been shown to be of any greater benefit.
#### Diuretics[edit]
Heart failure is usually associated with a volume overloaded state. Therefore, those with evidence of fluid overload should be treated initially with intravenous loop diuretics. In the absence of symptomatic low blood pressure intravenous nitroglycerin is often used in addition to diuretic therapy to improve congestive symptoms.[6]
Volume status should still be adequately evaluated. Some heart failure patients on chronic diuretics can undergo excessive diuresis. In the case of diastolic dysfunction without systolic dysfunction, fluid resuscitation may, in fact, improve circulation by decreasing heart rate, which will allow the ventricles more time to fill. Even if the patient is edematous, fluid resuscitation may be the first line of treatment if the person's blood pressure is low. The person may, in fact, have too little fluid in their blood vessels, but if the low blood pressure is due to cardiogenic shock, the administration of additional fluid may worsen the heart failure and associated low blood pressure. If the person's circulatory volume is adequate but there is persistent evidence of inadequate end-organ perfusion, inotropes may be administered. In certain circumstances, a left ventricular assist device (LVAD) may be necessary.
Once the person is stabilized, attention can be turned to treating pulmonary edema to improve oxygenation. Intravenous furosemide is generally the first line. However, people on long-standing diuretic regimens can become tolerant, and dosages must be progressively increased. If high doses of furosemide are inadequate, boluses or continuous infusions of bumetanide may be preferred. These loop diuretics may be combined with thiazide diuretics such as oral metolazone or intravenous chlorothiazide for a synergistic effect. Intravenous preparations are physiologically preferred because of more predictable absorption due to intestinal edema, however, oral preparations can be significantly more cost effective.[8]
#### Others[edit]
ACE inhibitors and ARBs
The effectiveness and safety of ACE inhibitors and angiotensin receptor blockers acutely in ADHF have not been well studied, but are potentially harmful. A person should be stabilized before therapy with either of these medication classes is initiated.[9] Individuals with poor kidney perfusion are especially at risk for kidney impairment inherent with these medications.[10]
Beta-blockers
Beta-blockers are stopped or decreased in people with acutely decompensated heart failure and a low blood pressure. However, continuation of beta-blockers may be appropriate if the blood pressure is adequate.[11]
Inotropic agents
Inotropes are indicated if low blood pressure ( SBP < 90 mmHg ) is present.
Opioids
Opioids have traditionally been used in the treatment of the acute pulmonary edema that results from acute decompensated heart failure. A 2006 review, however, found little evidence to support this practice.[12]
### Ventilation[edit]
Continuous positive airway pressure may be applied using a face mask; this has been shown to improve symptoms more quickly than oxygen therapy alone,[13] and has been shown to reduce the risk of death.[14][15] Severe respiratory failure requires treatment with endotracheal intubation and mechanical ventilation.
### Ultrafiltration[edit]
Ultrafiltration can be used to remove fluids in people with ADHF associated with kidney failure. Studies have found that it decreases health care utilization at 90 days.[16]
### Surgery[edit]
Certain scenarios will require emergent consultation with cardiothoracic surgery. Heart failure due to acute aortic regurgitation is a surgical emergency associated with high mortality. Heart failure may occur after rupture of ventricular aneurysm. These can form after myocardial infarction. If it ruptures on the free wall, it will cause cardiac tamponade. If it ruptures on the intraventricular septum, it can create a ventricular septal defect. Other causes of cardiac tamponade may also require surgical intervention, although emergent treatment at the bedside may be adequate. It should also be determined whether the patient had a history of a repaired congenital heart disease as they often have complex cardiac anatomy with artificial grafts and shunts that may sustain damage, leading to acute decompensated heart failure.
In some cases, doctors recommend surgery to treat the underlying problem that led to heart failure.[17] Different procedures are available depending on the level of necessity and include coronary artery bypass surgery, heart valve repair or replacement, or heart transplantation. During these procedures, devices such as heart pumps, pacemakers, or defibrillators might be implanted. The treatment of heart disease is rapidly changing and thus new therapies for acute heart failure treatment are being introduced to save more lives from these massive attacks.[18]
Bypass surgery is performed by removing a vein from the arm or leg, or an artery from the chest and replacing the blocked artery in the heart. This allows the blood to flow more freely through the heart. Valve repair is where the valve that is causing heart failure is modified by removing excess valve tissues that cause them to close too tightly. In some cases, annuloplasty is required to replace the ring around the valves. If the repair of the valve is not possible, it is replaced by an artificial heart valve. The final step is heart replacement. When severe heart failure is present and medicines or other heart procedures are not effective, the diseased heart needs to be replaced.
Another common procedure used to treat heart failure patients is an angioplasty. Is a procedure used to improve the symptoms of coronary artery disease (CAD), reduce the damage to the heart muscle after a heart attack, and reduce the risk of death in some patients.[19] This procedure is performed by placing a balloon in the heart to open an artery that is blocked by atherosclerosis or a buildup of plaque on the artery walls. People who are experiencing heart failure because of CAD or recent heart attack can benefit from this procedure.
A pacemaker is a small device that's placed in the chest or abdomen to help control abnormal heart rhythms.[20] They work by sending electric pulses to the heart to prompt it to beat at a rate that is considered to be normal and are used to treat patients with arrhythmias. They can be used to treat hearts that are classified as either a tachycardia that beats too fast, or a bradycardia that beats too slow.
## References[edit]
1. ^ Allen LA, O'Connor CM (13 March 2007). "Management of acute decompensated heart failure". CMAJ. 176 (6): 797–805. doi:10.1503/cmaj.051620. PMC 1808524. PMID 17353535.
2. ^ Heart Failure~clinical at eMedicine
3. ^ Fonarow GC, Abraham WT, Albert NM, et al. (April 2008). "Factors Identified as Precipitating Hospital Admissions for Heart Failure and Clinical Outcomes: Findings From OPTIMIZE-HF". Arch. Intern. Med. 168 (8): 847–54. doi:10.1001/archinte.168.8.847. PMID 18443260.
4. ^ Nieminen MS, Böhm M, Cowie MR, et al. (February 2005). "Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology". Eur. Heart J. 26 (4): 384–416. doi:10.1093/eurheartj/ehi044. PMID 15681577.
5. ^ Torres M, Moayedi S (May 2007). "Evaluation of the acutely dyspneic elderly patient". Clin. Geriatr. Med. 23 (2): 307–25, vi. doi:10.1016/j.cger.2007.01.007. PMID 17462519.
6. ^ a b c Heart Failure Society Of America (February 2006). "Evaluation and management of patients with acute decompensated heart failure". J. Card. Fail. 12 (1): e86–e103. doi:10.1016/j.cardfail.2005.11.017. PMID 16500576. Archived from the original on 2008-11-04. Retrieved 2008-12-06.
7. ^ Medications Commonly Used to Treat Heart Failure American Heart Association. Retrieved on 2010-01-22
8. ^ Lau, Brandyn D.; Pinto, Brian L.; Thiemann, David R.; Lehmann, Christoph U. (November 2011). "Budget Impact Analysis of Conversion from Intravenous to Oral Medication When Clinically Eligible for Oral Intake". Clinical Therapeutics. 33 (11): 1792–96. doi:10.1016/j.clinthera.2011.09.030. PMID 22001356.
9. ^ Gheorghiade M, Zannad F, Sopko G, et al. (December 2005). "Acute heart failure syndromes: current state and framework for future research". Circulation. 112 (25): 3958–68. doi:10.1161/CIRCULATIONAHA.105.590091. PMID 16365214.
10. ^ Valika, AA; Gheorghiade, M (Mar 2013). "Ace inhibitor therapy for heart failure in patients with impaired renal function: a review of the literature". Heart Failure Reviews. 18 (2): 135–40. doi:10.1007/s10741-011-9295-6. PMID 22213014. S2CID 44617135.
11. ^ Jondeau G, Neuder Y, Eicher JC, et al. (September 2009). "B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode". Eur. Heart J. 30 (18): 2186–92. doi:10.1093/eurheartj/ehp323. PMID 19717851.
12. ^ "BestBets: Does the application of opiates, during an attack of Acute Cardiogenic Pulmonary Oedema, reduce patients' mortality and morbidity?". Retrieved December 6, 2008.
13. ^ Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J (July 2008). "Noninvasive ventilation in acute cardiogenic pulmonary edema". N. Engl. J. Med. 359 (2): 142–51. doi:10.1056/NEJMoa0707992. PMID 18614781.
14. ^ Peter JV, Moran JL, Phillips-Hughes J, Graham P, Bersten AD (April 2006). "Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis". Lancet. 367 (9517): 1155–63. doi:10.1016/S0140-6736(06)68506-1. PMID 16616558. S2CID 21490309.
15. ^ Weng CL, Zhao YT, Liu QH, et al. (May 2010). "Meta-analysis: Noninvasive ventilation in acute cardiogenic pulmonary edema". Ann. Intern. Med. 152 (9): 590–600. doi:10.7326/0003-4819-152-9-201005040-00009. PMID 20439577. S2CID 207535976.
