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## Clinical Features D'Arcy et al. (1978) studied the family of a girl who between ages 8 and 11 rapidly developed hip pain and stiffness with flexion contractures and protrusio acetabuli. The mother and a brother had limitation of hip motion, while radiologic criteria for protrusio were present in the mother and 4 of the proband's 8 sibs. Only 1 complained of hip pain. At age 16 the proband underwent bilateral hip replacement. The histologic changes were those of fibrocartilaginous replacement and osteophyte formation. The 5 oldest sibs were affected. MacDonald (1971) studied 4 generations of a Scottish family in which all 3 members of the second generation showed marked protrusio acetabulum and members of the other generations had abnormally deep acetabuli. Francis (1959) studied 6 families, finding affected members in 3 generations of one. Rechtman (1936) was first to comment on familiality. Friedenberg (1953) was impressed with an increased frequency in American Blacks. In South Africa an extraordinarily high frequency was found in Bantu as compared with East Indians and Europeans (Crichton and Curlewis, 1962). Ventruto et al. (1980) reported an Italian family with 9 members (and presumably a tenth member) with primary protrusio acetabuli in 4 generations and 6 sibships. Joints \- Hip pain and stiffness \- Hip flexion contractures Radiology \- Protrusio acetabuli 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	PROTRUSIO ACETABULI	c0409495	7,000	omim	https://www.omim.org/entry/177050	2019-09-22T16:35:38	{"omim": ["177050"], "icd-10": ["M24.7"]}
By study of mouse-human hybrid cells, Wright and Shows (1978) assigned to chromosome 10 a human gene that in combination with the murine genome induces formation of multinucleate cells in rat cell line. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	POLYKARYOCYTOSIS INDUCER	c3887935	7,001	omim	https://www.omim.org/entry/174750	2019-09-22T16:36:01	{"omim": ["174750"]}
Liebenberg syndrome is a condition that involves abnormal development of the arms, resulting in characteristic arm malformations that can vary in severity. In people with this condition, bones and other tissues in the elbows, forearms, wrists, and hands have characteristics of related structures in the lower limbs. For example, bones in the elbows are abnormally shaped, which affects mobility of the joints. The stiff elbows function more like knees, unable to rotate as freely as elbows normally do. Bones in the wrists are joined together (fused), forming structures that resemble those in the ankles and heels and causing permanent bending of the hand toward the thumb (radial deviation). The bones in the hands (metacarpals) are longer than normal, and the fingers are short (brachydactyly), similar to the proportions of bones found in the feet. In addition, muscles and tendons that are typically found only in the hands and not in the feet are missing in people with Liebenberg syndrome. Affected individuals also have joint deformities (contractures) that limit movement of the elbows, wrists, and hands. Development of the lower limbs is normal in people with this condition. Individuals with Liebenberg syndrome have no other health problems related to this condition, and life expectancy is normal. ## Frequency Liebenberg syndrome is a rare condition. Fewer than 10 affected families have been described in the medical literature. ## Causes Liebenberg syndrome is caused by genetic changes near the PITX1 gene. The protein produced from this gene plays a critical role in lower limb development by controlling the activity of other genes involved in limb development, directing the shape and structure of bones and other tissues in the legs and feet. The genetic changes involved in Liebenberg syndrome delete, insert, or rearrange genetic material near the PITX1 gene. These changes affect regions of DNA known as regulatory elements, which help turn on or turn off genes (known as enhancers or repressors, respectively). They control when and where certain genes are active. The mutations that cause Liebenberg syndrome are thought to relocate enhancers that normally promote the activity of genes involved in upper limb development to be near the PITX1 gene, where they can promote its activity. Alternatively, the mutations may remove repressors that normally turn off the PITX1 gene during upper limb development. As a result, the PITX1 gene is abnormally active during development of the upper limbs. Because the PITX1 protein normally directs lower limb structure, bones, muscles, and tendons in the arms and hands develop more like those in the legs and feet, leading to the features of Liebenberg syndrome. ### Learn more about the gene associated with Liebenberg syndrome * PITX1 ## Inheritance Pattern Liebenberg syndrome is inherited in an autosomal dominant pattern, which means having a genetic change that affects the PITX1 gene on one copy of the chromosome in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with 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	Liebenberg syndrome	c1861313	7,002	medlineplus	https://medlineplus.gov/genetics/condition/liebenberg-syndrome/	2021-01-27T08:25:09	{"gard": ["966"], "mesh": ["C566090"], "omim": ["186550"], "synonyms": []}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (February 2016) (Learn how and when to remove this template message) 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: "Lethal yellowing" – news · newspapers · books · scholar · JSTOR (February 2016) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Lethal yellowing Palm tree dying of lethal yellowing Common namesCoconut lethal yellowing phytoplasma Causal agentsPhytoplasma sp HostsArecaceae (palms) Vectorsplanthoppers (Haplaxius crudus) EPPO CodePHYP56 DistributionFlorida, parts of the Caribbean, parts of Australia and Central America, East Africa Lethal yellowing (LY) is a phytoplasma disease that attacks many species of palms, including some commercially important species such as the coconut and date palm. In the Caribbean it is spread by the planthopper Haplaxius crudus (former name Myndus crudus) which is native to Florida, parts of the Caribbean, parts of Australia and Central America.[1] The only effective cure is prevention, i.e. planting resistant varieties of coconut palm and preventing a park-like or golf-course-like environment which attracts the planthopper.[citation needed] Some cultivars, such as the Jamaica Tall coconut cultivar, nearly died out by lethal yellowing. Heavy turf grasses and similar green ground cover will attract the planthopper to lay its eggs and the nymphs develop at the roots of these grasses. The planthoppers' eggs and nymphs may pose a great threat to coconut growing countries' economies, into which grass seeds for golf courses and lawns are imported from the Americas. It is not clearly understood how the disease was spread to East Africa as the planthopper Haplaxius crudus is not native in East Africa. The only explanation is that it was imported with grass seed from Florida that was used to create golf courses and lawns in beach resorts. There is a direct connection between green lawns and the spread of lethal yellowing in Florida. Even so-called 'resistant cultivars' such as the Malayan Dwarf or the Maypan hybrid between that dwarf and the Panama Tall were never claimed to have a 100% immunity. The nymphs of the planthoppers develop on roots of grasses, hence the areas of grass in the vicinity of palm trees is connected with the spread of this phytoplasma disease. The problem arose as a direct result of using coconut and date palms for ornamental and landscaping purposes in lawns, golf courses and gardens together with these grasses. When these two important food palms were grown in traditional ways (without grasses) in plantations and along the shores, the palm groves were not noticeably affected by lethal yellowing. There is no evidence that disease can be spread when instruments used to cut an infected palm are then used to cut or trim a healthy one. Seed transmission has never been demonstrated, although the phytoplasma can be found in coconut seednuts, but phytosanitary quarantine procedures that prevent movement of coconut seed, seedlings and mature palms out of an LY epidemic area should be applied to grasses and other plants that may be carrying infected vectors. Beside coconut palm (Cocus nucifera), more than 30 palm species have also been reported as susceptible to lethal phytoplasmas around the globe.[2] ## See also[edit] * Texas phoenix palm decline * Phytosanitary ## References[edit] 1. ^ Brown, S.E., Been, B.O. & McLaughlin, W.A. (2006). Detection and variability of the lethal yellowing group (16Sr IV) phytoplasmas in the Cedusa sp. (Hemiptera: Auchenorrhyncha: Derbidae) in Jamaica. Annals of Applied Biology, 149(1), pp. 53–62 2. ^ Howard, F. (1992). Lethal yellowing susceptibility of date palms in Florida. Principes, 36(4), pp. 217–222 ## External links[edit] * EPPO quarantine data sheet: Palm lethal yellowing (pdf file) * Lethal Yellowing of Palm * Lethal Yellowing of Palm Trees in Florida [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Lethal yellowing	None	7,003	wikipedia	https://en.wikipedia.org/wiki/Lethal_yellowing	2021-01-18T18:53:06	{"wikidata": ["Q6533266"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (June 2019) (Learn how and when to remove this template message) 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: "ROSAH syndrome" – news · newspapers · books · scholar · JSTOR (June 2019) (Learn how and when to remove this template message) (Learn how and when to remove this template message) ROSAH syndrome ROSAH syndrome is inherited via an autosomal dominant manner CausesMutation in ALPK1 gene ROSAH syndrome is a rare genetic disorder characterised by Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis and migraine Headache.[1] ## Contents * 1 Presentation * 2 Genetics * 3 Diagnosis * 4 Management * 5 Epidemiology * 6 History * 7 References ## Presentation[edit] The main characteristics of this condition are retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and migraine headache. Other features include ocular inflammation, pancytopenia, recurrent infections and mild renal impairment. ## Genetics[edit] This condition is caused by mutations in the ɑ-kinase gene (ALPK1) gene. This gene is located on the long arm of chromosome 4 (4q25). The inheritance of this condition is autosomal dominant. ## Diagnosis[edit] This diagnosis is made by sequencing the ALPK1 gene. ## Management[edit] There is presently no curative treatment. Management is supportive. ## Epidemiology[edit] The prevalence is not known but this is considered to be a rare disease. Only twelve families have been described to date. ## History[edit] This condition was first described in 2019.[1] ## References[edit] 1. ^ a b Williams LB, Javed A, Sabri A, Morgan DJ, Huff CD, Grigg JR, Heng XT, Khng AJ, Hollink IHIM, Morrison MA, Owen LA, Anderson K, Kinard K, Greenlees R, Novacic D, Nida Sen H, Zein WM, Rodgers GM, Vitale AT, Haider NB, Hillmer AM, Ng PC, Shankaracharya, Cheng A, Zheng L, Gillies MC, van Slegtenhorst M, van Hagen PM, Missotten TOAR, Farley GL, Polo M, Malatack J, Curtin J, Martin F, Arbuckle S, Alexander SI, Chircop M, Davila S, Digre KB, Jamieson RV, DeAngelis MM (2019) ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet Med doi: 10.1038/s41436-019-0476-3 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	ROSAH syndrome	c3554278	7,004	wikipedia	https://en.wikipedia.org/wiki/ROSAH_syndrome	2021-01-18T18:38:45	{"umls": ["C3554278"], "orphanet": ["313800"], "wikidata": ["Q55784422"]}
Postencephalitic trophic ulcer is an ulceration of the nose similar to trigeminal trophic lesions, and has been reported following epidemic encephalitis and herpes zoster of the trigeminal nerve.[1]:65 ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 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	Postencephalitic trophic ulcer	None	7,005	wikipedia	https://en.wikipedia.org/wiki/Postencephalitic_trophic_ulcer	2021-01-18T19:11:01	{"wikidata": ["Q7234154"]}
LIG4 syndrome Other namesLigase IV syndrome Person at age 12 showing dysmorphic features LIG4 syndrome (also known as Ligase IV syndrome) is an extremely rare condition caused by mutations in the DNA Ligase IV (LIG4) gene. Some mutations in this gene are associated with a resistance against multiple myeloma and Severe Combined Immunodeficiency.[1] Severity of symptoms depends on the degree of reduced enzymatic activity of Ligase IV or gene expression. Ligase IV is a critical component of the non-homologous end joining (NHEJ) mechanism that repairs DNA double-strand breaks.[2] It is employed in repairing DNA double-strand breaks caused by reactive oxygen species produced by normal metabolism, or by DNA damaging agents such as ionizing radiation. NHEJ is also used to repair the DNA double-strand break intermediates that occur in the production of T and B lymphocyte receptors.[citation needed] As DNA ligase IV is essential in V(D)J recombination, the mechanism by which immunoglobulins, B cell and T cell receptors are formed, patients with LIG4 syndrome may suffer from less effective or defective V(D)J recombination. Some patients have a severe immunodeficiency characterized by pancytopenia, causing chronic respiratory infections and sinusitis.[3] Clinical features also include Seckel syndrome-like facial abnormalities and microcephaly. Patients also suffer from growth retardation and skin conditions, including photosensitivity, psoriasis and telangiectasia. Although not present in all, patients may also present with hypothyroidism and type II diabetes and possibly malignancies such as acute T-cell leukemia.[3][4] The clinical phenotype of LIG4 syndrome closely resembles that of Nijmegen breakage syndrome (NBS).[citation needed] ## See also[edit] * LIG4 * List of cutaneous conditions ## References[edit] 1. ^ "LIGASE IV, DNA, ATP-DEPENDENT; LIG4". OMIM. Retrieved 2 January 2012. 2. ^ Altmann T, Gennery AR (October 2016). "DNA ligase IV syndrome; a review". Orphanet J Rare Dis. 11 (1): 137. doi:10.1186/s13023-016-0520-1. PMC 5055698. PMID 27717373. 3. ^ a b O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P (2001). "DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency". Mol Cell. 8: 1175–85. doi:10.1016/S1097-2765(01)00408-7. PMID 11779494. 4. ^ Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM (2005). "A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome". Am J Med Genet A. 137A (3): 283–7. doi:10.1002/ajmg.a.30869. PMID 16088910. ## External links[edit] Classification D * ICD-10: D81.1 * OMIM: 606593 * MeSH: C564694 External resources * Orphanet: 99812 This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	LIG4 syndrome	c1847827	7,006	wikipedia	https://en.wikipedia.org/wiki/LIG4_syndrome	2021-01-18T18:30:47	{"mesh": ["C564694"], "umls": ["C1847827"], "orphanet": ["99812"], "wikidata": ["Q6458655"]}
Danon disease Other namesLysosomal glycogen storage disease with normal acid maltase activity, GSD due to LAMP-2 deficiency This condition is inherited via X-linked recessive manner SpecialtyEndocrinology Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder.[1] Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability.[2] ## Contents * 1 Symptoms and signs * 2 Causes * 3 Genetics * 4 Diagnosis * 5 Treatment * 6 History * 7 References * 8 External links ## Symptoms and signs[edit] Males In males the symptoms of Danon Disease are more severe. Features of Danon Disease in males are:[citation needed] * An early age of onset of muscle weakness and heart disease (onset in childhood or adolescence) * Some learning problems or intellectual disability can be present * Muscle weakness can be severe and can affect endurance and the ability to walk * Heart disease (cardiomyopathy) can be severe and can lead to a need for medications. It usually progress to heart failure, commonly complicated by atrial fibrillation and embolic strokes with severe neurological disability,[3] leading to death unless heart transplant is performed. * Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease. * Symptoms are usually gradually progressive * Some individuals may have visual disturbances, and/or retinal pigment abnormalities * Danon Disease is rare and unfamiliar to most physicians. It can be mistaken for other forms of heart disease and/or muscular dystrophies, including Pompe disease. Females In females the symptoms of Danon Disease are less severe. Common symptoms of Danon Disease in females are:[citation needed] * A later age of onset of symptoms. Many females will not have obvious symptoms until late adolescence or even adulthood. * Learning problems and intellectual disability are usually absent. * Muscle weakness is often absent or subtle. Some females will tire easily with exercise * Cardiomyopathy is often absent in childhood. Some women will develop this in adulthood. Cardiomyopathy can be associated with atrial fibrillation and embolic strokes. * Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease. * Symptoms in females progress more slowly than in males. * Some females may have visual disturbances, and/or retinal pigment abnormalities * Danon Disease is rare and unfamiliar to most physicians. The milder and more subtle symptoms in females can make it more difficult to diagnose females with Danon Disease ## Causes[edit] Although the genetic cause of Danon Disease is known, the mechanism of disease is not well understood. Danon disease involves a genetic defect (mutation) in a gene called LAMP2, which results in a change to the normal protein structure. While the function of the LAMP2 gene is not well understood, it is known that LAMP2 protein is primarily located in small structures within cells called lysosomes.[citation needed] ## Genetics[edit] It is associated with LAMP2.[4] The status of this condition as a GSD has been disputed.[5] ## Diagnosis[edit] Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional. Testing Resources The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Orphanet lists international laboratories offering diagnostic testing for this condition. ## Treatment[edit] RP-A501 is an AAV-based gene therapy aimed to restore the LAMP-2 gene which is defective in male patients afflicted with Danon Disease and how to cure it.[6] Cardiac transplantation has been performed as a treatment, however most patients die early in life. [7] ## History[edit] Danon disease was characterized by Moris Danon in 1981.[8] Dr. Danon first described the disease in 2 boys with heart and skeletal muscle disease (muscle weakness), and intellectual disability. The first case of Danon disease reported in the Middle East was a family diagnosed in the eastern region of United Arab Emirates with a new LAMP2 mutation; discovered by the Egyptian cardiologist Dr. Mahmoud Ramadan[9] the associate professor of Cardiology in Mansoura University[10] (Egypt) after doing genetic analysis for all the family members in Bergamo, Italy where 6 males were diagnosed as Danon disease patients and 5 female were diagnosed as carriers; as published in Al-Bayan newspaper in 20 February 2016[11] making this family the largest one with patients and carriers of Danon disease. Danon Disease has overlapping symptoms with another rare genetic condition called 'Pompe' disease. Microscopically, muscles from Danon Disease patients appear similar to muscles from Pompe disease patients. However, intellectual disability is rarely, if ever, a symptom of Pompe disease. Negative enzymatic or molecular genetic testing for Pompe disease can help rule out this disorder as a differential diagnosis.[citation needed] ## References[edit] 1. ^ "OMIM Entry - # 300257 - DANON DISEASE". omim.org. Retrieved 2017-07-11. 2. ^ Maron BJ, Roberts WC, Arad M, et al. (March 2009). "Clinical Outcome and Phenotypic Expression in LAMP2 Cardiomyopathy". JAMA. 301 (12): 1253–1259. doi:10.1001/jama.2009.371. PMC 4106257. PMID 19318653. 3. ^ Spinazzi M, Fanin M, Melacini P, Nascimbeni AC, Angelini C. Cardioembolic stroke in Danon disease. Clin Genet. 2008;73:388-90. 4. ^ Lobrinus JA, Schorderet DF, Payot M, et al. (April 2005). "Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease)". Neuromuscular Disorders. 15 (4): 293–8. doi:10.1016/j.nmd.2004.12.007. PMID 15792868. S2CID 31934222. 5. ^ Nishino I, Fu J, Tanji K, et al. (August 2000). "Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease)". Nature. 406 (6798): 906–10. Bibcode:2000Natur.406..906N. doi:10.1038/35022604. PMID 10972294. S2CID 4332055. 6. ^ https://clinicaltrials.gov/ct2/show/NCT03882437 7. ^ Bejar, David; Colombo, Paolo C; Latif, Farhana; Yuzefpolskaya, Melana (8 July 2015). "Infiltrative Cardiomyopathies". Clinical Medicine Insights. Cardiology. 9 (Suppl 2): 29–38. doi:10.4137/CMC.S19706. ISSN 1179-5468. PMC 4498662. PMID 26244036. 8. ^ Danon MJ, Oh SJ, DiMauro S, et al. (January 1981). "Lysosomal glycogen storage disease with normal acid maltase". Neurology. 31 (1): 51–7. doi:10.1212/wnl.31.1.51. PMID 6450334. S2CID 32860087. 9. ^ "Mahmoud Ramadan". ResearchGate. 10. ^ "Mansoura University, Egypt". 11. ^ الفجيرة - ابتسام الشاعر (2016-02-19). ""دانون" مرض نادر يصيب القلب بالتضخم". البيان. ## External links[edit] Classification D * ICD-10: E74.0 * OMIM: 300257 * MeSH: D052120 External resources * Orphanet: 34587 * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia * v * t * e Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders Peroxisome biogenesis disorder * Zellweger syndrome * Neonatal adrenoleukodystrophy * Infantile Refsum disease * Adult Refsum disease-2 * RCP 1 Enzyme-related * Acatalasia * RCP 2&3 * Mevalonate kinase deficiency * D-bifunctional protein deficiency * Adult Refsum disease-1 Transporter-related * X-linked adrenoleukodystrophy Lysosomal * Danon disease See also: proteins, intermediates [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Danon disease	c0878677	7,007	wikipedia	https://en.wikipedia.org/wiki/Danon_disease	2021-01-18T18:29:03	{"gard": ["9730"], "mesh": ["D052120"], "umls": ["C0878677"], "icd-10": ["E74.0"], "orphanet": ["34587"], "wikidata": ["Q5220984"]}
A number sign (#) is used with this entry because polymorphisms in several genes are believed to predispose to nicotine dependence and smoking behavior, including the gene encoding G protein-coupled receptor-51 (GPR51; 607340) on chromosome 9q22. Li et al. (2006) found evidence of significant linkage of chromosome 10q22-q25 to smoking quantity (SQTL1; 611003). Saccone et al. (2007) found evidence of linkage of chromosome 22q12 to a heavy smoking phenotype (SQTL2; 611004). See also SQTL3 (612052), which is associated with polymorphisms in the nicotinic acetylcholine receptor gene cluster on chromosome 15q25.1. Li (2008) provided a review of susceptibility loci for nicotine dependence identified to date. Thirteen regions, located on chromosomes 3 through 7, 9 through 11, 17, 20, and 22 are suggestive or significant in at least 2 independent samples. Inheritance Evidence for moderate genetic influences on lifetime smoking practices was found by Carmelli et al. (1992) in an analysis of male twins in the National Academy of Sciences--National Research Twin Registry. The registry included male twins who were born in the United States between 1917 and 1927 and who were members of the Armed Forces during World World II. Information on smoking history was available for 4,775 pairs of twins who were first surveyed when they were in their forties and then resurveyed when they were aged 56 to 66. Eighty percent of the subjects had smoked at some time, 60% were still smokers in their forties, and 39% were smoking at the time of the resurvey. Monozygotic twins showed a higher concordance rate than dizygotic twins for having never smoked, for continuing to smoke, for quitting smoking, and for cigar or pipe smoking. For moderate smokers, there was no evidence of either familial or genetic influences; genetic factors seemed to contribute only in light smokers and heavy smokers. A metaanalysis of the data from 5 studies, each involving more than 1,000 twin pairs, showed an estimated heritability of 60% for the propensity to smoke (Heath and Madden, 1995). Twin studies also showed that the genetic factors involved in the initiation and cessation of smoking are partially overlapping but mostly independent (Heath and Martin, 1993). Mapping Gelernter et al. (2004) completed a genomewide scan to map loci increasing the risk for cigarette smoking in a set of families originally identified because they segregated panic disorder. They studied 142 genotyped individuals in a total of 12 families. Of these, 69 individuals were affected with habitual cigarette smoking. The 3 highest multipoint Zlr scores (3.43, 3.04, and 3.01; p = 0.0003, 0.0012, and 0.0013, respectively) reflected suggestive evidence for linkage and were observed in multipoint linkage analyses on chromosomes 11p and 9. Gelernter et al. (2004) noted that the chromosome 11 region has previously been linked to alcohol dependence and illegal drug abuse (e.g., Long et al., 1998), while the chromosome 9 region has previously been identified as significantly linked to panic disorder in Icelandic pedigrees (see 607853). In a genomewide scan of 505 individuals consisting mostly of dizygotic twin pairs from 153 Finnish families ascertained for nicotine dependence, Loukola et al. (2008) found suggestive evidence for linkage to chromosomes 7q31 and 11p15 (maximum lod scores of 2.50 at D7S486 and 2.25 at D11S4181, respectively). Both regions also showed evidence for linkage to the comorbid phenotype of smoking and alcohol use. A male-specific locus for isolated smoking and for the comorbid phenotype was also found at chromosome 7q35 (maximum 2-point lod scores of 2.90 and 2.74 at D7S661, respectively). Loukola et al. (2008) suggested that these findings may represent shared genetic etiology for these traits. The Tobacco and Genetics Consortium (2010) reported the findings of genomewide association studies for number of cigarettes smoked per day among 73,853 European individuals from multiple different cohorts, including those of Liu et al. (2010) and Thorgeirsson et al. (2010). An association was also found for the G allele of rs3733829 in the EGLN2 gene (606424) on chromosome 19q13 (p = 1.04 x 10(-8)). One part of this cohort was reported independently and simultaneously by Thorgeirsson et al. (2010), who conducted genomewide association metaanalyses for the number of cigarettes smoked per day among 31,266 individuals. Significant associations were found with the C allele of rs4105144 on 19q13 (p = 1.2 x 10(-9)). When combined with the studies of The Tobacco and Genetics Consortium (2010) and Liu et al. (2010) (n = 83,317), the p value for rs4105144 became 2.2 x 10(-12). Thorgeirsson et al. (2010) also found an association with the T allele of rs6474412 on chromosome 8p11 (p = 1.4 x 10(-8)) when combining the 3 studies. These 2 loci include genes involved in nicotine metabolism, such as CYP2A6 (122720) and CYP2B6 (123930) on 19q13, and nicotinic acetylcholine receptor subunits on 8p11 (CHRNB3; 118508) and CHRNA6 (606888). No associations were found when considering smoking initiation. Molecular Genetics ### Glutamate Transporters In a group of 23 individuals, including 5 nonalcoholic nonsmokers, 5 alcoholic nonsmokers, 7 nonalcoholic smokers, and 6 alcoholic smokers, Flatscher-Bader et al. (2008) found that expression levels of the glutamate transporters SLC1A2 (600300), SLC17A6 (607563), and SLC17A7 (605208) were robustly induced by smoking, an effect that was reduced by alcohol coexposure. Bonferroni post hoc analyses identified a relative increase in SLC1A2 mRNA levels by real-time PCR analysis in chronic smokers with and without alcohol abuse compared with nonsmoking alcoholics (3.99 times, p = 6 x 10(-3); 2.94 times, p = 6 x 10(-3), respectively), although this was not significant at the protein level. There was a striking induction of higher SLC17A6 relative expression in nonalcoholic smokers compared with controls (27.91 times, p = 2 x 10(-7)), as well as smoking chronic alcoholics (3.08 times, p = 3 x 10(-2)) and nonsmoking chronic alcoholics (13.27 times, p = 3 x 10(-6)). Additionally, relative SLC17A6 expression was significantly elevated in smoking chronic alcoholics compared with controls (9.06 times, p = 10(-4)) and nonsmoking alcohol abusers (4.31 times, p = 3 x 10(-3)). Relative SLC17A7 transcription was highly induced in heavy smokers compared with controls (18.64 times, p = 5 x 10(-3)), nonsmoking alcoholics, (15.16 times, p = 2 x 10(-3)), and smoking chronic alcoholics (9.97 times, p = 6 x 10(-4)). Glutamatergic transmission is vital for the control of the VTA and may also be critical to the weighting of novelty and importance of a stimulus, an essential output of this brain region. Flatscher-Bader et al. (2008) concluded that plasticity within the VTA may be a major molecular mechanism for the maintenance of smoking addiction and that alcohol, nicotine, and coabuse have distinct impacts on neuronal plasticity and glutamatergic transmission. ### Dopamine Transporter/Receptors Sabol et al. (1999) and Lerman et al. (1999) found a significant association between a particular polymorphism of the dopamine transporter gene SLC6A3 (126455) and smoking status. Individuals with the SLC6A39 allele were significantly less likely to be smokers, especially if they also had the DRD2A2 genotype at the dopamine receptor D2 locus (DRD2; 126450). The search for susceptibility loci for smoking-related behavior was discussed by Li et al. (2004). The review included a metaanalysis of 12 reported studies showing a significantly higher prevalence of the DRD2 TaqI A1 allele in smokers than in nonsmokers. For other candidate genes, insufficient published studies were available to allow a metaanalysis to be performed, or metaanalysis showed no significant difference between smokers and nonsmokers. Huang et al. (2008) found a significant association between nicotine dependence and a SNP (rs686) in the DRD1 gene (126449) among 1,366 African Americans. In a pooled sample of 1,366 African Americans and 671 European Americans, rs686 and rs4532 were both significantly associated with nicotine dependence. Several haplotypes related to these SNPs also suggested an association. In vitro functional expression studies indicated that rs686, which is located in the 3-prime untranslated region, is functionally involved in the regulation of DRD1 expression. ### DOPA Decarboxylase DOPA decarboxylase (DDC; 107930) is involved in the synthesis of dopamine, norepinephrine, and serotonin, and is located on chromosome 7p11, which showed a 'suggestive linkage' to nicotine dependence (ND) in a genomewide scan in the Framingham Heart Study population. Ma et al. (2005) tested 8 SNPs within DDC for association with ND, which was assessed by smoking quantity (SQ), heaviness of smoking index (HSI), and the Fagerstrom test for ND (FTND) score, in a total of 2,037 smokers and nonsmokers from 602 nuclear families of African American or European American ancestry. Association analysis for individual SNPs indicated that rs921451 was significantly associated with 2 of the 3 adjusted ND measures in European Americans. Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in African Americans, which was significantly associated with all 3 adjusted ND measures after correction for multiple testing. In contrast, the authors found a high-risk T-G-T-G haplotype for a different SNP combination in European Americans, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association with the SQ and FTND score. ### Cholinergic Receptors Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine were logical candidates for vulnerability to nicotine addiction. Feng et al. (2004) studied 6 SNPs in the CHRNA4 gene (118504) on chromosome 20q13.2-q13.3 and 4 SNPs in the CHRNB2 gene (118507) on chromosome 1q21 in relation to nicotine dependence in a collection of 901 subjects (815 sibs and 86 parents) from 222 nuclear families with multiple nicotine-addicted sibs. Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses. Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles of 2 SNPs in exon 5 of the CHRNA4 gene (118504.0005, 118504.0006) were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype that was significantly associated with a protective effect against nicotine addiction. The determination of gene-by-gene and gene-by-environment interactions represents one of the greatest challenges in genetics. Combinatorial approaches, such as the multifactor dimensionality reduction (MDR) method of Ritchie et al. (2001), are useful but have limitations such as not allowing for covariates that restrict their practical use. Lou et al. (2007) reported a generalized MDR (GMDR) method that permitted adjustment for discrete and quantitative covariates and was applicable to both dichotomous and continuous phenotypes in population-based studies of various designs. Computer simulations indicated that the GMDR method had superior performance in its ability to identify epistatic loci, compared with current methods in the literature. Lou et al. (2007) applied the method to a genetic study of 4 genes that were reported to be associated with nicotine dependence: CHRNA2 (118502), CHRNB4 (118509), BDNF (113503), and NTRK2 (600456). They found significant joint action between CHRNB4 and NTRK2. Lou et al. (2007) commented that ubiquity of joint actions appears to be a natural property of complex inherited traits and that the term 'epistasis,' coined for a specific type of gene-by-gene interaction, has evolved to have different meanings in biologic and statistical genetics. Thorgeirsson et al. (2008) identified a common variant, rs1051730, in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, nicotine dependence, and the risk of 2 smoking-related diseases (lung cancer and peripheral artery disease) in populations of European descent. The SNP rs1051730, which resides in the CHRNA3 gene (118503.0001), was strongly associated with smoking quantity (P = 5 x 10(-16)). The same variant was associated with nicotine dependence in a previous genomewide association study that used low-quantity smokers as controls (Saccone et al., 2007; Bierut et al., 2007). With a similar approach, Thorgeirsson et al. (2008) observed a highly significant association with nicotine dependence. The authors also demonstrated an association with lung cancer in a gene-environment interaction; see 612052. Keskitalo et al. (2009) measured the number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level (a nicotine metabolite) in 516 daily smokers (aged 30-75 years; 303 males and 213 females) from an adult Finnish population. Association of 21 SNPs from a 100-kb region of chromosome 15q25.1 with cotinine and CPD were examined. The SNP rs1051730 showed the strongest association to both measures; however, this SNP accounted for nearly a 5-fold larger proportion of variance in cotinine levels than in CPD (R(2) 4.3% vs 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Keskitalo et al. (2009) concluded that variation at the CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers. Hong et al. (2010) found a significant association (p = 0.020) between the CHRNA5 D398N variant (118505.0001) and smoking among 149 smokers and 148 nonsmokers (odds ratio of 1.84, p = 0.03 for 1 allele; odds ratio of 3.59, p = 0.032 for 2 alleles). The sample included individuals with psychiatric illnesses, which are associated with smoking; however, the D398N variant was not associated with psychiatric illness. Among 93 smokers and 79 nonsmokers who completed a functional MRI scan, smokers had significantly decreased functional connectivity between the dorsal anterior cingulate (dACC)-ventral striatum compared to nonsmokers, and the decrease was associated with the N389 risk allele. In addition, reduced connectivity of this circuit correlated with greater severity of nicotine addiction. Nonsmoker carriers of the N389 risk allele also showed reduced connectivity of this circuit, confirming a genetic effect independent of smoking status. Hong et al. (2010) postulated that variation in the nAChR alpha-4/beta-2/alpha-5 receptor may modulate dopamine release, which may regulate the reinforcing effects and addictive properties of nicotine. ### G Protein-Coupled Receptor-51 Beuten et al. (2005) concluded from findings in association studies that variants in the GABABR2 gene (607340), which encodes subunit 2 of the gamma-aminobutyric acid type B receptor, play an important role in the etiology of nicotine dependence. ### Serotonin Transporter Gerra et al. (2005) examined the association of the serotonin transporter promoter polymorphism (SLC6A4; 182138.0001) with smoking behavior among adolescents. They genotyped 210 Caucasian high school students, including 103 nonsmokers and 107 tobacco smokers, aged 14 to 19 years. They also assessed aggressiveness levels, temperamental traits, and school performance. Short-short (SS) genotype frequency was higher among smokers compared to nonsmokers (p = 0.023). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 1.17 (95% CI, 0.30-2.05) when smokers were compared with nonsmokers. The SS genotype frequency was higher among heavy smokers with early onset compared with moderate smokers with late onset (p = 0.042). Irritability scores and school failure frequency were significantly higher in the smokers than in the nonsmokers. Multivariate model-fitting analyses evidenced a significantly greater relationship of genotype with irritability levels (0.34, p less than 0.001) and temperament traits (0.36, p less than 0.001) than with school performance (rate of school underachievement, 0.18, p less than 0.05) and nicotine smoking (0.24, p less than 0.01). Gerra et al. (2005) suggested that decreased expression of the SLC6A4 gene caused by the S allele may be associated with smoking behavior among adolescents and with increased risk for developing nicotine dependence, possibly in relationship to personality traits, temperamental characteristics, and school underachievement. Kremer et al. (2005) studied 330 families and 244 individuals who had ever smoked (54 past smokers, 190 current smokers) along with various personality measures by genotyping them for the serotonin transporter gene promoter polymorphism. In contrast to the findings of Gerra et al. (2005), they found a significant excess of the long allele of the SLC6A4 promoter polymorphism in current smokers, past smokers, and ever smokers compared to participants who had never smoked. ### Taste Receptor Polymorphisms Mangold et al. (2008) presented evidence suggesting that the 3 SNPs in the TAS2R38 gene (607751.0001-607751.0003) identified by Kim et al. (2003) may play a role in the development of nicotine dependence among African Americans. The taster haplotype PAV was inversely associated (p = 0.0165), and the nontaster haplotype AVI was positively associated (p = 0.0120), with smoking quantity in a study of 1,053 African American smokers. The nontaster haplotype was positively associated with all measures of nicotine dependence in female African American smokers (p = 0.01-0.003). No significant associations were observed in a sample of 515 European smokers. Mangold et al. (2008) postulated that heightened oral sensitivity confers protection against nicotine dependence. Misc \- Smoking habit Inheritance \- Genetic factors seem to contribute only in light smokers and heavy smokers ▲ 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	TOBACCO ADDICTION, SUSCEPTIBILITY TO	c1861063	7,008	omim	https://www.omim.org/entry/188890	2019-09-22T16:32:31	{"omim": ["188890"], "synonyms": ["Alternative titles", "CIGARETTE HABITUATION, SUSCEPTIBILITY TO", "SMOKING HABIT, SUSCEPTIBILITY TO", "NICOTINE DEPENDENCE, SUSCEPTIBILITY TO", "NICOTINE ADDICTION, SUSCEPTIBILITY TO", "NICOTINE DEPENDENCE, PROTECTION AGAINST"]}