16. ^ Costanzo MR, Guglin ME, Saltzberg MT, et al. (February 2007). "Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure". J. Am. Coll. Cardiol. 49 (6): 675–83. doi:10.1016/j.jacc.2006.07.073. PMID 17291932.
17. ^ Treatments and drugs for Heart Failure Mayo Clinic. Retrieved on 2010-01-22
18. ^ Acute Heart Failures Definition And Management Archived 2010-01-15 at the Wayback Machine Retrieved on 2010-01-22
19. ^ What Is Coronary Angioplasty National Heart Lung and Blood Institute. Retrieved on 2010-01-22
20. ^ What Is Coronary Angioplasty National Heart Lung and Blood Institute. Retrieved on 2010-01-22
## External links[edit]
Classification
D
* ICD-10: I50
* ICD-9-CM: 428.0
* MeSH: D006333
* DiseasesDB: 16209
External resources
* MedlinePlus: 000158
* eMedicine: med/3552 emerg/108 radio/189 med/1367150 ped/2636
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
*[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
|
Acute decompensated heart failure
|
c1609524
| 25,589 |
wikipedia
|
https://en.wikipedia.org/wiki/Acute_decompensated_heart_failure
| 2021-01-18T18:58:18 |
{"icd-9": ["428.0"], "icd-10": ["I50"], "wikidata": ["Q4677930"]}
|
Nevi and melanomas
SpecialtyOncology
Nevi and melanomas are a group of neoplasia.
Although a nevus and a melanoma are often treated as independent entities, there is evidence that a nevus can be a precursor for a melanoma.[1]
Common mutations have been identified in nevi and melanomas.[2][3][4]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ "6.1 Melanoma Precursors : BC Cancer Agency". Archived from the original on 2008-10-27.
2. ^ Pollock PM, Harper UL, Hansen KS, et al. (January 2003). "High frequency of BRAF mutations in nevi". Nat. Genet. 33 (1): 19–20. doi:10.1038/ng1054. PMID 12447372.
3. ^ Poynter JN, Elder JT, Fullen DR, et al. (August 2006). "BRAF and NRAS mutations in melanoma and melanocytic nevi". Melanoma Res. 16 (4): 267–73. doi:10.1097/01.cmr.0000222600.73179.f3. PMID 16845322.
4. ^ Thomas NE (April 2006). "BRAF somatic mutations in malignant melanoma and melanocytic naevi". Melanoma Res. 16 (2): 97–103. doi:10.1097/01.cmr.0000215035.38436.87. PMID 16567964.
## External links[edit]
Classification
D
* MeSH: D018326
This article related to pathology is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
* v
* t
* e
Skin cancer of nevi and melanomas
Melanoma
* Mucosal melanoma
* Superficial spreading melanoma
* Nodular melanoma
* lentigo
* Lentigo maligna/Lentigo maligna melanoma
* Acral lentiginous melanoma
* Amelanotic melanoma
* Desmoplastic melanoma
* Melanoma with features of a Spitz nevus
* Melanoma with small nevus-like cells
* Polypoid melanoma
* Nevoid melanoma
* Melanocytic tumors of uncertain malignant potential
Nevus/
melanocytic nevus
* Nevus of Ito/Nevus of Ota
* Spitz nevus
* Pigmented spindle cell nevus
* Halo nevus
* Pseudomelanoma
* Blue nevus
* of Jadassohn–Tièche
* Cellular
* Epithelioid
* Deep penetrating
* Amelanotic
* Malignant
* Congenital melanocytic nevus (Giant
* Medium-sized
* Small-sized)
* Balloon cell nevus
* Dysplastic nevus/Dysplastic nevus syndrome
* Acral nevus
* Becker's nevus
* Benign melanocytic nevus
* Nevus spilus
*[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
|
Nevi and melanomas
|
c0206769
| 25,590 |
wikipedia
|
https://en.wikipedia.org/wiki/Nevi_and_melanomas
| 2021-01-18T18:50:31 |
{"mesh": ["D018326"], "wikidata": ["Q7004538"]}
|
Microcephalic primordial dwarfism due to ZNF335 deficiency is characterized by severe antenatal microencephaly, simplified gyration, agenesis of the corpus callosum, absence of basal ganglia (very rare), pontocerebellar atrophy and involvement of the white matter with secondary cerebral atrophy. Congenital cataract, choanal atresia, multiple arthrogryposis and spastic tetraparesis can occur.
*[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
|
Microcephalic primordial dwarfism due to ZNF335 deficiency
|
c3554499
| 25,591 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329228
| 2021-01-23T17:30:44 |
{"omim": ["615095"], "icd-10": ["Q87.1"], "synonyms": ["Microcephalic primordial dwarfism, Walsh type"]}
|
A number sign (#) is used with this entry because of evidence that isolated growth hormone deficiency type V (IGHD5) is caused by compound heterozygous mutation in the RNPC3 gene (618016) on chromosome 1p21. One such family has been reported.
For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400.
Description
Isolated growth hormone deficiency type V is characterized by severe postnatal growth failure, delayed bone age without bone dysplasia, and hypoplasia of the anterior pituitary (Argente et al., 2014).
Clinical Features
Argente et al. (2014) reported 3 sisters, born with normal length to normal-statured nonconsanguineous parents, who developed severe postnatal proportionate growth retardation. They showed features typical of growth hormone (GH; see 139250) deficiency, including marked short stature, frontal bossing, cherubic face, mild microcephaly, delayed bone maturation without bone dysplasia, and otherwise normal development. GH levels after standard stimulation, as well as basal IGF1 (147440) and IGFBP3 (146732) levels, were almost undetectable. Pituitary hormone levels were in the low-normal to normal range, with brain MRI showing hypoplasia of the anterior pituitary. Total ghrelin levels were extremely elevated, with normal acylated ghrelin levels; no other biochemical abnormalities were found. The patients responded well to GH, with reduction of total ghrelin levels in all 3.
Martos-Moreno et al. (2018) provided follow-up on 3 Romanian sisters with GH deficiency originally described by Argente et al. (2014). In all 3 patients, treatment with recombinant human GH (rhGH) was highly effective despite the severity of their short stature, with increases in height between 4.0 and 5.9 SDS after 4.5 to 6.5 years on rhGH. In addition, lumbar spine bone mineral density improved and trabecular bone structure normalized. The oldest sister had onset of puberty shortly after starting treatment at 15.5 years of age, with menarche at age 16. However, she had oligomenorrhea despite pubertal levels of follicle-stimulating hormone (FSH; see 136530), luteinizing hormone (LH; see 152780), and estradiol, and a pubertal-shaped uterus with endometrium present on ultrasound. An intense lipolytic effect of rhGH treatment was also observed in the oldest sister, whose truncal obesity resolved completely in the first year of treatment, with body fat decreasing from 44% to 27%.
Molecular Genetics
In 3 sisters with isolated GH deficiency, in whom involvement of GH deficiency-associated and combined pituitary hormone deficiency-associated genes had been excluded, Argente et al. (2014) performed exome analysis and identified compound heterozygosity for a missense mutation (P474T; 618016.0001) and a nonsense mutation (R502X; 618016.0002) in the RNPC3 gene. The mutations segregated with disease in the family and were not found in 300 Spanish controls or in public variant databases.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, severe proportionate Weight \- Central obesity Other \- Postnatal growth failure HEAD & NECK Head \- Microcephaly, mild Face \- Frontal bossing \- Cherubic face ABDOMEN External Features \- Truncal obesity SKELETAL \- Delayed bone maturation Skull \- Microcephaly, mild NEUROLOGIC Central Nervous System \- Hypoplasia of the anterior pituitary ENDOCRINE FEATURES \- Growth hormone deficiency \- Hypoplasia of the anterior pituitary LABORATORY ABNORMALITIES \- Elevated ghrelin levels MISCELLANEOUS \- Based on a report of 3 Romanian sisters (last curated October 2018) \- Patients respond well to growth hormone therapy MOLECULAR BASIS \- Caused by mutation in the RNA-binding region-containing protein-3 gene (RNPC3, 618016.0001 ) ▲ 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
|
ISOLATED GROWTH HORMONE DEFICIENCY, TYPE V
|
c0342573
| 25,592 |
omim
|
https://www.omim.org/entry/618160
| 2019-09-22T15:43:19 |
{"mesh": ["C537404"], "omim": ["262400", "618160"], "orphanet": ["231662"], "synonyms": ["Congenital IGHD type IA", "Congenital isolated GH deficiency type IA", "Congenital isolated growth hormone deficiency type IA"]}
|
## Clinical Features
Dincsoy et al. (1995) described male and female infant sibs, born to consanguineous parents, with defects of the midline, including cleft lip and palate, flat nose, hypotelorism, and dysgenesis of the corpus callosum, in addition to short limbs, an unusual radiolucent tibial notch, digital anomalies (camptodactyly with overlapping fingers and flexion deformity), ambiguous genitalia, and hypopituitarism. The disorder shared some overlapping features, including short limbs, with the hydrolethalus syndrome (236680) and the pseudotrisomy 13 syndrome (264480), but the sibs did not have have renal or gastrointestinal anomalies or preaxial or postaxial polydactyly. Dincsoy et al. (1995) noted that the bilateral radiolucent tibial notch was a distinctive feature in their patients.
Inheritance
Dincsoy et al. (1995) suggested autosomal recessive inheritance of this disorder.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Hypotelorism Nose \- Flat nose Mouth \- Cleft lip \- Cleft palate GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia External Genitalia (Female) \- Ambiguous genitalia SKELETAL Limbs \- Short limbs \- Radiolucent midshaft tibial notch Hands \- Digital anomalies \- Camptodactyly \- Overlapping fingers \- Flexion finger deformity \- No polydactyly NEUROLOGIC Central Nervous System \- Dysgenesis of corpus callosum ENDOCRINE FEATURES \- Hypopituitarism ▲ 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
|
MIDLINE MALFORMATIONS, MULTIPLE, WITH LIMB ABNORMALITIES AND HYPOPITUITARISM
|
c1832874
| 25,593 |
omim
|
https://www.omim.org/entry/601016
| 2019-09-22T16:15:30 |
{"mesh": ["C536177"], "omim": ["601016"], "orphanet": ["1678"], "synonyms": ["Alternative titles", "DINCSOY SYNDROME"]}
|
Primary effusion lymphoma (PEL) is a large B-cell lymphoma located in the body cavities, characterized by pleural, peritoneal, and pericardial fluid lymphomatous effusions and that is always associated with human herpes virus-8 (HHV-8).
## Epidemiology
The prevalence is unknown but it accounts for less than 1% of non-AIDS related lymphomas and approximately 3% of AIDS-related lymphomas.
## Clinical description
PEL is most frequently found in young men that are positive for HIV or have pre-existing AIDS. Very rare non-HIV related cases have been reported but these patients are almost all elderly or immunodeficient due to another cause. Peritoneal, pleural, and pericardial fluid lymphomatous effusions are observed with, in the majority of cases, no mass-like extranodal extension of lymphoma. Symptoms of PEL depend on the body cavity affected and are caused by the accumulation of the malignant effusion. Pleural or pericardial disease has dyspnea as a symptom while abdominal distension is experienced in peritoneal disease. PEL is usually extremely aggressive and dissemination of lymphoma to distant sites, opportunistic infections and HIV-related complications are often fatal. In the rare HIV-negative cases the outcome may be better.
## Etiology
The precise etiology is unknown. PEL is always associated with HHV-8, also known as Kaposi sarcoma-associated herpes (KSHV) and is most frequently found in immunodeficient patients, especially those with advanced AIDS. An infection with Epstein-Barr virus (EBV) is also present in the majority of PEL cases. The gene products of these viral genomes are thought to inhibit cell apoptosis and promote uncontrolled cell division and subsequent neoplastic transformation.
## Diagnostic methods
Body cavity fluid is analyzed cytologically and by flow cytometry for the presence of clonal large neoplastic cells (with immunoblastic, anaplastic or plasmablastic appearances) with prominent nucleoli, round to irregular nuclei and occasionally vacuolated cytoplasm. To be given a diagnosis with PEL an infection with HHV-8 must be present. A latency-associated nuclear antigen-1 (LANA-1) assay detects any evidence of HHV-8 in tissue samples. Complete blood counts and positron emission tomography/computed tomography (PET/CT) scans should also be performed to determine the extent of the disease.
## Differential diagnosis
Differential diagnoses include diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, which can present with lymphomatous effusion, anaplastic large cell lymphoma (ALCL; see these terms) and pyothorax-associated lymphoma (PAL).
## Management and treatment
PEL is usually refractory to conventional chemotherapy and treatment guidelines are not well defined. Highly active antiretroviral therapy (HAART) should be administered concurrently with chemotherapy in all HIV positive PEL patients. The chemotherapy regimen cyclophosamide, doxorubicin, vincristine and prednisone (CHOP) is most commonly used. Research into molecular targeting therapy for the treatment of PEL is ongoing. There is a single case report of a durable remission for more than 18 months with the use of sobuzoxane.
## Prognosis
PEL has a very poor prognosis with an average life expectancy of 3-4 months after diagnosis. Rare patients with HIV-negative PEL have durable progression free survival after chemotherapy.
*[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
|
Primary effusion lymphoma
|
c1292753
| 25,594 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=48686
| 2021-01-23T18:44:13 |
{"gard": ["9247"], "mesh": ["D054685"], "umls": ["C1292753"], "icd-10": ["C83.8"], "synonyms": ["Body cavity-based lymphoma", "PEL"]}
|
Abortion in Ohio is legal.[citation needed]
The number of abortion clinics in Ohio has declined over the years, with 55 in 1982, 45 in 1992 and 12 in 2014. There were 21,186 legal abortions in 2014 and 20,976 in 2015.
## Contents
* 1 Terminology
* 2 Context
* 3 History
* 3.1 Legislative history
* 3.2 Judicial history
* 3.3 Clinic history
* 4 Statistics
* 5 Abortion rights views and activities
* 5.1 Protests
* 6 Opposition to abortion
* 6.1 Violence
* 7 Footnotes
* 8 References
## Terminology[edit]
Main article: Abortion
The abortion debate most commonly relates to the induced abortion of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[note 1] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[1]
Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[2][3] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[4][5] Both "pro-choice" and "pro-life" are examples of terms labeled as political framing: they are terms which purposely try to define their philosophies in the best possible light, while by definition attempting to describe their opposition in the worst possible light. "Pro-choice" implies that the alternative viewpoint is "anti-choice", while "pro-life" implies the alternative viewpoint is "pro-death" or "anti-life".[6] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[7]
## Context[edit]
See also: Abortion in the United States
Free birth control correlates to teenage girls having fewer pregnancies and fewer abortions. A 2014 New England Journal of Medicine study found such a link. At the same time, a 2011 study by Center for Reproductive Rights and Ibis Reproductive Health also found that states with more abortion restrictions have higher rates of maternal death, higher rates of uninsured pregnant women, higher rates of infant and child deaths, higher rates of teen drug and alcohol abuse, and lower rates of cancer screening.[8]
According to a 2017 report from the Center for Reproductive Rights and Ibis Reproductive Health, states that tried to pass additional constraints on a woman's ability to access legal abortions had fewer policies supporting women's health, maternal health and children's health. These states also tended to resist expanding Medicaid, family leave, medical leave, and sex education in public schools.[9] According to Megan Donovan, a senior policy manager at the Guttmacher Institute, states with legislation that protects a woman's right to access abortion services have the lowest rates of infant mortality in the United States.[9] In 2017, Georgia, Ohio, Missouri, Louisiana, Alabama and Mississippi had among the highest rates of infant mortality in the United States.[9] In 2017, Ohio had an infant mortality rate of 7.2 deaths per 1,000 live births.[9]
## History[edit]
### Legislative history[edit]
Dates of when heartbeat laws come into effect (as of May 25, 2019)
By the end of the 1800s, all states in the Union except Louisiana had therapeutic exceptions in their legislative bans on abortions.[10] In 1978, Akron, Ohio passed a city ordinance that restricted abortion rights.[11]
The state was one of 23 states in 2007 to have a detailed abortion-specific informed consent requirement.[12] Mississippi, Nebraska, North Dakota and Ohio all had statutes in 2007 that required specific informed consent on abortion but also, by statute, allowed medical doctors performing abortions to disassociate themselves with the anti-abortion materials they were required to provide to their female patients.[13] The Ohio legislature was one of five states nationwide that tried, and failed, to pass a fetal heartbeat bill in 2013. Only North Dakota successfully passed such a law, but it was later struck down by the courts.[14] They tried with this type of legislation again unsuccessfully in 2018.[14]
Among those who believe that abortion is murder, some believe it may be appropriate to punish it with death. While attempts to criminalize abortion generally focus on the doctor, Texas state Rep. Tony Tinderholt (R) introduced a bill in 2017 and 2019 that may enable the death penalty in Texas for women who have abortions,[15] and the Ohio legislature considered a similar bill in 2018.[16]
In Ohio, a fetal heartbeat law, HB 125, was introduced in the state legislature in October 2011.[17] It was the only state in the country to try to pass such legislation that year.[14] The bill was shelved by the Republican majority Senate to avoid controversy.[18] This bill was notably supported by John C. Willke.[19] A related law was signed in Ohio in 2013 by John Kasich, which mandates, among other things, that doctors who do not test for a fetal heartbeat must be subject to criminal penalties; specifically, "The doctor’s failure to do so would be a first-degree misdemeanor, carrying up to six months in jail, for the first violation and a fourth-degree felony, carrying up to 18 months in jail, for subsequent violations."[20] A bill similar to the 2011–2012 bill was introduced in 2013, titled HB 248.[21] A further fetal heartbeat law was introduced on August 14, 2013, by Lynn Wachtmann and others.[22] In 2013, Ohio passed a Targeted Regulation of Abortion Providers (TRAP) bill containing provisions related to admitting privileges and licensing and requiring clinics to have a transfer agreement with a hospital.[23] Fetal heartbeat bills appeared again in the state legislature in 2014.[14] On March 25, 2015, another heartbeat bill (House Bill 69) passed the Ohio House of Representatives.[24] The Guardian reported that "The bill is unlikely to go any further, facing stiff opposition in the senate as well as from John Kasich, the Republican governor of Ohio."[25] On December 6, 2016, the Ohio Senate added a heartbeat ban provision to an unrelated bill, House Bill 493, previously passed by the Ohio House of Representatives. The bill was returned to the House and passed by the House the same day.[26][27] The bill as passed would make abortion after the detection of a fetal heartbeat a fifth-degree felony except in cases where a physician judges the abortion necessary "to prevent the death of the pregnant woman or to prevent a serious risk of the substantial and irreversible impairment of a major bodily function of the pregnant woman."[28][27] On December 13, 2016, Kasich vetoed the bill.[29][27] Attempts to pass a fetal heartbeat law continued in 2016, with Ohio being was one of eight states nationwide that tried and failed to pass such legislation.[14]