"Montezuma's revenge" and "Delhi belly" redirect here. For the film, see Delhi Belly (film). For other uses, see Montezuma's revenge (disambiguation). stomach and intestinal infection Travelers' diarrhea Other namesTravellers' diarrhoea, tourist diarrhea,[1] traveler's dysentery[1] The bacterium E. coli, the most common cause of Travelers' diarrhea SpecialtyInfectious disease SymptomsUnformed stool while traveling, fever, abdominal cramps[2][3] DurationTypically < 5 days[3] CausesOften bacterial[3] Risk factorsTravel in the developing world Diagnostic methodBased on symptoms and travel history PreventionEating only properly prepared food, drinking bottled water, frequent hand washing[4] TreatmentOral rehydration therapy, antibiotics, loperamide[3][4] Frequency~35% of travelers to the developing world[3] Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling.[2][3] It may be accompanied by abdominal cramps, nausea, fever, and bloating.[3] Occasionally bloody diarrhea may occur.[5] Most travelers recover within four days with little or no treatment.[3] About 10% of people may have symptoms for a week.[3] Bacteria are responsible for more than half of cases.[3] The bacteria enterotoxigenic Escherichia coli (ETEC) are typically the most common except in Southeast Asia, where Campylobacter is more prominent.[2][3] About 10 to 20 percent of cases are due to norovirus.[3] Protozoa such as Giardia may cause longer term disease.[3] The risk is greatest in the first two weeks of travel and among young adults.[2] People affected are more often from the developed world.[2] Recommendations for prevention include eating only properly cleaned and cooked food, drinking bottled water, and frequent hand washing.[4] The oral cholera vaccine, while effective for cholera, is of questionable use for travelers' diarrhea.[6] Preventive antibiotics are generally discouraged.[3] Primary treatment includes rehydration and replacing lost salts (oral rehydration therapy).[3][4] Antibiotics are recommended for significant or persistent symptoms, and can be taken with loperamide to decrease diarrhea.[3] Hospitalization is required in less than 3 percent of cases.[2] Estimates of the percentage of people affected range from 20 to 50 percent among travelers to the developing world.[3] TD is particularly common among people travelling to Asia (except for Japan and Singapore), the Middle East, Africa, Mexico, and Central and South America.[4][7] The risk is moderate in Southern Europe, Russia, and China.[8] TD has been linked to later irritable bowel syndrome and Guillain–Barré syndrome.[2][3] It has colloquially been known by a number of names, including "Montezuma's revenge" and "Delhi belly".[9] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Risk factors * 2.2 Immunity * 3 Prevention * 3.1 Sanitation * 3.2 Water * 3.3 Medications * 3.4 Vaccination * 3.5 Probiotics * 4 Treatment * 4.1 Antibiotics * 4.2 Antimotility agents * 5 Epidemiology * 6 Society and culture * 6.1 Wilderness diarrhea * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] The onset of TD usually occurs within the first week of travel, but may occur at any time while traveling, and even after returning home, depending on the incubation period of the infectious agent. Bacterial TD typically begins abruptly, but Cryptosporidium may incubate for seven days, and Giardia for 14 days or more, before symptoms develop. Typically, a traveler experiences four to five loose or watery bowel movements each day. Other commonly associated symptoms are abdominal cramping, bloating, fever, and malaise. Appetite may decrease significantly.[10] Though unpleasant, most cases of TD are mild, and resolve in a few days without medical intervention.[11] Blood or mucus in the diarrhea, significant abdominal pain, or high fever suggests a more serious cause, such as cholera, characterized by a rapid onset of weakness and torrents of watery diarrhea with flecks of mucus (described as "rice water" stools). Medical care should be sought in such cases; dehydration is a serious consequence of cholera, and may trigger serious sequelae—including, in rare instances, death—as rapidly as 24 hours after onset if not addressed promptly.[11] ## Causes[edit] E. coli, enterotoxigenic 20–75% E. coli, enteroaggregative 0–20% E. coli, enteroinvasive 0–6% Shigella spp. 2–30% Salmonella spp. 0–33% Campylobacter jejuni 3–17% Vibrio parahaemolyticus 0–31% Aeromonas hydrophila 0–30% Giardia lamblia 0–20% Entamoeba histolytica 0–5% Cryptosporidium spp. 0–20% Cyclospora cayetanensis ? Rotavirus 0–36% Norovirus 0–10% Infectious agents are the primary cause of travelers' diarrhea. Bacterial enteropathogens cause about 80% of cases. Viruses and protozoans account for most of the rest.[10] The most common causative agent isolated in countries surveyed has been enterotoxigenic Escherichia coli (ETEC).[10] Enteroaggregative E. coli is increasingly recognized.[11] Shigella spp. and Salmonella spp. are other common bacterial pathogens. Campylobacter, Yersinia, Aeromonas, and Plesiomonas spp. are less frequently found. Mechanisms of action vary: some bacteria release toxins which bind to the intestinal wall and cause diarrhea; others damage the intestines themselves by their direct presence.[citation needed] Brachyspira pilosicoli pathogen also appears to be responsible for many chronic intermittent watery diarrea and is only diagnosed through colonic biopsies and microscopic discovery of a false brush border [12] on H&E or Warthin silver stain: its brush-border is stonger and longer that Brachyspira aalborgi's brush-border. It is unfortunately often not diagnosed as coproculture does not allow growth and 16S PCR panel primers do not match Brachyspira sequences.[13] While viruses are associated with less than 20% of adult cases of travelers' diarrhea, they may be responsible for nearly 70% of cases in infants and children. Diarrhea due to viral agents is unaffected by antibiotic therapy, but is usually self-limited.[11] Protozoans such as Giardia lamblia, Cryptosporidium and Cyclospora cayetanensis can also cause diarrhea. Pathogens commonly implicated in travelers' diarrhea appear in the table in this section.[11][14] A subtype of travelers' diarrhea afflicting hikers and campers, sometimes known as wilderness diarrhea, may have a somewhat different frequency of distribution of pathogens.[15] ### Risk factors[edit] The primary source of infection is ingestion of fecally contaminated food or water. Attack rates are similar for men and women.[10] The most important determinant of risk is the traveler's destination. High-risk destinations include developing countries in Latin America, Africa, the Middle East, and Asia.[10] Among backpackers, additional risk factors include drinking untreated surface water and failure to maintain personal hygiene practices and clean cookware.[16] Campsites often have very primitive (if any) sanitation facilities, making them potentially as dangerous as any developing country.[citation needed] Although travelers' diarrhea usually resolves within three to five days (mean duration: 3.6 days), in about 20% of cases, the illness is severe enough to require bedrest, and in 10%, the illness duration exceeds one week.[11] For those prone to serious infections, such as bacillary dysentery, amoebic dysentery, and cholera, TD can occasionally be life-threatening.[11] Others at higher-than-average risk include young adults, immunosuppressed persons, persons with inflammatory bowel disease or diabetes, and those taking H2 blockers or antacids.[10] ### Immunity[edit] Travelers often get diarrhea from eating and drinking foods and beverages that have no adverse effects on local residents. This is due to immunity that develops with constant, repeated exposure to pathogenic organisms. The extent and duration of exposure necessary to acquire immunity has not been determined; it may vary with each individual organism. A study among expatriates in Nepal suggests that immunity may take up to seven years to develop—presumably in adults who avoid deliberate pathogen exposure.[17] Conversely, immunity acquired by American students while living in Mexico disappeared, in one study, as quickly as eight weeks after cessation of exposure.[18] ## Prevention[edit] ### Sanitation[edit] Recommendations include avoidance of questionable foods and drinks, on the assumption that TD is fundamentally a sanitation failure, leading to bacterial contamination of drinking water and food.[10] While the effectiveness of this strategy has been questioned, given that travelers have little or no control over sanitation in hotels and restaurants, and little evidence supports the contention that food vigilance reduces the risk of contracting TD,[19] guidelines continue to recommend basic, common-sense precautions when making food and beverage choices:[3] * Maintain good hygiene and use only safe water for drinking and brushing teeth.[11] * Safe beverages include bottled water, bottled carbonated beverages, and water boiled or appropriately treated by the traveler (as described below).[11] Caution should be exercised with tea, coffee, and other hot beverages that may be only heated, not boiled.[10] * In restaurants, insist that bottled water be unsealed in your presence; reports of locals filling empty bottles with untreated tap water and reselling them as purified water have surfaced.[11] When in doubt, a bottled carbonated beverage is the safest choice, since it is difficult to simulate carbonation when refilling a used bottle. * Avoid ice, which may not have been made with safe water.[10] * Avoid green salads, because the lettuce and other uncooked ingredients are unlikely to have been washed with safe water.[10] * Avoid eating raw fruits and vegetables unless cleaned and peeled personally.[10] If handled properly, thoroughly cooked fresh and packaged foods are usually safe.[10] Raw or undercooked meat and seafood should be avoided. Unpasteurized milk, dairy products, mayonnaise, and pastry icing are associated with increased risk for TD, as are foods and beverages purchased from street vendors and other establishments where unhygienic conditions may be present.[11] ### Water[edit] Although safe bottled water is now widely available in most remote destinations, travelers can treat their own water if necessary, or as an extra precaution.[11] Techniques include boiling, filtering, chemical treatment, and ultraviolet light; boiling is by far the most effective of these methods.[20] Boiling rapidly kills all active bacteria, viruses, and protozoa. Prolonged boiling is usually unnecessary; most microorganisms are killed within seconds at water temperature above 55–70 °C (130–160 °F).[21][22] The second-most effective method is to combine filtration and chemical disinfection.[23] Filters eliminate most bacteria and protozoa, but not viruses. Chemical treatment with halogens—chlorine bleach, tincture of iodine, or commercial tablets—have low-to-moderate effectiveness against protozoa such as Giardia, but work well against bacteria and viruses. UV light is effective against both viruses and cellular organisms, but only works in clear water, and it is ineffective unless manufacturer's instructions are carefully followed for maximum water depth/distance from UV source, and for dose/exposure time. Other claimed advantages include short treatment time, elimination of the need for boiling, no taste alteration, and decreased long-term cost compared with bottled water. The effectiveness of UV devices is reduced when water is muddy or turbid; as UV is a type of light, any suspended particles create shadows that hide microorganisms from UV exposure.[24] ### Medications[edit] Bismuth subsalicylate four times daily reduces rates of travelers' diarrhea.[2][25] Though many travelers find a four-times-per-day regimen inconvenient, lower doses have not been shown to be effective.[2][25] Potential side effects include black tongue, black stools, nausea, constipation, and ringing in the ears. Bismuth subsalicylate should not be taken by those with aspirin allergy, kidney disease, or gout, nor concurrently with certain antibiotics such as the quinolones, and should not be taken continuously for more than three weeks.[medical citation needed] Some countries do not recommend it due to the risk of rare but serious side effects.[25] A hyperimmune bovine colostrum to be taken by mouth is marketed in Australia for prevention of ETEC-induced TD. As yet, no studies show efficacy under actual travel conditions.[3] Though effective, antibiotics are not recommended for prevention of TD in most situations because of the risk of allergy or adverse reactions to the antibiotics, and because intake of preventive antibiotics may decrease effectiveness of such drugs should a serious infection develop subsequently. Antibiotics can also cause vaginal yeast infections, or overgrowth of the bacterium Clostridium difficile, leading to pseudomembranous colitis and its associated severe, unrelenting diarrhea.[26] Antibiotics may be warranted in special situations where benefits outweigh the above risks, such as immunocompromised travelers, chronic intestinal disorders, prior history of repeated disabling bouts of TD, or scenarios in which the onset of diarrhea might prove particularly troublesome. Options for prophylactic treatment include the quinolone antibiotics (such as ciprofloxacin), azithromycin, and trimethoprim/sulfamethoxazole, though the latter has proved less effective in recent years.[27] Rifaximin may also be useful.[25][28] Quinolone antibiotics may bind to metallic cations such as bismuth, and should not be taken concurrently with bismuth subsalicylate. Trimethoprim/sulfamethoxazole should not be taken by anyone with a history of sulfa allergy.[medical citation needed] ### Vaccination[edit] The oral cholera vaccine, while effective for prevention of cholera, is of questionable use for prevention of TD.[6] A 2008 review found tentative evidence of benefit.[29] A 2015 review stated it may be reasonable for those at high risk of complications from TD.[3] Several vaccine candidates targeting ETEC or Shigella are in various stages of development.[30][31] ### Probiotics[edit] One 2007 review found that probiotics may be safe and effective for prevention of TD, while another review found no benefit.[2] A 2009 review confirmed that more study is needed, as the evidence to date is mixed.[25] ## Treatment[edit] Most cases of TD are mild and resolve in a few days without treatment, but severe or protracted cases may result in significant fluid loss and dangerous electrolytic imbalance. Dehydration due to diarrhea can also alter the effectiveness of medicinal and contraceptive drugs. Adequate fluid intake (oral rehydration therapy) is therefore a high priority. Commercial rehydration drinks[32] are widely available; alternatively, purified water or other clear liquids are recommended, along with salty crackers or oral rehydration salts (available in stores and pharmacies in most countries) to replenish lost electrolytes.[10] Carbonated water or soda, left open to allow dissipation of the carbonation, is useful when nothing else is available.[11] In severe or protracted cases, the oversight of a medical professional is advised. ### Antibiotics[edit] If diarrhea becomes severe (typically defined as three or more loose stools in an eight-hour period), especially if associated with nausea, vomiting, abdominal cramps, fever, or blood in stools, medical treatment should be sought. Such patients may benefit from antimicrobial therapy.[10] A 2000 literature review found that antibiotic treatment shortens the duration and severity of TD; most reported side effects were minor, or resolved on stopping the antibiotic.[33] The antibiotic recommended varies based upon the destination of travel.[34] Trimethoprim–sulfamethoxazole and doxycycline are no longer recommended because of high levels of resistance to these agents.[10] Antibiotics are typically given for three to five days, but single doses of azithromycin or levofloxacin have been used.[35] Rifaximin and rifamycin are approved in the U.S. for treatment of TD caused by ETEC.[36][37] If diarrhea persists despite therapy, travelers should be evaluated for bacterial strains resistant to the prescribed antibiotic, possible viral or parasitic infections,[10] bacterial or amoebic dysentery, Giardia, helminths, or cholera.[11] ### Antimotility agents[edit] Antimotility drugs such as loperamide and diphenoxylate reduce the symptoms of diarrhea by slowing transit time in the gut. They may be taken to slow the frequency of stools, but not enough to stop bowel movements completely, which delays expulsion of the causative organisms from the intestines.[10] They should be avoided in patients with fever, bloody diarrhea, and possible inflammatory diarrhea.[38] Adverse reactions may include nausea, vomiting, abdominal pain, hives or rash, and loss of appetite.[39] Antimotility agents should not, as a rule, be taken by children under age two.[medical citation needed] ## Epidemiology[edit] An estimated 10 million people—20 to 50% of international travelers—develop TD each year.[10] It is more common in the developing world, where rates exceed 60%, but has been reported in some form in virtually every travel destination in the world.[40] ## Society and culture[edit] Moctezuma's revenge is a colloquial term for travelers' diarrhea contracted in Mexico. The name refers to Moctezuma II (1466–1520), the Tlatoani (ruler) of the Aztec civilization who was overthrown by the Spanish conquistador Hernán Cortés in the early 16th century, thereby bringing large portions of what is now Mexico and Central America under the rule of the Spanish crown.[citation needed] ### Wilderness diarrhea[edit] Main article: Wilderness acquired diarrhea Wilderness diarrhea, also called wilderness-acquired diarrhea (WAD) or backcountry diarrhea, refers to diarrhea among backpackers, hikers, campers and other outdoor recreationalists in wilderness or backcountry situations, either at home or abroad.[15] It is caused by the same fecal microorganisms as other forms of travelers' diarrhea, usually bacterial or viral. Since wilderness campsites seldom provide access to sanitation facilities, the infection risk is similar to that of any developing country.[16] Water treatment, good hygiene, and dish washing have all been shown to reduce the incidence of WAD.[41][42] ## See also[edit] * Diarrhea ## References[edit] 1. ^ a b Ensminger, Marion Eugene; Ensminger, Audrey H. (1993-11-09). Foods & Nutrition Encyclopedia, Two Volume Set. CRC Press. p. 143. ISBN 9780849389801. 2. ^ a b c d e f g h i j Giddings, SL; Stevens, AM; Leung, DT (March 2016). "Traveler's Diarrhea". The Medical Clinics of North America. 100 (2): 317–30. doi:10.1016/j.mcna.2015.08.017. PMC 4764790. PMID 26900116. 3. ^ a b c d e f g h i j k l m n o p q r s t u Leder, K (2015). "Advising travellers about management of travellers' diarrhoea". Australian Family Physician. 44 (1–2): 34–37. PMID 25688957. Archived from the original on 2017-01-12. 4. ^ a b c d e "Travelers' Diarrhea". cdc.gov. April 26, 2013. Archived from the original on March 13, 2016. 5. ^ Feldman, Mark (2015). Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management (10th ed.). Elsevier Health Sciences. p. 1924. ISBN 9781455749898. Archived from the original on 2016-03-10. 6. ^ a b Ahmed, T; Bhuiyan, TR; Zaman, K; Sinclair, D; Qadri, F (5 July 2013). "Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea". The Cochrane Database of Systematic Reviews. 7 (7): CD009029. doi:10.1002/14651858.CD009029.pub2. PMC 6532719. PMID 23828581. 7. ^ "Health Information for Travelers to Singapore - Clinician view \| Travelers' Health \| CDC". wwwnc.cdc.gov. Retrieved 5 February 2019. 8. ^ Diemert, D. J. (17 July 2006). "Prevention and Self-Treatment of Traveler's Diarrhea". Clinical Microbiology Reviews. 19 (3): 583–594. doi:10.1128/CMR.00052-05. PMC 1539099. PMID 16847088. 9. ^ "Traveler's Diarrhea-Topic Overview". WebMD. 2013-03-27. Archived from the original on 2015-06-30. Retrieved 2015-07-02. "Traveler's diarrhea is sometimes called by its more colorful names: Montezuma's revenge, Delhi belly, and Turkey trots." 10. ^ a b c d e f g h i j k l m n o p q r "Travelers' Diarrhea". Centers for Disease Control and Prevention. November 21, 2006. Archived from the original on April 3, 2008. 11. ^ a b c d e f g h i j k l m n "Travelers' diarrhea". safewateronline.com. Archived from the original on 6 June 2008. 12. ^ Hampson, David J. (2017-11-29). "The Spirochete Brachyspira pilosicoli, Enteric Pathogen of Animals and Humans". Clinical Microbiology Reviews. 31 (1). doi:10.1128/CMR.00087-17. ISSN 0893-8512. PMC 5740978. PMID 29187397. 13. ^ Thorell, Kaisa; Inganäs, Linn; Backhans, Annette; Agréus, Lars; Öst, Åke; Walker, Marjorie M.; Talley, Nicholas J.; Kjellström, Lars; Andreasson, Anna; Engstrand, Lars (2019-10-04). "Isolates from Colonic Spirochetosis in Humans Show High Genomic Divergence and Potential Pathogenic Features but Are Not Detected Using Standard Primers for the Human Microbiota". Journal of Bacteriology. 201 (21). doi:10.1128/JB.00272-19. ISSN 0021-9193. PMC 6779451. PMID 31405919. 14. ^ Ortega, Ynés R.; Sanchez, Roxana (2010). "Update on Cyclospora cayetanensis, a Food-Borne and Waterborne Parasite". Clinical Microbiology Reviews. 23 (1): 218–234. doi:10.1128/CMR.00026-09. PMC 2806662. PMID 20065331. 15. ^ a b Zell SC (1992). "Epidemiology of Wilderness-acquired Diarrhea: Implications for Prevention and Treatment". J Wilderness Med. 3 (3): 241–9. doi:10.1580/0953-9859-3.3.241. 16. ^ a b Hargreaves JS (2006). "Laboratory evaluation of the 3-bowl system used for washing-up eating utensils in the field". Wilderness Environ Med. 17 (2): 94–102. doi:10.1580/PR17-05.1. PMID 16805145. 17. ^ David R. Shlim, Understanding Diarrhea in Travelers. A Guide to the Prevention, Diagnosis, and Treatment of the World's Most Common Travel-Related Illness Archived 2008-05-24 at the Wayback Machine. CIWEC Clinic Travel Medicine Center, 2004. 18. ^ Luis Ostrosky-Zeichner, Charles D. Ericsson, Travelers' diarrhea. In Jane N. Zucherman, Ed., Principles and Practice of Travel Medicine, John Wiley and Sons, 2001. p.153 Google books preview Archived 2017-09-08 at the Wayback Machine 19. ^ Shlim, DR (1 December 2005). "Looking for evidence that personal hygiene precautions prevent traveler's diarrhea". Clinical Infectious Diseases. 41 Suppl 8: S531–5. doi:10.1086/432947. PMID 16267714. 20. ^ "Water Disinfection for Travelers - Chapter 2 - 2018 Yellow Book \| Travelers' Health \| CDC". 21. ^ National Advisory Committee on Microbiological Criteria for Foods: Requisite Scientific Parameters for Establishing the Equivalence of Alternative Methods of Pasteurization, USDA, 2004 22. ^ McGee, Harold (2011-08-23). "Bending the Rules on Bacteria and Food Safety". The New York Times. Archived from the original on 2017-09-08. Retrieved 2014-10-24.CS1 maint: bot: original URL status unknown (link). Retrieved October 24, 2014. 23. ^ https://www.cdc.gov/healthywater/pdf/drinking/Backcountry_Water_Treatment.pdf 24. ^ Ultraviolet Light Disinfection in the Use of Individual Water Purification Devices. Technical Information Paper # 31-006-0211 U.S. Army Public Health Command Archived 2014-03-08 at the Wayback Machine, retrieved January 5, 2016. 25. ^ a b c d e DuPont, HL; Ericsson, CD; Farthing, MJ; Gorbach, S; Pickering, LK; Rombo, L; Steffen, R; Weinke, T (2009). "Expert review of the evidence base for prevention of travelers' diarrhea". Journal of Travel Medicine. 16 (3): 149–60. doi:10.1111/j.1708-8305.2008.00299.x. PMID 19538575. 26. ^ Travelers' Diarrhea. The Travel Doctor Archived 2011-02-01 at the Wayback Machine Retrieved March 21, 2011. 27. ^ Adachi J, et al. Empirical Antimicrobial Therapy for Traveler's Diarrhea. Clinical Infectious Diseases; Vol. 31 Issue 4 (10/1/2000), p1079. 28. ^ DuPont, H (2007). "Therapy for and Prevention of Traveler's Diarrhea". Clinical Infectious Diseases. 45 (45 (Suppl 1)): S78–S84. doi:10.1086/518155. PMID 17582576. 29. ^ Jelinek T, Kollaritsch H (2008). "Vaccination with Dukoral against travelers' diarrhea (ETEC) and cholera". Expert Rev Vaccines. 7 (5): 561–7. doi:10.1586/14760584.7.5.561. PMID 18564011. S2CID 20442764. 30. ^ World Health Organization. Enterotoxigenic Escherichia coli (ETEC). Archived 2012-05-15 at the Wayback Machine 31. ^ "World Health Organization. Shigellosis". who.int. Archived from the original on 2008-12-15. 32. ^ Rehydration drinks. EMedicineHealth.com. Archived 2014-08-19 at the Wayback Machine Retrieved August 18, 2014. 33. ^ De Bruyn G, Hahn S, Borwick A (2000). "Antibiotic treatment for travellers' diarrhoea". Cochrane Database of Systematic Reviews (3): CD002242. doi:10.1002/14651858.CD002242. PMC 6532602. PMID 10908534. 34. ^ "Travelers' Diarrhea". CDC. Retrieved 19 November 2018. 35. ^ Sanders JW, Frenck RW, Putnam SD, et al. (August 2007). "Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler's diarrhea in United States military personnel in Turkey". Clin. Infect. Dis. 45 (3): 294–301. doi:10.1086/519264. PMID 18688944. 36. ^ "Xifaxan label information" (PDF). Retrieved November 15, 2008. 37. ^ "Press Announcements - FDA approves new drug to treat travelers' diarrhea". www.fda.gov. Retrieved 19 November 2018. 38. ^ "Disease Management Project - Missing Chapter". Archived from the original on 2016-03-04. Retrieved 2015-07-25. 39. ^ Diphenoxylate package insert. Drugs.com. Archived 2011-06-22 at the Wayback Machine Retrieved 2010-10-07. 40. ^ Steffen, R (Dec 1, 2005). "Epidemiology of traveler's diarrhea" (PDF). Clinical Infectious Diseases. 41 Suppl 8: S536–40. doi:10.1086/432948. PMID 16267715. 41. ^ Boulware, DR (2003). "Medical risks of wilderness hiking". American Journal of Medicine. 114 (March): 288–93. doi:10.1016/S0002-9343(02)01494-8. PMID 12681456. 42. ^ McIntosh, SE (2007). "Medical Incidents and Evacuations on Wilderness Expeditions". Wilderness and Environmental Medicine. 18 (Winter): 298–304. doi:10.1580/07-WEME-OR-093R1.1. PMID 18076301. This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. ## External links[edit] Classification D * ICD-9-CM: 009.2 Wikivoyage has a travel guide for Travellers' diarrhea. * "Travelers' Diarrhea". Centers for Disease Control and Prevention. * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum * v * t * e Symptoms and signs relating to the human digestive system or abdomen Gastrointestinal tract * Nausea * Vomiting * Heartburn * Aerophagia * Pagophagia * Dysphagia * oropharyngeal * esophageal * Odynophagia * Bad breath * Xerostomia * Hypersalivation * Burping * Wet burp * Goodsall's rule * Chilaiditi syndrome * Dance's sign * Aaron's sign * Arapov's sign * Markle sign * McBurney's point * Sherren's triangle * Radiologic signs: Hampton's line * Klemm's sign Accessory * liver: Councilman body * Mallory body * biliary: Boas' sign * Courvoisier's law * Charcot's cholangitis triad/Reynolds' pentad * cholecystitis (Murphy's sign * Lépine's sign * Mirizzi's syndrome) * Nardi test Defecation * Flatulence * Fecal incontinence * Encopresis * Fecal occult blood * Rectal tenesmus * Constipation * Obstructed defecation * Diarrhea * Rectal discharge * Psoas sign * Obturator sign * Rovsing's sign * Hamburger sign * Heel tap sign * Aure-Rozanova's sign * Dunphy sign * Alder's sign * Lockwood's sign * Rosenstein's sign Abdomen Pain * Abdominal pain * Acute abdomen * Colic * Baby colic * Abdominal guarding * Blumberg sign Distension * Abdominal distension * Bloating * Ascites * Tympanites * Shifting dullness * Ascites * Fluid wave test Masses * Abdominal mass * Hepatosplenomegaly * Hepatomegaly * Splenomegaly Other * Jaundice * Mallet-Guy sign * Puddle sign * Ballance's sign * Aortic insufficiency * Castell's sign * Kehr's sign * Cullen's sign * Grey Turner's sign Hernia * Howship–Romberg sign * Hannington-Kiff sign Other * Cupola sign * Fothergill's sign * Carnett's sign * Sister Mary Joseph nodule [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Travelers' diarrhea	c0277528	7,009	wikipedia	https://en.wikipedia.org/wiki/Travelers%27_diarrhea	2021-01-18T18:59:32	{"icd-9": ["009.2"], "icd-10": ["A09"], "wikidata": ["Q138885"]}
A number sign (#) is used with this entry because Robinow-Sorauf syndrome is caused by heterozygous mutation in the TWIST gene (601622.0009). Some authors (e.g., Reardon and Winter, 1994) have suggested that the disorder is not distinct, but part of the phenotypic spectrum of Saethre-Chotzen syndrome (101400), which is also caused by TWIST mutations. Clinical Features Carter et al. (1982) and Young and Harper (1982) described a distinct acrocephalosyndactyly syndrome that the first group of authors suggested be called the Robinow-Sorauf syndrome in recognition of the priority of description by those authors (Robinow and Sorauf, 1975). The patients were described by Carter et al. (1982) as having facies like those of the Saethre-Chotzen syndrome and bilaterally broad big toes owing to partial or complete duplication of the distal phalanx. The syndrome was considered distinct from the Pfeiffer syndrome (101600) in which the facies more nearly resembles Crouzon syndrome (123500) and in which the proximal phalanx of the big toe (and often of the thumb) is abnormal. Two instances of male-to-male transmission were noted in the family reported by Young and Harper (1982). Reardon and Winter (1994) reviewed observations leading them to suggest that it is 'unlikely that there is continued justification' for affording the Robinow-Sorauf syndrome an entry separate from that for Saethre-Chotzen syndrome. Molecular Genetics In a proband and his mother affected with Robinow-Sorauf syndrome, Kunz et al. (1999) reported a frameshift mutation in the TWIST gene (601622.0009). The authors considered this mutation to be confirmation that the Saethre-Chotzen and Robinow-Sorauf syndromes are at least allelic, if not part of a clinical spectrum of the same condition. Cai et al. (2003) suggested that the diagnosis of Robinow-Sorauf syndrome in the family reported by Kunz et al. (1999) could be questioned because the affected individuals lacked certain characteristics, such as syndactyly, that were found repeatedly in all members of the original Robinow-Sorauf pedigree. Cai et al. (2003) studied the original family reported by Robinow and Sorauf (1975) and found that the affected individuals were heterozygous for a 221C-T transition in the TWIST gene, resulting in a premature stop codon at amino acid position 71 (Q71X; 180750.0012). This novel nonsense mutation was 5-prime of the DNA-binding region where other nonsense mutations had been found in families with Saethre-Chotzen syndrome. Cai et al. (2003) stated that they examined 3 of the 11 affected members of the original family in addition to the propositus and found that all had second interdigital syndactyly as well as a toe deformity (either polydactyly or hallux valgus). Cai et al. (2003) stated that the reported 'Robinow-Sorauf' families are examples of variable expression of the TWIST mutant phenotype and provide further proof that the 'Robinow-Sorauf' syndrome lies within the spectrum of the SCS syndrome. Eyes \- Shallow orbits \- Hypertelorism \- Plagiocephaly (asymmetry of orbits) \- Strabismus Inheritance \- Autosomal dominant \- ? same as Saethre-Chotzen syndrome Facies \- Flat facies \- Thin, long, pointed nose Limbs \- Broad great toes \- Duplicated great toe distal phalanx ▲ 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	ROBINOW-SORAUF SYNDROME	c1867146	7,010	omim	https://www.omim.org/entry/180750	2019-09-22T16:35:06	{"mesh": ["C537183"], "omim": ["180750"], "orphanet": ["3106"], "synonyms": ["Alternative titles", "CRANIOSYNOSTOSIS-BIFID HALLUX SYNDROME", "ACROCEPHALOSYNDACTYLY, ROBINOW-SORAUF TYPE"]}
Antiphospholipid syndrome is a disorder characterized by an increased tendency to form abnormal blood clots (thromboses) that can block blood vessels. This clotting tendency is known as thrombophilia. In antiphospholipid syndrome, the thromboses can develop in nearly any blood vessel in the body, but most frequently occur in the vessels of the lower limbs. If a blood clot forms in the vessels in the brain, blood flow is impaired and can lead to stroke. Antiphospholipid syndrome is an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs. Women with antiphospholipid syndrome are at increased risk of complications during pregnancy. These complications include pregnancy-induced high blood pressure (preeclampsia), an underdeveloped placenta (placental insufficiency), early delivery, or pregnancy loss (miscarriage). In addition, women with antiphospholipid syndrome are at greater risk of having a thrombosis during pregnancy than at other times during their lives. At birth, infants of mothers with antiphospholipid syndrome may be small and underweight. A thrombosis or pregnancy complication is typically the first sign of antiphospholipid syndrome. This condition usually appears in early to mid-adulthood but can begin at any age. Other signs and symptoms of antiphospholipid syndrome that affect blood cells and vessels include a reduced amount of cells involved in blood clotting called platelets (thrombocytopenia), a shortage of red blood cells (anemia) due to their premature breakdown (hemolysis), and a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. In addition, affected individuals may have open sores (ulcers) on the skin, migraine headaches, heart disease, or intellectual disability. Many people with antiphospholipid syndrome also have other autoimmune disorders such as systemic lupus erythematosus. Rarely, people with antiphospholipid syndrome develop thromboses in multiple blood vessels throughout their body. These thromboses block blood flow in affected organs, which impairs their function and ultimately causes organ failure. These individuals are said to have catastrophic antiphospholipid syndrome (CAPS). CAPS typically affects the kidneys, lungs, brain, heart, and liver, and is fatal in over half of affected individuals. Less than 1 percent of individuals with antiphospholipid syndrome develop CAPS. ## Frequency The exact prevalence of antiphospholipid syndrome is unknown. This condition is thought to be fairly common, and may be responsible for up to one percent of all thromboses. It is estimated that 20 percent of individuals younger than age 50 who have a stroke have antiphospholipid syndrome. Ten to 15 percent of people with systemic lupus erythematosus have antiphospholipid syndrome. Similarly, 10 to 15 percent of women with recurrent miscarriages likely have this condition. Approximately 70 percent of individuals diagnosed with antiphospholipid syndrome are female. ## Causes The genetic cause of antiphospholipid syndrome is unknown. This condition is associated with the presence of three abnormal immune proteins (antibodies) in the blood: lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibodies in antiphospholipid syndrome attack normal human proteins. When these antibodies attach (bind) to proteins, the proteins change shape and bind to other molecules and receptors on the surface of cells. Binding to cells, particularly immune cells, turns on (activates) the blood clotting pathway and other immune responses. The production of lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I may coincide with exposure to foreign invaders, such as viruses and bacteria, that are similar to normal human proteins. Exposure to these foreign invaders may cause the body to produce antibodies to fight the infection, but because the invaders are so similar to the body's own proteins, the antibodies also attack the human proteins. Similar triggers may occur during pregnancy when a woman's physiology, particularly her immune system, adapts to accommodate the developing fetus. These changes during pregnancy may explain the high rate of affected females. Certain genetic variations (polymorphisms) in a few genes have been found in people with antiphospholipid syndrome and may predispose individuals to produce the specific antibodies known to contribute to the formation of thromboses. However, the contribution of these genetic changes to the development of the condition is unclear. People who test positive for all three antibodies but have not had a thrombosis or recurrent miscarriages are said to be antiphospholipid carriers. These individuals are at greater risk of developing a thrombosis than is the general population. ## Inheritance Pattern Most cases of antiphospholipid syndrome are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing antiphospholipid 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	Antiphospholipid syndrome	c2930802	7,011	medlineplus	https://medlineplus.gov/genetics/condition/antiphospholipid-syndrome/	2021-01-27T08:24:42	{"gard": ["5824", "9820"], "mesh": ["C531622"], "omim": ["107320"], "synonyms": []}
Brachydactyly-elbow wrist dysplasia syndrome is a rare, genetic bone development disorder characterized by dysplasia of all the bony components of the elbow joint, abnormally shaped carpal bones, wrist joint radial deviation and brachydactyly. Patients typically present with slight flexion at the elbow joints (with impossibilty to perform active extension) and usually associate a limited range of motion of the elbow, wrist and finger articulations. Camptodactyly and syndactyly have also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Brachydactyly-elbow wrist dysplasia syndrome	c1861313	7,012	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1275	2021-01-23T18:40:16	{"gard": ["966"], "mesh": ["C566090"], "omim": ["186550"], "icd-10": ["Q73.8"], "synonyms": ["Brachydactyly-joint dysplasia syndrome", "Liebenberg syndrome"]}
Orphan disease TEMPI syndrome Other namesTelangiectasia-erythrocytosis-monoclonal gammopathy-perinephric-fluid collections-intrapulmonary shunting syndrome TEMPI Syndrome is an orphan disease where the patients share five characteristics from which the acronym is derived: telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunting. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] TEMPI Symptom T Telangiectasias E Elevated Erythropoietin and Erythrocytosis M Monoclonal gammopathy P Perinephric fluid collections I Intrapulmonary shunting The patients were all diagnosed at middle age. The symptoms were slowly and steadily progressive. Telangiectasias developed over the face, trunk and arms. Increased serum erythropoietin levels, eventually exceeding 5000 mU /ml, preceded the intrapulmonary shunting and the development of hypoxemia. Sampling of the perinephric fluid revealed a clear, serous fluid with low levels of protein, few leukocytes and no cholesterol or triglycerides. A monoclonal gammopathy was implicated in all patients tested. Spontaneous venous thromboses occurred in some patients, sometimes accompanied with spontaneous intracranial bleeding in the absence of blood vessels malformations.[1] ## Cause[edit] The cause of the syndrome is unknown. The abnormal plasma-cell clone and/or the monoclonal gammopathy are suggested to be triggers of the disease.[citation needed] ## Diagnosis[edit] The diagnosis is based on the five characteristics described above.[citation needed] ## Treatment[edit] Complete and partial disappearance of the symptoms of the TEMPI syndrome was reported with the drugs bortezomib,[2] daratumumab [3] and autologous stem cell transplantation.[4] ## History[edit] In 2010, the case of a man with unexplained erythrocytosis and perinephric fluid collection as main features was described in the Case Records of the Massachusetts General Hospital.[5] As a consequence two strikingly similar cases were identified and a review of the literature revealed three more patients with similar characteristics and a novel multisystem disease, the TEMPI syndrome, was reported.[1] As of January 2020, a total of 22 patients worldwide with the TEMPI syndrome have been identified (D.B.Sykes, Personal Communication). ## References[edit] 1. ^ a b Sykes, David B.; Schroyens, Wilfried; O'Connell, Casey (2011). "TEMPI Syndrome – A Novel Multisystem Disease". N Engl J Med. 365 (5): 475–477. doi:10.1056/NEJMc1106670. PMID 21812700. 2. ^ Schroyens, Wilfried; O'Connell, Casey; Sykes, David B. (2012). "Complete and Partial Responses of the TEMPI Syndrome to Bortezomib" (PDF). N Engl J Med. 367 (8): 778–780. doi:10.1056/NEJMc1205806. PMID 22913703. 3. ^ Sykes, David B.; Schroyens, W. (2018). "Complete Responses in the TEMPI Syndrome after Treatment with Daratumumab". N Engl J Med. 378 (23): 2240–2242. doi:10.1056/NEJMc1804415. PMID 29874534. 4. ^ Kenderian, S.S..; Rosado, F.G; Sykes, D.B.; Hoyer, J.D.; Lacy, M.Q. (2015). "Long-term complete clinical and hematological responses of the TEMPI syndrome after autologous stem cell transplantation". Leukemia. 29 (12): 2414–2416. doi:10.1038/leu.2015.298. PMID 26500143. 5. ^ Bazari, Hasan; Attar, Eyal C.; Dahl, Douglas M.; Uppot, Raul N.; Colvin, Robert B. (2010). "Case Records of the Massachusetts General Hospital. Case 23-2010: A 49-Year-Old Man with Erythrocytosis, Perinephric Fluid Collections, and Renal Failure". N Engl J Med. 363 (5): 463–475. doi:10.1056/NEJMcpc1004086. PMID 20818867. ## External links[edit] * Office of Rare Diseases Research (US) * Orpha.net (EU) Classification D External resources * Orphanet: 284227 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	TEMPI syndrome	c3854394	7,013	wikipedia	https://en.wikipedia.org/wiki/TEMPI_syndrome	2021-01-18T18:50:20	{"gard": ["10962"], "umls": ["C3854394"], "orphanet": ["284227"], "wikidata": ["Q7698379"]}
Skin disorders are among the most common health problems in dogs, and have many causes. The condition of a dog's skin and coat are also an important indicator of its general health. Skin disorders of dogs vary from acute, self-limiting problems to chronic or long-lasting problems requiring life-time treatment. Skin disorders may be primary or secondary (due to scratching, itch) in nature, making diagnosis complicated.[1] ## Contents * 1 Immune-mediated skin disorders * 1.1 Atopic dermatitis * 1.2 Autoimmune skin diseases * 2 Physical and environmental skin diseases * 2.1 Hot spots * 2.2 Acral lick granulomas * 3 Infectious skin diseases * 3.1 Flea allergy dermatitis * 4 Hereditary and developmental skin diseases * 5 Cutaneous manifestations of internal diseases * 6 Nutritional basis of skin disorders * 6.1 Essential fatty acids * 6.2 Vitamins * 6.3 Minerals * 7 References ## Immune-mediated skin disorders[edit] Skin disease may result from deficiency or overactivity of immune responses. In cases where there are insufficient immune responses, the disease is usually described by the secondary disease that results. Examples include increased susceptibility to demodectic mange and recurrent skin infections, such as Malassezia infection or bacterial infections. Increased but harmful immune responses can be divided into hypersensitivity disorders such as atopic dermatitis and autoimmune disorders (autoimmunity), such as pemphigus and discoid lupus erythematosus.[2][3] ### Atopic dermatitis[edit] Dog with atopic dermatitis, with signs around the eye created by rubbing. Atopy is a hereditary[4] and chronic (lifelong) allergic skin disease. Signs usually begin between 6 months and 3 years of age, with some breeds of dog, such as the golden retriever, showing signs at an earlier age. Dogs with atopic dermatitis are itchy, especially around the eyes, muzzle, ears and feet. In severe cases, the irritation is generalised. If the allergens are seasonal, the signs of irritation are similarly seasonal. Many dogs with house dust mite allergy have perennial disease.[5] Some of the allergens associated with atopy in dogs include pollens of trees, grasses and weeds, as well as molds and house dust mites. Ear and skin infections by the bacteria Staphylococcus pseudintermedius and the yeast Malassezia pachydermatis are commonly secondary to atopic dermatitis. Food allergy can be associated with identical signs and some authorities consider food allergy to be a type of atopic dermatitis.[6] Food allergy can be identified through the use of elimination diet trials in which a novel or hydrolysed protein diet is used for a minimum of 6 weeks. Diagnosis of atopic dermatitis is by elimination of other causes of irritation, including fleas, mites, and other parasites, such as Cheyletiella and lice. Allergies to aeroallergens can be identified using intradermal allergy testing and/or blood testing (allergen-specific IgE ELISA). Treatment includes avoidance of the offending allergens if possible, but for most dogs this is not practical or effective. Other treatments modulate the adverse immune response to allergens and include antihistamines, steroids, ciclosporin, and immunotherapy (a process in which allergens are injected to try to induce tolerance).[7] In many cases, shampoos, medicated wipes and ear cleaners are needed to try to prevent the return of infections. ### Autoimmune skin diseases[edit] Pemphigus foliaceus is the most common autoimmune disease of the dog.[2] Blisters in the epidermis rapidly break to form crusts and erosions, most often affecting the face and ears initially, but in some cases spreading to include the whole body. The paw pads can be affected, causing marked hyperkeratosis (thickening of the pads with scale). Other autoimmune diseases include bullous pemphigoid and epidermolysis bullosa acquisita. Treatment of autoimmune skin requires methods to reduce the abnormal immune response; steroids, azathioprine and other drugs are used as immunosuppressive agents.[2] ## Physical and environmental skin diseases[edit] ### Hot spots[edit] Main article: Hot spot (veterinary medicine) A hot spot, or acute moist dermatitis, is an acutely inflamed and infected area of skin irritation created and made worse by a dog licking and biting at itself. A hot spot can manifest and spread rapidly in a matter of hours, as secondary Staphylococcus infection causes the top layers of the skin to break down and pus becomes trapped in the hair. Hot spots can be treated with corticosteroid medications and oral or topical antibiotic applications, as well as clipping hair from around the lesion. Underlying causes include flea allergy dermatitis or other allergic skin diseases. Dogs with thick undercoats are most susceptible to developing hot spots.[8] ### Acral lick granulomas[edit] Lick granuloma from excessive licking Lick granulomas are raised, usually ulcerated areas on a dog's extremity caused by the dog's own incessant, compulsive licking. Compulsive licking is defined as licking in excess of that required for standard grooming or exploration, and represents a change in the animal's typical behavior and interferes with other activities or functions (e.g., eating, drinking, playing, interacting with people) and cannot easily be interrupted.[9] ## Infectious skin diseases[edit] A dog with skin irritation and hair loss on its leg caused by demodectic mange Infectious skin diseases of dogs include contagious and non-contagious infections or infestations. Contagious infections include parasitic, bacterial, fungal and viral skin diseases. One of the most common contagious parasitic skin diseases is Sarcoptic mange (scabies). Another is mange caused by Demodex mites (Demodicosis), though this form of mange is not contagious. Another contagious infestation is caused by a mite, Cheyletiella. Dogs can be infested with contagious lice. Other ectoparasites, including flea and tick infestations are not considered directly contagious but are acquired from an environment where other infested hosts have established the parasite's life cycle. Ringworm is a fungal skin infection and is more common in puppies than in adult dogs. Dog with dermatitis caused by Malassezia (yeast) Non-contagious skin infections can result when normal bacterial or fungal skin flora is allowed to proliferate and cause skin disease. Common examples in dogs include Staphylococcus intermedius pyoderma, and Malassezia dermatitis caused by overgrowth of Malassezia pachydermatis. Alabama rot, which is believed to be caused by E. coli toxins, also causes skin lesions and eventual kidney failure in 25% of cases.[citation needed] ### Flea allergy dermatitis[edit] Main article: Flea allergy dermatitis ## Hereditary and developmental skin diseases[edit] Some diseases are inherent abnormalities of skin structure or function. These include seborrheic dermatitis, ichthyosis, skin fragility syndrome (Ehlers-Danlos), hereditary canine follicular dysplasia and hypotrichosis, such as color dilution alopecia. Juvenile cellulitis, also known as puppy strangles, is a skin disease of puppies of unknown etiology, which most likely has a hereditary component related to the immune system.[10] ## Cutaneous manifestations of internal diseases[edit] Some systemic diseases can become symptomatic as a skin disorder. These include many endocrine (hormonal) abnormalities, such as hypothyroidism, Cushing's syndrome (hyperadrenocorticism), and tumors of the ovaries or testicles. ## Nutritional basis of skin disorders[edit] ### Essential fatty acids[edit] Further information: Coat (dog) Many canine skin disorders can have a basis in poor nutrition. The supplementation of both omega fatty acids 3 and 6 have been shown to mediate the inflammatory skin response seen in chronic diseases.