In early 2018, the House considered a bill passed by the Senate to ban abortion after 13 weeks and require that fetal remains be cremated or buried.[30] In 2018, the state was one of eleven where the legislature introduced a bill that failed to pass that would have banned abortion in almost all cases.[14]
Nationally, 2019 was one of the most active years for state legislatures in terms of trying to pass abortion rights restrictions. State governments with Republican majorities started to push these bills after Brett M. Kavanaugh was confirmed as a US Supreme Court judge, replacing the more liberal Anthony M. Kennedy. These state governments generally saw this as a positive sign that new moves to restrict abortion rights would be less likely face resistance in the courts.[31] Two fetal heartbeat bills were introduced in the Ohio General Assembly in 2019, marking the 133rd Session of the Ohio General Assembly as the fifth time such legislation has been proposed in the state.[32] On February 11, 2019, Christina Hagan and Ron Hood filed HB 68,[33] which was introduced in the Ohio House of Representatives on February 12, 2019.[34] On February 12, 2019, Kristina Roegner filed SB 23 in the Ohio Senate;[35] the bill was referred to the Health, Human Services and Medicaid Committee on February 13, 2019.[36] On February 21, 2019, the President of the Ohio Senate, Larry Obhof pledged to pass SB 23 out of the upper chamber stating, “We are going to pass that bill by the middle of March. I have no doubt at all.”[37] On March 13, 2019, SB 23 was passed out of the Ohio Senate by a vote of 19 to 13.[38] The next month, the Ohio House amended the bill, and passed it, 56-40; the changes were ratified in the Senate, 18–13.[39] The bill was signed into law by Governor Mike DeWine on April 11, 2019.[40][41] At the time the bill passed, only 27% of the state legislators were female.[42] The law, slated to go into effect in July 2019, would make abortion illegal after the fetus's heartbeat can be detected, usually between five or six weeks into the pregnancy. No exceptions for cases of rape or incest are made.[43][31]
In July 2019 a federal judge blocked the Ohio heartbeat law.[44]
In November 2019, a bill introduced by Candice Keller and Ron Hood, House Bill 413, bans abortion outright and requires doctors to reimplant an ectopic pregnancy, a medical procedure that obstetricians and gynecologists contend is currently impossible.[45]
### Judicial history[edit]
In 1913 in the case of State v. Tipple, the Ohio Supreme Court said, "The reason and policy of the statue is to protect women and unborn babes from dangerous criminal practice, and to discourage secret immorality between the sexes, and a vicious and craven custom amongst married pairs who wish to evade the responsibilities of rearing offspring."[10] The US Supreme Court's decision in 1973's Roe v. Wade ruling meant the state could no longer regulate abortion in the first trimester.[10]
Akron v. Akron Center for Reproductive Health in 1983 refused to allow the state to require women seeking abortions during the second trimester to be hospitalized or that a woman be required to listen to a "parade of horribles" before being allowed to have an abortion.[10][46][47] The full law that was struck down also required women to wait 24 hours after seeking an abortion, parental consent for minors and that a fetus that is aborted be dealt with in a "human" manner.[46][47]
### Clinic history[edit]
Number of abortion clinics in Ohio by year.
See also: Abortion clinic
Between 1982 and 1992, the number of abortion clinics in the state decreased by ten, going from 55 in 1982 to 45 in 1992.[48] In 2014, there were twelve abortion clinics in the state.[49] In 2014, 93% of the counties in the state did not have an abortion clinic. That year, 56% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[27] In March 2016, there were 28 Planned Parenthood clinics in the state.[50] In 2017, there were 27 Planned Parenthood clinics serving a population of 2,585,171 women aged 15 – 49. 3 of the Planned Parenthood clinics offered abortion services.[51]
## Statistics[edit]
In the period between 1972 and 1974, the state had an illegal abortion mortality rate per million women aged 15 – 44 of between 0.1 and 0.9.[52] In 1990, 1,314,000 women in the state faced the risk of an unintended pregnancy.[48] In 2010, the state had 9 publicly funded abortions, of which were 9 federally funded and 0 were state funded.[53] In 2014, 48% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[54]
Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[55] Census division and state Number Rate % change 1992–1996
1992 1995 1996 1992 1995 1996
East North Central 204,810 185,800 190,050 20.7 18.9 19.3 –7
Illinois 68,420 68,160 69,390 25.4 25.6 26.1 3
Indiana 15,840 14,030 14,850 12 10.6 11.2 –7
Michigan 55,580 49,370 48,780 25.2 22.6 22.3 –11
Ohio 49,520 40,940 42,870 19.5 16.2 17 –13
Wisconsin 15,450 13,300 14,160 13.6 11.6 12.3 –9
Number, rate, and ratio of reported abortions, by reporting area of residence and occurrence and by percentage of abortions obtained by out-of-state residents, US CDC estimates Location Residence Occurrence % obtained by
out-of-state residents
Year Ref
No. Rate^ Ratio^^ No. Rate^ Ratio^^
Ohio 21,650 9.8 155 21,186 9.6 152 5.5 2014 [56]
Ohio 21,215 9.6 152 20,976 9.5 151 5.8 2015 [57]
Ohio 20,790 9.5 151 20,672 9.4 150 5.5 2016 [58]
^number of abortions per 1,000 women aged 15-44; ^^number of abortions per 1,000 live births
## Abortion rights views and activities[edit]
### Protests[edit]
Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[59] In May 2019, women participated in a heartbeat ban bill protest in Cleveland as part of #StoptheBans movement. It was organized by NARAL Pro Choice Ohio, Planned Parenthood Advocates of Ohio and Cleveland State University students.[41] A #StoptheBans protest in Cincinnati saw dozens of people participating outside the Hamilton County Courthouse where they chanted "Right to life, that's a lie, you don't care if women die".[59]
## Opposition to abortion[edit]
Truth Truck at Ohio State University in 2008.
Political signage on I-70 in Columbus in August 2018.
### Violence[edit]
The first clinic arson occurred in Oregon in March 1976 and the first bombing occurred in February 1978 in Ohio.[60] In 1978, there were 3 arson attacks and 4 bomb attacks on abortion facilities in the United States. All but two of these took place in Ohio. These 7 attacks caused combined damage of US$800,000.[60]
In 1977, there were four arson attacks on abortion clinics. These took place in Minnesota, Vermont, Nebraska and Ohio. Combined, they caused over US$1.1 million in damage.[61] By 2000, an act of violence had taken place at an abortion clinic in Shelby County, Ohio.[61] On March 7, 2016, Rachel Ann Jackson, 71, vandalized a Planned Parenthood clinic in Columbus, Ohio, with the message "SATAN DEN OF BABY KILLERS..." She pleaded guilty to felony counts of breaking and entering and vandalism and a misdemeanor count of aggravated trespass.[62][63] Jackson was sentenced to probation, with the judge citing her struggle with serious mental illness as a mitigating factor.[63]
## Footnotes[edit]
1. ^ According to the Supreme Court's decision in Roe v. Wade:
> (a) For the stage prior to approximately the end of the first trimester, the abortion decision and its effectuation must be left to the medical judgement of the pregnant woman's attending physician. (b) For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. (c) For the stage subsequent to viability, the State in promoting its interest in the potentiality of human life may, if it chooses, regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgement, for the preservation of the life or health of the mother.
Likewise, Black's Law Dictionary defines abortion as "knowing destruction" or "intentional expulsion or removal".
## References[edit]
1. ^ Watson, Katie (20 Dec 2019). "Why We Should Stop Using the Term "Elective Abortion"". AMA Journal of Ethics. 20 (12): E1175-1180. doi:10.1001/amajethics.2018.1175. PMID 30585581.
2. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1). Archived from the original on 2016-06-13. Retrieved 2019-05-22.
3. ^ "The Roberts Court Takes on Abortion". Archived 2019-02-01 at the Wayback Machine New York Times. November 5, 2006. Retrieved January 18, 2008.
4. ^ Brennan 'Dehumanizing the vulnerable' 2000
5. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review. Archived from the original on 2016-08-30. Retrieved 2019-05-22.
6. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on 2011-07-27. Retrieved 2011-11-16.
7. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007.
8. ^ Castillo, Stephanie (2014-10-03). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Archived from the original on May 27, 2019. Retrieved May 27, 2019.