[11] Omega 3 fatty acids are increasingly being used to treat pruritic, irritated skin. A group of dogs supplemented with omega 3 fatty acids (660 mg/kg [300 mg/lb] of body weight/d) not only improved the condition of their pruritus, but showed an overall improvement in skin condition.[11] Furthermore, diets lacking in essential fatty acids usually present as matted and unkept fur as the first sign of a deficiency.[11] Eicosapentaenoic acid (EPA), a well known omega 3, works by preventing the synthesis of another omega metabolite known as arachidonic acid.[12] Arachidonic acid is an omega 6, making it pro-inflammatory. Though not always the case, omega 6 fatty acids promote inflammation of the skin, which in turn reduces overall appearance and health.[12] There are skin benefits of both these lipids, as a deficiency in omega 6 leads to a reduced ability to heal and a higher risk of infection, which also diminishes skin health.[11] Lipids in general benefit skin health of dogs, as they nourish the epidermis and retain moisture to prevent dry, flaky skin.[13] ### Vitamins[edit] Vitamins are one of many of the nutritional factors that change the outward appearance of a dog. The fat soluble vitamins A and E play a critical role in maintaining skin health. Vitamin A, which can also be supplemented as beta-carotene, prevents the deterioration of epithelial tissues associated with chronic skin diseases and aging.[14] A deficiency in vitamin A can lead to scaly of skin and other dermatitis-related issues like alopecia.[15] Vitamin E is an antioxidant.[16] Vitamin E neutralizes free radicals that accumulate in highly proliferative cells like skin and prevent the deterioration of fibrous tissue caused by these ionized molecules.[17] There are also a couple of water-soluble vitamins that contribute to skin health. Riboflavin (B2) is a cofactor to the metabolism of carbohydrates and when deficient in the diet leads to cracked, brittle skin.[18] Biotin (B7) is another B vitamin that, when deficient, leads to alopecia.[18] ### Minerals[edit] Minerals have many roles in the body, which include acting as beneficial antioxidants.[17] Selenium is an essential nutrient, that should be present in trace amounts in the diet.[17] Like other antioxidants, selenium acts as a cofactor to neutralize free radicals.[17] Other minerals act as essential cofactors to biological processes relating to skin health. Zinc plays a crucial role in protein synthesis, which aids in maintaining elasticity of skin. By including zinc in the diet it will not only aid in the development of collagen and wound healing, but it will also prevent the skin from becoming dry and flaky.[19] Copper is involved in multiple enzymatic pathways.[20] In dogs, a deficiency in copper results in incomplete keratinization leading to dry skin and hypopigmentation.[20] The complicated combination of trace minerals in the diet are a key component of skin health and a part of a complete and balanced diet. ## References[edit] Wikimedia Commons has media related to dog skin disorders. 1. ^ Dog Health Guide, Disease and Conditions Canine Skin 2011 2. ^ a b c "Autoimmune Skin Disease in Dogs". vca_corporate. Retrieved 2019-11-17. 3. ^ "Immune-Mediated Skin Disorders of Dogs". Today's Veterinary Nurse. Retrieved 2019-11-17. 4. ^ Shaw, Stephen; Wood, J.L.; Freeman, J.; Littlewood, J.D.; Hannant, D. (2004). "Estimation of heritability of atopic dermatitis in Labrador and Golden Retrievers". American Journal of Veterinary Research. 65 (7): 1014–1020. doi:10.2460/ajvr.2004.65.1014. 5. ^ Favrot, Claude; Steffan, J.; Seewald, W.; Picco, F. (2010). "A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis". Veterinary Dermatology. 21 (1): 23–31. doi:10.1111/j.1365-3164.2009.00758.x. PMID 20187911. 6. ^ Picco, F; Zini, E.; Nett, C.; Naegeli, C.; Bigler, B.; Rufenacht, S.; Roosje, P.; Gutzwiller, M.E.; Wilhelm, S.; Pfister, J.; Meng, E.; Favrot, C. (2008). "A prospective study on canine atopic dermatitis and food-induced allergic dermatitis in Switzerland" (PDF). Veterinary Dermatology. 19 (3): 150–155. doi:10.1111/j.1365-3164.2008.00669.x. PMID 18477331. 7. ^ Olivry, Thiery; Foster, A.P.; Mueller, R.S.; McEwan, N.A.; Chesney, C.; Williams, H.C. (2010). "Interventions for atopic dermatitis in dogs: a systematic review of randomized controlled trials". Veterinary Dermatology. 21 (1): 4–22. doi:10.1111/j.1365-3164.2009.00784.x. PMID 20187910. 8. ^ "Hot Spots in Dogs". Pet Health Network. Retrieved 2019-11-17. 9. ^ "Treatment of other Canine Behavioral Problems". The Merck Veterinary Manual. 2008. Retrieved 2009-01-28. 10. ^ Martens, S.M. (February 2016). "Juvenile cellulitis in a 7-week-old golden retriever dog". The Canadian Veterinary Journal. 57 (2): 202–3. PMC 4713003. PMID 26834274. 11. ^ a b c d Kirby, Naomi A.; Hester, Shaleah L.; Bauer, John E. (2007). "Dietary fats and the skin and coat of dogs". Journal of the American Veterinary Medical Association. 230 (11): 1641–1644. doi:10.2460/javma.230.11.1641. PMID 17542730. 12. ^ a b Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung (2016-01-04). "Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances". Nutrients. 8 (1): 23. doi:10.3390/nu8010023. PMC 4728637. PMID 26742061. 13. ^ Bellows, Jan; Colitz, Carmen M. H.; Daristotle, Leighann; Ingram, Donald K.; Lepine, Allan; Marks, Stanley L.; Sanderson, Sherry Lynn; Tomlinson, Julia; Zhang, Jin (2014-12-17). "Common physical and functional changes associated with aging in dogs". Journal of the American Veterinary Medical Association. 246 (1): 67–75. doi:10.2460/javma.246.1.67. ISSN 0003-1488. PMID 25517328. 14. ^ Watson, Tim D. G. (1998). "Diet and Skin Disease in Dogs and Cats". The Journal of Nutrition. 128 (12): 2783–2789. doi:10.1093/jn/128.12.2783s. 15. ^ Baviskar, S; Jayanthy, C; Nagarajan, B (2013). "Vitamin A responsive dermatosis in a dog". Intras Polivet. 14 (2): 210. 16. ^ Debier, C.; Larondelle, Y. (February 2005). "Vitamins A and E: metabolism, roles and transfer to offspring". The British Journal of Nutrition. 93 (2): 153–174. doi:10.1079/bjn20041308. ISSN 0007-1145. PMID 15788108. 17. ^ a b c d Canine and feline nutrition : a resource for companion animal professionals. Case, Linda P. (3rd ed.). Maryland Heights, Mo.: Mosby. 2011. ISBN 9780323066198. OCLC 664112342.CS1 maint: others (link) 18. ^ a b Last, John M. (2007). A dictionary of public health. Oxford: Oxford University Press. ISBN 9780195160901. OCLC 63176655. 19. ^ Marsh, K.a.; Ruedisueli, F.l.; Coe, S.l.; Watson, T.g.d. (2000-12-01). "Effects of zinc and linoleic acid supplementation on the skin and coat quality of dogs receiving a complete and balanced diet". Veterinary Dermatology. 11 (4): 277–284. doi:10.1046/j.1365-3164.2000.00202.x. ISSN 1365-3164. 20. ^ a b Tewari, D.; Singh, V. K.; Gautam, S.; Dwivedi, V. (2013). "Nutritional dermatosis - a review". Intras Polivet. 14 (2): 199–202. 1. * v * t * e Dogs Behavior * Barking * Communication * Human–canine bond * Intelligence * Dog–cat relationship Health * Aging * Anatomy * Coat * Conformation * Diseases * Dog food * Odor * Rabies * Reproduction * Skin disorders * Vaccination Training * Clicker * Crate training * Training * Housebreaking * Socialization Types * African village dogs * Bichons * Bulldogs * Curs * Dogos * Feists * Hairless dogs * Herding dogs * Hounds * Scenthounds * Sighthounds * Laikas * Livestock guardian dogs * Mastiffs * Pinschers * Pointers * Retrievers * Setters * Schnauzers * Spaniels * Spitz * Street dogs * Terriers * Water dogs * Wolfdogs Breeds * List of breeds * List of crossbreeds * Breeding * Crossbreeds * Extinct breeds * Most popular * Pure breeds Roles * Assistance dogs * Attack dogs * Bay dogs * Catch dogs * Companion dogs * Detection dogs * Fighting dogs * Guard dogs * Guide dogs * Gun dogs * Hearing dogs * Herding dog * Hunting dogs * Lap dogs * Meat dogs * Mercy dog * Pet dogs * Police dogs * Search and rescue dogs * Sled dogs * Therapy dogs * Toy dogs * Turnspit dogs * War dogs Human–dog interaction * Animal testing * Baiting * Breed-specific legislation * Dog attack * Dog fighting * Dog park * Human-canine bond * Dog sports * Dog walking * Dog daycare * Dog grooming * Famous dogs * Therapy * Fear of dogs * Dog licence * Dog meat * Dog food * dog biscuit * 2007 recalls * Dogs in religion * Dogs in space * Origin of the domestic dog * 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	Dog skin disorders	None	7,014	wikipedia	https://en.wikipedia.org/wiki/Dog_skin_disorders	2021-01-18T19:02:08	{"wikidata": ["Q5288286"]}
Unilateral hearing loss Other namesSingle-sided deafness (SSD) SpecialtyAudiology, ear, nose, and throat Unilateral hearing loss (UHL) is a type of hearing impairment where there is normal hearing in one ear and impaired hearing in the other ear. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Prevalence * 4 Treatment * 5 Profound unilateral hearing loss * 6 Management * 6.1 Evaluation * 7 Other Hearing issues * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] Patients with unilateral hearing loss have difficulty: * Hearing conversation on their impaired side * Localizing sound * Understanding speech in the presence of background noise * In interpersonal interaction in social settings * Focusing on individual sound sources in large, open environments * Heavy impairment of the auditory Figure–ground perception In quiet conditions, speech discrimination is no worse than normal hearing in those with partial deafness;[1] however, in noisy environments speech discrimination is almost always severe.[1][2] The prevalence is 3-8.3% of the population.[3] Individuals who are diagnosed with Single Sided Deafness have difficulties with sound localization and speech in noise discrimination.[3] Children with SSD are more likely to experience developmental delays- school, speech, behavioral problems.[3] ## Causes[edit] Known causes include genetics, maternal illness and injury. Examples of these causes are physical trauma, acoustic neuroma, maternal prenatal illness such as measles, labyrinthitis, microtia, meningitis, Ménière's disease, Waardenburg syndrome, mumps (epidemic parotitis), and mastoiditis. SSD's most severe form of unilateral hearing loss is caused by: sudden sensorineural hearing loss (SSNHL), acoustic neuroma, anomalies inner ear abnormalities, cochlear nerve deficiency (CND), mumps, congenital cytomegalovirus (CMV) infection, meningitis and auditory neuropathy spectrum disorder (ANSD) treatment is based on the cause of the hearing loss. Limited treatment when the cause is the Central auditory system or Auditory nerve.[4] ## Prevalence[edit] A 1998 study of schoolchildren found that per thousand, 6–12 had some form of unilateral hearing loss and 0–5 had moderate to profound unilateral hearing loss. It was estimated that in 1998 some 391,000 school-aged children in the United States had unilateral hearing loss.[5] ## Treatment[edit] There are multiple treatments for hearing loss which include either surgical or non-surgical options. Deciding one or the other comes down to whether there is little or no hearing in the affected ear. If there is some hearing in the affected ear then an amplified hearing device may be suggested and it is a non-surgical option. If there is no hearing a special type of hearing aid called a CROS hearing aid is often used as a non-surgical option. There are also surgical options for a cochlear implant, or a bone conduction device. It ultimately comes down to the severity of the hearing loss and which route is best for the patient. ## Profound unilateral hearing loss[edit] Profound unilateral hearing loss is a specific type of hearing loss when one ear has no functional hearing ability (91 dB or greater hearing loss). People with profound unilateral hearing loss can only hear in monaural (mono). Profound unilateral hearing loss or single-sided deafness, SSD, makes hearing comprehension very difficult. With speech and background noise presented at the same level, persons with unilateral deafness were found to listen only about 30–35% of the conversation.[6] A person with SSD needs to make more effort when communicating with others.[7] When a patient can hear from only one ear, and there are limited possibilities to compensate for the handicap, e.g., changing listening position, group discussions and dynamic listening situations become difficult. Individuals with profound unilateral hearing loss are often perceived as socially awkward due to constant attempts to maximize hearing leading to socially unique body language and mannerisms.[8] SSD also negatively affects hearing and comprehension by making it impossible for the patient to determine the direction, distance and movement of sound sources.[8] In an evaluation using the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire, SSD results in a greater handicap than subjects with a severe hearing loss in both ears. Profound SSD is often confused with sensory discrimination disorder (SDD), a type of sensory processing disorder, and can lead to incorrect processing of sensory information or auditory input during interpersonal communications. SSD is known to cause: * Irritability * Sound aversion: any presence of noise, no matter how low * Body language and mannerisms which appear socially awkward or unusual, like staring at others mouths or tilt the head frequently * Frequent headaches, stress * Social isolation * Chronic interpersonal communication difficulties due to inability of brain to isolate or beam form sounds and voices of other individuals * Appearance of anxiousness even in low noise situations * Jumpiness * Trouble figuring out where sounds are coming from. * Variable light dizziness * Trouble paying attention to what people are saying: "evasive" behaviour. * Misdiagnoses as ADHD * Seeming lack of awareness of other people's personal space and moods since brain is hyper-focused on deciphering auditory information in lieu of non-verbal social cues. * Lack of sound depth: any background noise (in the room, in the car) is flat and wrongly interpreted by the brain. The effect is similar to what happens when trying to hear someone speaking in a noisy crowd on a mono TV. The effect is also similar to talking on the phone to someone who is in a noisy environment (see also: King-Kopetzky syndrome) * Inability to filter out background noise or selectively listen to only the important portion of the noise in the environment. * For sensorineural hearing loss, the lack of input coming from the damaged sensory apparatus can cause "ghost beeps" or ringing/tinnitus as the brain attempts to interpret the now missing sensory data. The frequency and the volume of the noise can increase according to one's physical condition (stress, fatigue, etc.). This can aggravate social problems and increase the difficulty of speech comprehension. * Talking loudly or "broadcasting": the affected person cannot perceive the volume of his or her voice relative to other people in the same room or close company, resulting in being characterized by others (who may be located beyond normal auditory range) as domineering or boorish ## Management[edit] Adaptation in the central nervous system through "neural-plasticity" or biological maturation over time does not improve the performance of monaural listening.[2] In addition to conventional methods for improving the performance of the impaired ear, there are also hearing aids adapted to unilateral hearing loss which are of very limited effectiveness due to the fact that they don't restore the binaural hearing ability, and tend to overload the working ear. * Contralateral Routing of Signals (CROS) hearing aids are hearing aids that take sound from the ear with poorer hearing and transmit to the ear with better hearing. There are several types of CROS hearing aid:[9] * conventional CROS comprises a microphone placed near the impaired ear and an amplifier (hearing aid) near the normal ear. The two units are connected either by a wire behind the neck or by wireless transmission. The aid appears as two behind-the-ear hearing aids and is sometimes incorporated into eyeglasses. * CIC transcranial CROS comprises a bone conduction hearing aid completely in the ear canal (CIC). A high-power conventional air conduction hearing aid fits deeply into the patient’s deaf ear. Vibration of the bony walls of the ear canal and middle ear stimulates the normal ear by means of bone conduction through the skull. * BAHA transcranial CROS Bone Anchored Hearing Aid (BAHA): a surgically implanted abutment transmits sound from the deaf ear by direct bone conduction and stimulates the cochlea of the normal hearing ear. * SoundBite Intraoral bone conduction which uses bone conduction via the teeth. One component resembles a conventional behind-the-ear hearing aid that wirelessly connects to a second component worn in the mouth that resembles a conventional dental appliance.[10] In Germany and Canada, cochlear implants have been used to mostly restore the stereo hearing ability, minimizing the impacts of the SSD and increasing the quality of life of the patient.[11] ### Evaluation[edit] As of 2012 there has only been one small-scale study comparing CROS systems.[9] One study of the BAHA system showed a benefit depending on the patient's transcranial attenuation.[12] Another study showed that sound localisation was not improved, but the effect of the head shadow was reduced.[13] ## Other Hearing issues[edit] School-age children with unilateral hearing loss tend to have poorer grades and require educational assistance. This is not the case with everyone, however. They can also be perceived to have behavioral issues.[14] People afflicted with UHL have great difficulty locating the source of any sound. They may be unable to locate an alarm or a ringing telephone. The swimming game Marco Polo is generally impossible for them. When wearing stereo headphones, people with unilateral hearing loss can hear only one channel, hence the panning information (volume and time differences between channels) is lost; some instruments may be heard better than others if they are mixed predominantly to one channel, and in extreme cases of sound production, such as complete stereo separation or stereo-switching, only part of the composition can be heard; in games using 3D audio effects, sound may not be perceived appropriately due to coming to the disabled ear. This can be corrected by using settings in the software or hardware—audio player, OS, amplifier or sound source—to adjust balance to one channel (only if the setting downmixes sound from both channels to one), or there may be an option to outright downmix both channels to mono. Such settings may be available via the device or software's accessibility features.[15][16] ## See also[edit] * Cocktail party effect * SoundBite Hearing System ## References[edit] 1. ^ a b Sargent EW, Herrmann B, Hollenbeak CS, Bankaitis AE (July 2001). "The minimum speech test battery in profound unilateral hearing loss". Otol. Neurotol. 22 (4): 480–6. doi:10.1097/00129492-200107000-00012. PMID 11449104. 2. ^ a b Welsh LW, Welsh JJ, Rosen LF, Dragonette JE (December 2004). "Functional impairments due to unilateral deafness". Ann. Otol. Rhinol. Laryngol. 113 (12): 987–93. doi:10.1177/000348940411301209. PMID 15633902. 3. ^ a b c Sharma, Anu; Glick, Hannah; Campbell, Julia; Torres, Jennifer; Dorman, Michael; Zeitler, Daniel M. (2016). "Cortical Plasticity and Re-organization in Pediatric Single-Sided Deafness Pre- and Post- Cochlear Implantation: A Case Study". Otology & Neurotology. 37 (2): e26–e34. doi:10.1097/MAO.0000000000000904. PMC 6530986. PMID 26756152. 4. ^ Usami, Shin-ichi; Kitoh, Ryosuke; Moteki, Hideaki; Nishio, Shin-ya; Kitano, Tomohiro; Kobayashi, Masafumi; Shinagawa, Jun; Yokota, Yoh; Sugiyama, Kenjiro; Watanabe, Kizuki (April 2017). "Etiology of single-sided deafness and asymmetrical hearing loss". Acta Oto-Laryngologica. 137 (sup565): S2–S7. doi:10.1080/00016489.2017.1300321. PMID 28366032. 5. ^ Lee DJ, Gómez-Marín O, Lee HM (August 1998). "Prevalence of unilateral hearing loss in children: the National Health and Nutrition Examination Survey II and the Hispanic Health and Nutrition Examination Survey". Ear Hear. 19 (4): 329–32. doi:10.1097/00003446-199808000-00008. PMID 9728728.CS1 maint: multiple names: authors list (link) 6. ^ Christensen L, Richter GT, Dornhoffer JL (Feb 2010). "Update on bone-anchored hearing aids in pediatric patients with profound unilateral sensorineural hearing loss". Archives of Otolaryngology–Head & Neck Surgery. 136 (2): 175–7. doi:10.1001/archoto.2009.203. PMID 20157065. 7. ^ Bess FH, Tharpe AM (February 1986). "An introduction to unilateral sensorineural hearing loss in children". Ear Hear. 7 (1): 3–13. doi:10.1097/00003446-198602000-00003. PMID 3512353. 8. ^ a b Noble W, Gatehouse S (2004). "Interaural asymmetry of hearing loss, Speech, Spatial and Qualities of Hearing Scale (SSQ) disabilities, and handicap". International Journal of Audiology. 43 (2): 100–14. doi:10.1080/14992020400050015. PMID 15035562. 9. ^ a b Hol, M. K. S.; Kunst, S. J. W.; Snik, A. F. M.; Cremers, C. W. R. J. (2009). "Pilot study on the effectiveness of the conventional CROS, the transcranial CROS and the BAHA transcranial CROS in adults with unilateral inner ear deafness". European Archives of Oto-Rhino-Laryngology. 267 (6): 889–896. doi:10.1007/s00405-009-1147-9. PMC 2857795. PMID 19904546. 10. ^ Popelka, G. (2010). "SoundBite Hearing System by Sonitus Medical: A New Approach to Single-Sided Deafness". Seminars in Hearing. 31 (4): 393–409. doi:10.1055/s-0030-1268037. 11. ^ Jacob, R; Stelzig, Y; Nopp, P; Schleich, P (2011). "Audiological results with cochlear implants for single-sided deafness". Hno. 59 (5): 453–460. doi:10.1007/s00106-011-2321-0. PMID 21533601. 12. ^ Stenfelt S (March 2005). "Bilateral fitting of BAHAs and BAHA fitted in unilateral deaf persons: acoustical aspects". Int J Audiol. 44 (3): 178–89. doi:10.1080/14992020500031561. PMID 15916119. 13. ^ Hol MK, Bosman AJ, Snik AF, Mylanus EA, Cremers CW (September 2005). "Bone-anchored hearing aids in unilateral inner ear deafness: an evaluation of audiometric and patient outcome measurements". Otol. Neurotol. 26 (5): 999–1006. doi:10.1097/01.mao.0000185065.04834.95. PMID 16151349. 14. ^ Lieu, J. E. C. (2004). "Speech-Language and Educational Consequences of Unilateral Hearing Loss in Children". Archives of Otolaryngology–Head & Neck Surgery. 130 (5): 524–530. doi:10.1001/archotol.130.5.524. PMID 15148171. 15. ^ OS X Mavericks: Audio pane of Accessibility preferences 16. ^ Apple - Accessibility - iOS ## External links[edit] Classification D * ICD-10: H90.1, H90.4, H90.7 * MeSH: D046088 * Profound Unilateral Hearing Loss FAQ's and Flash Animation * BoysTownHospital.org * Unilateral Hearing Loss - Notes * v * t * e Diseases of the outer and middle ear Outer ear * Otitis externa * Otomycosis Middle ear and mastoid * Otitis media * Mastoiditis * Bezold's abscess * Gradenigo's syndrome * Tympanosclerosis * Cholesteatoma * Perforated eardrum Symptoms * Ear pain * Hearing loss Tests * Otoscope * pneumatic * tympanometry [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Unilateral hearing loss	c2607947	7,015	wikipedia	https://en.wikipedia.org/wiki/Unilateral_hearing_loss	2021-01-18T18:50:54	{"mesh": ["D046088"], "umls": ["C2607947"], "icd-10": ["H90.7", "H90.1", "H90.4"], "wikidata": ["Q3813334"]}
A number sign (#) is used with this entry because autosomal dominant erythrocytosis-7 (ECYT7) can be caused by heterozygous mutation in the alpha-globin genes (HBA1, 141800 or HBA2, 141850) that result in a high oxygen affinity hemoglobin. Description Familial erythrocytosis-7 is characterized by an increased oxygen affinity of hemoglobin (Hb), which results in decreased delivery of oxygen into the peripheral tissues and compensatory polycythemia. Patients are generally asymptomatic, as compensatory polycythemia assures normal oxygen tissue delivery. Patients have normal red cell morphology (summary by Kralovics and Prchal, 2000). Wajcman and Galacteros (2005) noted that although high oxygen affinity hemoglobins are usually well tolerated in young patients, they can lead to thrombotic complications in older patients or when they are associated with another cause that increases thrombotic risk. Wajcman and Galacteros (2005) also noted that the effect of increased oxygen affinity of Hb caused by an alpha chain variant is usually milder than that caused by a beta chain variant (see 617980). Clinical Features Charache et al. (1966) were the first to report a case of erythrocytosis due to the presence of an abnormal Hb. They described an 81-year-old patient with mild angina pectoris who had a Hb level of 19.9 g/dL and an abnormal Hb band on electrophoresis. The oxygen equilibrium curve of the patient's blood was significantly shifted to the left. A family study revealed 15 other members with both erythrocytosis and the abnormal Hb, which was isolated and confirmed to have a marked increased oxygen affinity. Inheritance Erythrocytosis caused by high oxygen affinity Hb variants is inherited in an autosomal dominant manner (Wajcman and Galacteros, 2005). Diagnosis Because some high oxygen affinity hemoglobins are electrophoretically silent, the determination of hemoglobin oxygen dissociation kinetics is the best initial screening laboratory test for suspected congenital secondary polycythemia. A decreased P(50) indicates mutant hemoglobin or, even rarer, 2,3-bisphosphoglycerate deficiency (summary by Kralovics and Prchal, 2000). Pathogenesis The hemoglobin tetramer oscillates between the R (relaxed; fully oxygenated hemoglobin) and T (tense; fully deoxygenated hemoglobin) state of the quaternary protein conformation, requiring the cooperative interaction of globin subunits. Mutations affecting the equilibrium between R and T states result in a change of oxygen affinity. Most of these mutations occur in the alpha1/beta2 interface of the tetramer, but some interfere with the 2,3-bisphosphate binding site, and others occur at the C terminus of one of the globin subunits and interfere with binding of heme (summary by Kralovics and Prchal, 2000). Molecular Genetics In affected members of a family with erythrocytosis, Charache et al. (1966) identified a heterozygous mutation in the HBA1 gene (Hb Chesapeake; 141800.0018). Erythrocytosis is a feature of several variants in the alpha globin genes; see, e.g., hemoglobins Nonobiki (141800.0109), Sassari (141800.0126), Inkster (141850.0015), Columbia-Missouri (141850.0016), and Hanamaki (141850.0023). Gonzalez Fernandez et al. (2009) noted that 89 Hb variants that show high affinity for oxygen had been described: 18 in the alpha chain and 71 in the beta chain. Two thirds of them are not accompanied by erythrocytosis either because the affinity increase is slight or moderate and only found during in vitro studies or when molecular instability is also present, determining a concomitant hemolysis; or if the mutating gene expression is low, as occurs in the alpha chain variations, or is reduced, as in Hb Crete (141900.0058). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	ERYTHROCYTOSIS, FAMILIAL, 7	c4693823	7,016	omim	https://www.omim.org/entry/617981	2019-09-22T15:44:12	{"omim": ["617981"], "synonyms": ["Alternative titles", "ERYTHROCYTOSIS, ALPHA-GLOBIN TYPE", "POLYCYTHEMIA, ALPHA-GLOBIN TYPE"]}
Task-specific focal dystonia is a movement disorder that interferes with the performance of particular tasks, such as writing, playing a musical instrument, or participating in a sport. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions, tremors, and other uncontrolled movements. The term "focal" refers to a type of dystonia that affects a single part of the body, such as the hand or jaw. Researchers have described several forms of task-specific focal dystonia. The most common is writer's cramp, in which muscle cramps or spasms in the hand, wrist, or forearm interfere with holding a pen or pencil. Writer's cramp begins in the hand used for writing (the dominant hand) and is usually limited to that task, but with time it can spread to the other hand and affect other fine-motor activities such as shaving or typing. Musician's dystonia is a form of task-specific focal dystonia characterized by muscle cramps and spasms that occur while playing a musical instrument. This condition can affect amateur or professional musicians, and the location of the dystonia depends on the instrument. Some musicians (such as piano, guitar, and violin players) develop focal hand dystonia, which causes loss of fine-motor control in the hand and wrist muscles. This condition reduces finger coordination, speed, and endurance while playing. Musicians who play woodwind or brass instruments can develop what is known as embouchure dystonia. This condition causes muscle cramps or spasms involving the lips, tongue, or jaw, which prevents normal positioning of the mouth around the instrument's mouthpiece. Musician's dystonia often occurs only when playing a particular instrument. However, over time focal hand dystonia may impair other activities, and embouchure dystonia can worsen to affect eating and speech. Task-specific focal dystonia can affect people who play sports and engage in other occupations involving repetitive, highly practiced movements. For example, some golfers experience involuntary jerking of the wrists during putting, a condition known informally as "the yips." Cramps and spasms of the hand and arm muscles can also affect tennis players, billiards players, dart throwers, and other athletes. Additionally, task-specific dystonia has been reported in tailors, shoemakers, hair stylists, and people who frequently type or use a computer mouse. The abnormal movements associated with task-specific focal dystonia are usually painless, although they can cause anxiety when they interfere with musical performance and other activities. Severe cases can cause professional disability. ## Frequency Task-specific focal dystonia affects an estimated 7 to 69 per million people in the general population. Musician's dystonia that is severe enough to impact performance occurs in about 1 percent of musicians. ## Causes The causes of task-specific focal dystonia are unknown, although the disorder likely results from a combination of genetic and environmental factors. Certain genetic changes probably increase the likelihood of developing this condition, and environmental factors may trigger the onset of symptoms in people who are at risk. It is possible that the different forms of task-specific focal dystonia have different underlying causes. Having a family history of dystonia, particularly focal dystonia, is one of the only established risk factors for task-specific focal dystonia. Studies suggest that previous injury, changes in practice routine, and exposure to anti-psychotic drugs (which can cause other types of dystonia) are not major risk factors. Nor does the condition appear to be a form of performance anxiety. Task-specific focal dystonia may be associated with dysfunction in areas of the brain that regulate movement. In particular, researchers have found that at least some cases of the condition are related to malfunction of the basal ganglia, which are structures deep within the brain that help start and control movement. Although genetic factors are almost certainly involved in task-specific focal dystonia, no genes have been clearly associated with the condition. Researchers have looked for mutations in several genes known to be involved in other forms of dystonia, but these genetic changes do not appear to be a major cause of task-specific focal dystonia. Researchers are working to determine which genetic factors are related to this disorder. ## Inheritance Pattern Most cases of task-specific focal dystonia are sporadic, which means they occur in people with no history of the condition in their family. However, at least 10 percent of affected individuals have a family history of focal dystonia. (For example, writer's cramp and musician's dystonia have been reported to occur in the same family.) The dystonia often appears to have an autosomal dominant pattern of inheritance, based on the observation that some affected people have a parent with 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	Task-specific focal dystonia	c1969807	7,017	medlineplus	https://medlineplus.gov/genetics/condition/task-specific-focal-dystonia/	2021-01-27T08:25:20	{"gard": ["6458"], "mesh": ["C566973"], "omim": ["611284"], "synonyms": []}
Shulman et al. (1976) described a Mexican-American family in which 3 of 5 sibs had severe laryngomalacia requiring neonatal tracheostomy. Histologic studies of tracheal cartilage showed hypercellularity and tinctorial peculiarities of the matrix. The mother had experienced respiratory difficulties in the first year of life. Thus inheritance may be dominant. In diastrophic dwarfism (222600) tracheomalacia and laryngomalacia with respiratory distress occur. Shohat et al. (1992) described a family in which laryngomalacia evidenced by congenital stridor was present in 9 persons in 3 generations, supporting autosomal dominant inheritance. There was no instance of male-to-male transmission, however, and a mating in the second generation was consanguineous. Resp \- Laryngomalacia \- Congenital stridor \- Respiratory distress Lab \- Tracheal cartilage hypercellularity and tinctorial peculiarities of the matrix 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	LARYNGOMALACIA	c0345160	7,018	omim	https://www.omim.org/entry/150280	2019-09-22T16:39:04	{"omim": ["150280"], "orphanet": ["2373"]}
Infectious disease For other uses, see Scarlet fever (disambiguation). Scarlet fever Other namesScarlatina,[1] scarletina[2] Strawberry tongue seen in scarlet fever SpecialtyInfectious disease SymptomsSore throat, fever, headaches, swollen lymph nodes, characteristic rash[1] ComplicationsGlomerulonephritis, rheumatic heart disease, arthritis[1] Usual onset5–15 years old[1] CausesStrep throat, streptococcal skin infections[1] Diagnostic methodThroat culture[1] PreventionHandwashing, not sharing personal items, staying away from sick people[1] TreatmentAntibiotics[1] PrognosisTypically good[3] Scarlet fever is a disease resulting from a group A streptococcus (group A strep) infection, also known as Streptococcus pyogenes.[1] The signs and symptoms include a sore throat, fever, headaches, swollen lymph nodes, and a characteristic rash.[1] The rash is red and feels like sandpaper and the tongue may be red and bumpy.[1] It most commonly affects children between five and 15 years of age.[1] Scarlet fever affects a small number of people who have strep throat or streptococcal skin infections.[1] The bacteria are usually spread by people coughing or sneezing.[1] It can also be spread when a person touches an object that has the bacteria on it and then touches their mouth or nose.[1] The characteristic rash is due to the erythrogenic toxin, a substance produced by some types of the bacterium.[1][4] The diagnosis is typically confirmed by culturing the throat.[1] As of 2020[update] there is no vaccine.[5] Prevention is by frequent handwashing, not sharing personal items, and staying away from other people when sick.[1] The disease is treatable with antibiotics, which prevent most complications.[1] Outcomes with scarlet fever are typically good if treated.[3] Long-term complications as a result of scarlet fever include kidney disease, rheumatic heart disease, and arthritis.[1] In the early 20th century, before antibiotics were available, it was a leading cause of death in children.[6][7] An antitoxin was produced before antibiotics; however, it was never made in sufficient quantities, and could not be used to treat any other disease as antibiotics can. There have been signs of antibiotic resistance, and there have been recent outbreaks in Hong Kong in 2011 and in the UK in 2014, with occurrence rising 68% in the UK in the four years up to 2018. Research published in October 2020 has shown that infection of the bacterium by three viruses has led to stronger strains of the bacterium.[5] ## Contents * 1 Signs and symptoms * 1.1 Strep throat * 1.2 Rash * 1.3 Mouth * 1.4 Variable presentations * 1.5 Course * 1.6 Complications * 2 Cause * 3 Pathophysiology * 3.1 Microbiology * 4 Diagnosis * 4.1 Differential diagnosis * 5 Prevention * 6 Treatment * 6.1 Antibiotic resistance and resurgence * 7 Epidemiology * 8 History * 8.1 The Dick test * 9 References * 10 External links ## Signs and symptoms[edit] Characteristic strawberry tongue of scarlet fever The rash of scarlet fever Red cheeks and pale area around the mouth in scarlet fever Characteristic red cheeks and rash of scarlet fever Rash which has a characteristic appearance, spreading pattern, and desquamating process e.g. "Strawberry tongue": * The tongue initially has a white coating on it, while the papillae of the tongue are swollen and reddened. The protrusion of the red papillae through the white coating gives the tongue a "white strawberry" appearance. * A few days later (following the desquamating process, or the shedding of the tissue which created the white coating), the whiteness disappears, and the red and enlarged papillae give the tongue the "red strawberry" appearance.[8] The symptomatic appearance of the tongue is part of the rash that is characteristic of scarlet fever.[9] * Pastia's lines[10] * Lines of petechiae, which appear as pink/red areas located in arm pits and elbow pits[citation needed] * Vomiting and abdominal pain[11] ### Strep throat[edit] Typical symptoms of streptococcal pharyngitis (also known as strep throat):[11] * Sore throat, painful swallowing * Fever - typically over 39 °C (102.2 °F) * Fatigue * Enlarged and reddened tonsils with yellow or white exudates present (this is typically an exudative pharyngitis)[12] * Enlarged and tender lymph nodes usually located on the front of the neck[13] The following symptoms will usually be absent: cough, hoarseness, runny nose, diarrhea, and conjunctivitis.[11] Such symptoms indicate what is more likely a viral infection. ### Rash[edit] The rash begins 1–2 days following the onset of symptoms caused by the strep pharyngitis (sore throat, fever, fatigue).[14] This characteristic rash has been denoted as "scarlatiniform," and it appears as a diffuse redness of the skin with small papules, or bumps, which resemble goose bumps.[8][15] These bumps are what give the characteristic sandpaper texture to the rash. The reddened skin will blanch when pressure is applied to it. The skin may feel itchy, but it will not be painful.[8] The rash generally starts at the flexion of the elbow and other surfaces.[16] It appears next on the trunk and gradually spreads out to the arms and legs.[15] The palms, soles and face are usually left uninvolved by the rash. The face, however, is usually flushed, most prominently in the cheeks, with a ring of paleness around the mouth.[17] After the rash spreads, it becomes more pronounced in creases in the skin, such as the skin folds in the inguinal and axillary regions of the body.[10] Also in those areas, Pastia's Lines may appear: petechiae arranged in a linear pattern.[10] Within 1 week of onset, the rash begins to fade followed by a longer process of desquamation, or shedding of the outer layer of skin. This lasts several weeks.[13] The desquamation process usually begins on the face and progresses downward on the body.[8] After the desquamation, the skin will be left with a sunburned appearance.[14] ### Mouth[edit] Throat of a child with a positive throat culture for streptococcal pharyngitis The streptococcal pharyngitis, which is the usual presentation of scarlet fever in combination with the characteristic rash, commonly involves the tonsils. The tonsils will appear swollen and reddened. The palate and uvula are also commonly affected by the infection. The involvement of the soft palate can be seen as tiny red and round spots known as Forchheimer spots.[12] ### Variable presentations[edit] The features of scarlet fever can differ depending on the age and race of the person. Children less than 5 years old can have atypical presentations. Children less than 3 years old can present with nasal congestion and a lower grade fever.[18] Infants may present with symptoms of increased irritability and decreased appetite.[18] Children who have darker skin can have a different presentation, as the redness of the skin involved in the rash and the ring of paleness around the mouth can be less obvious.[8] Suspicion based on accompanying symptoms and diagnostic studies are important in these cases. ### Course[edit] Following exposure to streptococcus, onset of symptoms occur 12 hours to 7 days later. These may include fever, fatigue, and sore throat. The characteristic scarlatiniform rash appears 12–48 hours later. During the first few days of the rash development and rapid generalization, the Pastia's Lines and strawberry tongue are also present.[8] The rash starts fading within 3–4 days, followed by the desquamation of the rash, which lasts several weeks to a month.[14][12] If the case of scarlet fever is uncomplicated, recovery from the fever and clinical symptoms, other than the process of desquamation, occurs in 5–10 days.[19] ### Complications[edit] The complications, which can arise from scarlet fever when left untreated or inadequately treated, can be divided into two categories: suppurative and nonsuppurative. Suppurative complications: These are rare complications that arise either from direct spread to structures that are close to the primary site of infection, or spread through the lymphatic system or blood. In the first case, scarlet fever may spread to the pharynx. Possible problems from this method of spread include peritonsillar or retropharyngeal abscesses, cellulitis, mastoiditis or sinusitis. In the second case, the streptococcal infection may spread through the lymphatic system or the blood to areas of the body further away from the pharynx. A few examples of the many complications that can arise from those methods of spread include endocarditis, pneumonia, or meningitis.[17] Nonsuppurative complications: These complications arise from certain subtypes of group A streptococci that cause an autoimmune response in the body through what has been termed molecular mimicry. In these cases, the antibodies which the person's immune system developed to attack the group A streptococci are also able to attack the person's own tissues. The following complications result, depending on which tissues in the person's body are targeted by those antibodies.[15] * Acute rheumatic fever: This is a complication that results 2–6 weeks after a group A streptococcal infection of the upper respiratory tract.[14] It presents in developing countries, where antibiotic treatment of streptococcal infections is less common, as a febrile illness with several clinical manifestations, which are organized into what is called the Jones criteria. These criteria include arthritis, carditis, neurological issues, and skin findings. Diagnosis also depends on evidence of a prior group A streptococcal infection in the upper respiratory tract (as seen in streptococcal pharyngitis and scarlet fever). The carditis is the result of the immunologic response targeting the person's heart tissue, and it is the most serious sequelae that develops from acute rheumatic fever. When this involvement of the heart tissue occurs, it is called rheumatic heart disease. In most cases of rheumatic heart disease, the mitral valve is affected, ultimately leading to mitral stenosis.[18] The link to rheumatic fever and heart disease is a particular concern in Australia, because of the high prevalence of these diseases in Aboriginal and Torres Strait Islander communities.[5] * Poststreptococcal glomerulonephritis: This is inflammation of the kidney, which presents 1–2 weeks after a group A streptococcal pharyngitis. It can also develop after an episode of Impetigo or any group A streptococcal infection in the skin (this differs from acute rheumatic fever which only follows group A streptococcal pharyngitis).[14][20] It is the result of the autoimmune response to the streptococcal infection affecting part of the kidney. Persons present with what is called acute nephritic syndrome, in which they have high blood pressure, swelling, and urinary abnormalities. Urinary abnormalities include blood and protein found in the urine, as well as less urine production overall.[14] * Poststreptococcal reactive arthritis: The presentation of arthritis after a recent episode of group A streptococcal pharyngitis raises suspicion for acute rheumatic fever, since it is one of the Jones criteria for that separate complication. But, when the arthritis is an isolated symptom, it is referred to as poststreptococcal reactive arthritis. This arthritis can involve a variety of joints throughout the body, unlike the arthritis of acute rheumatic fever, which primarily affects larger joints such as the knee joints. It can present less than 10 days after the group A streptococcal pharyngitis.[14] ## Cause[edit] Strep throat spreads by close contact among people, via respiratory droplets (for example, saliva or nasal discharge).[14] A person in close contact with another person infected with group A streptococcal pharyngitis has a 35% chance of becoming infected.[18] One in ten children who are infected with group A streptococcal pharyngitis will develop scarlet fever.[13] ## Pathophysiology[edit] Streptococcus pyogenes (pictured) The rash of scarlet fever, which is what differentiates this disease from an isolated group A strep pharyngitis (or strep throat), is caused by specific strains of group A streptococcus which produce a pyrogenic exotoxin.[14] These toxin-producing strains cause scarlet fever in people who do not already have antitoxin antibodies. Streptococcal pyrogenic exotoxins A, B, and C (speA, speB, and speC) have been identified. The pyrogenic exotoxins are also called erythrogenic toxins and cause the erythematous rash of scarlet fever.[14] The strains of group A streptococcus that cause scarlet fever need specific bacteriophages in order for there to be pyrogenic exotoxin production. Specifically, bacteriophage T12 is responsible for the production of speA.[21] Streptococcal Pyrogenic Exotoxin A, speA, is the one which is most commonly associated with cases of scarlet fever which are complicated by the immune-mediated sequelae acute rheumatic fever and post-streptococcal glomerulonephritis.[12] These toxins are also known as “superantigens” because they are able to cause an extensive immune response within the body through activation of some of the main cells responsible for the person's immune system.[19] The body responds to these toxins by making antibodies to those specific toxins. However, those antibodies do not completely protect the person from future group A streptococcal infections, because there are 12 different pyrogenic exotoxins possible.[14] ### Microbiology[edit] The disease is caused by secretion of pyrogenic exotoxins by the infecting Streptococcus bacteria.[22][23] Streptococcal pyrogenic exotoxin A (speA) is probably the best studied of these toxins. It is carried by the bacteriophage T12 which integrates into the streptococcal genome from where the toxin is transcribed. The phage itself integrates into a serine tRNA gene on the chromosome.[24] The T12 virus itself has not been placed into a taxon by the International Committee on Taxonomy of Viruses. It has a double-stranded DNA genome and on morphological grounds appears to be a member of the Siphoviridae. The speA gene was cloned and sequenced in 1986.[25] It is 753 base pairs in length and encodes a 29.244 kiloDalton (kDa) protein. The protein contains a putative 30- amino-acid signal peptide; removal of the signal sequence gives a predicted molecular weight of 25.787 kDa for the secreted protein. Both a promoter and a ribosome binding site (Shine-Dalgarno sequence) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination codon. The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1. Streptococcal phages other than T12 may also carry the speA gene.[26] ## Diagnosis[edit] Although the presentation of scarlet fever can be clinically diagnosed, further testing may be required to distinguish it from other illnesses.[8] Also, history of a recent exposure to someone with strep throat can be useful in diagnosis.[14] There are two methods used to confirm suspicion of scarlet fever; rapid antigen detection test and throat culture.[18] The rapid antigen detection test is a very specific test but not very sensitive. This means that if the result is positive (indicating that the group A strep antigen was detected and therefore confirming that the person has a group A strep pharyngitis), then it is appropriate to treat the patient with antibiotics. But, if the rapid antigen detection test is negative (indicating that they do not have group A strep pharyngitis), then a throat culture is required to confirm, as the first test could have yielded a false negative result.[27] In the early 21st century, the throat culture is the current "gold standard" for diagnosis.[18] Serologic testing seeks evidence of the antibodies that the body produces against the streptococcal infection, including antistreptolysin-O and antideoxyribonuclease B. It takes the body 2–3 weeks to make these antibodies, so this type of testing is not useful for diagnosing a current infection. But, it is useful when assessing a person who may have one of the complications from a previous streptococcal infection.[13][18] Throat cultures done after antibiotic therapy can show if the infection has been removed. These throat swabs, however, are not indicated, because up to 25% of properly treated individuals can continue to carry the streptococcal infection while being asymptomatic.[20] ### Differential diagnosis[edit] * Viral exanthem: Viral infections are often accompanied by a rash which can be described as morbilliform or maculopapular. This type of rash is accompanied by a prodromal period of cough and runny nose in addition to a fever, indicative of a viral process.[15] * Allergic or contact dermatitis: The erythematous appearance of the skin will be in a more localized distribution rather than the diffuse and generalized rash seen in scarlet fever.[13] * Drug eruption: These are potential side effects of taking certain drugs such as penicillin. The reddened maculopapular rash which results can be itchy and be accompanied by a fever.[28] * Kawasaki disease: Children with this disease also present a strawberry tongue and undergo a desquamative process on their palms and soles. However, these children tend to be younger than 5 years old, their fever lasts longer (at least five days), and they have additional clinical criteria (including signs such as conjunctival redness and cracked lips), which can help distinguish this from scarlet fever.[29] * Toxic shock syndrome: Both streptococcal and staphylococcal bacteria can cause this syndrome. Clinical manifestations include diffuse rash and desquamation of the palms and soles. It can be distinguished from scarlet fever by low blood pressure, lack of sandpaper texture for the rash, and multi-organ system involvement.[30] * Staphylococcal scalded skin syndrome: This is a disease that occurs primarily in young children due to a toxin-producing strain of the bacteria Staphylococcus aureus. The abrupt start of the fever and diffused sunburned appearance of the rash can resemble scarlet fever. However, this rash is associated with tenderness and large blister formation. These blisters easily pop, followed by causing the skin to peel.[31] * Staphylococcal scarlet fever: The rash is identical to the streptococcal scarlet fever in distribution and texture, but the skin affected by the rash will be tender.[8] ## Prevention[edit] One method is long-term use of antibiotics to prevent future group A streptococcal infections. This method is only indicated for people who have had complications like recurrent attacks of acute rheumatic fever or rheumatic heart disease. Antibiotics are limited in their ability to prevent these infections since there are a variety of subtypes of group A streptococci that can cause the infection.[14] The vaccine approach has a greater likelihood of effectively preventing group A streptococcal infections because vaccine formulations can target multiple subtypes of the bacteria.[14] A vaccine developed by George and Gladys Dick in 1924 was discontinued due to poor efficacy and the introduction of antibiotics. Difficulties in vaccine development include the considerable strain variety of group A streptococci present in the environment and the amount of time and number of people needed for appropriate trials for safety and efficacy of any potential vaccine.[32] There have been several attempts to create a vaccine in the past few decades. These vaccines, which are still in the development phase, expose the person to proteins present on the surface of the group A streptococci to activate an immune response that will prepare the person to fight and prevent future infections.[33] There used to be a diphtheria scarlet fever vaccine.[34] It was, however, found not to be effective.[35] This product was discontinued by the end of World War II. ## Treatment[edit] Antibiotics to combat the streptococcal infection are the mainstay of treatment for scarlet fever. Prompt administration of appropriate antibiotics decreases the length of illness. Peeling of the outer layer of skin, however, will happen despite treatment.[8] One of the main goals of treatment is to prevent the child from developing one of the suppurative or nonsuppurative complications, especially acute rheumatic fever.[18] As long as antibiotics are started within nine days, it is very unlikely for the child to develop acute rheumatic fever.[14] Antibiotic therapy has not been shown to prevent the development of post-streptococcal glomerulonephritis.[15][8] Another important reason for prompt treatment with antibiotics is the ability to prevent transmission of the infection between children. An infected individual is most likely to pass on the infection to another person during the first 2 weeks.[20] A child is no longer contagious (able to pass the infection to another child) after 24 hours of antibiotics.[14] The antibiotic of choice is penicillin V which is taken by mouth in pill form. Children who are not able to take pills can be given amoxicillin which comes in a liquid form and is equally effective. Duration of treatment is 10 days.[18] Benzathine Penicillin G can be given as a one time intramuscular injection as another alternative if swallowing pills is not possible.[36] If the person is allergic to the family of antibiotics which both penicillin and amoxicillin are a part of (beta-lactam antibiotics), a first generation cephalosporin is used.[27] Cephalosporin antibiotics, however, can still cause adverse reactions in people whose allergic reaction to penicillin is a Type 1 Hypersensitivity reaction. In those cases it is appropriate to choose clindamycin or erythromycin instead.[27] Tonsillectomy, although once a reasonable treatment for recurrent streptococcal pharyngitis, is not indicated, as a person can still be infected with group A streptococcus without their tonsils.[20] ### Antibiotic resistance and resurgence[edit] A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin, but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, emerged in Hong Kong in 2011, accounting for at least two deaths in that city—the first such in over a decade.[37] About 60% of circulating strains of the group A streptococcus that cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, says Professor Kwok-yung Yuen, head of Hong Kong University's microbiology department. Previously, observed resistance rates had been 10–30%; the increase is likely the result of overuse of macrolide antibiotics in recent years.[citation needed] There was also an outbreak in the UK in 2014, and the National Health Service reported a 68% increase in the number of S. pyogenes identified in laboratory reports between 2014 and 2018.[5] New research published in October 2020 in the journal that the bacterium appears to be getting more robust after being infected with viruses,[5] specifically the North-East Asian serotype M12 (emm12) (group A Streptococcus, GAS).[38] They found three new genes, acquired from viruses, leading to the development of "superantigens" targeting white blood cells, leading to a more virulent strain of the bacterium.[5] A vaccine that will protect against the 180 to 200 types of 180 of bacteria causing the disease has been worked on for over 20 years, but as of 2020[update] a safe one had not yet been developed.[5] ## Epidemiology[edit] Scarlet fever occurs equally in both males and females.[13] Children are most commonly infected, typically between 5–15 years old. Although streptococcal infections can happen at any time of year, infection rates peak in the winter and spring months, typically in colder climates.[14] The morbidity and mortality of scarlet fever has declined since the 18th and 19th century when there were epidemics caused by this disease.[39] Around 1900 the mortality rate in multiple places reached 25%.[40] The improvement in prognosis can be attributed to the use of penicillin in the treatment of this disease.[11] The frequency of scarlet fever cases has also been declining over the past century. There have been several reported outbreaks of the disease in various countries in the past decade.[41] The reason for these recent increases remains unclear in the medical community. Between 2013 and 2016 population rates of scarlet fever in England increased from 8.2 to 33.2 per 100,000 and hospital admissions for scarlet fever increased by 97%.[42] ## History[edit] It is unclear when a description of this disease was first recorded.[43] Hippocrates, writing around 400 BC, described the condition of a person with a reddened skin and fever.[44] The first description of the disease in the medical literature appeared in the 1553 book De Tumoribus praeter Naturam by the Sicilian anatomist and physician Giovanni Filippo Ingrassia, where he referred to it as rossalia. He also made a point to distinguish that this presentation had different characteristics to measles.[44] It was redescribed by Johann Weyer during an epidemic in lower Germany between 1564 and 1565; he referred to it as scalatina anginosa. The first unequivocal description of scarlet fever appeared in a book by Joannes Coyttarus of Poitiers, De febre purpura epidemiale et contagiosa libri duo, which was published in 1578 in Paris. Daniel Sennert of Wittenberg described the classical 'scarlatinal desquamation' in 1572 and was also the first to describe the early arthritis, scarlatinal dropsy, and ascites associated with the disease. In 1675 the term that has been commonly used to refer to scarlet fever, "scarlatina", was written by Thomas Sydenham, an English physician.[44] In 1827, Richard Bright was the first to recognize the involvement of the renal system in scarlet fever. In 1879, The Ingalls and Nelson family contracted Scarlet Fever, making Mary Ingalls Blind. The association between streptococci and disease was first described in 1874 by Theodor Billroth, discussing people with skin infections.[44] Billroth also coined the genus name Streptococcus. In 1884 Friedrich Julius Rosenbach edited the name to its current one, Streptococcus pyogenes, after further looking at the bacteria in the skin lesions.[44] The organism was first cultured in 1883 by the German surgeon Friedrich Fehleisen from erysipelas lesions. Also in 1884, the German physician Friedrich Loeffler was the first to show the presence of streptococci in the throats of people with scarlet fever. Because not all people with pharyngeal streptococci developed scarlet fever, these findings remained controversial for some time. The association between streptococci and scarlet fever was confirmed by Alphonse Dochez and George and Gladys Dick in the early 1900s.[45] Nil Filatov (in 1895) and Clement Dukes (in 1894) described an exanthematous disease which they thought was a form of rubella, but in 1900, Dukes described it as a separate illness which came to be known as Dukes' disease,[46] Filatov's disease, or fourth disease. However, in 1979, Keith Powell identified it as in fact the same illness as the form of scarlet fever which is caused by staphylococcal exotoxin and is known as staphylococcal scalded skin syndrome.[47][48][49][50] Scarlet fever serum from horses' blood was used in the treatment of children beginning in 1900 and reduced mortality rates significantly. In 1906, the Austrian pediatrician Clemens von Pirquet postulated that disease-causing immune complexes were responsible for the nephritis that followed scarlet fever.[51] Bacteriophages were discovered in 1915 by Frederick Twort. His work was overlooked and bacteriophages were later rediscovered by Felix d'Herelle in 1917. The specific association of scarlet fever with the group A streptococci had to await the development of Lancefield's streptococcal grouping scheme in the 1920s. George and Gladys Dick showed that cell-free filtrates could induce the erythematous reaction characteristic of scarlet fever, proving that this reaction was due to a toxin. Karelitz and Stempien discovered that extracts from human serum globulin and placental globulin can be used as lightening agents for scarlet fever and this was used later as the basis for the Dick test. The association of scarlet fever and bacteriophages was described in 1926 by Cantucuzene and Boncieu.[52] An antitoxin for scarlet fever was developed in 1924. The first toxin which causes this disease was cloned and sequenced in 1986 by Weeks and Ferretti.[25] The discovery of penicillin and its subsequent widespread use has significantly reduced the mortality of this once feared disease. Reports of cases of scarlet fever have been on the rise in countries including England, Wales, South Korea, Vietnam, China, and Hong Kong in recent years. Researchers are unsure as to what has caused the spike in cases of the disease.[53][54] ### The Dick test[edit] The Dick test, invented in 1924 by George F. Dick and Gladys Dick, was used to identify those susceptible to scarlet fever.[55] The Dick test consisted of injecting a diluted strain of the streptococci known to cause scarlet fever into a person's skin. A local reaction in the skin at the site of injection appeared in people who were susceptible to developing scarlet fever. This reaction was most notable around 24 hours after the injection but could be seen as early as 4–6 hours. If there is no reaction seen in the skin, then that person was assumed to have already developed immunity to the disease and was not at risk of developing it.[56] * Otto Kalischer wrote a doctoral thesis on scarlet fever in 1891. * A 1930s American poster attempting to curb the spread of such diseases as scarlet fever by regulating milk supply * Gladys Henry Dick (pictured) and George Frederick Dick developed an antitoxin and vaccine for scarlet fever in 1924 which were later eclipsed by penicillin in the 1940s. ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t "Scarlet Fever: A Group A Streptococcal Infection". Center for Disease Control and Prevention. 19 January 2016. Archived from the original on 12 March 2016. Retrieved 12 March 2016. 2. ^ Shorter Oxford English dictionary. United Kingdom: Oxford University Press. 2007. p. 3804. ISBN 978-0199206872. 3. ^ a b Quinn, RW (1989). "Comprehensive review of morbidity and mortality trends for rheumatic fever, streptococcal disease, and scarlet fever: the decline of rheumatic fever". Reviews of Infectious Diseases. 11 (6): 928–53. doi:10.1093/clinids/11.6.928. PMID 2690288. 4. ^ Ralph, AP; Carapetis, JR (2013). Group a streptococcal diseases and their global burden. Current Topics in Microbiology and Immunology. 368. pp. 1–27. doi:10.1007/82_2012_280. ISBN 978-3-642-36339-9. PMID 23242849. 5. ^ a b c d e f g Richardson, Holly (7 October 2020). "Scarlet fever is making a comeback after being infected with a toxic virus, researchers say". ABC News (Australian Broadcasting Corporation). Retrieved 27 November 2020. 6. ^ Smallman-Raynor, Matthew (2012). Atlas of epidemic Britain : a twentieth century picture. Oxford: Oxford University Press. p. 48. ISBN 9780199572922. Archived from the original on 14 February 2017. 7. ^ Smallman-Raynor, Andrew Cliff, Peter Haggett, Matthew (2004). World Atlas of Epidemic Diseases. 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"Genetic diversity in temperate bacteriophages of Streptococcus pyogenes: identification of a second attachment site for phages carrying the erythrogenic toxin A gene". Journal of Bacteriology. 179 (20): 6509–6511. doi:10.1128/jb.179.20.6509-6511.1997. PMC 179571. PMID 9335304. 25. ^ a b Weeks, C. R.; Ferretti, J. J. (1986). "Nucleotide sequence of the type A streptococcal exotoxin (erythrogenic toxin) gene from Streptococcus pyogenes bacteriophage T12". Infection and Immunity. 52 (1): 144–150. doi:10.1128/IAI.52.1.144-150.1986. PMC 262210. PMID 3514452. 26. ^ Yu, C. E.; Ferretti, J. J. (1991). "Molecular characterization of new group A streptococcal bacteriophages containing the gene for streptococcal erythrogenic toxin A (speA)". Molecular and General Genetics. 231 (1): 161–168. doi:10.1007/BF00293833. PMID 1753942. S2CID 36197596. 27. ^ a b c American Academy of Pediatrics (2013). Baker, Carol (ed.). Red Book Atlas of Pediatric Infectious Diseases. American Academy of Pediatrics. pp. 473–476. ISBN 9781581107951. 28. ^ Ferri, Fred (2009). Ferri's Color Atlas and Text of Clinical Medicine. Saunders. pp. 47–48. 29. ^ Kato, Hirohisa (2010). Cardiology, Third Edition. Elsevier. pp. 1613–1626. 30. ^ Habif, Thomas (2016). Clinical Dermatology. Elsevier. pp. 534–576. 31. ^ Adams, James (2013). Emergency Medicine Clinical Essentials. Saunders. pp. 149–158. 32. ^ "Initiative for Vaccine Research (IVR)—Group A Streptococcus". World Health Organization. Archived from the original on 13 May 2012. Retrieved 15 June 2012. 33. ^ Chih-Feng, Kuo; Tsao, Nina; I-Chen, Hsieh; Yee-Shin, Lin; Jiunn-Jong, Wu; Yu-Ting, Hung (March 2017). "Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection". PLOS ONE. 12 (3): e0174464. Bibcode:2017PLoSO..1274464K. doi:10.1371/journal.pone.0174464. PMC 5371370. PMID 28355251. 34. ^ Rudolf Franck - Moderne Therapie in Innerer Medizin und Allgemeinpraxis - Ein Handbuch der Medikamentösen, Physikalischen und Diätetischen Behandlungsweisen der Letzten Jahre. Springer Verlag. 13 August 2013. ISBN 9783662221860. Archived from the original on 9 January 2017. Retrieved 9 January 2017. 35. ^ Ellis, Ronald W.; Brodeur, Bernard R. (2012). New Bacterial Vaccines. Springer Science & Business Media. p. 158. ISBN 9781461500537. Archived from the original on 9 January 2017. 36. ^ Ferri, Fred (2018). Ferri's Clinical Advisor 2018. Elsevier. p. 1143. 37. ^ "Second HK child dies of mutated scarlet fever". Associated Press (online). 22 June 2011. Archived from the original on 24 June 2011. Retrieved 23 June 2011. 38. ^ Brouwer, S.; Barnett, T.C.; et al. (6 October 2020). "Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes". Nat Commun. 11 (5018): 5018. doi:10.1038/s41467-020-18700-5. PMC 7538557. PMID 33024089. Retrieved 27 November 2020. 39. ^ "Managing scarlet fever". BMJ. 362: k3005. 2018. doi:10.1136/bmj.k3005. ISSN 0959-8138. PMID 30166279. S2CID 52136139. 40. ^ Guerrant, Richard; Walker, David; Weller, Peter (2011). Tropical Infectious Diseases: Principles, Pathogens and Practice. Elsevier. pp. 203–211. ISBN 9780702039355. 41. ^ Basetti, S.; Hodgson, J.; Rawson, T.M.; Majeed, A. (August 2017). "Scarlet Fever: A guide for general practitioners". London Journal of Primary Care. 9 (5): 77–79. doi:10.1080/17571472.2017.1365677. PMC 5649319. PMID 29081840. 42. ^ "Scarlet fever in England reaches highest level in 50 years". Pharmaceutical Journal. 30 November 2017. Retrieved 2 January 2018. 43. ^ Rolleston, J. D. (1928). "The History of Scarlet Fever". BMJ. 2 (3542): 926–929. doi:10.1136/bmj.2.3542.926. PMC 2456687. PMID 20774279. 44. ^ a b c d e Ferretti, Joseph; Kohler, Werner (February 2016). "History of Streptococcal Research". Streptococcus Pyogenes: Basic Biology to Clinical Manifestations. PMID 26866232. 45. ^ http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/dochez-alphonse.pdf 46. ^ Dukes, Clement (30 June 1900). "On the confusion of two different diseases under the name of rubella (rose-rash)". The Lancet. 156 (4011): 89–95. doi:10.1016/S0140-6736(00)65681-7. 47. ^ Weisse, Martin E (31 December 2000). "The fourth disease, 1900–2000". The Lancet. 357 (9252): 299–301. doi:10.1016/S0140-6736(00)03623-0. PMID 11214144. S2CID 35896288. 48. ^ Powell, KR (January 1979). "Filatow-Dukes' disease. Epidermolytic toxin-producing staphylococci as the etiologic agent of the fourth childhood exanthem". American Journal of Diseases of Children. 133 (1): 88–91. doi:10.1001/archpedi.1979.02130010094020. PMID 367152. 49. ^ Melish, ME; Glasgow, LA (June 1971). "Staphylococcal scalded skin syndrome: the expanded clinical syndrome". The Journal of Pediatrics. 78 (6): 958–67. doi:10.1016/S0022-3476(71)80425-0. PMID 4252715. 50. ^ Morens, David M; Katz, Alan R; Melish, Marian E (31 May 2001). "The fourth disease, 1900–1881, RIP". The Lancet. 357 (9273): 2059. doi:10.1016/S0140-6736(00)05151-5. PMID 11441870. S2CID 35925579. 51. ^ Huber, B. (2006). "100 years of allergy: Clemens von Pirquet—his idea of allergy and its immanent concept of disease" (PDF). Wiener klinische Wochenschrift. 118 (19–20): 573–579. doi:10.1007/s00508-006-0701-3. PMID 17136331. S2CID 46144926. 52. ^ Cantacuzène, J.; Bonciu, O. (1926). "Modifications subies par des streptocoques d'origine non scarlatineuse au contact de produits scarlatineux filtrès". Comptes rendus de l'Académie des Sciences (in French). 182: 1185–1187. 53. ^ Lamagni, Theresa; Guy, Rebecca; Chand, Meera (2018). "Resurgence of scarlet fever in England, 2014–16: a population-based surveillance study". The Lancet Infectious Diseases. The Lancet: Infectious Disease. 18 (2): 180–187. doi:10.1016/S1473-3099(17)30693-X. PMID 29191628. 54. ^ Branswell, Helen (27 November 2017). "Scarlet fever, a disease of yore, is making a comeback in parts of the world". STAT. 55. ^ Dick, G. F.; Dick, G. H. (1924). "A skin test for susceptibility to scarlet fever". Journal of the American Medical Association. 82 (4): 265–266. doi:10.1001/jama.1924.02650300011003. 56. ^ Claude, B; McCartney, J.E.; McGarrity, J. (January 1925). "The Dick test for susceptibility to scarlet fever". The Lancet. 205 (5292): 230–231. doi:10.1016/S0140-6736(00)56009-7. ## External links[edit] Classification D * ICD-10: A38 * ICD-9-CM: 034.1 * OMIM: 012541 * MeSH: D012541 * DiseasesDB: 29032 External resources * Patient UK: Scarlet fever Wikimedia Commons has media related to Scarlet fever. * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti syndrome * v * t * e * Firmicutes (low-G+C) Infectious diseases * Bacterial diseases: G+ Bacilli Lactobacillales (Cat-) Streptococcus α optochin susceptible * S. pneumoniae * Pneumococcal infection optochin resistant * Viridans streptococci: S. mitis * S. mutans * S. oralis * S. sanguinis * S. sobrinus * S. anginosus group β A * bacitracin susceptible: S. pyogenes * Group A streptococcal infection * Streptococcal pharyngitis * Scarlet fever * Erysipelas * Rheumatic fever B * bacitracin resistant, CAMP test+: S. agalactiae * Group B streptococcal infection ungrouped * Streptococcus iniae * Cutaneous Streptococcus iniae infection γ * D * BEA+: Streptococcus bovis Enterococcus * BEA+: Enterococcus faecalis * Urinary tract infection * Enterococcus faecium Bacillales (Cat+) Staphylococcus Cg+ * S. aureus * Staphylococcal scalded skin syndrome * Toxic shock syndrome * MRSA Cg- * novobiocin susceptible * S. epidermidis * novobiocin resistant * S. saprophyticus Bacillus * Bacillus anthracis * Anthrax * Bacillus cereus * Food poisoning Listeria * Listeria monocytogenes * Listeriosis Clostridia Clostridium (spore-forming) motile: * Clostridium difficile * Pseudomembranous colitis * Clostridium botulinum * Botulism * Clostridium tetani * Tetanus nonmotile: * Clostridium perfringens * Gas gangrene * Clostridial necrotizing enteritis Finegoldia (non-spore forming) * Finegoldia magna Mollicutes Mycoplasmataceae * Ureaplasma urealyticum * Ureaplasma infection * Mycoplasma genitalium * Mycoplasma pneumoniae * Mycoplasma pneumonia Anaeroplasmatales * Erysipelothrix rhusiopathiae * Erysipeloid * v * t * e Numbered Diseases of Childhood Diseases * First Disease (Measles) * Second Disease (Scarlet Fever) * Third Disease (Rubella) * Fourth Disease (Dukes' Disease) * Fifth Disease (Erythema Infectiosum) * Sixth Disease (Roseola) * Biology portal * Medicine portal Authority control * GND: 4395395-5 * LCCN: sh85118023 * NDL: 00572113 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Scarlet fever	c0036285	7,019	wikipedia	https://en.wikipedia.org/wiki/Scarlet_fever	2021-01-18T18:58:51	{"mesh": ["D012541"], "umls": ["C0036285", "C0343487"], "orphanet": ["36235"], "wikidata": ["Q180266"]}
## Description Kantaputra mesomelic dysplasia (MMDK) is a rare, autosomal dominant skeletal disease characterized by symmetric marked shortening of the upper and lower limbs. The ulnae are very short and the radii are bowed. The distal humerus has a dumbbell shape, whereas the hands are relatively normal but show progressive flexion contractures of the proximal interphalangeal joints. Carpal and tarsal synostoses are observed in some individuals. In the lower limbs, the feet are fixed in plantar flexion with the sole facing backward, causing 'ballerina-like standing.' The prominent distal fibula on the ventral aspect is considered to be the signature finding of the syndrome. The calcaneus is small or missing, and a small fibula and talus as well as fibulocalcaneal synostosis are characteristic features. The tibial bony knot articulates with the proximal end of the fibula (summary by Kantaputra et al., 2010). See 613681 for discussion of the chromosome 2q31.1 duplication syndrome, which shows cytogenetic and phenotypic overlap with MMDK. Clinical Features In a large Thai family, Kantaputra et al. (1992) described a distinct type of mesomelic dysplasia characterized by bilateral, symmetric marked shortening of the ulna and shortening and bowing of the radius. The proximal fibula was unusually short, and synostoses were present between the tibia and fibula and between the small, malformed calcaneus and talus. The prominent calcaneus on the ventral surface of the distal fibula was a characteristic feature. Carpal and tarsal synostoses were present in most affected persons. All affected persons walked on the tips of their toes with the dorsal foot deviated laterally. The average height of affected male adults was 152 cm. There were 15 affected individuals in 3 generations, including a pair of identical twins and many instances of male-to-male transmission. Mesomelia and synostosis are also cardinal features of the mesomelia-synostoses syndrome (600383). Kantaputra (2004) provided a follow-up on the family originally described by Kantaputra et al. (1992). In a 21-year-old male (previously examined at age 8 years), the author noted progressively bowed radii, overlapping carpal and tarsal bones, flexion contractures of proximal interphalangeal joints 4 and 5, narrower proximal and distal interphalangeal joints 4 and 5, and fusion of the right tibia with the malformed talus and distal fibula. Large, dumbbell-shaped distal humeri were seen in all affected adults. A 4-year-old member of the family had upper and lower limb abnormalities similar to those of her relatives, but with more flexion contractures of the interphalangeal joints than any other relative. Kantaputra (2004) noted that she had the fibular prominence that seemed to be the most consistent hallmark of the syndrome. Shears et al. (2004) described a Danish mother and son with mesomelic limb shortening in whom radiologic examination showed severe shortening of the radius and ulna with bowing of the radius and dislocation of the radial head. Multiple carpal and tarsal synostoses were present, and the talus and calcaneum were fused. Sequencing of the HOXD11 gene (142986) in the mother revealed no mutation. Shears et al. (2004) stated that this phenotype was most consistent with Kantaputra-type mesomelic dysplasia. Kantaputra (2004) reviewed the findings and concluded that with less severely affected radii and ulnae, the absence of 'ballerina-like' standing, and the absence of the characteristic fibular prominence, the syndrome described by Shears et al. (2004) represents a distinct entity that is probably allelic to MMDK. Kwee et al. (2004) reported a grandmother, her 3 children, and 3 grandchildren who had short stature and bilateral symmetric skeletal abnormalities consisting of very short, broad and bowed radii, very short and broad ulnae, mildly short lower legs, short proximal end of fibula, abnormal ankles, abnormal calcaneus, and talus and pes equinus. They had normal craniofacial features, normal intelligence, normal chromosomes, and no mutations or deletions in the SHOX gene (312865). Using markers that have shown linkage with the MMDK locus, Kwee et al. (2004) observed perfect cosegregation with the disease phenotype, but the family was too small to obtain a significant lod score. The authors concluded that these patients represented the third reported family with autosomal dominant mesomelic dysplasia of the Kantaputra type. Mapping Because of the location of the breakpoints of a balanced translocation, t(2;8)(q31;p21), in patients from an Italian family with a skeletal dysplasia similar to the Kantaputra type of mesomelic dysplasia, reported by Ventruto et al. (1983), Fujimoto et al. (1998) performed linkage analysis in the Thai family, using 50 CA-repeat markers mapping to the 2q22-q34 and 8p24-p21 regions. The results ruled out linkage of MMDK to marker loci in the 8p24-p21 region, whereas all 9 affected members available for the study shared a haplotype at 4 loci spanning about 22.7 cM in the 2q24-q32 region. The computer-assisted 2-point linkage analysis revealed lod scores greater than 4.2 at theta = 0.0 for all 4 of these loci. Fujimoto et al. (1998) suggested that MMDK may be allelic to dyschondrosteosis (127300). They suggested that the human HOXD genes (see 142987), especially those located at the 5-prime region of the gene cluster, are strong candidates for the site of the mutation responsible for the MMDK phenotype. Cytogenetics Cho et al. (2010) reported a Korean family with mesomelic dysplasia caused by a 1.0-Mb duplication at chromosome 2q31.1 (613681) and suggested that the disorder might be allelic to MMDK. Kantaputra et al. (2010) performed array CGH and identified 2 microduplications on chromosome 2 (2q31.1-q31.2) encompassing approximately 481 kb and 507 kb, separated by a segment of normal copy number. The more centromeric duplication, which extends approximately from position 176506582 to 176986597, encompasses the entire HOXD cluster, as well as the neighboring genes EVX2 (142991) and MTX2 (608555). Kantaputra et al. (2010) confirmed segregation of the duplications with the MDK phenotype by quantitative PCR analysis of a further 9 family members from the Thai family; 8 were affected and 1, who did not carry the duplication, was unaffected. The families reported by Shears et al. (2004) and Kwee et al. (2004) did not have a clinically relevant copy number change within chromosome 2q or elsewhere in the genome. Kantaputra et al. (2010) noted that the breakpoints of the duplication localized to the same region as the previously identified inversion of the mouse mutant ulnaless (Ul), which has a similar phenotype as MDK, as described by Peichel et al. (1997) and Herault et al. (1997). Kantaputra et al. (2010) proposed that MDK is caused by duplications that modify the topography of the locus and as such result in deregulation of HOXD gene expression. Molecular Genetics ### Exclusion Studies Because they had identified microdeletions on chromosome 8q13 involving the SULF1 (610012) and SLCO5A1 (613543) genes in patients with the mesomelic-synostoses syndrome (600383), Isidor et al. (2010) analyzed SULF1 and SLCO5A1 in 2 patients with the Kantaputra type of mesomelic dysplasia, previously reported by Shears et al. (2004) and Siwicka et al. (2008), respectively, but did not identify any mutations. No deletions or duplications at chromosome 8q13 or elsewhere in the genome were detected by 44K oligonucleotide array. INHERITANCE \- Autosomal dominant SKELETAL Limbs \- Mesomelic limb shortening \- Broad, shortened radius \- Broad, severely shortened ulna \- Radial bowing \- Shortened tibia \- Shortened fibula \- Tibial-fibula synostoses Hands \- Hands deviate ulnarly \- Carpal synostoses \- Normal metacarpals \- Normal phalanges Feet \- Malformed calcaneus \- Malformed talus \- Tibial-talar complex \- Fibulo-calcaneal complex \- Tarsal synostoses MISCELLANEOUS \- Patients walk on tips of toes with dorsal foot deviated laterally ▲ 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	MESOMELIC DYSPLASIA, KANTAPUTRA TYPE	c1835009	7,020	omim	https://www.omim.org/entry/156232	2019-09-22T16:38:17	{"mesh": ["C535547"], "omim": ["156232"], "orphanet": ["1836"], "synonyms": ["Alternative titles", "MDK", "MESOMELIC DYSPLASIA WITH ANKLE, CARPAL, AND TARSAL SYNOSTOSIS", "MESOMELIC DYSPLASIA, THAI TYPE"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Photodermatosis" – news · newspapers · books · scholar · JSTOR (December 2009) (Learn how and when to remove this template message) Photodermatosis SpecialtyDermatology Photodermatoses is a skin disease that is caused by exposure to sunlight. People with photodermatoses may develop skin rashes following exposure to the sun. Polymorphous light eruption is the most common type of photodermatoses. It is most likely due to an abnormal immune system reaction to the sun. Polymorphous light eruption occurs in approximately 10 to 20 percent of otherwise healthy individuals, so it is a relatively common condition. ## References[edit] This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e * v * t * e Radiation-related disorders / Photodermatoses Ultraviolet/ionizing * Sunburn * Phytophotodermatitis * Solar urticaria * Polymorphous light eruption * Benign summer light eruption * Juvenile spring eruption * Acne aestivalis * Hydroa vacciniforme * Solar erythema Non-ionizing Actinic rays * Actinic keratosis * Atrophic actinic keratosis * Hyperkeratotic actinic keratosis * Lichenoid actinic keratosis * Pigmented actinic keratosis * Actinic cheilitis * Actinic granuloma * Actinic prurigo * Chronic actinic dermatitis Infrared/heat * Erythema ab igne (Kangri ulcer * Kairo cancer * Kang cancer * Peat fire cancer) * Cutis rhomboidalis nuchae * Poikiloderma of Civatte Other * Radiation dermatitis * Acute * Chronic radiodermatitis) * Favre–Racouchot syndrome * Photoaging * Photosensitivity with HIV infection * Phototoxic tar dermatitis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Photodermatosis	c0920193	7,021	wikipedia	https://en.wikipedia.org/wiki/Photodermatosis	2021-01-18T18:59:49	{"umls": ["C0920193"], "icd-10": ["L56.8"], "orphanet": ["79390"], "wikidata": ["Q2986815"]}
A rare neurocutaneous disorder caused by an inborn error of lipid metabolism and characterized by congenital ichthyosis, intellectual deficit, and spasticity. ## Epidemiology Prevalence is estimated at 1/250,000 worldwide, but the syndrome is more common in Sweden due to a founder effect. ## Clinical description Clinical features develop perinatally and during infancy. Patients tend to be born preterm. Hyperkeratosis is usually present at birth and progresses to a generalized ichthyosis, particularly prominent on flexural areas, the nape of the neck, the trunk and the extremities. Pruritus is a prominent feature. Erythematous dermatitis is often present at birth, and then tends to fade with increasing age. Neurological signs appear during the first two years of life and consist of delay in reaching motor milestones due to spastic diplegia or, much less commonly, spastic tetraplegia. Approximately one-half of patients are non-ambulatory. Seizures occur in about 40% of cases. Intellectual deficit varies from mild to severe, although rare patients with normal intellect have been reported. Delayed speech and dysarthria are common. Ophthalmologic involvement is often present and is characterized by retinal crystalline inclusions (so-called glistening white dots) surrounding the fovea. Photophobia and myopia are common. ## Etiology SLS is caused by mutations in the ALDH3A2 gene (17p11.2) encoding fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehydes to fatty acids. More than 90 mutations in ALDH3A2 have been identified, including amino acid substitutions, deletions, insertions, splicing errors and contiguous gene deletions. ## Diagnostic methods SLS is diagnosed based on the clinical features, and by measuring FALDH or fatty alcohol oxidoreductase (FAO) activity in cultured fibroblasts from skin biopsies. DNA-based diagnosis is possible by directly sequencing the ALDH3A2 gene and identifying pathogenic mutations. ## Differential diagnosis In early infancy, before the onset of spasticity, the differential diagnosis includes other forms of congenital ichthyosis including lamellar ichthyosis and congenital ichthyosiform erythroderma. Once neurologic symptoms appear, the differential diagnosis includes other neuro-ichthyotic syndromes such as neutral lipid storage disease (Chanarin-Dorfman syndrome), ELOVL4 deficiency, multiple sulfatase deficiency and Refsum disease. ## Antenatal diagnosis Antenatal diagnosis is possible through biochemical or molecular analysis of amniocytes or chorionic villus cells. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy. ## Management and treatment Management should be multidisciplinary including neurologists, dermatologists, ophthalmologists, orthopedic surgeons, and physiotherapists. The treatment of ichthyosis consists of topical application of moisturizing creams and keratolytic agents, or use of systemic retinoids. Seizures usually respond to anti-convulsant medications and spasticity is alleviated by botulinum toxin injections or surgical procedures. Special diets with medium-chain fatty acid supplements may help the ichthyosis, but effects are limited. ## Prognosis Patients usually survive until adulthood but require life-long care. Minimal progression of the neurologic findings or intellectual deficit occurs after puberty. Patients with early symptoms tend to be more severely affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake 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	Sjögren-Larsson syndrome	c0037231	7,022	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=816	2021-01-23T18:36:11	{"gard": ["7654"], "mesh": ["D016111"], "omim": ["270200"], "umls": ["C0037231"], "icd-10": ["Q87.1"], "synonyms": ["Fatty acid alcohol oxidoreductase deficiency"]}