9. ^ a b c d "States pushing abortion bans have highest infant mortality rates". NBC News. Archived from the original on May 25, 2019. Retrieved May 25, 2019.
10. ^ a b c d Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66 (6): 1774–1831. PMID 11652642. Archived from the original on 2018-06-21. Retrieved 2019-05-22.
11. ^ Tyler, C. W. (1983). "The public health implications of abortion". Annual Review of Public Health. 4: 223–258. doi:10.1146/annurev.pu.04.050183.001255. ISSN 0163-7525. PMID 6860439.
12. ^ "STATE POLICY ON INFORMED CONSENT FOR ABORTION" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019.
13. ^ "State Abortion Counseling Policies and the Fundamental Principles of Informed Consent". Guttmacher Institute. 2007-11-12. Archived from the original on April 1, 2019. Retrieved May 22, 2019.
14. ^ a b c d e f Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved May 24, 2019.
15. ^ Gstalter, Morgan (2019-04-10). "GOP Texas lawmaker reintroduces bill to allow death penalty for women who have abortions". TheHill. Archived from the original on 2019-04-10. Retrieved 2019-04-10.
16. ^ Panetta, Grace (20 November 2018). "Ohio's legislature is considering laws to ban abortion after 6 weeks, and could punish patients and abortion providers with the death penalty". Business Insider. Archived from the original on 10 April 2019. Retrieved 2019-04-10.
17. ^ "Laws, Acts, and Legislation". state.oh.us. Archived from the original on 2016-03-04. Retrieved 2019-05-24.
18. ^ "Ohio Lawmakers Give Up On Anti-Choice Legislation". ThinkProgress. Archived from the original on 2016-03-04. Retrieved 2019-05-24.
19. ^ "Abortion foes push fetal heartbeat bills in states". msnbc.com. Archived from the original on 2019-06-07. Retrieved 2019-05-24.
20. ^ Provance, Jim (July 8, 2013). "Both sides of debate find Ohio abortion law decision to be historic". Toledo Blade. Archived from the original on July 19, 2013. Retrieved July 28, 2013.
21. ^ "Laws, Acts, and Legislation". state.oh.us. Archived from the original on 2015-01-24. Retrieved 2019-05-24.
22. ^ Hallett, Joe (August 15, 2013). "Fate unclear for new anti-abortion 'heartbeat bill'". Columbus Dispatch. Archived from the original on August 27, 2013. Retrieved August 23, 2013.
23. ^ "TRAP Laws Gain Political Traction While Abortion Clinics—and the Women They Serve—Pay the Price". Guttmacher Institute. 2013-06-27. Archived from the original on May 27, 2019. Retrieved May 27, 2019.
24. ^ Oates, Lindsey J. (April 6, 2015). "Ohio abortion bill creating controversy among college women". USA Today. Archived from the original on August 8, 2015. Retrieved August 11, 2015.
25. ^ Siddiqui, Sabrina (March 25, 2015). "Ohio anti-abortion 'heartbeat bill' passes in house but likely to face opposition". The Guardian. Archived from the original on August 12, 2015. Retrieved August 11, 2015.
26. ^ Cadinsky, Catherine; Ludlow, Randy; Siegel, Jim. "House joins Senate in approving heartbeat abortion bill". The Columbus Dispatch. The Columbus Dispatch. Archived from the original on December 7, 2016. Retrieved December 7, 2016.
27. ^ a b c d businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Archived from the original on May 24, 2019. Retrieved May 24, 2019.
28. ^ "House Bill 493, As Passed By The Senate" (PDF). The Ohio Legislature. The Ohio Legislature, 131st General Assembly. December 6, 2016. p. 46. Archived from the original on December 20, 2016. Retrieved December 7, 2016. "Sec. 2919.195. (A) Except as provided in division (B) of this section, no person shall knowingly and purposefully perform or induce an abortion on a pregnant woman with the specific intent of causing or abetting the termination of the life of the unborn human individual the pregnant woman is carrying and whose fetal heartbeat has been detected in accordance with division (A) of section 2919.192 of the Revised Code. Whoever violates this division is guilty of performing or inducing an abortion after the detection of a fetal heartbeat, a felony of the fifth degree. (B) Division (A) of this section does not apply to a physician who performs a medical procedure that, in the physician's reasonable medical judgment, is designed or intended to prevent the death of the pregnant woman or to prevent a serious risk of the substantial and irreversible impairment of a major bodily function of the pregnant woman. A physician who performs a medical procedure as described in this division shall declare, in a written document, that the medical procedure is necessary, to the best of the physician's reasonable medical judgment, to prevent the death of the pregnant woman or to prevent a serious risk of the substantial and irreversible impairment of a major bodily function of the pregnant woman. In the document, the physician shall specify the pregnant woman's medical condition that the medical procedure is asserted to address and the medical rationale for the physician's conclusion that the medical procedure is necessary to prevent the death of the pregnant woman or to prevent a serious risk of the substantial and irreversible impairment of a major bodily function of the pregnant woman. A physician who performs a medical procedure as described in this division shall place the written document required by this division in the pregnant woman's medical records. The physician shall maintain a copy of the document in the physician's own records for at least seven years from the date the document is created. (C) A person is not in violation of division (A) of this section if the person acts in accordance with division (A) of section 2919.192 of the Revised Code and the method used to determine the presence of a fetal heartbeat does not reveal a fetal heartbeat. (D) Division (A) of this section does not have the effect of repealing or limiting any other provision of the Revised Code that restricts or regulates the performance or inducement of an abortion by a particular method or during a particular stage of a pregnancy."
29. ^ Higgs, Robert (December 13, 2016). "Gov. John Kasich vetoes anti-abortion Heartbeat Bill, signs 20-week abortion ban". Cleveland.com. Columbus. Archived from the original on March 11, 2018. Retrieved December 6, 2017.
30. ^ "State legislatures see flurry of activity on abortion bills". PBS NewsHour. 2018-02-03. Archived from the original on May 26, 2019. Retrieved May 26, 2019.
31. ^ a b Tavernise, Sabrina (2019-05-15). "'The Time Is Now': States Are Rushing to Restrict Abortion, or to Protect It". The New York Times. ISSN 0362-4331. Archived from the original on May 24, 2019. Retrieved May 24, 2019.
32. ^ Kalser, Karen (February 13, 2019). "Heartbeat Bill Gets First Hearing For What Could Be Its Last Time Through The Legislature". The Statehouse News Bureau. Archived from the original on February 22, 2019. Retrieved February 22, 2019. "It’s the fifth time the Heartbeat Bill has been proposed. Republican House Speaker Larry Householder says he wants it to start in the Senate this time. But Rep. Ron Hood (R-Ashville) joined with fellow Republican Candice Keller (R-Middletown) to propose it in the House anyway, though he’s on board with the Senate version too."
33. ^ "Ohio abortion 'heartbeat bill' returns to Legislature". WLWT5 (NBC). The Associated Press. February 12, 2019. Archived from the original on May 24, 2019. Retrieved May 24, 2019.
34. ^ "133rd General Assembly - House Bill 68". legislature.ohio.gov. The Ohio Legislature. Archived from the original on February 13, 2019. Retrieved February 13, 2019.
35. ^ Frazin, Rachel (February 12, 2019). "Ohio lawmakers reintroduce 'heartbeat' abortion bill". thehill.com. Archived from the original on February 13, 2019. Retrieved February 13, 2019.
36. ^ "OH SB23 | 2019-2020 | 133rd General Assembly". legiscan.com. Archived from the original on February 22, 2019. Retrieved February 22, 2019. "Status: Introduced on February 12, 2019 . . . Action: 2019-02-13 - Refer to Committee: Health, Human Services and Medicaid"
37. ^ Kalser, Karen (February 21, 2019). "Senate President Says "Heartbeat Bill" Will Pass His Chamber Next Month". The Statehouse News Bureau. Archived from the original on February 22, 2019. Retrieved February 22, 2019. "“We are going to pass that bill by the middle of March. I have no doubt at all,” said Senate President Larry Obhof (R-Medina)."
38. ^ Kaplan, Talia (March 14, 2019). "Ohio 'heartbeat' abortion ban passes Senate as governor vows to sign it". Fox News. Archived from the original on March 18, 2019. Retrieved March 19, 2019.
39. ^ Frazin, Rachel (April 10, 2019). "Ohio legislature sends 'heartbeat' abortion bill to governor's desk". The Hill. Archived from the original on April 11, 2019. Retrieved April 13, 2019.
40. ^ Haynes, Danielle (April 11, 2019). "Ohio Gov. DeWine signs 'heartbeat' abortion bill". UPI. Archived from the original on April 12, 2019. Retrieved April 13, 2019.
41. ^ a b Kilpatrick, Mary (2019-05-20). "Abortion rights #StoptheBans rally set for Tuesday". cleveland.com. Archived from the original on May 25, 2019. Retrieved May 25, 2019.
42. ^ "Yes, you can blame the patriarchy for these horrible abortion laws. We did the math". Mother Jones. Archived from the original on May 18, 2019. Retrieved May 26, 2019.