Bacteriuria Other namesBacteruria Multiple rod-shaped bacteria shown between the larger white blood cells at urinary microscopy from a person with urinary tract infection. SpecialtyEmergency medicine, Infectious disease TypesAsymptomatic, symptomatic[1][2] Diagnostic methodUrinalysis, urine culture[3] Differential diagnosisContamination[1] TreatmentBased on symptoms or risk factors[3][4] FrequencyAsymptomatic: 3% (middle aged women), up to 50% (women in nursing homes)[5] Symptomatic: up to 10% of women a year[6][7] Bacteriuria is the presence of bacteria in urine.[1] Bacteriuria accompanied by symptoms is a urinary tract infection while that without is known as asymptomatic bacteriuria.[1][2] Diagnosis is by urinalysis or urine culture.[3] Escherichia coli is the most common bacterium found.[1] People without symptoms should generally not be tested for the condition.[3] Differential diagnosis include contamination.[1] If symptoms are present treatment is generally with antibiotics.[3] Bacteriuria without symptoms generally does not require treatment.[4] Exceptions may include pregnant women, those who have had a recent kidney transplant, young children with significant vesicoureteral reflux, and those undergoing surgery of the urinary tract.[3][4] Bacteriuria without symptoms is present in about 3% of otherwise healthy middle aged women.[5] In nursing homes rates are as high as 50% among women and 40% in men.[5] In those with a long term indwelling urinary catheter rates are 100%.[5] Up to 10% of women have a urinary tract infection in a given year and half of all women have at least one infection at some point in their lives.[6][7] ## Contents * 1 Signs and symptoms * 1.1 Asymptomatic * 1.2 Symptomatic * 2 Diagnosis * 2.1 Screening * 3 Treatment * 3.1 Asymptomatic * 3.2 Symptomatic * 4 Epidemiology * 5 References * 6 External links ## Signs and symptoms[edit] ### Asymptomatic[edit] Asymptomatic bacteriuria is bacteriuria without accompanying symptoms of a urinary tract infection. It is more common in women, in the elderly, in residents of long-term care facilities, and in people with diabetes, bladder catheters and spinal cord injuries. People with a long-term Foley catheter always show bacteriuria. Chronic asymptomatic bacteriuria occurs in as many as 50% of the population in long-term care.[8] There is an association between asymptomatic bacteriuria in pregnant women with low birth weight, preterm delivery, and infection of the newborn.[9][10] However, most of these studies were graded as poor quality.[9] Bacteriuria in pregnancy also increases the risk of preeclampsia.[10] ### Symptomatic[edit] Main article: Urinary tract infection Symptomatic bacteriuria is bacteriuria with the accompanying symptoms of a urinary tract infection (such as frequent urination, painful urination, fever, back pain) and includes pyelonephritis or cystitis. The most common cause of urinary tract infections is Escherichia coli. ## Diagnosis[edit] Testing for bacteriuria is usually performed in people with symptoms of a urinary tract infection. Certain populations which are not able to feel or express symptoms of an infection are also tested when showing nonspecific symptoms. For example, confusion or other changes in behaviour can be a sign of an infection in the elderly. Screening for asymptomatic bacteriuria in pregnancy is common routine in many countries, but controversial. * The gold standard for detecting bacteriuria is a bacterial culture which identifies the concentration of bacterial cells in the urine. The culture is usually combined with subsequent MALDI-TOF, which allows to identify the causal bacterial species, and antibiotic susceptibility testing. Urine culture is quantitative and very reliable, but takes at least one day to obtain a result. Miniaturisation of bacterial culture within dipstick format, Digital Dipstick,[11] allows bacterial detection, identification and quantification for bacteriuria within 10–12 hours at the point-of-care. Clinicians will often treat symptomatic bacteriuria based on the results of the urine dipstick test while waiting for the culture results. * Bacteriuria can usually be detected using a urine dipstick test. The nitrite test detects nitrate-reducing bacteria if growing in high numbers in urine. A negative dipstick test does not exclude bacteriuria, as not all bacteria which can colonise the urinary tract are nitrate-reducing. The leukocyte esterase test indirectly detects the presence of leukocytes (white blood cells) in urine which can be associated with a urinary tract infection. In elderly, the leukocyte esterase test is often positive even in the absence of an infection. The urine dipstick test is readily available and provides fast, but often unreliable results. * Microscopy can also be used to detect bacteriuria. It is rarely used in clinical routine, since it requires more time and equipment and does not allow reliable identification or quantification of the causal bacterial species. Bacteriuria is assumed if a single bacterial species is isolated in a concentration greater than 100,000 colony forming units per millilitre of urine in clean-catch midstream urine specimens.[12] In urine samples obtained from women, there is a risk for bacterial contamination from the vaginal flora. Therefore, in research, usually a second specimen is analysed to confirm asymptomatic bacteriuria in women. For urine collected via bladder catheterization in men and women, a single urine specimen with greater than 100,000 colony forming units of a single species per millilitre is considered diagnostic.[12] The threshold for women displaying UTI symptoms can be as low as 100 colony forming units of a single species per millilitre. However, bacteria below a threshold of 10000 colony forming units per millilitre are usually reported as "no growth" by clinical laboratories.[13][14] Using special techniques certain non-disease causing bacteria have also been found in the urine of healthy people.[15] These are part of the resident microbiota.[15] ### Screening[edit] Although controversial, many countries including the United States recommend a one time screening for bacteriuria during mid pregnancy.[16][17] The screening method is by urine culture.[17] Screening non pregnant adults is recommended against by the United States Preventive Task Force.[17] ## Treatment[edit] The decision to treat bacteriuria depends on the presence of accompany symptoms and comorbidities. ### Asymptomatic[edit] Asymptomatic bacteriuria generally does not require treatment.[4] Exceptions include those undergoing surgery of the urinary tract, children with vesicoureteral reflux or others with structural abnormalities of the urinary tract.[4][18] In many countries, regional guidelines recommend treatment of pregnant women.[9] There is no indication to treat asymptomatic bacteriuria in diabetics, renal transplant recipients, and in those with spinal cord injuries.[19] The overuse of antibiotics to treat asymptomatic bacteriuria has many adverse effects[20] such as an increased risk of diarrhea, the spread of antimicrobial resistance, and infection due to Clostridium difficile. ### Symptomatic[edit] Symptomatic bacteriuria is synonymous with urinary tract infection and typically treated with antibiotics. Common choices include nitrofurantoin and trimethoprim/sulfamethoxazole. ## Epidemiology[edit] Rates of asymptomatic bacteriuria[5] Group Prevalence (in %) Healthy premenopausal women 1.0 to 5.0 Pregnant women 1.9 to 9.5 Postmenopausal women (50 to 70 years of age) 2.8 to 8.6 People with diabetes mellitus Women 9.0 to 27.0 Men 0.7 to 1.0 Older community-dwelling people Women (older than 70 years) > 15.0 Men 3.6 to 19.0 Older long-term care residents Women 25.0 to 50.0 Men 15.0 to 40.0 People with spinal cord injury Intermittent catheter 23.0 to 89.0 Sphincterotomy and condom catheter 57.0 People undergoing hemodialysis 28.0 People with an indwelling urinary catheter Short-term 9.0 to 23.0 Long-term 100 ## References[edit] 1. ^ a b c d e f Das, K. V. Krishna; Das, K.V. Krishna (2017). Textbook of Medicine: Two Volume Set. JP Medical Ltd. p. 1250. ISBN 9789386056108. 2. ^ a b Sendi, P; Borens, O; Wahl, P; Clauss, M; Uçkay, I (2017). "Management of Asymptomatic Bacteriuria, Urinary Catheters and Symptomatic Urinary Tract Infections in Patients Undergoing Surgery for Joint Replacement: A Position Paper of the Expert Group". Journal of Bone and Joint Infection. 2 (3): 154–159. doi:10.7150/jbji.20425. PMC 5592375. PMID 28894690. 3. ^ a b c d e f "Bacterial Urinary Tract Infections (UTIs)". Merck Manuals Professional Edition. May 2016. Retrieved 12 December 2017. 4. ^ a b c d e Köves, B; Cai, T; Veeratterapillay, R; Pickard, R; Seisen, T; Lam, TB; Yuan, CY; Bruyere, F; Wagenlehner, F; Bartoletti, R; Geerlings, SE; Pilatz, A; Pradere, B; Hofmann, F; Bonkat, G; Wullt, B (25 July 2017). "Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel". European Urology. 72 (6): 865–868. doi:10.1016/j.eururo.2017.07.014. PMID 28754533. 5. ^ a b c d e Colgan, R; Nicolle, LE; McGlone, A; Hooton, TM (15 September 2006). "Asymptomatic bacteriuria in adults". American Family Physician. 74 (6): 985–90. PMID 17002033. 6. ^ a b Salvatore S, Salvatore S, Cattoni E, Siesto G, Serati M, Sorice P, Torella M (June 2011). "Urinary tract infections in women". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 156 (2): 131–6. doi:10.1016/j.ejogrb.2011.01.028. PMID 21349630. 7. ^ a b Nicolle LE (2008). "Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis". Urol Clin North Am. 35 (1): 1–12, v. doi:10.1016/j.ucl.2007.09.004. PMID 18061019. 8. ^ AMDA – The Society for Post-Acute and Long-Term Care Medicine (February 2014), "Ten Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, AMDA – The Society for Post-Acute and Long-Term Care Medicine, retrieved 20 April 2015 9. ^ a b c Smaill, Fiona M.; Vazquez, Juan C. (7 August 2015). "Antibiotics for asymptomatic bacteriuria in pregnancy". The Cochrane Database of Systematic Reviews (8): CD000490. doi:10.1002/14651858.CD000490.pub3. ISSN 1469-493X. PMID 26252501. 10. ^ a b Szweda, Hanna; Jóźwik, Marcin (2016). "Urinary tract infections during pregnancy - an updated overview". Developmental Period Medicine. 20 (4): 263–272. ISSN 1428-345X. PMID 28216479. 11. ^ Iseri, Emre; Biggel, Michael; Goossens, Herman; Moons, Pieter; van der Wijngaart, Wouter (2020). "Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care". Lab on a Chip. doi:10.1039/D0LC00793E. ISSN 1473-0197. 12. ^ a b Detweiler K, Mayers D, Fletcher SG (November 2015). "Bacteruria and Urinary Tract Infections in the Elderly". The Urologic Clinics of North America (Review). 42 (4): 561–8. doi:10.1016/j.ucl.2015.07.002. PMID 26475952. 13. ^ Hooton, Thomas M. (15 March 2012). "Uncomplicated Urinary Tract Infection". New England Journal of Medicine. 366 (11): 1028–1037. doi:10.1056/NEJMcp1104429. ISSN 0028-4793. PMID 22417256. 14. ^ Sam, Amir H.; James T.H. Teo (2010). Rapid Medicine. Wiley-Blackwell. ISBN 978-1-4051-8323-9. 15. ^ a b Schneeweiss J., Koch M., Umek W. (2016). "The human urinary microbiome and how it relates to urogynecology". Int Urogynecol J. 27 (9): 1307–12. doi:10.1007/s00192-016-2944-5. PMID 26811114. S2CID 6272587.CS1 maint: uses authors parameter (link) 16. ^ Moore, Ainsley; Doull, Marion; Grad, Roland; Groulx, Stéphane; Pottie, Kevin; Tonelli, Marcello; Courage, Susan; Garcia, Alejandra Jaramillo; Thombs, Brett D. (8 July 2018). "Recommendations on screening for asymptomatic bacteriuria in pregnancy". Canadian Medical Association Journal. 190 (27): E823–E830. doi:10.1503/cmaj.171325. PMC 6041243. PMID 29986858. 17. ^ a b c Owens, Douglas K.; Davidson, Karina W.; Krist, Alex H.; Barry, Michael J.; Cabana, Michael; Caughey, Aaron B.; Doubeni, Chyke A.; Epling, John W.; Kubik, Martha; Landefeld, C. Seth; Mangione, Carol M.; Pbert, Lori; Silverstein, Michael; Simon, Melissa A.; Tseng, Chien-Wen; Wong, John B. (24 September 2019). "Screening for Asymptomatic Bacteriuria in Adults". JAMA. 322 (12): 1188–1194. doi:10.1001/jama.2019.13069. PMID 31550038. 18. ^ Ramos, Jorge A.; Salinas, Diego F.; Osorio, Johanna; Ruano-Ravina, Alberto (September 2016). "Antibiotic prophylaxis and its appropriate timing for urological surgical procedures in patients with asymptomatic bacteriuria: A systematic review". Arab Journal of Urology. 14 (3): 234–239. doi:10.1016/j.aju.2016.05.002. ISSN 2090-598X. PMC 4983160. PMID 27547467. 19. ^ Nicolle, Lindsay E. (2014). "Urinary Tract Infections in Special Populations". Infectious Disease Clinics of North America. 28 (1): 91–104. doi:10.1016/j.idc.2013.09.006. PMID 24484577. 20. ^ Zalmanovici Trestioreanu, A; Lador, A; Sauerbrun-Cutler, MT; Leibovici, L (8 April 2015). "Antibiotics for asymptomatic bacteriuria". The Cochrane Database of Systematic Reviews. 4: CD009534. doi:10.1002/14651858.CD009534.pub2. PMID 25851268. ## External links[edit] Classification D * ICD-10-CM: R82.71 * MeSH: D001437 External resources * MedlinePlus: 000520 * v * t * e Components and results of urine tests Components * Albumin * Myoglobin * hCG * Leukocyte esterase * Urine pregnancy test * Ketone bodies * Glucose * Urobilinogen * Bilirubin * Creatinine * RBC * WBC * Urinary casts Chemical properties * Urine specific gravity * Isosthenuria * Urine osmolality * Hypersthenuria * Urine pH * Urine anion gap Abnormal findings Red blood cells * Hematuria (Microscopic hematuria) White blood cells * Eosinophiluria Proteinuria * Albuminuria/Microalbuminuria * Albumin/creatinine ratio * Urine protein/creatinine ratio * Myoglobinuria * Hemoglobinuria * Bence Jones protein Small molecules * Glycosuria * Ketonuria * Bilirubinuria * Hyperuricosuria * Aminoaciduria Other * Bacteriuria * Chyluria * Crystalluria * v * t * e Techniques in clinical microbiology Isolation and culture Isolation techniques * Asepsis * Streak plate * Selective media Cultures by body site * Blood culture * Genital culture * Sputum culture * Throat culture * Urine culture * Wound culture Cultures by organism * Bacterial culture * Fungal culture * Viral culture Identification and testing Manual testing: basic techniques * Colonial morphology * Hemolysis * Staining * Gram stain * Acid-fast stain * Giemsa stain * India ink stain * Ziehl-Neelsen stain * Wet prep * Rapid tests * Oxidase * Catalase * Indole * PYR Manual testing: biochemical and immunologic tests * ALA test * Amino acid decarboxylase test * Bile solubility test * CAMP test * Citrate test * Coagulase test * DNAse test * IMViC * KOH test * Methyl red test * Nitrite test * ONPG test * Oxidative/fermentation glucose test * Phenylalanine deaminase test * Reverse CAMP test * Salt tolerance test * Sulfide indole motility test * Triple sugar iron test * Urease test * rapid * Voges–Proskauer test * X and V factor test * Bacitracin susceptibility test * Optochin susceptibility test * Novobiocin susceptibility test * Lancefield grouping * RPR test Automated and point-of-care testing * Analytical profile index * MALDI-TOF * Polymerase chain reaction * VITEK system * Rapid strep test * Monospot test Antibiotic susceptibility testing * Beta-lactamase test * Disk diffusion test * Etest * McFarland standards * Minimum inhibitory concentration Equipment * Agar plate * Growth medium * Anaerobic jar * Gas-pak * Biosafety cabinet * Incubator * Inoculation loop * Inoculation needle [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Bacteriuria	c0004659	7,023	wikipedia	https://en.wikipedia.org/wiki/Bacteriuria	2021-01-18T19:04:10	{"mesh": ["D001437"], "umls": ["C0004659"], "wikidata": ["Q632522"]}
Retinal macular dystrophy type 2 is a rare, genetic macular dystrophy disorder characterized by slowly progressive ''bull's eye'' maculopathy associated, in most cases, with mild decrease in visual acuity and central scotomata. Usually, only the central retina is involved, however some cases of more widespread rod and cone anomalies have been reported. Rare additional features include empty sella turcica, impaired olfaction, renal infections, hematuria and recurrent miscarriages. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Retinal macular dystrophy type 2	c0339512	7,024	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319640	2021-01-23T17:57:07	{"mesh": ["C562746"], "omim": ["608051"], "umls": ["C0339512"], "icd-10": ["H35.5"], "synonyms": ["MCDR2"]}
A late-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism that, if untreated, is characterized by seizures, breathing difficulties, hypotonia, skin rash, alopecia, hearing loss and delayed development. ## Epidemiology Prevalence of clinical biotinidase deficiency (BD) is estimated to be 1/61,000. Carrier frequency in the general population is approximately 1/120. ## Clinical description Symptoms of BD deficiency typically appear within the first few months of life, but later onset has also been reported. Individuals with untreated profound deficiency (less than 10 % of mean normal serum biotinidase activity) have variable clinical findings including seizures, hypotonia, eczematoid rash, alopecia, ataxia, hearing loss, fungal infections, and developmental delay. Metabolically, untreated children can exhibit ketolactic acidosis, organic acidemia (-uria) and mild hyperammonemia. Individuals with untreated partial BD (10% to 30% of mean normal biotinidase activity) may be asymptomatic, but during periods of stress, such as illness, fever or fasting, may develop symptoms similar to those of individuals with profound BD. Multiple adults with optic neuropathy and/or peripheral neuropathy, that is often mistakenly diagnosed as multiple sclerosis, have been shown to have profound biotinidase deficiency. ## Etiology BD deficiency is caused by mutations in the BTD gene (3p25) resulting in reduced or absent biotinidase activity. This enzyme recycles free, non-protein bound, biotin which is required for multiple biotin-dependent metabolic processes. There are more than 150 known mutations of the BTD gene that cause BD. ## Diagnostic methods The disorder is detected through newborn screening when available. Other cases are diagnosed by clinical signs and symptoms and confirmed by demonstration of deficient serum biotinidase activity. Molecular mutation analysis of the BTD gene is also possible. ## Differential diagnosis The symptoms of BD overlap with those of other metabolic diseases, including holocarboxylase synthetase deficiency, isolated carboxylase deficiency, nutritional biotin deficiency, zinc deficiency and essential fatty acid deficiency. Testing for biotinidase deficiency should be considered in all individuals thought to have multiple sclerosis. ## Antenatal diagnosis Prenatal diagnosis for at-risk pregnancies is possible and can be performed by enzymatic analysis or by mutation analysis when the mutation is known. However, because of the treatability of the disorder, prenatal testing is not considered by most families. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child for each pregnancy. Siblings of patients with BDshould be tested for the deficiency even if they do not exhibit symptoms. ## Management and treatment Supplementation with oral biotin in the free, non-protein bound, form is the primary treatment and improves symptoms in symptomatic patients, and prevents symptoms in those identified by newborn screening or before symptoms have developed. Once some features, such as optic atrophy, hearing loss, or developmental delay develop, they may not be reversible with biotin treatment. Treatment with biotin should be maintained lifelong. There are no known, serious adverse effects of biotin therapy. Patients and their families should be warned about the importance of treatment compliance. Periodic ophthalmological, neurological and metabolic evaluations are recommended. Raw eggs should be avoided because of their avidin content (biotin-binding substance), but cooking inactivates the binding effect of avidin. ## Prognosis The prognosis for individuals diagnosed with BD is very good, provided they are treated before symptoms occur and are compliant with biotin therapy. In adult patients presenting with optic neuropathy and/or peripheral neuropathy, improvement in symptoms is likely with early intervention. However, if such individuals remain symptomatic for too long a period, their symptoms may be irreversible. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Biotinidase deficiency	c0220754	7,025	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79241	2021-01-23T18:50:37	{"gard": ["894"], "mesh": ["D028921"], "omim": ["253260"], "umls": ["C0220754", "C1854698"], "icd-10": ["E53.8"], "synonyms": ["Juvenile-onset multiple carboxylase deficiency", "Late-onset multiple carboxylase deficiency"]}
Ramos-Arroyo syndrome Other namesCorneal anesthesia-deafness-intellectual disability syndrome Ramos-Arroyo syndrome is inherited in an autosomal dominant manner Ramos-Arroyo syndrome is marked by corneal anesthesia, absence of the peripapillary choriocapillaris and retinal pigment epithelium, bilateral sensorineural hearing loss, unusual facial appearance, persistent ductus arteriosus, Hirschsprung disease, and moderate intellectual disability.[1] It appears to be a distinct autosomal dominant syndrome with variable expressivity.[2] As of 2008 this syndrome has only been reported in five individuals within three generations of the same family; two young children, their mother, their uncle and their maternal grandmother. This most recent generation to be diagnosed with Ramos-Arroyo syndrome supports the hypothesis that this disease is a distinct autosomal dominant disorder. If this syndrome could be identified in other families it may help to discriminate the gene responsible.[2] ## References[edit] 1. ^ Ramos-Arroyo, Maria A.; Clark, G. Gregory; Saksena, Sudha S.; Modes, M. E.; Opitz, John M.; Reynolds, James F. (1 February 1987). "Congenital corneal anesthesia with retinal abnormalities, deafness, unusual facies, persistent ductus arteriosus, and mental retardation: A new syndrome?". American Journal of Medical Genetics. 26 (2): 345–354. doi:10.1002/ajmg.1320260213. PMID 2433942. 2. ^ a b Spurrier, Jamie L.; Weaver, David D. (15 March 2008). "Ramos-Arroyo syndrome: Long-term follow-up of previously reported family". American Journal of Medical Genetics Part A. 146A (6): 675–682. doi:10.1002/ajmg.a.32203. PMID 18241069. ## External links[edit] Classification D * ICD-10: Q87.8 * OMIM: 122430 * MeSH: C535286 External resources * Orphanet: 1051 This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Ramos-Arroyo syndrome	c2930866	7,026	wikipedia	https://en.wikipedia.org/wiki/Ramos-Arroyo_syndrome	2021-01-18T19:08:50	{"gard": ["4636"], "mesh": ["C535286"], "umls": ["C2930866", "C1852543"], "orphanet": ["1051"], "wikidata": ["Q7289967"]}
Paraphilic infantilism, also known as autonepiophilia,[1] psychosexual infantilism[2] and adult baby syndrome,[3] is a sexual fetish that involves role-playing a regression to an infant-like state.[4][5] Behaviors may include drinking from a bottle or wearing diapers (diaper fetishism).[3][6] Individuals may engage in gentle and nurturing experiences[7] (an adult who engages only in infantile play is known as an adult baby)[8] or be attracted to masochistic, coercive, punishing or humiliating experiences.[7] Diaper fetishism involves "diaper lovers" wearing diapers for sexual or erotic reasons but may not involve infant-like behavior.[9] Individuals who experience both of these things are referred to as adult baby/diaper lovers (AB/DL).[10][11] When wearing diapers, infantilists may urinate and/or defecate in them.[5] There is no recognized etiology for infantilism and there is little research done on the subject. It has been linked to masochism and a variety of other paraphilias. Although it is commonly confused with pedophilia, the two conditions are distinct and infantilists do not seek children as sexual partners.[12][13] A variety of causes have been proposed, including altered lovemaps, imprinting gone wrong and errors in erotic targets, though there is no consensus. A variety of organizations exist to discuss infantilism or meet with other practitioners throughout the world. ## Contents * 1 Characteristics and behaviors * 2 Prevalence * 3 Relation to other conditions * 3.1 Definitions * 3.2 Masochism * 3.3 Pedophilia * 3.4 Other conditions * 3.4.1 Diaper fetishism * 3.4.2 Cross-dressing * 4 Causes * 4.1 Lovemap theory * 4.2 Imprinting * 4.3 Erotic location target error * 5 History * 6 See also * 7 Notes * 8 References * 9 Further reading ## Characteristics and behaviors[edit] The infantilist community is described by one practitioner[citation needed] as made up of two main types - adult babies (adults who role play infants) and sissy babies (men who tend to wear typically feminine clothing, and use female pronouns). There are also individuals who wear diapers but do not act as infants, either diaper lovers who eroticize diaper wearing, or sadomasochists who use diapers as a way of enforcing dominance and submission. Though the categories are discrete, in practice the behaviors found in each group often overlap.[11] Adult babies roleplaying as a baby or young child for erotic stimulation is considered the signature expression of paraphilic infantilism.[6][14] This may involve the use of adult-sized diapers and baby clothes or toys and furniture such as a crib to lend reality to the infantilist fantasy,[15][16] crawling on the floor,[16] and some individuals may urinate or defecate in their diapers.[5][14][16] If a partner is willing, adult babies may engage in parent-baby roleplay including being bathed, powdered and changed into diapers by one's partner, before being put to bed with a baby bottle.[16][6][14] Some may also simulate lactation with a willing partner.[14] Thereafter the adult baby may be comforted by their partner in the role of the parent and their diapers might be changed if wet or dirty.[6] For some infantilists, the ritual might instead involve being scolded, spanked or chastised for having wet or dirtied their diapers. In this latter instance the mode of arousal is masochistic.[6] Others may desire only gentle or nurturing treatment, based on the desire to be cared for or to "surrender the responsibilities of adult life".[17] Some infantilists may involve masturbation and ejaculation[16][17] while others may choose not to engage in sex since it is not babylike.[18] The erotic pleasure derived from either of these forms of infantilism may replace the need for sexual intercourse in reaching orgasm.[6] In one study of AB/DL website participants, 93% of the sample was male (excluding transgender individuals). 58% of the men and 34% of the women were heterosexual. Males on average first became interested in AB/DL at age 11, and started practicing it at 13, compared to 12 and 16 for females, respectively. The most frequent activities were wearing diapers, wetting, and using other baby items. 87% of the men and 91% of the women reported that their AB/DL had not caused any significant problems or distress.[19] ## Prevalence[edit] Meaningful information on the incidence or prevalence of any of the paraphilias are lacking due to the often clandestine nature of such practices.[16] Similarly, it has been observed that infantilism is a closeted activity and it is not well documented in the medical literature.[8][20] One study reported that 9% of Yahoo groups devoted to "fetishes" dealt with paraphilic infantilism, which was high in relation to other fetishes.[21] If exceptional behaviors do not cause functional impairment, personal distress or distress to others, or have legal implications they can escape the purview of psychiatric awareness and knowledge.[8] Additionally, infantilists may not consider themselves as suffering from a medical condition and may not want to change their behavior, a common occurrence among individuals with paraphilias.[8][18] Individuals with paraphilic infantilism may seek therapy only for other issues, or be encouraged or coerced to seek treatment if discovered by others.[22] Given these issues the potential of anonymous internet surveys for data collection on infantilist communities has been noted.[20] One study members of the ABDL online community, however, noted that males became interested in paraphilic infantilism earlier than females, at age 11 rather than 12, and also began to act on their interests earlier, at 13 rather than 16. The same study found that while most males interested in paraphilic infantilism were primarily straight (58%), most females were primarily bisexual (43%). 34% of women were primarily straight. Although both men and women varied in terms of education, only 66% of men and 39% of women earned more than $25,000 a year.[21] ## Relation to other conditions[edit] Infantilism is a diffuse phenomenon and different authorities have taken varied approaches to the question of its medical and sexological classification. ### Definitions[edit] The conventional definition of infantilism means the persistence of childlike traits in adults and medically the failure to attain sexual maturity,[23] and "sexual infantilism" is also used medically as a synonym for delayed puberty.[4][24] The term "psychosexual infantilism" was used in Sigmund Freud's theory of psychosexual development to refer to individuals who had not matured through its hypothetical stages into heterosexuality.[16] Psychologist Wilhelm Stekel used "psychosexual infantilism" as a category similar to paraphilia, including paraphilic infantilism[18] and other paraphilias and sexual orientations.[25] ### Masochism[edit] Main article: Sadomasochism The Diagnostic and Statistical Manual of Mental Disorders (DSM) states that along with other behaviors, sexual masochists "...may have a desire to be treated as a helpless infant and clothed in diapers ('infantilism')"[26] and this association is repeated by others.[27][28][29] Masochism appears to be particularly important for female infantilists.[19] Psychologists D. Richard Laws and William O'Donohue state that "Although infantilism is classified as a sexual masochism in the DSM-IV and DSM-IV-TR, it is questionable whether the criteria for sexual masochism are always met. For example, if the infantile role playing does not involve feelings of humiliation and suffering, then the diagnosis of sexual masochism would not be appropriate and a diagnosis of infantilism as a paraphilia [not otherwise specified] is warranted."[30] Sexologist John Money, in his book Lovemaps describes paraphilic infantilism as a possible "...adjunctive to masochistic discipline and humiliation."[31] Sexologist William B. Arndt considers paraphilic infantilism to combine forms of fetishism, transvestism and masochism.[12] Wilhelm Stekel considered sado-masochistic practices to be variant behavior arising from psychosexual infantilism.[32] A potential connection between paraphilic infantilism and sadomasochism has been noted in the Polish publication, Przegląd Seksuologiczny. Research results within the publication indicated that 28% of those paraphilic infantilists surveyed reported an interest in BDSM.[33] ### Pedophilia[edit] Main article: Pedophilia Confusing infantilism with pedophilia is a common misunderstanding[12] but infantilism involves role-playing exclusively with other adults;[13] infantilism is not related to pedophilia, or any form of child sexual abuse.[14] Sexologist Gloria Brame states that "...infantilists who recognize and accept their sexuality - and its possible roots in infantile trauma - tend to be acutely protective of real children."[7] John Money used the term "nepiophilia" to describe attraction to diaper-wearing babies. He described infantilism as "autonepiophilia," in which the individual desires to be and to impersonate a baby and does not desire an infant as a sexual partner.[34] In 1993, sexologists Ray Blanchard and Kurt Freund published and discussed a series of case studies involving infantilists[16] and noted a distinction between them and pedophiles. While pedophiles were attracted to children (and objects related to childhood) due to the desire for a child sexual partner, infantilists imagined themselves as children and adopted the objects of childhood or infancy to increase the power difference between themselves and their preferred sexual partners of adult women, with whom they acted out masochistic fantasies.[35] ### Other conditions[edit] In the limited number of extant medical case reports some clinicians have attempted to explain the behaviors associated with infantilism in terms of obsessive compulsive disorder,[36] as "a concurrent cluster of symptoms found in a variety of psychiatric disorders."[37] Psychiatrist Jay Feierman considers infantilism a form of chronophilia in which the infantilist desires a sexual partner of the same biological age, but their own "sexuoerotic age" does not match his or her own biological age (i.e. the adult infantilist wishes an adult sexual partner who treats them as a baby).[38] A 2011 letter to the editor in the Archives of Sexual Behavior reviewed several case studies and noted a common history of sexual abuse.[9] #### Diaper fetishism[edit] Individuals with diaper fetishism typically do not imagine themselves as babies. Rather, they more often see themselves as adults who are drawn to wearing diapers.[39] John Money distinguishes between infantilism or autonepiophilia and paraphilic diaper-wearing, stating that the latter is a paraphilic fetish that manifests as an erotic attraction to an article of clothing while the former is a non-fetishistic paraphilia directed at a change of status in terms of age identity.[40] #### Cross-dressing[edit] Infantilists, usually male, may also engage in cross-dressing and wear clothes stereotypically associated with young girls. This type of behavior is referred to as being a "sissy baby". Masochistic infantilists may wish to be forcibly cross-dressed.[11][41] ## Causes[edit] To date no broad-based scientific studies have been made on the cause, incidence and general impact of paraphilic infantilism on society at large. This may be due to both the relative rarity of the condition and because few paraphilic infantilists appear to seek professional mental health counseling,[8][18] and that even fewer appear to require any type of pro-active mental health intervention.[22] A 2002 case report by psychiatrists Jennifer Pate and Glen Goddard found little research on the topic, and they suggested the DSM lacked a category that captured their patient's disorder.[8] Research on the etiology of paraphilias in general is minimal and as of 2008 had essentially come to a standstill; it is not clear whether the development of infantilism shares a common cause with other paraphilias.[42] Criminologists Stephen and Ronald Holmes believe that while there is no simple answer to the origins of infantilism, the practices may involve an element of stress reduction similar to that of transvestism.[14] ### Lovemap theory[edit] John Money developed the theory of a lovemap, > "a developmental representation or template in the mind and in the brain depicting the idealized lover and the idealized program of sexual and erotic activity projected in imagery or actually engaged in". Many thought that the lovemap was normally fully developed by the age of 8, serving as a kind of sexual template through to the end of one's adult life.[43] Money believed all paraphilias were caused by the formation of abnormal lovemaps during the preadolescent years and that such abnormal lovemaps can be formed by any number of contributing factors or stressors during this developmental period.[44] Money also coined the term "autonepiophilia" meaning a "diaperism" or diaper fetishism in 1984 to describe the condition.[45] Nepon is Greek for infant.[46][47] ### Imprinting[edit] It has been hypothesized that, among other possible causes, sexual templates are established by a process akin to imprinting where lack of availability of female genitals during a critical period of development causes the imprinting mechanism to instead associate with the nearest visual or olfactory approximation. In the case of infantilism, the discipline of the mother or wearing diapers may create associations between pain, humiliation and sexuality.[48] ### Erotic location target error[edit] An additional theory is that infantilism is an erotic identity disorder where the erotic fantasy is centered on the self rather than on a sexual partner and results from an erotic targeting location error where the erotic target was children yet becomes inverted. According to this model, proposed by Ray Blanchard and Kurt Freund in 1993, infantilism is a sexual attraction to the idea of the self being a child.[16] ## History[edit] The first public event for adult babies was "Baby Week", occurring in San Francisco in the early 1990s. Subsequently the internet became a major forum, with numerous websites offering books, magazines, audio and video tapes and related paraphernalia, as well as a 24-hour hotline. Paraphilic infantilism has appeared as an alternative lifestyle in numerous Western countries including the United States, England, Germany and Australia.[49] The organization "Diaper Pail Friends" was established in San Francisco, growing to approximately 3,000 members in 1995 through magazine articles, books, talk shows and the Internet. The organization was studied in 1995 by a group of sexologists, though the results were not published.[50] In 2001, the New York organization "Still in Diapers" was founded for diaper fetishists.[11] In 2008, the Diaper Pail Friends had expanded to a national organization and claimed a membership of 15,000.[14] Tykables opened the first wholly dedicated paraphilic infantilism physical retail store, in Mount Prospect, Illinois in the Chicagoland area, in 2016 with controversy from the local community.[51] The store owner believes it helps to break the stigma about the community.[52] ## See also[edit] * Human sexuality portal * BDSM * Erotic lactation * Ageplay ## Notes[edit] 1. ^ Corsini, Raymond J. (2002). The Dictionary of Psychology. Psychology Press. ISBN 978-1-58391-328-4. Archived from the original on 2017-08-18. Retrieved 2016-02-21. 2. ^ Steckel, Wilhelm (1952). Patterns of Psychosexual Infantilism. New York: Liveright. 3. ^ a b Russell, J (2008). Exploring Psychology for AS Level AQA 'A'. Folens Limited. pp. 200. ISBN 978-1-85008-258-3. 4. ^ a b Hickey, Eric W. (2006). Sex Crimes and Paraphilia. Pearson Education. p. 355. ISBN 978-0-13-170350-6. 5. ^ a b c Speaker, TJ, Psychosexual Infantilism in Adults: The Eroticization of Regression, Sausalito, CA: Columbia Pacific University, p. 93 6. ^ a b c d e f Money 1986, p. 70. 7. ^ a b c Brame, GG; Brame WD; Jacobs J (1996). Different Loving: An Exploration of the World of Sexual Dominance and Submission. Random House of Canada. pp. 137–40. ISBN 978-0-679-76956-9. 8. ^ a b c d e f Pate, JE; Gabbard, GO (2003). "Adult baby syndrome". The American Journal of Psychiatry. 160 (11): 1932–6. doi:10.1176/appi.ajp.160.11.1932. PMID 14594737. Archived from the original on 2009-06-06. Retrieved 2006-03-07. 9. ^ a b Kise, K.; Nguyen, M. (2011). "Adult Baby Syndrome and Gender Identity Disorder". Archives of Sexual Behavior. 40 (5): 857–859. doi:10.1007/s10508-011-9783-8. PMID 21618045. S2CID 207090093. 10. ^ Watson, J (2005-06-09). "Baby Man". Phoenix New Times. Archived from the original on 2011-04-30. Retrieved 2011-02-28. 11. ^ a b c d Taormino, T (2002-08-13). "Still in Diapers". The Village Voice. Archived from the original on 2008-09-20. Retrieved 2007-05-08. 12. ^ a b c Arndt, William B. (1991). Gender Disorders and Paraphilias. International Universities Press. p. 394. ISBN 978-0-8236-2150-7. 13. ^ a b Tiefenwerth, Thomas J. (2007). Criminal Sexuality and Psychopathology: Pornography as a Contributory Risk Factor in the Psycho-Social Development of Violent Sex Offenders. p. 111. ISBN 978-0-549-14928-6. 14. ^ a b c d e f g Holmes, Ronald M.; Holmes, Stephen T. (2008). Sex Crimes: Patterns and Behavior. SAGE Publications. pp. 81. ISBN 978-1-4129-5298-9. 15. ^ Baumeister, RF (1989). Masochism and Self. Lawrence Erlbaum Associates. p. 159. ISBN 978-0-8058-0486-7. 16. ^ a b c d e f g h i Cantor J; Blanchard R; Barbaree H (2009). "Sexual Disorders". In Blaney PH & Millon T (ed.). Oxford Textbook of Psychopathology (2nd ed.). New York & Oxford: Oxford University Press. pp. 530–7. ISBN 978-0-19-537421-6. 17. ^ a b Ditmore, MH (2006). Encyclopedia of prostitution and sex work, Volume 1. Greenwood Publishing Group. pp. 238. ISBN 978-0-313-32968-5. 18. ^ a b c d Stekel 1952, pp. 143–144. 19. ^ a b Hawkinson, K., & Zamboni, B. D. (2014). "Adult Baby/Diaper Lovers: An Exploratory Study of an Online Community Sample". Archives of Sexual Behavior. 43 (5): 863–877. doi:10.1007/s10508-013-0241-7. PMID 24473941. S2CID 41206700.CS1 maint: multiple names: authors list (link) 20. ^ a b Pretlow, Robert A (2002). "The internet can reveal previously unknown causes of medical conditions, such as attraction to diapers as a cause of enuresis and incontinence". Mednet. Archived from the original on 2006-02-17. 21. ^ a b Hawkinson, Kaitlyn; Zamboni, Brian D. (2014-07-01). "Adult Baby/Diaper Lovers: An Exploratory Study of an Online Community Sample". Archives of Sexual Behavior. 43 (5): 863–877. doi:10.1007/s10508-013-0241-7. ISSN 0004-0002. PMID 24473941. S2CID 41206700. 22. ^ a b Pandita-Gunawardena, R (1990). "Paraphilic infantilism. A rare case of fetishistic behaviour". The British Journal of Psychiatry. 157 (5): 767–70. doi:10.1192/bjp.157.5.767. PMID 2279218. 23. ^ "Infantilism". dictionary.com. Archived from the original on 2011-09-27. Retrieved 2011-08-24. 24. ^ Greenspan, FS; Gardner DG (2004). "Puberty". Basic & Clinical Endocrinology. pp. 617–627. ISBN 978-0-07-140297-2. 25. ^ Stekel 1952, p. vii. 26. ^ American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC: American Psychiatric Association. p. 572. ISBN 978-0-89042-024-9. 27. ^ Lippincott Williams & Wilkins (2009). Catherine Harold (ed.). Professional Guide to Diseases (9th ed.). Lippincott Williams & Wilkins. p. 1341. ISBN 978-0-7817-7899-2. 28. ^ Kring, Ann; Johnson, Sheri; Davison, Gerald C.; Neale, John M. (2009). Abnormal Psychology (11th ed.). John Wiley and Sons. p. 719. ISBN 978-0-470-57712-7. 29. ^ Becker, Judith V.; Stinson, Jill D. (2008). "Human sexuality and sexual dysfunctions". In Robert E. Hales, Stuart C. Yudofsky & Glen O. Gabbard (ed.). The American Psychiatric Publishing Textbook of Psychiatry (5th ed.). Arlington VA: American Psychiatric Publishing. pp. 738. ISBN 978-1-58562-257-3. 30. ^ Laws, D. Richard; O'Donohue, William T. (2008). Sexual Deviance: Theory, Assessment, Treatment. Guilford Press. pp. 407. ISBN 978-1-59385-605-2. 31. ^ Money 1986, p. 259. 32. ^ Dailey, Dennis M. (1989). The Sexually Unusual: A Guide to Understanding and Helping. pp. 44. ISBN 978-0-86656-786-2. 33. ^ Wojciech, Oronowicz. "AB/DL group. Close relationships and sexuality". Przegląd Seksuologiczny. 3 (47): 10–17. 34. ^ Money, John (1997). Principles of Developmental Sexology. Continuum International Publishing Group. p. 255. ISBN 978-0-8264-1026-9. 35. ^ Freund K; Blanchard R (1993). "Erotic target location errors in male gender dysphorics, paedophiles, and fetishists". The British Journal of Psychiatry. 162 (4): 558–563. doi:10.1192/bjp.162.4.558. PMID 8481752. 36. ^ Croarkin, Paul; Nam, Theodore; Waldrep, Douglas (2004). "Comment on Adult Baby Syndrome (letter to the editor)". American Journal of Psychiatry. 161 (11): 2141. doi:10.1176/appi.ajp.161.11.2141-a. PMID 15514436. 37. ^ Evcimen, Harun; Gratz, Silvia (2006). "Adult Baby Syndrome (letter to the editor)". Archives of Sexual Behavior. 35 (2): 115–6. doi:10.1007/s10508-005-9002-6. PMID 16752115. S2CID 1818254. 38. ^ Feierman, Jay R. (1990). Pedophilia: biosocial dimensions. Springer-Verlag. p. 455. ISBN 978-0-387-97243-5. 39. ^ Malitz, S (1966). "Another report on the wearing of diapers and rubber pants by an adult male". The American Journal of Psychiatry. 122 (12): 1435–7. doi:10.1176/ajp.122.12.1435. PMID 5929499. 40. ^ Money 1986, p. 96. 41. ^ Marx, E (2009). 101 Things You Didn't Know about Sex. Adams Media. pp. 145. ISBN 978-1-60550-106-2. 42. ^ Rowland, DL; Incrocci L (2008). Handbook of Sexual and Gender Identity Disorders. John Wiley & Sons. pp. 522. ISBN 978-0-470-25721-0. 43. ^ Money 1986, p. 290. 44. ^ Money 1986, p. 34. 45. ^ Money, J. (1984). "Paraphilias: Phenomenology and classification". American Journal of Psychotherapy. 38 (2): 164–179. doi:10.1176/appi.psychotherapy.1984.38.2.164. PMID 6234812. 46. ^ Money 1986, p. 70. 47. ^ Money, John (1985). The Destroying Angel: Sex, Fitness and Food in the Legacy of Degeneracy Theory, Graham Crackers, Kellogg's Corn Flakes and American Health History. Prometheus Books. p. 147. ISBN 978-0-87975-277-4. 48. ^ Wilson, Glen Daniel (1987). Variant Sexuality: Research and Theory. Taylor and Francis. pp. 107–11. ISBN 978-0-7099-3698-5. 49. ^ Kaufman, F (1997). "Our Binkies, Our Selves: The adult baby boom". Spin. 13 (7): 55. ISSN 0886-3032. 50. ^ Noonan R, ed. (2004). The Continuum Complete International Encyclopedia of Sexuality (PDF). The Continuum International Publishing Group Inc. pp. 1248–9. ISBN 978-0-8264-1488-5. Archived from the original (PDF) on 2012-04-05. Retrieved 2011-08-31. 51. ^ Rice, Mae (2016-06-09). "Store Aimed At Adult Babies, Tykables, Opens In Mount Prospect". Chicagoist. Archived from the original on 2016-06-12. Retrieved 2017-07-08. 52. ^ Michelson, Noah (21 March 2017). "Inside The Misunderstood World Of Adult Baby Diaper Lovers". Huffington Post. Archived from the original on 6 March 2018. Retrieved 6 March 2018. ## References[edit] * Money, J (1986). Love Maps - Clinical Concepts of Sexual/Erotic Health and Pathology, Paraphilia, and Gender Transposition in Childhood, Adolescence, and Maturity. New York: Prometheus Books. ISBN 978-0-8290-1589-8. * Stekel, W (1952). Patterns of Psychosexual Infantilism. Washington Square Press. ISBN 978-0-87140-840-2. ## Further reading[edit] * Love, B (1992). Encyclopedia of Unusual Sex Practices. Barricade Books. ISBN 978-0-942637-64-9. * v * t * e Paraphilias List * Abasiophilia * Acrotomophilia * Agalmatophilia * Algolagnia * Apotemnophilia * Autassassinophilia * Biastophilia * Capnolagnia * Chremastistophilia * Chronophilia * Coprophagia * Coprophilia * Crurophilia * Crush fetish * Dacryphilia * Dendrophilia * Emetophilia * Eproctophilia * Erotic asphyxiation * Erotic hypnosis * Erotophonophilia * Exhibitionism * Formicophilia * Frotteurism * Gerontophilia * Homeovestism * Hybristophilia * Infantophilia * Kleptolagnia * Klismaphilia * Lactaphilia * Macrophilia * Masochism * Mechanophilia * Microphilia * Narratophilia * Nasophilia * Necrophilia * Object sexuality * Odaxelagnia * Olfactophilia * Omorashi * Paraphilic infantilism * Partialism * Pedophilia * Podophilia * Plushophilia * Pyrophilia * Sadism * Salirophilia * Scopophilia * Somnophilia * Sthenolagnia * Tamakeri * Telephone scatologia * Transvestic fetishism * Trichophilia * Troilism * Urolagnia * Urophagia * Vorarephilia * Voyeurism * Zoophilia * Zoosadism See also * Other specified paraphilic disorder * Erotic target location error * Courtship disorder * Polymorphous perversity * Sexual fetishism * Human sexual activity * Perversion * Sexology * Book * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Paraphilic infantilism	None	7,027	wikipedia	https://en.wikipedia.org/wiki/Paraphilic_infantilism	2021-01-18T18:30:08	{"wikidata": ["Q181757"]}