43. ^ Smith, Kate (May 13, 2019). "A pregnant 11-year-old rape victim in Ohio would no longer be allowed to have an abortion under new state law". CBS News. Archived from the original on May 13, 2019. Retrieved May 14, 2019.
44. ^ "U.S. judge blocks Ohio 'heartbeat' law to end most abortions". Reuters. 4 July 2019. Retrieved 20 October 2019.
45. ^ Glenza, Jessica (November 29, 2019). "Ohio bill orders doctors to 'reimplant ectopic pregnancy' or face 'abortion murder' charges". The Guardian. Retrieved November 29, 2019.
46. ^ a b Tribune, Chicago. "Timeline of abortion laws and events". chicagotribune.com. Archived from the original on May 9, 2019. Retrieved May 23, 2019.
47. ^ a b "Timeline of Important Reproductive Freedom Cases Decided by the Supreme Court". American Civil Liberties Union. Archived from the original on April 30, 2019. Retrieved May 25, 2019.
48. ^ a b Arndorfer, Elizabeth; Michael, Jodi; Moskowitz, Laura; Grant, Juli A.; Siebel, Liza (December 1998). A State-By-State Review of Abortion and Reproductive Rights. DIANE Publishing. ISBN 9780788174810.
49. ^ Gould, Rebecca Harrington, Skye. "The number of abortion clinics in the US has plunged in the last decade — here's how many are in each state". Business Insider. Archived from the original on May 23, 2019. Retrieved May 23, 2019.
50. ^ Bohatch, Emily. "27 states with the most Planned Parenthood clinics". thestate. Archived from the original on May 24, 2019. Retrieved May 24, 2019.
51. ^ "Here's Where Women Have Less Access to Planned Parenthood". Archived from the original on May 23, 2019. Retrieved May 23, 2019.
52. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86–92. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687.
53. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved May 24, 2019.
54. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics | Pew Research Centerlanguage=en-US". Archived from the original on April 10, 2019. Retrieved May 23, 2019.
55. ^ "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Archived from the original on 2019-06-02. Retrieved 2019-06-02.
56. ^ Jatlaoui, Tara C. (2017). "Abortion Surveillance — United States, 2014". MMWR. Surveillance Summaries. 66 (24): 1–48. doi:10.15585/mmwr.ss6624a1. ISSN 1546-0738. PMID 29166366.
57. ^ Jatlaoui, Tara C. (2018). "Abortion Surveillance — United States, 2015". MMWR. Surveillance Summaries. 67 (13): 1–45. doi:10.15585/mmwr.ss6713a1. ISSN 1546-0738. PMC 6289084. PMID 30462632.
58. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738.
59. ^ a b Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA TODAY. Archived from the original on May 22, 2019. Retrieved May 25, 2019.
60. ^ a b National Abortion Federation. (2007). "Arsons and Bombings "Archived copy". Archived from the original on September 26, 2011. Retrieved May 22, 2019.CS1 maint: archived copy as title (link)." Retrieved February 10, 2007.
61. ^ a b Jacobson, Mireille; Royer, Heather (December 2010). "Aftershocks: The Impact of Clinic Violence on Abortion Services". American Economic Journal: Applied Economics. 3: 189–223. doi:10.1257/app.3.1.189. Archived from the original on 2017-07-18. Retrieved 2019-05-23.
62. ^ 71-year-old admits to vandalism on Planned Parenthood building Archived 2017-02-05 at the Wayback Machine, WCMH (August 8, 2016).
63. ^ a b John Futty, Judge grants probation to 71-year-old woman who vandalized Planned Parenthood building Archived 2017-02-05 at the Wayback Machine, Columbus Dispatch (November 15, 2016).
Abortion in the United States by state
States
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* Arizona
* Arkansas
* California
* Colorado
* Connecticut
* Delaware
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* Georgia
* Hawaii
* Idaho
* Illinois
* Indiana
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* West Virginia
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Federal district
Washington, D.C.
Insular areas
* American Samoa
* Guam
* Northern Mariana Islands
* Puerto Rico
* U.S. Virgin Islands
*[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
|
Abortion in Ohio
|
None
| 25,595 |
wikipedia
|
https://en.wikipedia.org/wiki/Abortion_in_Ohio
| 2021-01-18T18:28:45 |
{"wikidata": ["Q64876948"]}
|
Latent autoimmune diabetes in adults
Other namesLADA, late-onset autoimmune diabetes of adulthood,[1] adult-onset autoimmune diabetes
Universal blue circle symbol for diabetes[2]
Pronunciation
* /daɪəbiːtiːs/
SpecialtyEndocrinology
Slowly evolving immune-mediated diabetes, or latent autoimmune diabetes in adults (LADA), is a form of diabetes that exhibits clinical features similar to both type 1 diabetes (T1D) and type 2 diabetes (T2D).[3][4] It is an autoimmune form of diabetes, similar to T1D, but patients with LADA often show insulin resistance, similar to T2D, and share some risk factors for the disease with T2D.[3] Studies have shown that LADA patients have certain types of antibodies against the insulin-producing cells, and that these cells stop producing insulin more slowly than in T1D patients.[3][5]
LADA appears to share genetic risk factors with both T1D and T2D but is genetically distinct from both.[6][7][8][9][4] Within the LADA patient group, a genetic and phenotypic heterogeneity has been observed with varying degrees of insulin resistance and autoimmunity.[5][10] With the knowledge we have today, LADA can thus be described as a hybrid form of T1D and T2D, showing phenotypic and genotypic similarities with both, as well as variation within LADA regarding the degree of autoimmunity and insulin resistance.
The concept of LADA was first introduced in 1993,[11] though The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term, instead including it under the standard definition of diabetes mellitus type 1.[12]
## Contents
* 1 Symptoms
* 2 Diagnosis
* 2.1 Autoantibodies
* 3 Prevalence
* 4 Risk factors
* 5 Management
* 6 History
* 7 References
* 7.1 Sources
* 8 External links
## Symptoms[edit]
The symptoms of latent autoimmune diabetes in adults are similar to those of other forms of diabetes: polydipsia (excessive thirst and drinking), polyuria (excessive urination), and often blurred vision.[13] Compared to juvenile type 1 diabetes, the symptoms develop comparatively slowly, over a period of at least six months.[14]
## Diagnosis[edit]
A fasting blood sugar level of ≥ 7.0 mmol / L is used in the general diagnosis of diabetes.[15] There are no clear guidelines for the diagnosis of LADA, but the criteria often used are that the patient should develop the disease in adulthood, not need insulin treatment for the first 6 months after diagnosis and have autoantibodies in the blood.[5][3][4]
Glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulinoma-associated (IA-2) autoantibody, and zinc transporter autoantibody (ZnT8) testing should be performed in order to correctly diagnose diabetes.[16]
Persons with LADA typically have low, although sometimes moderate, levels of C-peptide as the disease progresses. Those with insulin resistance or type 2 diabetes are more likely to have high levels of C-peptide due to an over production of insulin.[17][14]
### Autoantibodies[edit]
Destruction of Glutamate decarboxylase (pictured here) via autoantibodies is strongly linked with LADA type 1 diabetes.
Glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulinoma-associated (IA-2) autoantibodies, and zinc transporter autoantibodies (ZnT8) are all associated with LADA; GADAs are commonly found in cases of diabetes mellitus type 1.
The presence of islet cell complement fixing autoantibodies also aids in a differential diagnosis between LADA and type 2 diabetes. Persons with LADA often test positive for ICA, whereas type 2 diabetics only seldom do.[17]
Persons with LADA usually test positive for glutamic acid decarboxylase antibodies, whereas in type 1 diabetes these antibodies are more commonly seen in adults rather than in children.[17][18] In addition to being useful in making an early diagnosis for type 1 diabetes mellitus, GAD antibodies tests are used for differential diagnosis between LADA and type 2 diabetes[17][19][20] and may also be used for differential diagnosis of gestational diabetes, risk prediction in immediate family members for type 1, as well as a tool to monitor prognosis of the clinical progression of type 1 diabetes.
## Prevalence[edit]
Since there is no regular autoantibody screening, patients with LADA are at risk of being diagnosed with type 2 diabetes, which makes it difficult to estimate the prevalence of LADA.[4] Globally, it is estimated that about 8.5% of adults suffer from some form of diabetes[15] and it is estimated that LADA accounts for about 3-12% of all adult diabetes cases.[21] Estimates from 2015 are saying that there could be as many as 10–20% of people with diabetes having LADA.