ATR-16 syndrome Other namesAlpha thalassemia-intellectual disability syndrome, deletion type, Alpha thalassemia-mental retardation syndrome Chromosome 16 is linked to this condition ATR-16 syndrome, also called Alpha-Thalassemia-Intellectual disability syndrome is a rare disease characterized by monosomy on part of chromosome 16. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References * 7 External links ## Signs and symptoms[edit] ATR-16 syndrome affects the blood, development, and brain; symptoms vary based on the specific genes deleted on chromosome 16. Because it is so rare, it is difficult to determine the "core" symptoms of the disease. People with ATR-16 have alpha-thalassemia, a blood disorder where there is less normal hemoglobin in the blood than there should be, and the red blood cells are smaller than they should be (microcytic anemia). Affected children have various characteristic physical features, including clubfoot, "locked" little fingers, microcephaly (small head), hypertelorism (widely spaced eyes), broad, prominent nose bridge, downward-slanted palpebral fissures, small ears, retrognathia, and short neck. Children with ATR-16 syndrome also have mild to moderate intellectual disabilities, developmental delays/growth delays, and speech delays. Some children with ATR-16 have seizures, cryptorchidism (undescended testes), or hypospadias.[1][2][3] ## Genetics[edit] ATR-16 syndrome is caused by a deletion of part of chromosome 16, from p13.3 (a band on the short end of the chromosome) to the end of the chromosome. These can either be due to a balanced translocation or a de novo deletion.[1] The genes affected include hemoglobin, alpha 1 (HBA1) and hemoglobin, alpha 2 (HBA2).[2] ## Diagnosis[edit] Though only definitively diagnosable by genetic sequence testing, including a G band analysis, ATR-16 syndrome may be diagnosed from its constellation of symptoms. It must be distinguished from ATR-X syndrome, a very similar disease caused by a mutation on the X chromosome, and cases of alpha-thalassemia that co-occur with intellectual disabilities with no underlying genetic relationship.[1][2][3] ## Treatment[edit] Treatments for ATR-16 syndrome depend on the symptoms experienced by any individual. Alpha thalassemia is usually self-limiting, but in some cases may require a blood transfusion or chelating treatment.[1][2] ## Epidemiology[edit] The incidence rate of ATR-16 syndrome is not easy to estimate and it is thought to be underdiagnosed. Scientists have described more than 20 cases as of 2013.[1][2] ## References[edit] 1. ^ a b c d e "ATR-16 Syndrome – NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2015-10-25. 2. ^ a b c d e "Orphanet: Alpha thalassemia intellectual disability syndrome linked to chromosome 16 ATR 16 syndrome". www.orpha.net. Retrieved 2015-10-28. 3. ^ a b "OMIM Entry – # 141750 – ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, CHROMOSOME 16-RELATED". omim.org. Retrieved 2015-10-28. ## External links[edit] Classification D * ICD-10: D56.0 * OMIM: 141750 * MeSH: C563050 External resources * Orphanet: 98791 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	ATR-16 syndrome	c0475813	7,028	wikipedia	https://en.wikipedia.org/wiki/ATR-16_syndrome	2021-01-18T19:00:46	{"gard": ["10853"], "mesh": ["C563050"], "umls": ["C0475813"], "orphanet": ["98791"], "wikidata": ["Q3508561"]}
Sphingolipidoses Other namesSphingolipidosis Diagram showing some of the sphingolipidoses SpecialtyMedical genetics Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide,[1] also relating to sphingolipid metabolism. The main members of this group are Niemann–Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked recessive. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms. ## Contents * 1 Accumulated products * 2 Comparison * 3 Metabolic pathways * 4 See also * 5 References * 6 External links ## Accumulated products[edit] * Gangliosides: Gangliosidosis * GM1 gangliosidoses * GM2 gangliosidoses * Tay–Sachs disease * Sandhoff disease * GM2-gangliosidosis, AB variant * Glycolipids * Fabry's disease * Krabbe disease * Metachromatic leukodystrophy * Glucocerebrosides * Gaucher's disease ## Comparison[edit] Comparison of the main sphingolipidoses Disease Deficient enzyme[2] Accumulated products[2] Symptoms[2] Inheritance[2] Incidence Generally accepted treatments Prognosis Niemann-Pick disease Sphingomyelinase Sphingomyelin in brain and RBCs * Mental retardation * Spasticity * Seizures * Hepatosplenomegaly * Thrombocytopenia * Ataxia Autosomal recessive 1 in 100,000[3] Limited Usually fatal by the age of approx 1.5 years but may live well into adulthood[4] Fabry disease α-galactosidase A Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney * Ischemic infarction in affected organs * Acroparesthesia * Angiokeratomas * hypohidrosis X-linked[5] Between 1 in 40,000 to 1 in 120,000 live births for males[6] Enzyme replacement therapy (but expensive) Life expectancy among males of approximately 60 years[7] Krabbe disease Galactocerebrosidase Glycolipids, particularly galactocerebroside, in oligodendrocytes * Spasticity * Neurodenegeration (leading to death) * Hypertonia * Hyperreflexia * Decerebration-like posture * Blindness * Deafness Autosomal recessive About 1 in 100,000 births[8] Bone marrow transplant (high risk, potential failure, effectively provides enzyme replacement to the central nervous system from six months post-transplant, if done in the earliest stages; less effective enzyme replacement provision for the peripheral nervous system) Untransplanted, and in the case of a failed transplant, generally fatal before age 2 for infants Gaucher disease Glucocerebrosidase Glucocerebrosides in RBCs, liver and spleen * Hepatosplenomegaly * Pancytopenia * Bone pain * Erlenmeyer flask deformity Autosomal recessive About 1 in 20,000 live births,[9] more among Ashkenazi Jews Enzyme replacement therapy (but expensive) May live well into adulthood Tay–Sachs disease Hexosaminidase A GM2 gangliosides in neurons * Neurodegeneration * Developmental disability * Early death Autosomal recessive Approximately 1 in 320,000 newborns in the general population,[10] more in Ashkenazi Jews None Death by approx. 4 years for infantile Tay–Sachs[11] Metachromatic leukodystrophy (MLD) Arylsulfatase A or prosaposin Sulfatide compounds in neural tissue Demyelination in CNS and PNS: * Mental retardation * Motor dysfunction * Ataxia * Hyporeflexia * Seizures Autosomal recessive[12] 1 in 40,000 to 1 in 160,000[13] Bone marrow transplant (high risk, potential failure, effectively provides enzyme replacement to the central nervous system from six months post-transplant, if done in the earliest stages; less effective enzyme replacement provision for the peripheral nervous system) Untransplanted, and in the case of a failed transplant, death by approx. 5 years for infantile MLD ## Metabolic pathways[edit] ## See also[edit] * Lipid storage disorder ## References[edit] 1. ^ Lynn, D. Joanne, Newton, Herbert B. and Rae-Grant, Alexander D. eds. 5-Minute Neurology Consult, The. 2nd Edition. Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103 USA: Lippincott Williams & Wilkins, 2012. Books@Ovid. Web. 03 December, 2020 2. ^ a b c d If not otherwise specified, reference is: Marks, Dawn B.; Swanson, Todd; Sandra I Kim; Marc Glucksman (2007). Biochemistry and molecular biology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 0-7817-8624-X. 3. ^ Niemann-Pick disease from Genetics Home Reference. Reviewed: January 2008. Based on an incidence in a general population of 1 in 250,000 for types A and B and 1 in 150,000 for type C 4. ^ NINDS Niemann-Pick Disease Information Page at the National Institute of Neurological Disorders and Stroke. Last updated October 6, 2011 5. ^ Banikazemi M, Desnick RJ, Astrin KH (2009-07-08). "Fabry Disease". eMedicine Pediatrics: Genetics and Metabolic Disease. Medscape. Retrieved 2010-12-31. 6. ^ Mehta, A.; Ricci, R.; Widmer, U.; Dehout, F.; Garcia De Lorenzo, A.; Kampmann, C.; Linhart, A.; Sunder-Plassmann, G.; Ries, M.; Beck, M. (2004). "Fabry disease defined: Baseline clinical manifestations of 366 patients in the Fabry Outcome Survey". European Journal of Clinical Investigation. 34 (3): 236–242. doi:10.1111/j.1365-2362.2004.01309.x. PMID 15025684. 7. ^ Waldek, S.; Patel, M. R.; Banikazemi, M.; Lemay, R.; Lee, P. (2009). "Life expectancy and cause of death in males and females with Fabry disease: Findings from the Fabry Registry". Genetics in Medicine. 11 (11): 790–796. doi:10.1097/GIM.0b013e3181bb05bb. PMID 19745746. 8. ^ "Krabbe disease". Genetics Home Reference. United States National Library of Medicine. 2008-05-02. Retrieved 2008-05-07. 9. ^ Gaucher Disease at National Gaucher Foundation. Retrieved June 2012 10. ^ GM2 Gangliosidoses – Introduction And Epidemiology at Medscape. Author: David H Tegay. Updated: Mar 9, 2012 11. ^ Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert (2010). "Impact of Gene Patents and Licensing Practices on Access to Genetic Testing and Carrier Screening for Tay–Sachs and Canavan Disease". Genetics in Medicine. 12 (4 Suppl): S5–S14. doi:10.1097/GIM.0b013e3181d5a669. PMC 3042321. PMID 20393311. 12. ^ Gieselmann V, Zlotogora J, Harris A, Wenger DA, Morris CP (1994). "Molecular genetics of metachromatic leukodystrophy". Hum. Mutat. 4 (4): 233–42. doi:10.1002/humu.1380040402. PMID 7866401. 13. ^ Metachromatic leukodystrophy at Genetics Home Reference. Reviewed September 2007 ## External links[edit] Classification D * ICD-10: E75.3 * ICD-9-CM: 272.7 * MeSH: D013106 * DiseasesDB: 33438 * Sphingolipidoses at the US National Library of Medicine Medical Subject Headings (MeSH) * v * t * e Lysosomal storage diseases: Inborn errors of lipid metabolism (Lipid storage disorders) Sphingolipidoses (to ceramide) From ganglioside (gangliosidoses) * Ganglioside: GM1 gangliosidoses * GM2 gangliosidoses (Sandhoff disease * Tay–Sachs disease * AB variant) From globoside * Globotriaosylceramide: Fabry's disease From sphingomyelin * Sphingomyelin: phospholipid: Niemann–Pick disease (SMPD1-associated * type C) * Glucocerebroside: Gaucher's disease From sulfatide (sulfatidoses * leukodystrophy) * Sulfatide: Metachromatic leukodystrophy * Multiple sulfatase deficiency * Galactocerebroside: Krabbe disease To sphingosine * Ceramide: Farber disease NCL * Infantile * Jansky–Bielschowsky disease * Batten disease Other * Cerebrotendineous xanthomatosis * Cholesteryl ester storage disease (Lysosomal acid lipase deficiency/Wolman disease) * Sea-blue histiocytosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Sphingolipidoses	c0037899	7,029	wikipedia	https://en.wikipedia.org/wiki/Sphingolipidoses	2021-01-18T18:59:25	{"gard": ["7672"], "mesh": ["D013106"], "umls": ["C0037899"], "icd-9": ["272.7"], "orphanet": ["79225"], "wikidata": ["Q2309612"]}
For other uses, see Anemia (disambiguation). Medical condition Anemia Other namesAnaemia Blood smear from a person with iron-deficiency anemia. Note the red cells are small and pale. Pronunciation * /əˈniːmiə/ SpecialtyHematology SymptomsFeeling tired, pale skin, weakness, shortness of breath, feeling like passing out[1] CausesBlood loss, decreased red blood cell production, increased red blood cell breakdown[1] Diagnostic methodBlood hemoglobin measurement[1] Frequency2.36 billion / 33% (2015)[2] Anemia (also spelled anaemia) is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood,[3][4] or a lowered ability of the blood to carry oxygen.[5] When anemia comes on slowly, the symptoms are often vague and may include feeling tired, weakness, shortness of breath, and a poor ability to exercise.[1] When the anemia comes on quickly, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst.[1] Anemia must be significant before a person becomes noticeably pale.[1] Additional symptoms may occur depending on the underlying cause.[1] For people who require surgery, pre-operatve anemia can increase the risk of requiring a blood transfusion following surgery.[6] Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown.[1] Causes of blood loss include trauma and gastrointestinal bleeding.[1] Causes of decreased production include iron deficiency, vitamin B12 deficiency, thalassemia, and a number of neoplasms of the bone marrow.[1] Causes of increased breakdown include genetic conditions such as sickle cell anemia, infections such as malaria, and certain autoimmune diseases.[1] Anemia can also be classified based on the size of the red blood cells and amount of hemoglobin in each cell.[1] If the cells are small, it is called microcytic anemia; if they are large, it is called macrocytic anemia; and if they are normal sized, it is called normocytic anemia.[1] The diagnosis of anemia in men is based on a hemoglobin of less than 130 to 140 g/L (13 to 14 g/dL); in women, it is less than 120 to 130 g/L (12 to 13 g/dL).[1][7] Further testing is then required to determine the cause.[1][8] Certain groups of individuals, such as pregnant women, benefit from the use of iron pills for prevention.[1][9] Dietary supplementation, without determining the specific cause, is not recommended.[1] The use of blood transfusions is typically based on a person's signs and symptoms.[1] In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80 g/L (6 to 8 g/dL).[1][10] These recommendations may also apply to some people with acute bleeding.[1] Erythropoiesis-stimulating medications are only recommended in those with severe anemia.[10] Anemia is the most common blood disorder, affecting about a third of the global population.[1][2] Iron-deficiency anemia affects nearly 1 billion people.[11] In 2013, anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990.[12] It is more common in women than men,[11] during pregnancy, and in children and the elderly.[1] Anemia increases costs of medical care and lowers a person's productivity through a decreased ability to work.[7] The name is derived from Ancient Greek: ἀναιμία anaimia, meaning "lack of blood", from ἀν- an-, "not" and αἷμα haima, "blood".[13] Anemia is one of the six WHO global nutrition targets for 2025 and diet-related global NCD targets for 2025, endorsed by World Health Assembly in 2012 and 2013. Efforts to reach global targets contributes reaching Sustainable Development Goals (SDGs),[14] and Anemia being one of the targets in SDG 2.[15] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Impaired production * 2.2 Increased destruction * 2.3 Blood loss * 2.4 Fluid overload * 2.5 Intestinal inflammation * 3 Diagnosis * 3.1 Definitions * 3.2 Testing * 3.3 Red blood cell size * 3.4 Production vs. destruction or loss * 3.4.1 Microcytic * 3.4.2 Macrocytic * 3.4.3 Normocytic * 3.4.4 Dimorphic * 3.4.5 Heinz body anemia * 3.5 Hyperanemia * 3.6 Refractory anemia * 3.7 Transfusion dependent * 4 Treatment * 4.1 Oral iron * 4.2 Injectable iron * 4.3 Blood transfusions * 4.4 Erythropoiesis-stimulating agents * 4.5 Hyperbaric oxygen * 4.6 Pre-operative anemia * 5 Epidemiology * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] Main symptoms that may appear in anemia[16] The hand of a person with severe anemia (on the left) compared to one without (on the right) Anemia goes undetected in many people and symptoms can be minor. The symptoms can be related to an underlying cause or the anemia itself. Most commonly, people with anemia report feelings of weakness or fatigue, and sometimes poor concentration. They may also report shortness of breath on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure. On examination, the signs exhibited may include pallor (pale skin, lining mucosa, conjunctiva and nail beds), but this is not a reliable sign. A blue coloration of the sclera may be noticed in some cases of iron-deficiency anemia.[17] There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells – in hemolytic anemia), bone deformities (found in thalassemia major) or leg ulcers (seen in sickle-cell disease). In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement). There may be signs of heart failure. Pica, the consumption of non-food items such as ice, but also paper, wax, or grass, and even hair or dirt, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin. Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome is more common in people with iron-deficiency anemia than in the general population.[18] ## Causes[edit] Figure shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin.[19] The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia. The most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency.[20] ### Impaired production[edit] * Disturbance of proliferation and differentiation of stem cells * Pure red cell aplasia[21] * Aplastic anemia[21] affects all kinds of blood cells. Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities. * Anemia of kidney failure[21] due to insufficient production of the hormone erythropoietin * Anemia of endocrine disorders[22][medical citation needed] * Disturbance of proliferation and maturation of erythroblasts * Pernicious anemia[21] is a form of megaloblastic anemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12 causes non-pernicious megaloblastic anemia * Anemia of folate deficiency,[21] as with vitamin B12, causes megaloblastic anemia * Anemia of prematurity, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age. * Iron deficiency anemia, resulting in deficient heme synthesis[21] * Thalassemias, causing deficient globin synthesis[21] * Congenital dyserythropoietic anemias, causing ineffective erythropoiesis * Anemia of kidney failure[21] (also causing stem cell dysfunction) * Other mechanisms of impaired RBC production * Myelophthisic anemia[21] or myelophthisis is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors, fibrosis, or granulomas. * Myelodysplastic syndrome[21] * anemia of chronic inflammation[21] * Leukoerythroblastic anemia is caused by space-occupying lesions in the bone marrow that prevent normal production of blood cells.[23] ### Increased destruction[edit] Further information: Hemolytic anemia Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These are generally featuring jaundice and elevated lactate dehydrogenase levels.[medical citation needed] * Intrinsic (intracorpuscular) abnormalities[21] cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders.[24] * Hereditary spherocytosis[21] is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. * Hereditary elliptocytosis[21] is another defect in membrane skeleton proteins. * Abetalipoproteinemia,[21] causing defects in membrane lipids * Enzyme deficiencies * Pyruvate kinase and hexokinase deficiencies,[21] causing defect glycolysis * Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetase deficiency,[21] causing increased oxidative stress * Hemoglobinopathies * Sickle cell anemia[21] * Hemoglobinopathies causing unstable hemoglobins[21] * Paroxysmal nocturnal hemoglobinuria[21] * Extrinsic (extracorpuscular) abnormalities * Antibody-mediated * Warm autoimmune hemolytic anemia is caused by autoimmune attack against red blood cells, primarily by IgG. It is the most common of the autoimmune hemolytic diseases.[25] It can be idiopathic, that is, without any known cause, drug-associated or secondary to another disease such as systemic lupus erythematosus, or a malignancy, such as chronic lymphocytic leukemia.[26] * Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic[27] or result from an underlying condition. * Rh disease,[21] one of the causes of hemolytic disease of the newborn * Transfusion reaction to blood transfusions[21] * Mechanical trauma to red blood cells * Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation[21] * Infections, including malaria[21] * Heart surgery[medical citation needed] * Haemodialysis[medical citation needed] ### Blood loss[edit] * Anemia of prematurity, from frequent blood sampling for laboratory testing, combined with insufficient RBC production * Trauma[21] or surgery, causing acute blood loss * Gastrointestinal tract lesions,[21] causing either acute bleeds (e.g. variceal lesions, peptic ulcers) or chronic blood loss (e.g. angiodysplasia) * Gynecologic disturbances,[21] also generally causing chronic blood loss * From menstruation, mostly among young women or older women who have fibroids * Many type of cancers, including colorectal cancer and cancer of the urinary bladder, may cause acute or chronic blood loss, especially at advanced stages. * Infection by intestinal nematodes feeding on blood, such as hookworms[28] and the whipworm Trichuris trichiura.[29] * Iatrogenic anemia, blood loss from repeated blood draws and medical procedures[30][31] The roots of the words anemia and ischemia both refer to the basic idea of "lack of blood", but anemia and ischemia are not the same thing in modern medical terminology. The word anemia used alone implies widespread effects from blood that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-supplying ability (due to whatever type of hemoglobin or erythrocyte problem). In contrast, the word ischemia refers solely to the lack of blood (poor perfusion). Thus ischemia in a body part can cause localized anemic effects within those tissues. ### Fluid overload[edit] Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia: * General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space.[32] * From the 6th week of pregnancy hormonal changes cause an increase in the mother's blood volume due to an increase in plasma.[33] ### Intestinal inflammation[edit] Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of hepcidin that leads to decreased access of iron to the circulation.[34][35][36] * Helicobacter pylori infection.[37] * Gluten-related disorders: untreated celiac disease[36][37] and non-celiac gluten sensitivity.[38] Anemia can be the only manifestation of celiac disease, in absence of gastrointestinal or any other symptoms.[39] * Inflammatory bowel disease.[40][41] ## Diagnosis[edit] Peripheral blood smear microscopy of a patient with iron-deficiency anemia ### Definitions[edit] There are a number of definitions of anemia; reviews provide comparison and contrast of them.[42] A strict but broad definition is an absolute decrease in red blood cell mass,[43] however, a broader definition is a lowered ability of the blood to carry oxygen.[5] An operational definition is a decrease in whole-blood hemoglobin concentration of more than 2 standard deviations below the mean of an age- and sex-matched reference range.[44] It is difficult to directly measure RBC mass,[45] so the hematocrit (amount of RBCs) or the hemoglobin (Hb) in the blood are often used instead to indirectly estimate the value.[46] Hematocrit; however, is concentration dependent and is therefore not completely accurate. For example, during pregnancy a woman's RBC mass is normal but because of an increase in blood volume the hemoglobin and hematocrit are diluted and thus decreased. Another example would be bleeding where the RBC mass would decrease but the concentrations of hemoglobin and hematocrit initially remains normal until fluids shift from other areas of the body to the intravascular space. The anemia is also classified by severity into mild (110 g/L to normal), moderate (80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adult males and adult non pregnant females.[47] Different values are used in pregnancy and children.[47] ### Testing[edit] Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using a microscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.[medical citation needed] In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.[medical citation needed] WHO's Hemoglobin thresholds used to define anemia[48] (1 g/dL = 0.6206 mmol/L) Age or gender group Hb threshold (g/dl) Hb threshold (mmol/l) Children (0.5–5.0 yrs) 11.0 6.8 Children (5–12 yrs) 11.5 7.1 Teens (12–15 yrs) 12.0 7.4 Women, non-pregnant (>15yrs) 12.0 7.4 Women, pregnant 11.0 6.8 Men (>15yrs) 13.0 8.1 Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte count is a quantitative measure of the bone marrow's production of new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response. If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis can help assess whether the bone marrow will be able to compensate for the loss, and at what rate. When the cause is not obvious, clinicians use other tests, such as: ESR, ferritin, serum iron, transferrin, RBC folate level, serum vitamin B12, hemoglobin electrophoresis, renal function tests (e.g. serum creatinine) although the tests will depend on the clinical hypothesis that is being investigated. When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded.[medical citation needed] ### Red blood cell size[edit] In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis. Limitations of MCV include cases where the underlying cause is due to a combination of factors – such as iron deficiency (a cause of microcytosis) and vitamin B12 deficiency (a cause of macrocytosis) where the net result can be normocytic cells.[medical citation needed] ### Production vs. destruction or loss[edit] The "kinetic" approach to anemia yields arguably the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guaiac-positive stool, radiographic findings, or frank bleeding.[medical citation needed] The following is a simplified schematic of this approach:[medical citation needed] Anemia Reticulocyte production index shows inadequate production response to anemia.Reticulocyte production index shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem. No clinical findings consistent with hemolysis or blood loss: pure disorder of production.Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production.Clinical findings and normal MCV= acute hemolysis or loss without adequate time for bone marrow production to compensate. Macrocytic anemia (MCV>100)Normocytic anemia (80<MCV<100)Microcytic anemia (MCV<80) For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause. ** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss. Here is a schematic representation of how to consider anemia with MCV as the starting point: Anemia Macrocytic anemia (MCV>100)Normocytic anemia (MCV 80–100)Microcytic anemia (MCV<80) High reticulocyte countLow reticulocyte count Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow. #### Microcytic[edit] Main article: Microcytic anemia Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies: * Heme synthesis defect * Iron deficiency anemia (microcytosis is not always present) * Anemia of chronic disease (more commonly presenting as normocytic anemia) * Globin synthesis defect * Alpha-, and beta-thalassemia * HbE syndrome * HbC syndrome * Various other unstable hemoglobin diseases * Sideroblastic defect * Hereditary sideroblastic anemia * Acquired sideroblastic anemia, including lead toxicity[49] * Reversible sideroblastic anemia Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope. * Iron deficiency anemia is due to insufficient dietary intake or absorption of iron to meet the body's needs. Infants, toddlers, and pregnant women have higher than average needs. Increased iron intake is also needed to offset blood losses due to digestive tract issues, frequent blood donations, or heavy menstrual periods.[50] Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 12% of all women of childbearing age have iron deficiency, compared with only 2% of adult men. The incidence is as high as 20% among African American and Mexican American women.[51] Studies have shown iron deficiency without anemia causes poor school performance and lower IQ in teenage girls, although this may be due to socioeconomic factors.[52][53] Iron deficiency is the most prevalent deficiency state on a worldwide basis. It is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular stomatitis). * In the United States, the most common cause of iron deficiency is bleeding or blood loss, usually from the gastrointestinal tract. Fecal occult blood testing, upper endoscopy and lower endoscopy should be performed to identify bleeding lesions. In older men and women, the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyps or colorectal cancer. * Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookworms, amebiasis, schistosomiasis and whipworms).[54] The Mentzer index (mean cell volume divided by the RBC count) predicts whether microcytic anemia may be due to iron deficiency or thalassemia, although it requires confirmation.[55][citation needed] #### Macrocytic[edit] Main article: Macrocytic anemia * Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid, or both. Deficiency in folate or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does. * Pernicious anemia is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12. * Macrocytic anemia can also be caused by removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vitamin B12/folate absorption. Therefore, one must always be aware of anemia following this procedure. * Hypothyroidism * Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of liver disease can also cause macrocytosis. * Drugs such as methotrexate, zidovudine, and other substances may inhibit DNA replication such as heavy metals Macrocytic anemia can be further divided into "megaloblastic anemia" or "nonmegaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (six to 10 lobes). The nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired DNA globin synthesis,) which occur, for example, in alcoholism. In addition to the nonspecific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology.[56] Other features may include a smooth, red tongue and glossitis. The treatment for vitamin B12-deficient anemia was first devised by William Murphy, who bled dogs to make them anemic, and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. George Minot and George Whipple then set about to isolate the curative substance chemically and ultimately were able to isolate the vitamin B12 from the liver. All three shared the 1934 Nobel Prize in Medicine.[57] #### Normocytic[edit] Main article: Normocytic anemia Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size (mean corpuscular volume) remains normal. Causes include: * Acute blood loss * Anemia of chronic disease * Aplastic anemia (bone marrow failure) * Hemolytic anemia #### Dimorphic[edit] A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs. A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia.[citation needed] #### Heinz body anemia[edit] Heinz bodies form in the cytoplasm of RBCs and appear as small dark dots under the microscope. In animals, Heinz body anemia has many causes. It may be drug-induced, for example in cats and dogs by acetaminophen (paracetamol),[58] or may be caused by eating various plants or other substances: * In cats and dogs after eating either raw or cooked plants from the genus Allium, for example, onions or garlic.[59] * In dogs after ingestion of zinc, for example, after eating U.S. pennies minted after 1982.[58] * In horses which eat dry or wilted red maple leaves.[60] ### Hyperanemia[edit] Hyperanemia is a severe form of anemia, in which the hematocrit is below 10%.[61] ### Refractory anemia[edit] Refractory anemia, an anemia which does not respond to treatment,[62] is often seen secondary to myelodysplastic syndromes.[63] Iron deficiency anemia may also be refractory as a manifestation of gastrointestinal problems which disrupt iron absorption or cause occult bleeding. [64] ### Transfusion dependent[edit] Transfusion dependent anemia is a form of anemia where ongoing blood transfusion are required.[65] Most people with myelodysplastic syndrome develop this state at some point in time.[66] Beta thalassemia may also result in transfusion dependence.[67][68] Concerns from repeated blood transfusions include iron overload.[66] This iron overload may require chelation therapy.[69] ## Treatment[edit] Treatment for anemia depends on cause and severity. Vitamin supplements given orally (folic acid or vitamin B12) or intramuscularly (vitamin B12) will replace specific deficiencies.[medical citation needed] ### Oral iron[edit] Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and of women of childbearing age in most developing nations are estimated to have iron deficiency without anemia; one-third of them have iron deficiency with anemia.[70] Iron deficiency due to inadequate dietary iron intake is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of blood loss, such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with ferrous sulfate, ferrous fumarate, or ferrous gluconate. Daily iron supplements have been shown to be effective in reducing anemia in women of childbearing age.[71] When taking iron supplements, stomach upset or darkening of the feces are commonly experienced. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. Vitamin C aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit.[72] In the anemia of chronic kidney disease, recombinant erythropoietin or epoetin alfa is recommended to stimulate RBC production, and if iron deficiency and inflammation are also present, concurrent parenteral iron is also recommended.[73] ### Injectable iron[edit] In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively) or where absorption is impeded (for example in cases of inflammation), parenteral iron preparations can be used. Parenteral iron can improve iron stores rapidly and is also effective for treating people with postpartum haemorrhage, inflammatory bowel disease, and chronic heart failure.[6] The body can absorb up to 6 mg iron daily from the gastrointestinal tract. In many cases the patient has a deficit of over 1,000 mg of iron which would require several months to replace. This can be given concurrently with erythropoietin to ensure sufficient iron for increased rates of erythropoiesis.[74] ### Blood transfusions[edit] Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80 g/L (6 to 8 g/dL).[1] In those with coronary artery disease who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL).[10] Transfusing earlier does not improve survival.[75] Transfusions otherwise should only be undertaken in cases of cardiovascular instability.[76] A 2012 review concluded that when considering blood transfusions for anaemia in people with advanced cancer who have fatigue and breathlessness (not related to cancer treatment or haemorrhage), consideration should be given to whether there are alternative strategies can be tried before a blood transfusion.[77] ### Erythropoiesis-stimulating agents[edit] The objective for the administration of an erythropoiesis-stimulating agent (ESA) is to maintain hemoglobin at the lowest level that both minimizes transfusions and meets the individual person's needs.[78] They should not be used for mild or moderate anemia.[75] They are not recommended in people with chronic kidney disease unless hemoglobin levels are less than 10 g/dL or they have symptoms of anemia. Their use should be along with parenteral iron.[78][79] ### Hyperbaric oxygen[edit] Treatment of exceptional blood loss (anemia) is recognized as an indication for hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical Society.[80][81] The use of HBO is indicated when oxygen delivery to tissue is not sufficient in patients who cannot be given blood transfusions for medical or religious reasons. HBO may be used for medical reasons when threat of blood product incompatibility or concern for transmissible disease are factors.[80] The beliefs of some religions (ex: Jehovah's Witnesses) may require they use the HBO method.[80] A 2005 review of the use of HBO in severe anemia found all publications reported positive results.[82] ### Pre-operative anemia[edit] An estimated 30% of adults who require non-cardiac surgery have anemia.[83] In order to determine an appropriate pre-operative treatment, it is suggested that the cause of anemia be first determined.[84] There is moderate level medical evidence that supports a combination of iron supplementation and erythropoietin treatment to help reduce the requirement for red blood cell transfusions after surgery in those who have pre-operative anemia.[83] ## Epidemiology[edit] A moderate degree of iron-deficiency anemia affected approximately 610 million people worldwide or 8.8% of the population.[11] It is slightly more common in females (9.9%) than males (7.8%).[11] Mild iron deficiency anemia affects another 375 million.[11] ## History[edit] This section needs expansion. 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Classification D * ICD-10: D50-D64 * ICD-9-CM: 280-285 * MeSH: D000740 * DiseasesDB: 663 External resources * MedlinePlus: 000560 * eMedicine: med/132 emerg/808 emerg/734 * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical 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Authority control * GND: 4126536-1 * NARA: 10640166 * NDL: 00563219 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Anemia	c0002871	7,030	wikipedia	https://en.wikipedia.org/wiki/Anemia	2021-01-18T19:09:02	{"mesh": ["D000740"], "umls": ["C0002871"], "orphanet": ["108997"], "wikidata": ["Q5445"]}
A rare developmental defect during embryogenesis characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis. ## Epidemiology The prevalence is unknown, but Bannayan-Riley-Ruvalcaba syndrome (BRRS) is generally considered as a rare disease. ## Clinical description BRRS shares some of the clinical characteristics of Cowden syndrome (CS;) but with differing frequencies. Unlike CS, the classic presentation of BRRS occurs neonatally or shortly thereafter with macrocephaly, Hashimoto struma, lipomatosis, vascular malformations and speckled lentiginosis of the penis or vulva. Developmental delay and gastrointestinal hamartomatous polyposis occur in a subset of BRRS patients. There should be a low threshold to evaluate for autism spectrum disorder in BRRS, especially if a PTEN mutation is found. It is unclear if the case-based signs of myopathic processes in proximal muscles, pectus excavatum, joint hyperextensibility, scoliosis and high birth weight are truly components of BRRS. Although predisposition to cancer was not thought to be a feature of this syndrome, it is now believed that BRRS patients with a germline PTEN mutation share the same risk of cancer development as CS patients. ## Etiology BRRS is caused (in 60% of cases) by a mutation in the phosphatase and tensin homolog (PTEN) gene (10q23) that encodes PTEN, a dual-specificity phosphatase. When BRRS is accompanied by germline PTEN mutations, it belongs to the PHTS group. Because the non-PTEN CS-related genes (ex. SDHB-D, AKT1, PIK3CA and KLLN) have not been formally studied in BRRS, it is not clear if they are also etiologic for non-PTEN-related BRRS. ## Diagnostic methods There are no specific criteria for diagnosis of BRRS but it is usually determined by the clinical presentation. The pediatric criteria of the PTEN scoring systemcan be used and are heavily based on the presence or absence of macrocephaly and the presence of one of four sub-criteria (autism spectrum disorder, dermatologic features, vascular malformations and/or gastrointestinal polyposis). A germline PTEN mutation confirms that the BRRS patient belongs to the PHTS group. ## Differential diagnosis Differential diagnoses include Lhermitte-Duclos syndrome, juvenile polyposis syndrome, Peutz-Jeghers syndrome (PJS), Birt-Hogg-Dube syndrome, Proteus syndrome, Cowden syndrome, Gorlin syndrome, and neurofibromatosis type 1. ## Antenatal diagnosis Antenatal diagnosis is possible for at-risk pregnancies if the disease-causing mutation is discovered in an affected family member. ## Genetic counseling BRRS is inherited autosomal dominantly. Genetic counseling can be offered to patients with germline PTEN mutations and asymptomatic family members should also be tested for the mutation to identify those that need to be monitored before symptom onset. ## Management and treatment Management and treatment are multidisciplinary. Monitoring for symptoms of gastrointestinal hamartomatous polyposis is important as they can be more severe than those seen in CS. Once a germline PTEN mutation is identified, the patient should undergo a screening thyroid ultrasound exam, starting at the age of 7, and a low threshold for evaluation for autism spectrum disorder is strongly recommended. In patients over the age of 18, a yearly skin check is recommended. A colonoscopy and biennial renal imaging should begin between the ages of 35-40, unless symptomatic. Women should perform monthly breast self-examinations and yearly breast screenings as well as transvaginal ultrasounds (postmenopausal) or endometrial biopsies beginning at the age of 35. It is also important to pay attention to neurological and vascular malformations as well as GI symptoms. ## Prognosis The prognosis is unknown and is dependent on initial presentation and likely genotype. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Bannayan-Riley-Ruvalcaba syndrome	c0265326	7,031	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=109	2021-01-23T19:08:19	{"gard": ["5887"], "mesh": ["D006223"], "omim": ["158350"], "umls": ["C0265326"], "icd-10": ["Q87.8"], "synonyms": ["BRRS", "Myhre-Riley-Smith syndrome"]}
Thoracic aorta injury Anatomy of the thoracic aorta Injury of the thoracic aorta refers to any injury which affects the portion of the aorta which lies within the chest cavity. Injuries of the thoracic aorta are usually the result of physical trauma; however, they can also be the result of a pathological process. The main causes of this injury are deceleration (such as a car accident) and crush injuries. There are different grades to injuries to the aorta depending on the extent of injury, and the treatment whether surgical or medical depends on that grade.[1] It is difficult to determine if a patient has a thoracic injury just by their symptoms, but through imaging and a physical exam the extent of injury can be determined.[2] All patients with a thoracic aortic injury need to be treated either surgically with endovascular repair or open surgical repair or with medicine to keep their blood pressure and heart rate in the appropriate range.[3] However, most patients that have a thoracic aortic injury do not live for 24 hours.[4] ## Contents * 1 Mechanism * 2 Symptoms * 3 Diagnosis * 3.1 Classification * 3.2 Imaging * 4 Treatment * 4.1 Endovascular Repair * 4.2 Open Surgical Repair * 4.3 Medical Management * 5 Outcomes * 6 Epidemiology * 7 References * 8 External links ## Mechanism[edit] Injuries to the aorta are usually the result of trauma, such as deceleration and crush injuries. Deceleration injuries almost always occur during high speed impacts, such as those in motor vehicle crashes and falls from a substantial height. Several mechanical processes can occur and are reflected in the injury itself. A more recently proposed mechanism is that the aorta can be compressed between bony structures (such as the manubrium, clavicle, and first rib) and the spine. In the ascending aorta (the portion of the aorta which is almost vertical), one mechanism of injury is torsion (a two-way twisting).[5] There are clinical predictors of an aortic injury.[6] The predictors include if a patient is older than 50, was an unrestrained patient, has hypotension, has a thoracic injury requiring thoracotomy, has a spinal injury, or has a head injury.[6] If four of these criteria are met their likelihood for an aortic injury is 30%[6] The aortic wall is made up of three different components the inner layer (intima), the muscle layer (media), and the outer layer (adventitia). A traumatic injury to the thoracic aorta can cause disruption of any of these parts. Therefore, aortic injury is on a scale from injury to a part of the inner layer to a complete tear of all three layers.[7] There are 4 grades of aortic injury.[1] * Type I: Intimal tear * Type II: Intramural hematoma * Type III: Pseudoaneurysm * Type IV: Rupture In addition to the 4 grades of aortic injury, the risk of rupture can also be categorized. If both the inner layer and the muscle layer of the aortic wall are both involved in the injury then the injury is categorized as significant aortic injury.[8] If just the inner layer and a portion of the muscle layer are involved in the injury then the injury is characterized as minimal aortic injury.[8] Radiographically this would be seen as an intimal flap less than 1 cm in size.[8] Between the mobile ascending aorta and the relatively fixed descending thoracic aorta is the aortic isthmus. When there is a sudden deceleration the mobile ascending aorta pushes forward creating a whiplash effect on the aortic isthmus.[9] However, a different mechanism is involved when the ascending aorta proximal to the isthmus is torn. When there is a rapid deceleration the heart is pushed to the left posterior chest. This causes a sudden increase in intra-aortic pressure and can cause aortic rupture. This is known as the water hammer effect.[9] Based on the location of the injury in the thorax subsequent injuries can take place. If the injury is in the descending thoracic aorta this could lead to a hemothorax.[4] Where as an injury to the ascending aorta could lead to hemoperricardium and subsequent tamponade or could compress the SVC.[4] ## Symptoms[edit] It is difficult to rely on symptoms to diagnose a thoracic aortic injury. However some symptoms do include severe chest pain, cough, shortness of breath, difficulty swallowing due to compression of the esophagus, back pain, and hoarseness due to involvement of the recurrent laryngeal nerve.[4] There might be external signs such as bruising on the anterior chest wall due to a traumatic injury.[9] Clinical signs are uncommon and nonspecific but can include generalized hypertension due to the injury involving the sympathetic afferent nerves in the aortic isthmus.[9] A murmur can also be audible as turbulent blood flow goes over the tear.[9] ## Diagnosis[edit] ### Classification[edit] There are inconsistencies in the terminology of aortic injury. There are several terms which are interchangeably used to describe injury to the aorta such as tear, laceration, transection, and rupture. Laceration is used as a term for the consequence of a tear, whereas a transection is a section across an axis or cross section. For all intents and purposes, the latter is used when a tear occurs across all or nearly all of the circumference of the aorta. Rupture is defined as a forcible disruption of tissue. Some disagree with the usage of rupture as they believe it implies that a tear is incompatible with life; however, the term accurately gauges the severity of tears in the aorta. A rupture can be either complete or partial, and can be classified further by the position of the tear.[5] ### Imaging[edit] The gold standard for diagnosis of thoracic aortic injury is aortagraphy. This method involves inserting a catheter into the aorta and directly injecting contrast material. The primary benefit of aortagraphy is the ability to precisely determine the location of injury for surgical planning.[4] Another imaging modality is CT angiogram which has a sensitivity of 100%.[4] A CT angiogram relies on timing the CT scan after a bolus of IV contrast is administered from a peripheral IV site. Since a CT angiogram has a sensitivity of 100% and less invasive due to the peripheral placement of the IV line than aortagraphy it is the primary imaging choice.[4] This allows visualization of the aorta and provides precise locations of traumatic injury.[9] A CT angiogram does show both direct and indirect signs of aortic injury. The indirect sign that you can see is effacement of fat due to a hematoma.[2] This sign should clue in a radiologist that there is an underlying injury. Some direct signs from a CT include having an intimal flap, irregularity of the shape of the aorta, filling defects secondary to a thrombus, or out pouching of the aorta.[2] However, non contrasted CT scans, chest X-rays, and transesophageal echos can also be used. Chest X-rays most sensitive finding is a widened mediastinum of greater than 8 cm.[4] An apical cap and displacement of the trachea to either side of the chest from midline can also bee seen.[9] A normal chest X-ray, however, does not exclude a diagnosis of thoracic aortic injury.[4] A chest X-ray can also be useful to diagnose subsequent problems caused by aortic rupture such as pneumothorax or hemothorax.[9] Non contrasted CT scans might show an intimal flap, periaortic hematoma, luminal filling defect, aortic contour abnormality, pseudoaneurysm, contained rupture, vessel wall disruption, active extravasation of intravenous contrast from the aorta and is therefore useful to assess for minimal aortic injury.[9] Trans esophageal echos are useful in patients that are hemodynamically unstable, but the sensitivity and specificity of this study varies based on clinical user.[4] The trans esophageal echo relies on placement an ultrasound probe into the patient's esophagus in order to get an ultrasound of the heart. If esophageal injury is expected, the patient has a facial injury, or if the patient has difficulty maintaining their away then the trans esophageal echo is contraindicated.[8] ## Treatment[edit] The first line treatment for patients with thoracic aortic injury is maintaining the patient's airway with intubation and treating secondary injuries such as a hemothorax.[4] After ensuring the patient has a patent airway and other life-threatening injuries are treated then treatment for the aortic injury can be started. Due to the constant risk of sudden rupture or exsanguination urgent treatment is necessary. A patient can either undergo endovascular repair or surgical repair.[9] Endovascular repair is the current gold standard due to increased success rates and lower complications.[9][1] Patients that are able to undergo endovascular repair without contraindications should proceed with it.[1] Repair should be delayed if there is life-threatening intra-abdominal or intracranial bleeding or if the patient is at risk for infection.[9] ### Endovascular Repair[edit] Main article: Endovascular aneurysm repair Endovascular repair is done by first gaining vascular access usually through the femoral artery.[8] A catheter is inserted to the point of injury and a luminal stent is deployed.[1] Blood is then able to be pumped through the stent and prevent the aortic wall from rupturing.[1] ### Open Surgical Repair[edit] Main article: Open aortic surgery Surgical repair is done by way of a thoracotomy or opening of the chest wall.[8] From this point multiple methods can be used, but the most successful methods enable distal perfusion to prevent ischemia.[8] When the surgery is performed a constant check of blood flow to the parts of the body away from the injury should be monitored to know if oxygenation is occurring.[8] ### Medical Management[edit] While waiting for surgery careful regulation of blood pressure and heart rate is necessary.[3] Systolic blood pressure should be maintained between 100 and 120 mmHg allowing for perfusion distal to the injury but decreasing the risk of rupture while the heart rate should be kept under 100 beats per minute. Esmolol is first choice to maintain blood pressure and heart rate due to its short time of action, but if the blood pressure is not within range adding nitroprusside sodium can be added as a second agent.[9] The treatment is similar to what is done for aortic dissections.[7] If the patient has minimal aortic injury then the patient can be managed non surgically.[8] Rather the patient can be followed with serial images. If the patient does develop a more severe injury including a full thickness injury through the media layer then the patient should be treated with surgery.[8] ## Outcomes[edit] Thoracic aortic injury is the 2nd leading cause of death involving both blunt trauma. 80% of patients that have a thoracic aortic injury will die immediately.[4] Of the patients that do make it to be evaluated only 50% will survive 24 hours.[1] Of the patients that do survive the first 24 hours 14% develop paraplegia.[6] ## Epidemiology[edit] Thoracic aortic injury is most commonly caused by a penetrating trauma in up to 90% of cases.[10] Of these cases around 28% are confined to the thoracic portion of the aorta including the ascending aorta, aorta arch, and the descending aorta.[10] Of the thoracic aortic injuries the ligament arteriosum is the most common location followed by the portion of the aorta after the origin of the left subclavian artery.[10] The most common mechanism leading to thoracic aortic injury is a motor vehicle collision. Other mechanisms include airplane crashes, falling from a large height and landing on a hard surface, or any injury that causes substantial pressure to the sternum.[10] The incidence of thoracic aortic injuries is approximately 1 in 100,000.[6] ## References[edit] 1. ^ a b c d e f g Lee, W. Anthony; Matsumura, Jon; Mitchell, R. Scott; Farber, Mark; Greenburg, Roy; Murad, Mohammad; Fairman, Ronald (2011). "Endovascular repair of traumatic thoracic aortic injury: Clinical practice guidelines of the Society fo Vascular Surgery". Journal of Vascular Surgery. 53 (1): 187–192. doi:10.1016/j.jvs.2010.08.027. PMID 20974523. 2. ^ a b c Problem solving in chest imaging. Digumarthy, Subba R. (Subba Rao),, Abbara, Suhny,, Chung, Jonathan H. Philadelphia, PA. March 2019. ISBN 978-0-323-04132-4. OCLC 1126790420.CS1 maint: others (link) 3. ^ a b Emergency medicine secrets. Markovchick, Vincent J.,, Pons, Peter T.,, Bakes, Katherine M.,, Buchanan, Jennie A. (Sixth ed.). Philadelphia, PA. 2015-11-10. ISBN 978-0-323-37483-5. OCLC 932082432.CS1 maint: others (link) 4. ^ a b c d e f g h i j k l Emergency medicine : clinical essentials. Adams, James, 1962- (2nd ed.). Philadelphia, Pa: Elsevier/ Saunders. 2013. ISBN 978-1-4377-3548-2. OCLC 820203833.CS1 maint: others (link) 5. ^ a b Creasy JD, Chiles C, Routh WD, Dyer RB (1997). "Overview of traumatic injury of the thoracic aorta". Radiographics. 17 (1): 27–45. doi:10.1148/radiographics.17.1.9017797. PMID 9017797. 6. ^ a b c d e Müller's imaging of the chest. Walker, Christopher M.,, Chung, Jonathan H. (2nd ed.). Philadelphia, PA. 2018-08-17. ISBN 978-0-323-53179-5. OCLC 1051135278.CS1 maint: others (link) 7. ^ a b Miller's anesthesia. Gropper, Michael A., 1958-, Miller, Ronald D., 1939- (Ninth ed.). Philadelphia, PA. 2019-10-07. ISBN 978-0-323-61264-7. OCLC 1124935549.CS1 maint: others (link) 8. ^ a b c d e f g h i j Oh's intensive care manual. Bersten, Andrew D.,, Handy, Jonathan M. (Eighth ed.). [Oxford, U.K.] 2018-08-15. ISBN 978-0-7020-7606-0. OCLC 1053859479.CS1 maint: others (link) 9. ^ a b c d e f g h i j k l m Rosen's emergency medicine : concepts and clinical practice. Walls, Ron M.,, Hockberger, Robert S.,, Gausche-Hill, Marianne (Ninth ed.). Philadelphia, PA. 2017-03-09. ISBN 978-0-323-39016-3. OCLC 989157341.CS1 maint: others (link) 10. ^ a b c d Rutherford's vascular surgery and endovascular therapy. Sidawy, Anton N.,, Perler, Bruce A. (9th ed.). Philadelphia, PA. 2018-04-03. ISBN 978-0-323-58130-1. OCLC 1037557259.CS1 maint: others (link) ## External links[edit] Classification D * ICD-10: S25.0 * ICD-9-CM: 441, 901.0 External resources * MedlinePlus: 001062 * eMedicine: radio/44 * v * t * e Chest injury, excluding fractures Cardiac and circulatory system injuries * vascular: Traumatic aortic rupture * Thoracic aorta injury * heart: Myocardial contusion/Commotio cordis * Cardiac tamponade * Hemopericardium * Myocardial rupture Lung and lower respiratory tract injuries * Pneumothorax * Hemothorax * Hemopneumothorax * Pulmonary contusion * Pulmonary laceration * Tracheobronchial injury * Diaphragmatic rupture * v * t * e Trauma Principles * Polytrauma * Major trauma * Traumatology * Triage * Resuscitation * Trauma triad of death Assessment Clinical prediction rules * Revised Trauma Score * Injury Severity Score * Abbreviated Injury Scale * NACA score Investigations * Diagnostic peritoneal lavage * Focused assessment with sonography for trauma Management Principles * Advanced trauma life support * Trauma surgery * Trauma center * Trauma team * Damage control surgery * Early appropriate care Procedures * Resuscitative thoracotomy Pathophysiology Injury * MSK * Bone fracture * Joint dislocation * Degloving * Soft tissue injury * Resp * Flail chest * Pneumothorax * Hemothorax * Diaphragmatic rupture * Pulmonary contusion * Cardio * Internal bleeding * Thoracic aorta injury * Cardiac tamponade * GI * Blunt kidney trauma * Ruptured spleen * Neuro * Penetrating head injury * Traumatic brain injury * Intracranial hemorrhage Mechanism * Blast injury * Blunt trauma * Burn * Penetrating trauma * Crush injury * Stab wound * Ballistic trauma * Electrocution Region * Abdominal trauma * Chest trauma * Facial trauma * Head injury * Spinal cord injury Demographic * Geriatric trauma * Pediatric trauma Complications * Posttraumatic stress disorder * Wound healing * Acute lung injury * Crush syndrome * Rhabdomyolysis * Compartment syndrome * Contracture * Volkmann's contracture * Embolism * air * fat * Chronic traumatic encephalopathy * Subcutaneous emphysema [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Thoracic aorta injury	c0160690	7,032	wikipedia	https://en.wikipedia.org/wiki/Thoracic_aorta_injury	2021-01-18T19:02:29	{"icd-9": ["901.0", "441"], "icd-10": ["S25.0"], "wikidata": ["Q7796109"]}
"Dermatochalasia" redirects here. For the medical condition affecting eyelids, see Dermatochalasis. Cutis laxa Other namesChalazoderma, Dermatochalasia, Dermatolysis, Dermatomegaly, Generalized elastolysis, Generalized elastorrhexis Cutis laxa in an infant SpecialtyMedical genetics Cutis laxa [1] or pachydermatocele[2] is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.[3] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Treatment * 4 See also * 5 References * 6 Further reading * 7 External links ## Signs and symptoms[edit] It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin can be either generalised or localised.[4] Biopsies have shown reduction and degeneration of dermal elastic fibres in the affected areas of skin.[5] The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints may be loose (hypermobile) because of lax ligaments and tendons. When cutis laxa is severe, it can also affect the internal organs. The lungs, heart (supravalvular pulmonary stenosis), intestines, or arteries may be affected with a variety of severe impairments. In some cases, hernias and outpouching of the bladder can be observed. Patients can also present with whites of the eyes that are blue. ## Causes[edit] In many cases, cutis laxa is inherited. Autosomal dominant, autosomal recessive, and X-linked recessive forms have been described, but acquired forms also occur. Cutis laxa is associated with deficient or absent elastin fibers in the extracellular matrix.[6] This can be related to decreased elastin synthesis or structural defects in the extracellular matrix.[7] Cutis laxa may be caused by mutations in the genes: ELN,[8] ATP6V0A2,[9] ATP7A,[10] FBLN4,[11] FBLN5,[12] and PYCR1.[13] A related neurocutaneous syndrome may be caused by mutations in the gene ALDH18A1 (P5CS).[14] Cutis laxa may also be seen in association with inherited connective tissue disorders such as Ehlers–Danlos syndromes. Another syndrome associated with cutis laxa is Lenz-Majewski syndrome which is due to a mutation in the phosphatidylserine synthase 1 (PTDSS1) gene. In contrast, acquired cutis laxa often has a triggering event such as urticaria, drugs (such as penicillin) or neoplasms.[15] Acquired cutis laxa may also be immunologically mediated, as it can involve dermal deposit of immunoglobulins and it can occur with autoimmune diseases.[5] Acquired cutis laxa has been associated with granular immunoglobulin A deposits as well as abundant neutrophils.[5] One hypothesis for the cause is excessive elastase release from neutrophils and macrophages.[15] It has also been considered that mutations in elastin (ELN) and fibulin-5 (FBLN5) genes can increase susceptibility of elastic fibres to inflammatory degradation in acquired cutis laxa.[15] Acquired cutis laxa has also been seen in conjunction with a number of conditions including: rheumatoid arthritis,[16] systemic lupus erythematosus,[17] celiac disease,[5] and monoclonal gammopathies.[18] It can also occur as a postinflammatory response after urticaria.[19] Urticarial skin fibroblasts have shown a 2- to 3- fold increase in elastase activity in a patient with acquired cutis laxa.[20] ## Treatment[edit] As of 2019, there is no treatment for cutis laxa. Procedures aimed at mitigating symptoms and identifying subsequent conditions are often advised. No pharmacological agent has been able to stop the progression of the disease.[15] However, cosmetic surgeries are potentially an option as cutis laxa does not generally involve vascular fragility.[15] ## See also[edit] * Occipital horn syndrome * List of cutaneous conditions ## References[edit] 1. ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ James WD, Elston DM, Berger TG, Andrews GC (1969). 'Andrews' Diseases of the Skin: Clinical Dermatology' (10th ed.). Saunders. p. 515. ISBN 0-7216-2921-0. 3. ^ Millington P (2009). Skin. Cambridge University Press. p. 100. ISBN 978-0-521-10681-8. 4. ^ Nygaard RH, Maynard S, Schjerling P, Kjaer M, Qvortrup K, Bohr VA, et al. (2016-02-13). "Acquired Localized Cutis Laxa due to Increased Elastin Turnover". Case Reports in Dermatology. 8 (1): 42–51. doi:10.1159/000443696. PMC 4899661. PMID 27293393. 5. ^ a b c d García-Patos V, Pujol RM, Barnadas MA, Pérez M, Moreno A, Condomines J, et al. (July 1996). "Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres". The British Journal of Dermatology. 135 (1): 130–4. doi:10.1046/j.1365-2133.1996.d01-950.x. PMID 8776377. 6. ^ Plopper G (2007). The extracellular matrix and cell adhesion, in Cells (eds Lewin B, Cassimeris L, Lingappa V, Plopper G). Sudbury, MA: Jones and Bartlett. ISBN 978-0-7637-3905-8. 7. ^ Nygaard RH, Maynard S, Schjerling P, Kjaer M, Qvortrup K, Bohr VA, et al. (2016-02-13). "Acquired Localized Cutis Laxa due to Increased Elastin Turnover". Case Reports in Dermatology. 8 (1): 42–51. doi:10.1159/000443696. PMC 4899661. PMID 27293393. 8. ^ Online Mendelian Inheritance in Man (OMIM): Cutis Laxa, Autosomal Dominant - 123700 9. ^ Online Mendelian Inheritance in Man (OMIM): Cutis Laxa, Autosomal Recessive, Type II - 219200 10. ^ Online Mendelian Inheritance in Man (OMIM): Cutis Laxa, X-Linked - 304150 11. ^ Online Mendelian Inheritance in Man (OMIM): Cutis Laxa, Autosomal Recessive, Type I - 219100 12. ^ Online Mendelian Inheritance in Man (OMIM): Fibulin 5; FBLN5 - 604580 13. ^ Online Mendelian Inheritance in Man (OMIM): Pyrroline-5-Carboxylate Reductase 1; PYCR1 - 179035 14. ^ Online Mendelian Inheritance in Man (OMIM): Aldehyde Dehydrogenase 18 Family, Member A1; ALDH18A1 - 138250 15. ^ a b c d e Reddy GP, Mishra B, Upadhyaya DN (2019). "Acquired Localized Cutis Laxa: A Case Report and the Role of Plastic Surgery". Indian Journal of Dermatology. 64 (1): 55–58. doi:10.4103/ijd.IJD_14_18. PMC 6340237. PMID 30745636. 16. ^ Rongioletti F, Cutolo M, Bondavalli P, Rebora A (January 2002). "Acral localized acquired cutis laxa associated with rheumatoid arthritis". Journal of the American Academy of Dermatology. 46 (1): 128–30. doi:10.1067/mjd.2002.117394. PMID 11756959. 17. ^ Randle HW, Muller S (June 1983). "Generalized elastolysis associated with systemic lupus erythematosus". Journal of the American Academy of Dermatology. 8 (6): 869–73. doi:10.1016/S0190-9622(83)80019-X. PMID 6345611. 18. ^ Maruani A, Arbeille B, Machet MC, Barbet C, Laure B, Martin L, Machet L (July 2010). "Ultrastructural demonstration of a relationship between acquired cutis laxa and monoclonal gammopathy". Acta Dermato-Venereologica. 90 (4): 406–8. doi:10.2340/00015555-0887. PMID 20574607. 19. ^ Nygaard RH, Maynard S, Schjerling P, Kjaer M, Qvortrup K, Bohr VA, et al. (2016-02-13). "Acquired Localized Cutis Laxa due to Increased Elastin Turnover". Case Reports in Dermatology. 8 (1): 42–51. doi:10.1159/000443696. PMC 4899661. PMID 27293393. 20. ^ Bouloc A, Godeau G, Zeller J, Wechsler J, Revuz J, Cosnes A (1999). "Increased fibroblast elastase activity in acquired cutis laxa". Dermatology. 198 (4): 346–50. doi:10.1159/000018146. PMID 10449932. S2CID 23679878. ## Further reading[edit] * Van Maldergem L, Loeys B (2011-10-13). FBLN5-Related Cutis Laxa. University of Washington, Seattle. NBK5201. In Pagon RA, Bird TD, Dolan CR, et al., eds. (1993). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. * Van Maldergem L, Dobyns W, Kornak U (2011-05-10). ATP6V0A2-Related Cutis Laxa. University of Washington, Seattle. NBK5200. In GeneReviews * Loeys B, De Paepe A, Urban Z (2011-05-12). EFEMP2-Related Cutis Laxa. University of Washington, Seattle. PMID 21563328. NBK54467. In GeneReviews * G Kaler S (2010-10-14). ATP7A-Related Copper Transport Disorders. University of Washington, Seattle. PMID 20301586. NBK1413. In GeneReviews ## External links[edit] Classification D * ICD-10: L57.4, Q82.8 (ILDS Q82.816) * ICD-9-CM: 701.8, 756.83 * OMIM: 123700 219100 219200 304150 * MeSH: D003483 * DiseasesDB: 29439 External resources * eMedicine: derm/03 * GeneReviews: FBLN5-Related Cutis Laxa * Orphanet: 209 * Medscape entry on Cutis Laxa * v * t * e Radiation-related disorders / Photodermatoses Ultraviolet/ionizing * Sunburn * Phytophotodermatitis * Solar urticaria * Polymorphous light eruption * Benign summer light eruption * Juvenile spring eruption * Acne aestivalis * Hydroa vacciniforme * Solar erythema Non-ionizing Actinic rays * Actinic keratosis * Atrophic actinic keratosis * Hyperkeratotic actinic keratosis * Lichenoid actinic keratosis * Pigmented actinic keratosis * Actinic cheilitis * Actinic granuloma * Actinic prurigo * Chronic actinic dermatitis Infrared/heat * Erythema ab igne (Kangri ulcer * Kairo cancer * Kang cancer * Peat fire cancer) * Cutis rhomboidalis nuchae * Poikiloderma of Civatte Other * Radiation dermatitis * Acute * Chronic radiodermatitis) * Favre–Racouchot syndrome * Photoaging * Photosensitivity with HIV infection * Phototoxic tar dermatitis * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Cutis laxa	c0010495	7,033	wikipedia	https://en.wikipedia.org/wiki/Cutis_laxa	2021-01-18T18:42:08	{"gard": ["6227"], "mesh": ["D003483"], "umls": ["C0010495"], "icd-9": ["756.83", "701.8"], "orphanet": ["209"], "wikidata": ["Q2735907"]}
For a general phenotypic description and a discussion of genetic heterogeneity of glioma, see GLM1 (137800). Mapping Working from the hypothesis that coinheritance of low-risk variants contributes to the 2-fold increased risk of glioma in relatives of individuals with primary brain tumors, Shete et al. (2009) conducted a metaanalysis of 2 glioma genomewide association studies by genotyping 550,000 tagged SNPs in a total of 1,878 cases and 3,670 controls, with validation in 3 additional independent series totaling 2,545 cases and 2,953 controls. They observed significant association of a single-nucleotide polymorphism (SNP), rs4977756 (OR = 1.24, 95% CI 1.19-1.30, P = 7.24 x 10(-15)) located 59 kb telomeric to the CDKN2B gene (600431) within a 122-kb region of linkage disequilibrium on chromosome 9p21.3. This region encompasses the CDKN2A (600160)-CDKN2B tumor suppressor genes, which have an established role in glioma. Homozygous deletion in CDKN2A is detectable in approximately 50% of tumors (Cancer Genome Atlas Research Network, 2008, Parsons et al., 2008), and loss of expression is linked to poor prognosis. Furthermore, germline mutation of CDKN2A causes the melanoma-astrocytoma syndrome (155755). Regulation of p16/p14(ARF) is important for sensitivity to ionizing radiation, the only environmental factor strongly linked to gliomagenesis. Wrensch et al. (2009) conducted a principal component-adjusted genomewide association study of 275,895 autosomal variants among 692 adult high-grade glioma cases, 622 from the San Francisco Adult Glioma Study and 70 from the Cancer Genome Atlas, and 3,992 controls. The replication sample was performed in the 13 SNPs with a P value of less than 10(-6) using independent data from 176 high-grade glioma cases and 174 controls from the Mayo Clinic. On chromosome 9p21, rs1412829 near CDKN2B had a combined P value of 1.85 x 10(-10). Molecular Genetics ### Somatic Mutation Bigner et al. (1988) found chromosome abnormalities in 12 of 54 malignant gliomas. Structural abnormalities of 9p were increased to a statistically significant degree. Olopade et al. (1992) found molecular evidence of deletion in 9p in 10 of 15 glioma-derived cell lines and 13 of 35 primary gliomas. The shortest region of overlap of these deletions mapped to the interval between the centromeric end of the interferon gene cluster and the methylthioadenosine phosphorylase locus (156540). Simons et al. (1999) used representational difference analysis (RDA) of a human glioblastoma xenograft to isolate 5 tumor-associated homozygously deleted DNA fragments, all originating from the 9p21 region. Subsequent analysis of a series of 10 glioblastomas using the newly isolated RDA fragments in conjunction with a series of known 9p21 DNA markers revealed homozygous deletions in 9 of the 10 tumors. These deletions encompassed the p15 (CDKN2B) and p14/p16 (CDKN2A) complex and 2 additional putative tumor suppressor loci. The RDA fragments corresponded to the latter 2 loci. Taken together, these results suggested the involvement of multiple tumor suppressor genes from the 9p21 region in glioblastoma tumorigenesis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	GLIOMA SUSCEPTIBILITY 5	c0017638	7,034	omim	https://www.omim.org/entry/613030	2019-09-22T15:59:56	{"mesh": ["D005910"], "omim": ["613030"], "orphanet": ["182067"]}
A number sign (#) is used with this entry because beta-mannosidosis (MANSB) is caused by homozygous or compound heterozygous mutation in the gene encoding beta-mannosidase (MANBA; 609489) on chromosome 4q. Description Beta-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal beta-mannosidase activity. The most severely affected patients show developmental delay and mental retardation, but there are differing levels of severity and some patients may have comparatively mild disease (Bedilu et al., 2002) The disorder was first described in goats (Jones and Dawson, 1981), who have a more severe neurodegenerative disorder than that seen in humans. Clinical Features Wenger et al. (1986) described a 46-month-old boy with a severe deficiency in beta-mannosidase activity, whose parents had an intermediate level of enzyme consistent with autosomal recessive inheritance. Beta-mannosidase activity levels near zero were found in all available samples from the patient, including leukocytes, plasma, and cultured skin fibroblasts. In addition to the deficiency of beta-mannosidase, this patient also had a low level of heparin sulfamidase activity in cultured skin fibroblasts. The patient's urine contained excess disaccharide that was identified as mannosyl(1-4)-N-acetylglucosamine and heparan sulfate. The patient showed coarsening facial features, mild bone disease, delayed speech development, hyperactivity, and mental retardation. Many of the findings resembled those found to have defects in the catabolism of the oligosaccharide chains of glycoproteins such as fucosidosis (230000), sialidosis (256550), and aspartylglucosaminuria (208400). The deficiency of heparin sulfamidase and the excess of heparan sulfate in the urine, both findings consistent with Sanfilippo syndrome type A (252900), suggested the presence of 2 disorders. Hu et al. (1990) used complementation studies to show that the patient reported by Wenger et al. (1986) had both Sanfilippo syndrome and beta-mannosidosis. Cooper et al. (1986) reported an Indian-Hindu man with beta-mannosidosis; his parents were not related. Intellectual impairment was first observed when the patient began to attend school. Clinical assessment at the age of 44 years showed mental retardation but no other neurologic signs; CT scan of the brain was normal. The patient had angiokeratomas on the scrotum and the shaft of the penis and marked tortuosity of conjunctival vessels. He did not have facial dysmorphism, hepatosplenomegaly, or radiologic changes of the bones. The urine was free of albumin, red cells, and casts. The patient's 19-year-old mentally retarded brother had similar skin lesions. Both brothers had deficiency of beta-mannosidase, and the parents had intermediate levels. Cooper et al. (1988) found markedly decreased beta-mannosidase activity in plasma, white cells, fibroblasts, and urine obtained from the 2 affected Indian brothers (the younger brother was stated to be 29 years old); all other lysosomal enzymes measured, including sulfamidase, showed normal activity. Biopsy of a skin lesion from the 'bathing trunk' area showed marked cytoplasmic vacuolization. Urinary mucopolysaccharide excretion was normal, but thin-layer chromatography of urinary oligosaccharides showed an abnormal band shown to be a disaccharide. Cooper et al. (1988) noted that the difference in storage material in the caprine disease may account for the clinical differences; a trisaccharide accumulates in the goat. By analyzing urinary oligosaccharides and by measuring enzyme activity in leukocytes and plasma, Dorland et al. (1988) diagnosed beta-mannosidosis in 2 sons of a first-cousin Turkish couple. Behavioral abnormalities and deafness with speech retardation were the main clinical features. Kleijer et al. (1990) reported 2 affected sibs from a Czech Gypsy family with beta-mannosidosis. The girl was severely affected; an older brother had milder manifestations. Heterozygous levels of beta-mannosidase were found in the fibroblasts and/or plasma of the parents and a sister. Cooper et al. (1991) reported a female infant with severe beta-mannosidosis. She had no dysmorphic features except brachycephaly. She showed moderate developmental delay, developed refractive seizures at age 12 months, and died at age 15 months. Urinary analysis showed mannose disaccharides. Poenaru et al. (1992) described a case in which speech impairment was the first symptom of infantile onset. The patient had mental retardation, recurrent infections, hyperactivity, and mild facial dysmorphism. Beta-mannosidase activity was completely lacking in the patient and a heterozygous level was found in the parents. Mannosyl-N-acetylglucosamine was identified in the patient's urine. In a black African 14-year-old boy, Levade et al. (1994) described severe deficiency of beta-mannosidase activity manifested by bilateral thenar and hypothenar amyotrophy, electrophysiologically demonstrable demyelinating peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and lymphoid cells. The authors cited reports of 10 patients in 7 families. Rodriguez-Serna et al. (1996) described a 22-year-old woman who since the age of 12 years had progressive angiokeratoma affecting the lower limbs and buttocks, with no other abnormalities. Enzyme studies revealed beta-mannosidase deficiency in cultured fibroblasts and in serum and leukocytes. The patient's parents exhibited intermediate enzyme levels, confirming autosomal recessive inheritance. Rodriguez-Serna et al. (1996) stated that a total of 11 cases of beta-mannosidase deficiency occurring in 8 families had been reported. Mental retardation and neurologic disorders were present in most reported patients. Sedel et al. (2006) reported an 18-year-old male patient with beta-mannosidosis who exhibited motor and vocal tics since childhood, attention deficit, hyperactivity, impulsivity, and aggressiveness consistent with Gilles de la Tourette syndrome (GTS; 137580). He also had bilateral hearing loss and mild cognitive impairment. Molecular analysis identified compound heterozygosity for 2 mutations in the MANBA gene (609489.0003 and 609489.0004). Molecular Genetics In 2 affected sibs from a Czech Gypsy family with beta-mannosidosis reported by Kleijer et al. (1990), Alkhayat et al. (1998) identified a homozygous null mutation in the MANBA gene (609489.0001). In 2 patients with beta-mannosidosis, an Indian Hindu man originally reported by Cooper et al. (1986) and a Turkish woman originally reported by Wijburg et al. (1992), Bedilu et al. (2002) identified compound heterozygosity and homozygosity, respectively, for null mutations in the MANBA gene (608489.0007-608489.0009). Bedilu et al. (2002) noted that disease presentation in patients with null mutations is variable: the Czech Gypsy sibs described by Kleijer et al. (1990) had facial dysmorphism and skeletal involvement, whereas the Indian Hindu man and his affected younger brother did not have those features, and the Turkish woman had no apparent dysmorphology at 5 years of age but developed epicanthus, broad nasal bridge, and coarse facies by 18 years of age as well as a unilateral hip abnormality. Bedilu et al. (2002) concluded that beta-mannosidosis in humans may be milder than typical of other lysosomal storage disorders. In a patient of European descent with severe beta-mannosidosis previously reported by Poenaru et al. (1992), Riise Stensland et al. (2008) identified compound heterozygosity for 2 mutations in the MANBA gene (609489.0005 and 609489.0006). Riise Stensland et al. (2008) stated that 20 patients from 16 families had been reported. Animal Model In goats, deficiency of beta-mannosidase causes a severe disorder that affects peripheral and central nervous system myelin, resulting in tremor, nystagmus, ataxia, and early death (Jones and Dawson, 1981; Malachowski and Jones, 1983; Lovell and Jones, 1983; Jones et al., 1983). Indeed, the caprine disorder was thoroughly described several years before the human disorder as a severe neurologic disease with CNS demyelination and early death. Although several laboratories sought the human equivalent, it was not found until 1986. Bovine beta-mannosidosis was reported in 1991 in neonatal Salers calves in North America and New Zealand (Jones and Abbitt, 1993). Leipprandt et al. (1996) identified a single-base deletion at position 1398 in the beta-mannosidase DNA isolated from a goat with beta-mannosidosis. This deletion resulted in a shift in the reading frame and premature termination of translation, yielding a deduced peptide of 481 amino acids. Affected animals were homozygous for the mutation and obligate carriers were heterozygous. The assay for the presence or absence of the mutation was used for prenatal diagnosis using DNA collected from fetal fluids. The assay also confirmed chimerism in a goat with an atypically mild beta-mannosidosis phenotype. Zhu et al. (2006) reported that Manba-null mice were viable, fertile, and showed no differences in general appearance or behavior from wildtype mice at over 12 months of age. Histologic evidence of storage material, manifest as intracytoplasmic vacuoles, was present in several organs, including epididymis, liver, kidney, and thyroid, although the accumulated amounts were small. All Manba-null animals examined had cytoplasmic vacuolation in the central nervous system, but there was variation in severity and distribution. Affected areas included pyramidal cells in the dorsolateral cerebral cortex, choroid plexus, hippocampus, and spinal cord, among others. The storage material was a disaccharide, similar to that found in humans with beta-mannosidosis. Biochemical studies showed that the mutant mice had increased alpha-mannosidase activity. The clinical and biochemical phenotype was distinct from that seen in ruminants. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Mild facial dysmorphism may occur Ears \- Deafness Eyes \- Tortuosity of conjunctival vessels CARDIOVASCULAR Vascular \- Tortuosity of conjunctival vessels SKIN, NAILS, & HAIR Skin \- Angiokeratoma Skin Histology \- Cytoplasmic vacuolization MUSCLE, SOFT TISSUES \- Thenar amyotrophy (rare) NEUROLOGIC Central Nervous System \- Mental retardation \- Speech impairment \- Hypotonia \- Seizures (rare) \- Gilles de la Tourette syndrome (reported in 1 patient) Peripheral Nervous System \- Demyelinating peripheral neuropathy, progressive (rare) Behavioral Psychiatric Manifestations \- Aggression \- Hyperactivity IMMUNOLOGY \- Recurrent infections LABORATORY ABNORMALITIES \- Decreased beta-mannosidase activity in plasma, fibroblasts, and leukocytes \- Increased urinary disaccharides (mannosyl-N-acetylglucosamine) MOLECULAR BASIS \- Caused by mutation in the beta-mannosidase gene (MANBA, 609489.0001 ) ▲ 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	MANNOSIDOSIS, BETA A, LYSOSOMAL	c2931893	7,035	omim	https://www.omim.org/entry/248510	2019-09-22T16:25:36	{"doid": ["3633"], "omim": ["248510"], "orphanet": ["118"], "synonyms": ["Alternative titles", "BETA-MANNOSIDOSIS", "LYSOSOMAL BETA-MANNOSIDASE DEFICIENCY", "BETA-MANNOSIDASE DEFICIENCY"]}
A rare multiple congenital anomalies/dysmorphic syndrome characterized by Hirschsprung disease, facial dysmorphism (sloping forehead, high arched eyebrows, long eyelashes, telecanthus/hypertelorism, ptosis, prominent ears, thick earlobes, prominent nasal bridge, thick philtrum, everted lower lip vermillion and pointed chin), global developmental delay, intellectual disability and variable cerebral abnormalities (focal or generalized polymicrogyria, or hypoplastic corpus callosum). ## Epidemiology Worldwide prevalence is less than 1/1,000,000; to date 24 cases have been described in the scientific and medical literature. ## Clinical description Disease onset is typically in the neonatal period with microcephaly and Hirschsprung disease. The clinical spectrum of Hirschsprung disease is broad, ranging from chronic constipation to life-threatening intestinal obstruction in neonates. Facial dysmorphism is present at birth but becomes more evident later on. Additional dysmorphic features may include maxillary hypoplasia, hypodontia, high arched palate, short neck, small hands, brachydactyly, fifth finger clinodactyly, fetal finger pads and flatfoot. Hypotonia, severe global developmental delay (with greatest impairment in expressive language skills) and moderate to severe intellectual disability are constant features. Cerebral magnetic resonance imaging reveals abnormalities in half of patients and may include polymicrogyria, corpus callosum hypoplasia, or subarachnoid space enlargement. Other highly variable features include ocular abnormalities (e.g. hyperopia, bilateral megalocornea), congenital heart defects (such as ventricular septal defects, aortic valve incompetence), urogenital abnormalities (incl. cryptorchidism, vesicoureteral reflux, multicystic renal dysplasia), skeletal involvement (e.g. short stature, scoliosis, femoral neck anteversion), and recurrent respiratory infections. ## Etiology Disease is caused by bi-allelic mutations in KIF1BP (10q21.3-q22.1), encoding kinesin family member 1 binding protein. KIF1BP loss of function disrupts cytoskeletal homeostasis. ## Diagnostic methods Diagnosis is based on clinical presentation of the typical features and should be confirmed with genetic testing. Hirschsprung disease is confirmed by rectal biopsy with histological findings of aganglionosis of the submucosal plexus. ## Differential diagnosis Main differential diagnoses include Mowat-Wilson (MWS) and Baraitser-Winter syndromes. Different facial characteristics (thick, horizontal eyebrows and uplifted earlobes with a central depression), presence of seizures and hypospadias, and absence of polymicrogyria and oligodontia distinguish MWS. Key overlapping features with Baraitser-Winter syndrome include intellectual disability, microcephaly, congenital ptosis, high-arched eyebrows, ocular coloboma and short stature; however, Hirschsprung disease, congenital heart defects, and urogenital malformations have not been reported in this syndrome. ## Antenatal diagnosis Genetic prenatal diagnosis is possible if bi-allelic mutations have previously been identified in the family. In absence of a familial case, diagnostic antenatal ultrasound is challenging. Antenatal detection of brain developmental anomalies, microcephaly, growth retardation and/or hyperechogenic gut are suspicious for the disease but must be confirmed by genetic testing. ## Genetic counseling The pattern of inheritance is autosomal recessive. For parents of an affected child the sibling-recurrence risk is 25%. ## Management and treatment Multidisciplinary medical care and preventive actions, such as treatment of cardiac, ocular, urogenital and skeletal issues and Hirschsprung disease, are required. Developmental assessments are needed to tailor medical care to individual needs and to increase the individual's quality of life. ## Prognosis Little information is available about the long-term outlook for individuals with Goldberg-Schprintzen megacolon syndrome. Quality of life and life expectancy depend on the presence and severity of birth defects. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Goldberg-Shprintzen megacolon syndrome	c1836123	7,036	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66629	2021-01-23T18:10:45	{"gard": ["9849"], "mesh": ["C537279"], "omim": ["609460"], "umls": ["C1836123"], "icd-10": ["Q87.8"], "synonyms": ["GOSHS", "Megacolon-microcephaly syndrome"]}