## Risk factors[edit]
There is limited research on LADA and its etiology.[21][4] As with both T1D and T2D, the risk of LADA depends on both genetic and environmental factors.[21][15] Genetic risk factors for LADA are similar to T1D, i.e. is affected by the HLA complex, but also genetic variants associated with T2D have been identified in LADA.[21] LADA has several lifestyle risk factors in common with T2D, such as obesity, physical inactivity, smoking and consumption of sweetened beverages, all of which are linked to insulin resistance.[21]
Obesity has been shown to increase the risk of LADA in several studies, and one study showed that the risk was particularly high in combination with having diabetes in the family.[21][22][23] Physical activity also affects the risk of LADA, with less physical activity increasing the risk.[21] A Swedish study showed that low birth weight, in addition to increasing the risk of T2D, increases the risk of LADA.[24]
Although smoking has been shown to increase the risk of T2D while coffee consumption has been shown to reduce the risk of T2D, the results regarding these products and LADA are unclear.[21] However, results from two studies based on the same population seem to indicate that coffee consumption increases the risk of LADA.[25][26] Other foods that have been shown to increase the risk of LADA are sweetened beverages and processed red meat[27][28][29] while consumption of fatty fish has been shown to have a protective effect.[30]
## Management[edit]
Main article: Diabetes management
Diabetes is a chronic disease, i.e. it cannot be cured, but symptoms and complications can be minimized with proper treatment. Diabetes can lead to elevated blood sugar levels, which in turn can lead to damage to the heart, blood vessels, kidneys, eyes and nerves.[15] There are very few studies on how to treat LADA, specifically, which is probably due to difficulties in classifying and diagnosing the disease. LADA patients often do not need insulin treatment immediately after being diagnosed because their own insulin production decreases more slowly than T1D patients, but in the long run they will need it.[5][3] About 80% of all LADA patients initially misdiagnosed with type 2 (and who have GAD antibodies) will become insulin-dependent within 3 to 15 years (according to differing LADA sources).[31]
The treatment for Type 1 diabetes/LADA is exogenous insulin to control glucose levels, prevent further destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from diabetic ketoacidosis (DKA). Although LADA may appear to initially respond to similar treatment (lifestyle and medications) as type 2 diabetes, it will not halt or slow the progression of beta cell destruction, and people with LADA will eventually become insulin-dependent.[32] People with LADA have insulin resistance similar to long-term type 1 diabetes; some studies showed that people with LADA have less insulin resistance, compared with those with type 2 diabetes; however, others have not found a difference.[33]
## History[edit]
Although type 1 diabetes has been identified as an autoimmune disease since the 1970s,[34] the concept of latent autoimmune diabetes mellitus was not noted until 1993, when it was used to describe slow-onset type 1 autoimmune diabetes occurring in adults.[35] This followed the concept that GAD autoantibodies were a feature of type 1 diabetes and not type 2 diabetes.[36]
## References[edit]
1. ^ Williams, Wilkins & Munden 2006, p. 20.
2. ^ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. Archived from the original on 5 August 2007.
3. ^ a b c d e Carlsson, Sofia (2019). "Etiology and Pathogenesis of Latent Autoimmune Diabetes in Adults (LADA) Compared to Type 2 Diabetes". Frontiers in Physiology. 10: 320. doi:10.3389/fphys.2019.00320. ISSN 1664-042X. PMC 6444059. PMID 30971952.
4. ^ a b c d e Mishra, Rajashree; Hodge, Kenyaita M.; Cousminer, Diana L.; Leslie, Richard D.; Grant, Struan F. A. (2018-09-01). "A Global Perspective of Latent Autoimmune Diabetes in Adults". Trends in Endocrinology & Metabolism. 29 (9): 638–650. doi:10.1016/j.tem.2018.07.001. ISSN 1043-2760. PMID 30041834. S2CID 51715011.
5. ^ a b c d Buzzetti, Raffaella; Zampetti, Simona; Maddaloni, Ernesto (November 2017). "Adult-onset autoimmune diabetes: current knowledge and implications for management". Nature Reviews Endocrinology. 13 (11): 674–686. doi:10.1038/nrendo.2017.99. ISSN 1759-5037. PMID 28885622. S2CID 3339346.
6. ^ Andersen, Mette K.; Lundgren, Virve; Turunen, Joni A.; Forsblom, Carol; Isomaa, Bo; Groop, Per-Henrik; Groop, Leif; Tuomi, Tiinamaija (2010-09-01). "Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years". Diabetes Care. 33 (9): 2062–2064. doi:10.2337/dc09-2188. ISSN 0149-5992. PMC 2928363. PMID 20805278.
7. ^ Andersen, Mette K.; Sterner, Maria; Forsén, Tom; Käräjämäki, Annemari; Rolandsson, Olov; Forsblom, Carol; Groop, Per-Henrik; Lahti, Kaj; Nilsson, Peter M.; Groop, Leif; Tuomi, Tiinamaija (2014-09-01). "Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes". Diabetologia. 57 (9): 1859–1868. doi:10.1007/s00125-014-3287-8. ISSN 1432-0428. PMID 24906951. S2CID 10477815.
8. ^ Cervin, Camilla; Lyssenko, Valeriya; Bakhtadze, Ekaterine; Lindholm, Eero; Nilsson, Peter; Tuomi, Tiinamaija; Cilio, Corrado M.; Groop, Leif (2008-05-01). "Genetic Similarities Between Latent Autoimmune Diabetes in Adults, Type 1 Diabetes, and Type 2 Diabetes". Diabetes. 57 (5): 1433–1437. doi:10.2337/db07-0299. ISSN 0012-1797. PMID 18310307.
9. ^ Cousminer, Diana L.; Ahlqvist, Emma; Mishra, Rajashree; Andersen, Mette K.; Chesi, Alessandra; Hawa, Mohammad I.; Davis, Asa; Hodge, Kenyaita M.; Bradfield, Jonathan P.; Zhou, Kaixin; Guy, Vanessa C. (2018-11-01). "First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes". Diabetes Care. 41 (11): 2396–2403. doi:10.2337/dc18-1032. ISSN 0149-5992. PMC 6196829. PMID 30254083.
10. ^ Pettersen, Elin; Skorpen, Frank; Kvaløy, Kirsti; Midthjell, Kristian; Grill, Valdemar (2010-01-01). "Genetic Heterogeneity in Latent Autoimmune Diabetes Is Linked to Various Degrees of Autoimmune Activity: Results From the Nord-Trøndelag Health Study". Diabetes. 59 (1): 302–310. doi:10.2337/db09-0923. ISSN 0012-1797. PMC 2797937. PMID 19833889.
11. ^ Vandewalle C.L.; Decraene, T.; Schuit, F.C.; De Leeuw, I.H.; Pipeleers, D.G.; F.K. Gorus (November 1993). "Insulin autoantibodies and high titre islet cell antibodies are preferentially associated with the HLA DQA1*0301-DQB1*0302 haplotype at clinical type 1 (insulin-dependent) diabetes mellitus before age 10 years, but not at onset between age 10 and 40 years". Diabetologia. 36 (11): 1155–62. doi:10.1007/bf00401060. PMID 8270130.
12. ^ American Diabetes, Association (January 2007). "Diagnosis and classification of diabetes mellitus". Diabetes Care. 30 Suppl 1: S42–7. doi:10.2337/dc07-S042. PMID 17192378.
13. ^ Flynn, Choi & Wooster 2013, p. 286.
14. ^ a b Eisenbarth 2010, p. 316.
15. ^ a b c d World Health Organization. (2016). Global Report on Diabetes. Geneva: World Health Organization.
16. ^ Landin-Olsson, Mona (April 2002). "Latent autoimmune diabetes in adults". Annals of the New York Academy of Sciences. 958 (1): 112–116. Bibcode:2002NYASA.958..112L. doi:10.1111/j.1749-6632.2002.tb02953.x. PMID 12021090. S2CID 6804673. Archived from the original on 2006-05-22. Retrieved 2006-05-22.
17. ^ a b c d Pipi, Elena; Marietta Market; Alexandra Tsirogianni (August 15, 2014). "Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus". World Journal of Diabetes. 5 (4): 505–10. doi:10.4239/wjd.v5.i4.505. PMC 4127585. PMID 25126396.
18. ^ Khardori, Romesh (September 30, 2016). Griffing, George T. (ed.). "Diabetes Mellitus, Type 1: A Review". eMedicine.com. Retrieved January 20, 2017.
19. ^ Latent Autoimmune Diabetes in Adults; David Leslie, Cristina Valerie DiabetesVoice.org; 2003
20. ^ Unnikrishnan AG, Singh SK, Sanjeevi CB (December 2004). "Prevalence of GAD65 antibodies in lean subjects with type 2 diabetes". Annals of the New York Academy of Sciences. 1037 (1): 118–21. Bibcode:2004NYASA1037..118U. doi:10.1196/annals.1337.018. PMID 15699503. S2CID 2179462.
21. ^ a b c d e f g h Carlsson S. (2019). Environmental (Lifestyle) Risk Factors for LADA. Current diabetes reviews, 15(3), 178–187. https://doi.org/10.2174/1573399814666180716150253.
22. ^ Hjort, Rebecka; Ahlqvist, Emma; Carlsson, Per-Ola; Grill, Valdemar; Groop, Leif; Martinell, Mats; Rasouli, Bahareh; Rosengren, Anders; Tuomi, Tiinamaija; Åsvold, Bjørn Olav; Carlsson, Sofia (2018-06-01). "Overweight, obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study". Diabetologia. 61 (6): 1333–1343. doi:10.1007/s00125-018-4596-0. ISSN 1432-0428. PMC 6448998. PMID 29589073.
23. ^ Hjort, R., Löfvenborg, J. E., Ahlqvist, E., Alfredsson, L., Andersson, T., Grill, V., Groop, L., Sørgjerd, E. P., Tuomi, T., Åsvold, B. O., & Carlsson, S. (2019). Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes. The Journal of clinical endocrinology and metabolism, 104(10), 4815–4826. https://doi.org/10.1210/jc.2019-00183.
24. ^ Hjort, Rebecka; Alfredsson, Lars; Carlsson, Per-Ola; Groop, Leif; Martinell, Mats; Storm, Petter; Tuomi, Tiinamaija; Carlsson, Sofia (2015-11-01). "Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case–control study". Diabetologia. 58 (11): 2525–2532. doi:10.1007/s00125-015-3711-8. ISSN 1432-0428. PMID 26208603.
25. ^ Löfvenborg, J. E.; Andersson, T.; Carlsson, P.-O.; Dorkhan, M.; Groop, L.; Martinell, M.; Rasouli, B.; Storm, P.; Tuomi, T.; Carlsson, S. (2014). "Coffee consumption and the risk of latent autoimmune diabetes in adults—results from a Swedish case–control study". Diabetic Medicine. 31 (7): 799–805. doi:10.1111/dme.12469. ISSN 1464-5491. PMID 24750356. S2CID 2394699.
26. ^ Rasouli, B.; Ahlqvist, E.; Alfredsson, L.; Andersson, T.; Carlsson, P. -O.; Groop, L.; Löfvenborg, J. E.; Martinell, M.; Rosengren, A.; Tuomi, T.; Wolk, A. (2018-09-01). "Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study". Diabetes & Metabolism. 44 (4): 354–360. doi:10.1016/j.diabet.2018.05.002. hdl:10138/305740. ISSN 1262-3636. PMID 29861145.
27. ^ Löfvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Dorkhan, Mozhgan; Groop, Leif; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2020-02-01). "Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes". European Journal of Nutrition. 59 (1): 127–135. doi:10.1007/s00394-019-01893-x. ISSN 1436-6215. PMC 7000500. PMID 30656477.
28. ^ Löfvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Groop, Leif; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2020-05-22). "Consumption of red meat, genetic susceptibility, and risk of LADA and type 2 diabetes". European Journal of Nutrition. doi:10.1007/s00394-020-02285-2. ISSN 1436-6215. PMID 32444887.
29. ^ Löfvenborg, Josefin E.; Andersson, Tomas; Carlsson, Per-Ola; Dorkhan, Mozhgan; Groop, Leif; Martinell, Mats; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2016-12-01). "Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes". European Journal of Endocrinology. 175 (6): 605–614. doi:10.1530/EJE-16-0376. ISSN 0804-4643. PMID 27926472.
30. ^ Löfvenborg, J. E.; Andersson, T.; Carlsson, P.-O.; Dorkhan, M.; Groop, L.; Martinell, M.; Tuomi, T.; Wolk, A.; Carlsson, S. (October 2014). "Fatty fish consumption and risk of latent autoimmune diabetes in adults". Nutrition & Diabetes. 4 (10): e139. doi:10.1038/nutd.2014.36. ISSN 2044-4052. PMC 4216999. PMID 25329601.
31. ^ Eisenbarth, George. "Prediction of Type I Diabetes". University of Colorado, Denver. Retrieved March 23, 2016.
32. ^ Castro, M. Regina. "Latent autoimmune diabetes". Mayo Clinic. Retrieved May 26, 2014.
33. ^ Nguyen, Than; Tara L. Muzyk (October 15, 2009). "LADA: A Little Known Type of Diabetes". Pharmacy Times. Retrieved May 26, 2014.
34. ^ Bottazzo, GF; Florin-Christensen, A; Doniach, D (Nov 30, 1974). "Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies". Lancet. 2 (7892): 1279–83. doi:10.1016/s0140-6736(74)90140-8. PMID 4139522.
35. ^ Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR (February 1993). "Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease". Diabetes. 42 (2): 359–62. doi:10.2337/diab.42.2.359. PMID 8425674.
36. ^ Hagopian, W A; Karlsen, A E; Gottsäter, A; Landin-olsson, M; Grubin, C E; Sundkvist, G; Petersen, J S; Boel, E; Dyrberg, T; Lernmark, A (January 1993). "Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type Hagopian, W A; Karlsen, A E; Gottsäter, A; Landin-olsson, M; Grubin, C E; Sundkvist, G; Petersen, J S; Boel, E; Dyrberg, T; Lernmark, A". The Journal of Clinical Investigation. 91 (1): 368–74. doi:10.1172/JCI116195. PMC 330036. PMID 8423232.
### Sources[edit]
* Eisenbarth, George S., ed. (2010). Immunoendocrinology: Scientific and Clinical Aspects. Contemporary Endocrinology. Humana Press. ISBN 978-1-603-27477-7.
* Flynn, John A.; Michael J. Choi; L. Dwight Wooster, eds. (2013). Oxford American Handbook of Clinical Medicine. Oxford American Handbooks in Medicine. Oxford University Press. ISBN 978-0-195-18849-3.
* Munden, Julie, ed. (2006). Diabetes Mellitus: A Guide to Patient Care. Lippincott Williams & Wilkins. ISBN 978-1-58255-732-8.
## External links[edit]
Classification
D
* MeSH: D000071698
* v
* t
* e
Diabetes
Types
* Type 1
* Type 2
* LADA
* Gestational diabetes
* Diabetes and pregnancy
* Prediabetes
* Impaired fasting glucose
* Impaired glucose tolerance
* Insulin resistance
* KPD
* MODY
* Neonatal
* Transient
* Permanent
* Type 3c (pancreatogenic)
* Type 3
Blood tests
* Blood sugar level
* Glycosylated hemoglobin
* Glucose tolerance test
* Postprandial glucose test
* Fructosamine
* Glucose test
* C-peptide
* Noninvasive glucose monitor
* Insulin tolerance test
Management
* Diabetic diet
* Anti-diabetic drugs
* Insulin therapy
* intensive
* conventional
* pulsatile
* Cure
* Embryonic stem cells
* Artificial pancreas
* Other
* Gastric bypass surgery
Complications
* Diabetic comas
* Hypoglycemia
* Ketoacidosis
* Hyperosmolar hyperglycemic state
* Diabetic foot
* ulcer
* Neuropathic arthropathy
* Organs in diabetes
* Blood vessels
* Muscle
* Kidney
* Nerves
* Retina
* Heart
* Diabetic skin disease
* Diabetic dermopathy
* Diabetic bulla
* Diabetic cheiroarthropathy
* Neuropathic ulcer
* Hyperglycemia
* Hypoglycemia
Other
* Glossary of diabetes
* History of diabetes
* Notable people with type 1 diabetes
*[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
|
Latent autoimmune diabetes in adults
|
c1739108
| 25,596 |
wikipedia
|
https://en.wikipedia.org/wiki/Latent_autoimmune_diabetes_in_adults
| 2021-01-18T18:49:47 |
{"mesh": ["D000071698"], "umls": ["C1739108"], "wikidata": ["Q1797833"]}
|
Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by global development delay with very limited or absent speech and language, severe intellectual disability, long slender fingers, ocular abnormalities (typically strabismus or hypermetropia), and facial dysmorphism that includes a grimacing facial expression, a tubular-shaped nose with a prominent, broad base and tip, and other variable features, such as broad forehead, hypertelorism, deep-set eyes, narrow palpebral fissures, short philtrum and/or broad mouth.
*[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
|
Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome
|
c3554448
| 25,597 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363686
| 2021-01-23T17:09:56 |
{"gard": ["12815"], "omim": ["615074"], "icd-10": ["Q87.8"]}
|
Macrothrombocytopenia with mitral valve insufficiency is a rare hemorrhagic disorder due to a platelet anomaly characterized by dysfunctional platelets of abnormally large size, moderate thrombocytopenia, prolonged bleeding time and mild bleeding diathesis (ecchymoses and epistaxis), associated with mitral valve insufficiency.
*[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
|
Macrothrombocytopenia with mitral valve insufficiency
|
None
| 25,598 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=220448
| 2021-01-23T18:28:24 |
{"icd-10": ["D69.4"]}
|
Myosin storage myopathy is an inherited condition that affects the muscles. Signs and symptoms generally begin during infancy or early childhood; however, some affected people may not develop symptoms until early adulthood and there are even reports of people who are asymptomatic into their 40s. Myosin storage myopathy is primarily characterized by muscle weakness with minimal or very slow progression. As a result, affected people may experience delayed motor milestones (i.e. walking), trouble climbing stairs, difficulty lifting arms above shoulder level, and less commonly, breathing problems. Myosin storage myopathy is caused by changes (mutations) in the MYH7 gene and is typically inherited in an autosomal dominant manner. Treatment is generally supportive and may include orthopedic treatments, as well as physical, occupational or speech therapy.
*[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
|
Myosin storage myopathy
|
c1842160
| 25,599 |
gard
|
https://rarediseases.info.nih.gov/diseases/7148/myosin-storage-myopathy
| 2021-01-18T17:58:49 |
{"mesh": ["C564253"], "omim": ["608358", "255160"], "orphanet": ["53698"], "synonyms": ["Hyaline body myopathy"]}
|
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