A number sign (#) is used with this entry because multiple types of cataract (CTRCT3) are caused by heterozygous mutation in the beta-B2-crystallin gene (CRYBB2; 123620) on chromosome 22q11. Description Mutations in the CRYBB2 gene have been found to cause several types of cataract, which have been described as congenital cerulean, 'blue dot,' Coppock-like, sutural with punctate and cerulean opacities, pulverulent embryonal, pulverulent with cortical opacities, dense posterior star-shaped subcapsular with pulverulent opacities in the cortical and embryonal regions, and dense embryonal. Before it was known that mutations in the CRYBB2 gene cause several types of cataract, the preferred title of this entry was 'Cataract, Congenital, Cerulean Type 2,' with the symbol CCA2. Clinical Features Bodker et al. (1990) reported a kindred in which autosomal dominant cataract was known to have occurred in at least 6 generations. Of a total of 159 relatives, 17 affected persons were evaluated. Visual acuity was normal to mildly decreased until adult life except in 1 female, the product of affected first cousins, who was born with bilateral microphthalmia and dense congenital cataracts. Bodker et al. (1990) suggested that this represented the homozygous state. There were no extraocular abnormalities; specifically, the patient was of normal intelligence. Linkage at short distances could be excluded for all 18 markers that were informative. Kramer et al. (1996) reported studies on a family that included 24 individuals affected with the cerulean blue form of autosomal dominant congenital cataract. This family represents a branch of a family originally reported by Bodker et al. (1990). In younger affected family members the cataracts were characterized by numerous peripheral blue flakes and occasional spoke-like central opacifications. Kramer et al. (1996) reported that most affected individuals experienced only mild reduction of visual acuity during childhood and adolescence. Cataract extraction became necessary in most affected individuals between 20 and 40 years of age. One affected family member, who is the daughter of affected first cousins, exhibited bilateral microphthalmia and microcornea at birth. Gill et al. (2000) studied a 4-generation Swiss family with autosomal dominant Coppock-like cataract in which the locus on chromosome 2 (see 604307) was excluded. The cataracts were bilateral, symmetrical, and characterized by a pulverulent opacification of the embryonal nucleus, giving a gray disc appearance associated with zonular opacities to a variable degree. Although the progressive nature of this cataract was not clearly documented, a steady decrease in the visual acuity starting in the teens and premature nuclear sclerosis were observed. Visual impairment was usually first noticed in the teenage years, and most affected individuals required cataract surgery in their forties. Vanita et al. (2001) reported a 5-generation Indian family with sutural cataract with punctate and cerulean opacities. Slit-lamp examination showed prominent, dense, white opacification around the anterior and posterior Y sutures. The posterior Y sutures and the posterior pole of the lens were more severely affected than the anterior pole. It also showed grayish and bluish, sharply defined, elongated, spindle shaped, and oval punctate and cerulean opacities of various sizes arranged in lamellar form. The spots were bigger and more concentrated towards the peripheral layers. These did not delineate the embryonal or fetal nucleus. No pulverulent disc-like opacity was observed in the nuclear region. The sutural opacities appeared denser and whiter compared to the punctate and cerulean spots and were also more elongated and larger in size. Phenotypic variation with respect to the size and density of the sutural opacities as well as the number and position of punctate and cerulean spots was observed among the affected members. Some subjects showed severely affected sutures with dense white opacifications spreading along the secondary divisions of the Y sutures. In some affected subjects the spots were present only as a single layer in the cortex while in the others the spots occurred in concentric layers involving the whole cortex. Vanita et al. (2001) stated that the phenotype of this family differed from all other forms of cataract reported to that time. Bateman et al. (2007) reported a 4-generation Chilean family segregating autosomal dominant cataract with variable location, morphology, color, and density of the opacities among affected family members. In the affected individuals examined, morphology and density were the same in each eye. Cataracts included pulverulent embryonal cataract, pulverulent cortical opacities, dense posterior star-shaped subcapsular cataract with pulverulent opacities in the cortical and embryonal regions, and dense embryonal cataracts. Mapping In a family with the cerulean blue form of cataract, Kramer et al. (1996) found linkage of the disorder to chromosome 22 and maximum multipoint location scores occurred at D22S258 (lod = 7.59) and CYBB2 (lod = 7.53) in the beta-crystallin gene cluster (see 600929). Haplotype analysis in this family indicated that the disease locus is located in a 7-cM region between TOP1P2 and D22S351. The beta-crystallin genes CRYBB2 (123620), CRYBB3 (123630), and CRYBB2P1 lie within this region and were therefore candidate genes. The severely affected female who presented at birth with microphthalmia and microcornea was homozygous for the disease-bearing chromosome. Kramer et al. (1996) noted that an individual who carried the disease chromosome was unaffected. In a 4-generation Swiss family with autosomal dominant Coppock-like cataract in which the locus on chromosome 2 was excluded, Gill et al. (2000) mapped the phenotype to 22q11.2-q13.1 by linkage analysis. In an Indian family with sutural cataract with punctate and cerulean opacities, Vanita et al. (2001) mapped the phenotype to chromosome 22 by linkage analysis. Molecular Genetics In affected members of a family with cerulean cataract reported by Kramer et al. (1996), Litt et al. (1997) identified heterozygosity for a nonsense mutation in the CRYBB2 gene (Q155X; 123620.0001). A severely affected female family member, who was born of first-cousin affected parents and exhibited microphthalmia and microcornea in addition to cataract, was homozygous for the mutation. In affected members of a 4-generation Swiss family with autosomal dominant Coppock-like cataract mapping to chromosome 22q11.2-q13.1, Gill et al. (2000) identified a premature termination mutation in the CRYBB2 gene (123620.0001). Hejtmancik (1998) presented a table of 9 loci, including this one, that had been implicated in nonsyndromal cataract and mapped to specific chromosomal sites. Eight animal models of cataract in which molecular defects had been identified were also tabulated. In an Indian family with sutural cataract with punctate and cerulean opacities, Vanita et al. (2001) detected 2 sequence changes in the CRYBB2 gene (123620) cosegregating with the phenotype. The first was the previously described Q144X mutation. The second mutation (c.483C-T; 123620.0002) was a silent polymorphism found exclusively in patients. The authors ascribed this mutation to gene conversion between the CRYBB2 gene and its pseudogene, CRYBB2P1. In a 4-generation Chilean family segregating multiple types of autosomal dominant cataract, Bateman et al. (2007) identified the Q155X mutation and the previously reported 483C-T silent polymorphism. No mutations were found in the CRYBB1 gene. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Cerulean cataract \- Coppock-like cataract \- Sutural cataract with punctate and cerulean opacities \- Pulverulent embryonal cataract \- Pulverulent cortical opacities \- Dense posterior star-shaped subcapsular cataract with pulverulent opacities in the cortical and embryonal regions \- Dense embryonal cataract MISCELLANEOUS \- Intra- and inter familial phenotypic variability, interocular asymmetry, and variable progression MOLECULAR BASIS \- Caused by mutation in the beta-B2-crystallin gene (CRYBB2, 123620.0001 ) ▲ 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	CATARACT 3, MULTIPLE TYPES	c1861829	7,037	omim	https://www.omim.org/entry/601547	2019-09-22T16:14:37	{"doid": ["0110269"], "mesh": ["C538287"], "omim": ["601547"], "icd-10": ["Q12.0"], "orphanet": ["91492", "1377", "98994"], "synonyms": ["Alternative titles", "CATARACT 3, MULTIPLE TYPES, WITH OR WITHOUT MICROCORNEA", "CATARACT, CONGENITAL, CERULEAN TYPE, 2"]}
Situs ambiguus Other namesSitus ambiguous, heterotaxy, heterotaxia SpecialtyCardiology Situs ambiguus is a rare congenital defect in which the major visceral organs are distributed abnormally within the chest and abdomen. Heterotaxy in general refers to any defect of left-right laterality and arrangement of the visceral organs. This does not include the congenital defect situs inversus,[1] which results when arrangement of all the organs in the abdomen and chest are mirrored, so the positions are opposite the normal placement. Situs inversus is the mirror image of situs solitus, which is normal asymmetric distribution of the abdominothoracic visceral organs. Situs ambiguus can also be subdivided into left-isomerism and right isomerism based on the defects observed in the spleen, lungs and atria of the heart. Individuals with situs inversus or situs solitus do not experience fatal dysfunction of their organ systems, as general anatomy and morphology of the abdominothoracic organ-vessel systems are conserved. Due to abnormal arrangement of organs in situs ambiguus, orientation across the left-right axis of the body is disrupted early in fetal development, resulting in severely flawed cardiac development and function in 50–80% of cases. They also experience complications with systemic and pulmonary blood vessels, significant morbidity, and sometimes death.[2] All patients with situs ambiguus lack lateralization and symmetry of organs in the abdominal and thoracic cavities and are clinically considered to have a form of heterotaxy syndrome. Heterotaxy syndrome with atrial isomerism occurs in 1 out of every 10,000 live births and is associated with approximately 3% of congenital heart disease cases.[3] Additional estimation of incidence and prevalence of isomerism proves difficult due to failure to diagnose and underestimation of the disease by clinicians. Furthermore, right isomerism is much more easily recognized than left isomerism, contributing to the failure to diagnose.[4] Situs ambiguus is a growing field of research with findings dating back to 1973.[5] ## Contents * 1 Signs and symptoms * 1.1 Right atrial appendage isomerism * 1.2 Left atrial appendage isomerism * 1.3 Conductive nodes and tissues * 1.4 Bronchial tree and lungs * 1.5 Abdominal organs * 2 Causes * 3 Pathophysiology * 3.1 Molecular and cellular mechanism * 3.2 Classical pathology * 3.3 Bronchial tree and lungs * 4 Diagnosis * 4.1 Diagnostic techniques for cardiac causes * 4.2 Diagnostic techniques for non-cardiac causes * 4.3 Other diagnostic features * 5 Management * 6 Prognosis * 7 Research * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] There are a variety of clinical manifestations of situs ambiguus. Acute symptoms can be due to both cardiac and non-cardiac defects. Cyanosis or blue skin coloration, primarily affecting the lips and fingernails, can indicate a systemic or circulatory issue. Poor feeding, failure to thrive, and rapid shallow breathing may also be observed due to poor circulation. Upon examination, arrhythmia and heart murmur may raise further suspicion of a cardiac abnormality. Non-cardiac symptoms include impairments of the liver and gastrointestinal tract. Biliary atresia, or inflammation and destruction of the bile ducts, may lead to jaundice. Vomiting and swelling of the abdominal region are features that suggest improper positioning of the intestines. Poor positioning of the intestine also makes it more prone to blockage, which can result in numerous chronic health issues.[4] Asplenia and polysplenia are also possible features of heterotaxy syndrome.[6] Due to abnormal cardiac development, patients with situs ambiguus usually develop right atrial isomerism consisting of two bilaterally paired right atria, or left atrial isomerism consisting of two bilaterally paired left atria. Clinical features and symptoms can vary dependent upon assignment of left versus right atrial isomerism. In either instance, the apex of the heart will be poorly positioned, which should alert a clinician of the likelihood of atrial isomerism. It is estimated that 5-10% of isomeric patients have mesocardia, in which the heart is positioned at the center of the thorax, 25-50% have dextrocardia, in which the apex of the heart is pointed toward the right side of the thorax, and 50 - 70% have levocardia, in which the apex of the heart is pointed toward the left side of the thorax.[2] ### Right atrial appendage isomerism[edit] Right atrial appendage isomerism, also called right atrial isomerism, is a cardiac development defect in which the heart has bilateral right atria and atrial attachments in the muscle wall, as opposed to the normal right atrium and left atrium. In right atrial isomerism, the pulmonary blood oxygen tract is damaged due to right-left shunting of blood. In addition, the atrial septum which distinguishes the 2 atria is absent. These impairments, in addition to congestion in the pulmonary tract, allows deoxygenated blood to mix with oxygenated blood, contributing to cyanosis and possible respiratory distress. Poor systemic circulation also results due to improper positioning of the aorta.[2] ### Left atrial appendage isomerism[edit] Left atrial appendage isomerism, also called left atrial isomerism, is a cardiac development defect in which the heart has 2 bilateral left atria and atrial appendages in the muscle wall. Left atrial isomerism can have varied clinical manifestations, including a later onset of symptoms. Heart failure is often a concern because the inferior vena cava is disrupted due to the inappropriate morphology of the left ventricle to support the vena cava.[2] ### Conductive nodes and tissues[edit] Abnormal development of the heart results in impaired doubles of conductive nodes, as well as faulty electrical fibers throughout the ventricles. Individuals with right atrial isomerism develop 2 sinoatrial nodes, as they have 2 mirrored right atria, whereas those with left atrial isomerism fail to develop a sinus node at all. Thus, patients with left atrial isomerism are more likely to experience atrial fibrillation, or irregular rapid heart beat, and abnormal heart rhythm, known as atrial flutter. Development of the atrioventricular node and bundle of His largely depends on physiological looping of the ventricles. Abnormal looping of the ventricles contributes to arrhythmia and heart block in fetuses.[2] ### Bronchial tree and lungs[edit] Isomerism of the bronchial tree is not typically damaging and presents no significant clinical complications.[7] Pulmonary valve stenosis results in issues of blood flow to the lungs. ### Abdominal organs[edit] Abdominal organs, including the liver, stomach, intestinal tract, and spleen may be randomly arranged throughout the left-right axis of the body. Distribution of these organs largely dictates treatment, clinical outcomes, and further evaluation. The liver is typically symmetrical across the left-right axis in patients with situs ambiguus, which is abnormal. A majority of left atrial isomeric patients have defects throughout the biliary tree, which is responsible for bile production, even when the gall bladder is functional and morphologically normal. This biliary atresia can lead to acute problems such as nutrient malabsorption, pale stools, dark urine, and abdominal swelling. If this condition continues without proper treatment, cirrhosis and liver failure become a major concern. Biliary atresia is not usually observed in patients with right atrial isomerism.[2] Random positioning of the stomach is often one of the first signals of situs ambiguus upon examination. Malrotation of the entire intestinal tract, or improper folding and bulging of the stomach and intestines, results in bowel obstruction. This impairment leads to vomiting, abdominal distention, mucus and blood in the stool. Patients may also experience abdominal pain. Intestinal malrotation is more commonly identified in patients with right atrial isomerism than in those with left atrial isomerism.[citation needed] Isomeric patients often experience disruptions to splenic development during embryogenesis, resulting in an overall lack a spleen (asplenia) or development of many spleens (polysplenia). Asplenia is most often observed in patients with right atrial isomerism. Polysplenia results in 90% of patients with left atrial isomerism. Although they have many spleens, each is usually ineffective resulting in functional asplenia. Rarely, left atrial isomeric patients have a single, normal, functional spleen. Patients lacking a functional spleen are in danger of sepsis and must be monitored.[2] ## Causes[edit] Although its cause is poorly understood, situs ambiguus has been linked to family history of malformations[8][9] and maternal cocaine use,[10] suggesting both genetic and environmental factors play a role.[11] Several genes in the TGF-beta pathway, which controls left-right patterning of visceral organs across the body axis, have been indicated in sporadic and familial cases of atrial isomerism. Disrupted mitochondria function has also been recently linked to heterotaxy. [12] ## Pathophysiology[edit] ### Molecular and cellular mechanism[edit] Several genes have been identified in normal development of the right-left axis.[13] These genes have been extensively researched. Gene mutations that lead to atrial isomerism is a growing area of research. Mutations in genes that encode proteins in the TGF-beta pathway, including NODAL, NKX2-5, and ZIC3, have been linked to tetralogy of fallot and hypoplastic left heart syndrome.[14][15] Mutations in the ZIC3 gene, which encodes for the first zinc finger transcription factor, is linked to a 50% risk of atrial isomerism in families. It is also an X-linked disorder, so testing for ZIC3 mutations is highly encouraged in male births.[16] The most prevalent and best characterized genetic associations of heterotaxy include:[2] Type OMIM Gene Locus HTX1 306955 ZIC3 Xq26.2 HTX2 605376 CFC1 2q21.1 HTX3 606325 PA26 6q21 HTX4 613751 ACVR2B 992 HTX5 270100 NODAL 10q22.1 HTX6 614779 CCDC11 18q21.1 ### Classical pathology[edit] * Cardiac looping malformations: * Fallot's tetralogy * transposition of the great vessels * Ventricular and atrial septal defects. * Deranged abdominal organ asymmetry: * The stomach and spleen are prone to isolated reversal * The stomach, liver, and a single adrenal gland are occasionally found in the midline. * Organ malformations: * asplenia and polysplenia often lead to sepsis * More rarely, the head of the pancreas fails to form * Horseshoe kidneys develop, which can lead to cancer, kidney stones, and/or infection. * Malrotation errors cause volvulus and/or faulty peritoneal attachments, which completely obstruct the bowel. * Vascular abnormalities: * Interrupted inferior vena cava, * Bilateral superior or inferior venae cavae * Intrahepatic interruption of the inferior vena cava with connection to the azygos or hemiazygos veins * Aberrant portal veins. ### Bronchial tree and lungs[edit] Pathophysiology in the bronchial tree can be observed by radiography. Under normal development, the bronchial tree consists of two main bronchi that are anatomically different: * Hyparterial bronchus (below the pulmonary artery): supplies blood to the bi-lobed left lung * Eparterial bronchus (adjacent to the artery): supplies blood to the tri-lobed right lung In situs ambiguus, there is a duplication of either the hyparterial or eparterial bronchus. These features are not associated with any significant clinical complications.[17] Mechanisms leading to bronchial duplication are not thoroughly understood. In pulmonary valve stenosis, there is a reduction in blood flow to the lungs due to an obstruction of the heart at the pulmonic valve. This contributes to cyanosis and pulmonary hypertension.[18] ## Diagnosis[edit] For proper diagnosis of situs ambiguus, cardiac and non-cardiac features must be evaluated. Diagnostic criteria for atrial isomerism includes observation of symmetry of thoracic visceral organs upon echocardiogram, arrhythmia upon electrocardiogram, and chest x-ray for confirmation of the heart's location across the left-right axis. In addition, a series of gastrointestinal tests can be conducted for observation of intestinal malrotation, as well as a scan of the liver and spleen for biliary function.[2] ### Diagnostic techniques for cardiac causes[edit] * Echocardiography * Electrocardiography * Cardiac Imaging * Magnetic Resonance Imaging * Cardiac catheterization and angiography * Chest X-Ray ### Diagnostic techniques for non-cardiac causes[edit] * Splenic Function Analysis * Evaluation of Biliary Anatomy and Cholangiogram * Evaluation of Intestinal Malrotation * Pulse Oximetry ### Other diagnostic features[edit] * Assessment of Family History * Genetic Testing ## Management[edit] Each of the symptoms of situs ambiguus must be managed with appropriate treatment dependent upon the organ system involved. Intestinal malrotation is treated surgically using the Ladd procedure. This procedure widens a fold in the peritoneum so that the intestines can be placed in non-rotated formation. It is not possible to return the bowel to a normal morphology[19] However, 89% of patients that undergo the Ladd surgery experience a complete resolution of symptoms. Following cholangiogram, a Kasai procedure is usually performed in cases of biliary atresia. In this surgery, a Y-shaped shunt is used to passage bile from the liver directly to the intestine. If this is unsuccessful, liver transplantation can be considered based on the overall health of the patient. The Kasai procedure is successful in approximately 80% of patients.[20] Following the operation, patients are advised to take fat-soluble vitamins, choleretics, and anti-inflammatory medications. Functionally asplenic patients have an elevated lifetime risk of sepsis, as they have no functional spleen for fighting infection. For this reason, asplenic patients are under constant observation for any signs of fever or infection. In the case of infection, patients are placed on controlled empiric antibiotic therapy to avoid development of antibiotic resistance.[21] This therapy battles infection by both gram-positive and gram-negative bacteria. Right-atrial and left-atrial isomerism and associated pulmonary issues are treated in a series of steps based on the severity of symptoms. Isomeric patients are first treated by inserting a shunt that will move incoming blood through the pulmonary circuit. The Fontan procedure routes blood through the patient's single ventricle, to the lungs, and into systemic circulation. This process is favorable in patients aged 2 to 5 years old. About 20-30% of patients will require a heart transplant.[22] Left-atrial isomeric patients have less severe complications, as they typically have 2 functional ventricles. In this case, they can undergo biventricular repair to form 2 separate ventricles and functional associated valves. ## Prognosis[edit] Prognosis for patients with situs ambiguus is quite varied, considering the spectrum of clinical complications. Infants who experience severe cyanosis at birth die within hours of delivery if medical intervention is not immediate. Alternatively, longevity of neonates with mild cardiac lesions is unaffected.[23] Ten percent of patients born with right atrial isomerism die by the age of 5 without intervention. Improvements in therapies has increased the 5-year survival to 30-74% for right atrial isomeric patients and 65-84% for left atrial isomeric patients based on the cause of their disease. ## Research[edit] There have been vast amounts of research on the clinical features, racial disparities, and physiological mechanisms of heterotaxy syndrome dating back to 1973. Mishra et al. published a review in November 2015 describing current knowledge of cardiac and non-cardiac abnormalities associated with situs ambiguus. The author stresses the importance of genetic testing prior to deciding a prognosis for affected patients.[24] She also proposes prenatal screening and evaluation in cases at risk for development of situs ambiguus. Recent studies have shown higher rates of heterotaxy syndrome among Hispanic infants of Mexican descent, as well as female infants of non-Hispanic black and white mothers. Additional studies must be done to clarify the mechanisms behind racial disparities in heterotaxy syndrome.[25] Individuals of Asian descent show a higher prevalence of heterotaxy syndrome in general than members of the Western world.[26] The National Birth Defects Prevention study (October 2014) attempted to link clinical presentations of situs ambiguus to demographics in an epidemiological study.[27] This proved a difficult task due to the vast differences in presentation of this disorder. However, the authors are hopeful that finding a link can help inform clinical decision-making, predictive analyses, and future outcomes. ## See also[edit] * Situs inversus * Situs solitus * Chirality (mathematics) * Asplenia * Polysplenia * Ivemark syndrome ## References[edit] 1. ^ "heterotaxy syndrome". United States National Library of Medicine. Retrieved 23 May 2016. 2. ^ a b c d e f g h i Lowenthal, A.; et al. (September 26, 2015). "Anatomy, clinical manifestations and diagnosis of heterotaxy (isomerism of the atrial appendages)". Up To Date. Retrieved November 4, 2015. 3. ^ Zhu, Lirong; Belmont, John W.; Ware, Stephanie M. (2005-10-26). "Genetics of human heterotaxias". European Journal of Human Genetics. 14 (1): 17–25. doi:10.1038/sj.ejhg.5201506. ISSN 1018-4813. PMID 16251896. 4. ^ a b Kim, Soo-Jin (2011). "Heterotaxy Syndrome". Korean Circulation Journal. 41 (5): 227–32. doi:10.4070/kcj.2011.41.5.227. PMC 3116098. PMID 21731561. 5. ^ Freedom, Robert M.; Treves, S. (1973-05-01). "Splenic Scintigraphy and Radionuclide Venography in the Heterotaxy Syndrome". Radiology. 107 (2): 381–386. doi:10.1148/107.2.381. ISSN 0033-8419. PMID 4695908. 6. ^ Van Praagh, R; et al. (December 15, 1990). "Atrial isomerism in the heterotaxy syndromes with asplenia, or polysplenia, or normally formed spleen: an erroneous concept". Am J Cardiol. 66 (20): 1504–6. doi:10.1016/0002-9149(90)90543-a. PMID 2252000. 7. ^ Cohen, Meryl S.; Anderson, Robert H.; Cohen, Mitchell I.; Atz, Andrew M.; Fogel, Mark; Gruber, Peter J.; Lopez, Leo; Rome, Jonathan J.; Weinberg, Paul M. (2007). "Controversies, genetics, diagnostic assessment, and outcomes relating to the heterotaxy syndrome". Cardiology in the Young. 17 (S2): 29–43. doi:10.1017/s104795110700114x. PMID 18039397. 8. ^ Martínez-Frías ML (March 2001). "Heterotaxia as an outcome of maternal diabetes: an epidemiological study". American Journal of Medical Genetics. 99 (2): 142–6. doi:10.1002/1096-8628(2000)9999:999<00::AID-AJMG1139>3.0.CO;2-Z. PMID 11241474. 9. ^ Maeyama K, Kosaki R, Yoshihashi H, Casey B, Kosaki K (March 2001). "Mutation analysis of left-right axis determining genes in NOD and ICR, strains susceptible to maternal diabetes". Teratology. 63 (3): 119–26. doi:10.1002/tera.1022. PMID 11283968. 10. ^ Kuehl KS, Loffredo C (November 2002). "Risk factors for heart disease associated with abnormal sidedness". Teratology. 66 (5): 242–8. doi:10.1002/tera.10099. PMID 12397632. 11. ^ Kuehl KS, Loffredo CA (March 2003). "Population-based study of l-transposition of the great arteries: possible associations with environmental factors". Birth Defects Research. Part A, Clinical and Molecular Teratology. 67 (3): 162–7. doi:10.1002/bdra.10015. PMID 12797457. 12. ^ Burkhalter MD, Sridhar A, Sampaio P, Jacinto R, Burczyk MS, Donow C, Angenendt M, Competence Network for Congenital Heart Defects Investigators, Hempel M, Walther P, Pennekamp P, Omran H, Lopes SS, Ware SM, Philipp M (2019). "Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis". J Clin Invest. 129 (7): 2841–2855. doi:10.1172/JCI98890. PMC 6597216. PMID 31094706.CS1 maint: multiple names: authors list (link) 13. ^ Chen, CM; et al. (April 2010). "Transcriptional Control of Left–Right Patterning in Cardiac Development". Pediatric Cardiology. 31 (3): 371–377. doi:10.1007/s00246-009-9610-3. PMID 20054532. S2CID 300003. 14. ^ Kosaki, K; Bassi, M T; Kosaki, R; Lewin, M; Belmont, J; Schauer, G; Casey, B (1999-03-01). "Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development". American Journal of Human Genetics. 64 (3): 712–721. doi:10.1086/302289. ISSN 0002-9297. PMC 1377788. PMID 10053005. 15. ^ Mohapatra, Bhagyalaxmi; Casey, Brett; Li, Hua; Ho-Dawson, Trang; Smith, Liana; Fernbach, Susan D.; Molinari, Laura; Niesh, Stephen R.; Jefferies, John Lynn (2009-03-01). "Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations". Human Molecular Genetics. 18 (5): 861–871. doi:10.1093/hmg/ddn411. ISSN 1460-2083. PMC 2722226. PMID 19064609. 16. ^ Gebbia, Marinella; Ferrero, Giovanni B.; Pilia, Giuseppe; Bassi, Maria T.; Aylsworth, Arthur S.; Penman-Splitt, Miranda; Bird, Lynne M.; Bamforth, John S.; Burn, John (1997-11-01). "X-linked situs abnormalities result from mutations in ZIC3". Nature Genetics. 17 (3): 305–308. doi:10.1038/ng1197-305. PMID 9354794. S2CID 22916101. 17. ^ Applegate, Kimberly E.; Goske, Marilyn J.; Pierce, Gregory; Murphy, Daniel (1999-07-01). "Situs Revisited: Imaging of the Heterotaxy Syndrome". RadioGraphics. 19 (4): 837–852. doi:10.1148/radiographics.19.4.g99jl31837. ISSN 0271-5333. PMID 10464794. 18. ^ Lowenthal, Alexander; et al. (October 27, 2015). "Management and outcome of heterotaxy (isomerism of the atrial appendages)". UpToDate. Retrieved December 8, 2015. 19. ^ Brandt, Mary; et al. (October 24, 2015). "Intestinal Malrotation". UpToDate. Retrieved December 10, 2015. 20. ^ Erlichman, Jessi; et al. (August 3, 2015). "Biliary Atresia". UpToDate. Retrieved December 9, 2015. 21. ^ Pasternack, Mark S; et al. (December 11, 2014). "Clinical features and management of sepsis in the asplenic patient". UpToDate. Retrieved December 10, 2015. 22. ^ Anderson PA, Sleeper LA, Mahony L, et al. (2008). ""Contemporary outcomes after the Fontan procedure: A Pediatric Heart Network multicenter study."". Journal of the American College of Cardiology. 52 (2): 85–93. doi:10.1016/j.jacc.2008.01.074. PMC 4385517. PMID 18598886. 23. ^ Hashmi, Aijaz; Abu-Sulaiman, Riyadh; McCrindle, Brian W; Smallhorn, Jeffrey F; Williams, William G; Freedom, Robert M (1998-04-01). "Management and Outcomes of Right Atrial Isomerism: A 26-Year Experience". Journal of the American College of Cardiology. 31 (5): 1120–1126. doi:10.1016/S0735-1097(98)00062-X. PMID 9562017. 24. ^ Mishra, Smita (2015-11-26). "Cardiac and Non-Cardiac Abnormalities in Heterotaxy Syndrome". The Indian Journal of Pediatrics. 82 (12): 1135–1146. doi:10.1007/s12098-015-1925-x. ISSN 0019-5456. PMID 26612104. S2CID 207388492. 25. ^ Lopez, Keila N.; Marengo, Lisa K.; Canfield, Mark A.; Belmont, John W.; Dickerson, Heather A. (2015-09-01). "Racial disparities in heterotaxy syndrome". Birth Defects Research Part A: Clinical and Molecular Teratology. 103 (11): 941–950. doi:10.1002/bdra.23416. ISSN 1542-0760. PMID 26333177. 26. ^ Kim, Soo-Jin; Kim, Woong-Han; Lim, Hong-Gook; Lee, Jae-Young (July 2008). "Outcome of 200 patients after an extracardiac Fontan procedure". The Journal of Thoracic and Cardiovascular Surgery. 136 (1): 108–116. doi:10.1016/j.jtcvs.2007.12.032. hdl:10371/60103. PMID 18603062. 27. ^ Lin, Angela E.; Krikov, Sergey; Riehle-Colarusso, Tiffany; Frías, Jaime L.; Belmont, John; Anderka, Marlene; Geva, Tal; Getz, Kelly D.; Botto, Lorenzo D. (2014-10-01). "Laterality defects in the national birth defects prevention study (1998–2007): Birth prevalence and descriptive epidemiology". American Journal of Medical Genetics Part A. 164 (10): 2581–2591. doi:10.1002/ajmg.a.36695. ISSN 1552-4833. PMC 4462240. PMID 25099286. ## External links[edit] * radio/639 at eMedicine Classification D External resources * Orphanet: 157769 * v * t * e Laterality Side Left Both Right General Ambidexterity In cognitive abilities Geschwind–Galaburda hypothesis In brain * Brain asymmetry * Dual brain theory * Bicameralism In eyes Ocular dominance In hands Left-handedness Cross-dominance Right-handedness Handedness in boxing Southpaw stance Orthodox stance Handedness in people Musicians Handedness related to * Sexual orientation * Maths Handedness measurement Edinburgh Handedness Inventory Handedness genetics LRRTM1 In heart Levocardia Dextrocardia In major viscera Situs solitus Situs ambiguus Situs inversus In feet Footedness Footedness in surfing Regular foot Goofy foot [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Situs ambiguus	c0266642	7,038	wikipedia	https://en.wikipedia.org/wiki/Situs_ambiguus	2021-01-18T18:32:07	{"mesh": ["D059446"], "wikidata": ["Q83851589"]}
Fetal and neonatal alloimmune thrombocytopenia (NAIT) is a blood disorder that affects pregnant women and their babies. NAIT was first reported in the literature in 1953 and is estimated to occur in as many as 1 in 1200 live births. NAIT results in the destruction of platelets in the fetus or infant due to a mismatch between the mother’s platelets and those of the baby. Certain molecules (antigens) on the surface of the baby's platelets are recognized as foreign by the mother's immune system. The mother’s immune system then creates antibodies that attack and destroy the baby’s platelets. Though NAIT can occur whenever the mother’s blood mixes with that of the baby, it is usually triggered when the mother is exposed to the baby’s blood during delivery. Many cases of NAIT are mild. Signs and symptoms may include a low platelet count (thrombocytopenia) and signs of bleeding into the skin such as petechiae and purpura. In the most severe cases, NAIT can cause bleeding episodes that may result in death or long-term disability. Bleeding episodes can occur either during pregnancy or after birth. Management of the infant with neonatal alloimmune thrombocytopenia may include platelet transfusions, ultrasounds, and intravenous immunoglobulin (IVIG). Treatment for pregnant mothers at risk for NAIT may include IVIG and steroids. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Fetal and neonatal alloimmune thrombocytopenia	c3854603	7,039	gard	https://rarediseases.info.nih.gov/diseases/2295/fetal-and-neonatal-alloimmune-thrombocytopenia	2021-01-18T18:00:30	{"orphanet": ["853"], "synonyms": ["NAIT"]}
A rare genetic skeletal muscle disease characterized by neonatal to childhood onset of slowly progressive muscle weakness and atrophy primarily affecting the lower limbs, joint contractures, kyphosis or lordosis of the spine, lateral tongue atrophy, and pes equinus. Progression to upper limb involvement, facial weakness, language impairment, intellectual disability, and behavioral abnormalities have been reported in addition. Muscle biopsy shows myopathic changes with increased fiber size variation, internalized nuclei, fiber atrophy, as well as rod structures and core targetoid defects. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome	c4310711	7,040	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=496686	2021-01-23T18:18:08	{"omim": ["617114"]}
Fuchs' dystrophy Other namesFuchs endothelial corneal dystrophy (FECD) Fuchs corneal dystrophy. Light microscopic appearance of the cornea showing numerous excrescences (guttae) on the posterior surface of Descemet's membrane and the presence of cysts in the corneal epithelium beneath ectopically placed intraepithelial basement membrane. Periodic acid-Schiff stain. From a review by Klintworth, 2009.[1] Pronunciation * /fuːksˈdɪstrəfi/ fooks-DIS-trə-fee SpecialtyOphthalmology Fuchs dystrophy, also referred to as Fuchs corneal endothelial dystrophy (FCED) and Fuchs endothelial dystrophy (FED), is a slowly progressing corneal dystrophy that usually affects both eyes and is slightly more common in women than in men. Although early signs of Fuchs dystrophy are sometimes seen in people in their 30s and 40s, the disease rarely affects vision until people reach their 50s and 60s. ## Contents * 1 History * 2 Signs and symptoms * 3 Cause * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 See also * 8 References * 9 External links ## History[edit] The condition was first described by Austrian ophthalmologist Ernst Fuchs (1851–1930), after whom it is named. In 1910, Fuchs first reported 13 cases of central corneal clouding, loss of corneal sensation and the formation of epithelial bullae, or blisters, which he labeled 'dystrophia epithelialis corneae'. It was characterized by late onset, slow progression, decreased visual acuity in the morning, lack of inflammation, diffuse corneal opacity, intense centrally, and roughened epithelium with vesicle-like features.[2] A shift to the understanding of FCED as primarily a disease of the corneal endothelium resulted after a number of observations in the 1920s. Crystal-like features of the endothelium were noted by Kraupa in 1920, who suggested that the epithelial changes were dependent on the endothelium. Using a slit lamp, Vogt described the excrescences associated with FCD as drop-like in appearance in 1921. In 1924, Graves then provided an extremely detailed explanation of the endothelial elevations visible with slit-lamp biomicroscopy. A patient with unilateral epithelial dystrophy and bilateral endothelial changes was described by the Friedenwalds in 1925; subsequent involvement of the second eye led them to emphasize that endothelial changes preceded epithelial changes. As only a subset of patients with endothelial changes proceeded to epithelial involvement, Graves stated on 19 October 1925 to the New York Academy of Medicine that "Fuchs' epithelial dystrophy may be a very late sequel to severer cases of the deeper affection".[3] ## Signs and symptoms[edit] This article's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (October 2013) (Learn how and when to remove this template message) FED may be discovered as an incidental finding at a routine visit to an optometrist, or by an ophthalmologist during assessment for cataract surgery. As a result of irregularities on the inner surface of the cornea, affected individuals may simply notice a reduction in the quality of vision or glare or haloes particularly when driving at night. Individuals with symptomatic Fuchs dystrophy typically awaken with blurred vision which improves during the day.[4] This occurs because the cornea is normally more swollen in the morning due to nocturnal fluid retention in the absence of normal evaporation due to the lids being closed. During waking hours this fluid evaporates once the eyes are open. As the disease worsens vision remains blurred despite evaporation due to endothelial pump failure and fluid retention. As Fuchs dystrophy typically occurs in older individuals there may also be cataract of the lens, which also reduces vision. Researchers are finding that Fuchs is a genetically heterogeneous disease, and many different genes and loci have been associated as contributing to a small percentage of overall Fuchs' cases. Certain genetic lesions have been correlated with more severe disease and earlier onset.[5][6][7] Therefore, some individuals may experience symptoms of the disease at a much earlier age, while others may not experience symptoms until late in life. ## Cause[edit] FCED is a degenerative disease of the corneal endothelium with accumulation of focal outgrowths called guttae (drops) and thickening of Descemet's membrane, leading to corneal edema and loss of vision. The corneal endothelial cell layer and its basement membrane (Descemet's membrane) acts as a barrier to hydration of the corneal stroma by aqueous humor and are "pump" cells of the cornea that function to maintain hydration of the cornea at a specific level that maintains corneal stromal clarity through precise spatial arrangement of collagen fibers. In FED, Descemet's membrane is grossly thickened with accumulation of abnormal wide-spaced collagen and numerous guttae. Corneal endothelial cells in end-stage FED are reduced in number and appear attenuated, causing progressive stromal edema (swelling). Progressive endothelial cell loss causes relative influx of aqueous humor into the cornea, leading to swelling (corneal stromal edema), which results in blurred vision. Eventually, the epithelium also becomes edematous, resulting in more severe visual impairment. Focal blisters of epithelial edema ("bullae") may be particularly painful when they burst. The inheritance of FCED is complex and polymorphic such that although inheritance is autosomal dominant there are genetic and environmental modifiers that determine the degree to which members of the same family express the disease. There is reasonable evidence of associations between transcription factor 4 (TCF4) genetic polymorphisms and risk of Fuchs' endothelial dystrophy (FED).[8] Endothelial cell loss may be aggravated or accelerated by intraocular trauma or surgery. A common scenario involves prolonged corneal swelling or edema following cataract surgery or other types of ocular surgery. Hence, patients with a history of Fuchs' dystrophy may be at a greater risk of corneal edema after ocular surgery as they have fewer functioning endothelial cells. FCED is classified into 4 stages, from early signs of guttae formation to end-stage subepithelial scarring. Diagnosis is made by biomicroscopic examination in the clinic. Other modalities, such as corneal thickness measurement (pachymetry), in-vivo confocal biomicroscopy, and specular microscopy can be used in conjunction. Exact pathogenesis is unknown but factors include endothelial cell apoptosis, sex hormones, inflammation, and aqueous humor flow and composition. Mutations in collagen VIII, a major component of Descemet's membrane secreted by endothelial cells, have been linked to the early-onset FCED.[9] Genes include: Type OMIM Gene Locus FECD1 136800 COL8A2 1p34.3-p32.3 FECD4 610206 SLC4A11 20p13-p12 FECD6 189909 ZEB1 10p11.2 ## Diagnosis[edit] This section is empty. You can help by adding to it. (April 2018) ## Treatment[edit] Non-surgical treatments of FCED may be used to treat symptoms of early disease. Medical management includes topical hypertonic saline, the use of a hairdryer to dehydrate the precorneal tear film, and therapeutic soft contact lenses. Hypertonic saline draws water out of the cornea through osmosis. When using a hairdryer, the patient is instructed to hold it at an arm's length or directed across the face on a cold setting, to dry out the epithelial blisters. This can be done two or three times a day. Definitive treatment, however, (especially with increased corneal edema) is surgical in the form of corneal transplantation. The most common types of surgery for FCED are Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK), which account for over half of corneal transplants in the United States.[10] The use of Scleral lenses can greatly improve vision when it is affected by irregularities on the surface of the cornea.[11] More speculative future directions in the treatment of FED include in-vitro expansion of human corneal endothelial cells for transplantation, artificial corneas (keratoprosthesis) and genetic modification. Surgery where the central diseased endothelium is stripped off but not replaced with donor tissue, with subsequent Rho-Associated Kinase (ROCK) inhibition of endothelial cell division may offer a viable medical treatment.[12] A greater understanding of FED pathophysiology may assist in the future with the development of treatments to prevent progression of disease. Although much progress has been made in the research and treatment of FED, many questions remain to be answered. The exact causes of illness, the prediction of disease progression and delivery of an accurate prognosis, methods of prevention and effective nonsurgical treatment are all the subject of inquiries that necessitate an answer. Increased attention must be given to research that can address the most basic questions of how the disease develops: what are the biomolecular pathways implicated in disease, and what genetic or environmental factors contribute to its progression? In addition to shaping our understanding of FED, identification of these factors would be essential for the prevention and management of this condition.[3] ## Epidemiology[edit] Few studies have examined the prevalence of FCED on a large scale. First assessed in a clinical setting, Fuchs himself estimated the occurrence of dystrophia epithelialis corneae to be one in every 2000 patients; a rate that is likely reflective of those who progress to advanced disease. Cross-sectional studies suggest a relatively higher prevalence of disease in European countries relative to other areas of the world. Fuchs dystrophy rarely affects individuals under 50 years of age.[4] ## See also[edit] * Fuchs heterochromic iridocyclitis (a disease of the iris) * Ocular straylight ## References[edit] 1. ^ Klintworth GK (2009). "Corneal dystrophies". Orphanet J Rare Dis. 4 (1): 7. doi:10.1186/1750-1172-4-7. PMC 2695576. PMID 19236704. 2. ^ Fuchs E. Dystrophia epithelialis corneae. Graefes Arch Clin Exp Ophthalmol. 1910:478–508. 3. ^ a b Eghrari, Allen O; John D Gottsch (April 2010). "Fuchs' corneal dystrophy". Expert Rev Ophthalmol. 5 (2): 147–159. doi:10.1586/eop.10.8. PMC 2897712. PMID 20625449. 4. ^ a b Kunimoto, Derek; Kunal Kanitkar; Mary Makar (2004). The Wills eye manual: office and emergency room diagnosis and treatment of eye disease (4th ed.). Philadelphia, PA: Lippincott Williams & Wilkins. p. 80. ISBN 978-0781742078. 5. ^ Eghrari, AO; McGlumphy, EJ; Iliff, BW; Wang, J; Emmert, D; Riazuddin, SA; Katsanis, N; Gottsch, JD (June 2012). "Prevalence and severity of fuchs corneal dystrophy in Tangier Island". American Journal of Ophthalmology. 153 (6): 1067–72. doi:10.1016/j.ajo.2011.11.033. PMC 4154491. PMID 22321803. 6. ^ Meadows, DN; Eghrari, AO; Riazuddin, SA; Emmert, DG; Katsanis, N; Gottsch, JD (December 2009). "Progression of Fuchs corneal dystrophy in a family linked to the FCD1 locus". Investigative Ophthalmology & Visual Science. 50 (12): 5662–6. doi:10.1167/iovs.09-3568. PMID 19608546. 7. ^ McGlumphy, EJ; Yeo, WS; Riazuddin, SA; Al-Saif, A; Wang, J; Eghrari, AO; Meadows, DN; Emmert, DG; Katsanis, N; Gottsch, JD (December 2010). "Age-severity relationships in families linked to FCD2 with retroillumination photography". Investigative Ophthalmology & Visual Science. 51 (12): 6298–302. doi:10.1167/iovs.10-5187. PMC 3055756. PMID 20811064. 8. ^ Li, Dan; Peng, XiaoYan; Sun, HuiYu (2015-01-01). "Association of TCF4 polymorphisms and Fuchs' endothelial dystrophy: a meta-analysis". BMC Ophthalmology. 15: 61. doi:10.1186/s12886-015-0055-6. ISSN 1471-2415. PMC 4474332. PMID 26087656. 9. ^ Gottsch JD, Sundin OH, Liu SH, et al. (June 2005). "Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs corneal dystrophy". Invest. Ophthalmol. Vis. Sci. 46 (6): 1934–9. doi:10.1167/iovs.04-0937. PMID 15914606. Archived from the original on 2013-04-15. 10. ^ Stuart AJ, Virgili G, Shortt AJ (2016). "Descemet's membrane endothelial keratoplasty versus Descemet's stripping automated endothelial keratoplasty for corneal endothelial failure". Cochrane Database Syst Rev (3): CD012097. doi:10.1002/14651858.CD012097. 11. ^ Jedlicka, Jason, OD, Scleral Contact Lenses, https://www.allaboutvision.com/contacts/scleral-lenses.htm 12. ^ Okumura, Naoki; Sakamoto, Yuji; Fujii, Keita; Kitano, Junji; Nakano, Shinichiro; Tsujimoto, Yuki; Nakamura, Shin-Ichiro; Ueno, Morio; Hagiya, Michio (2016-01-01). "Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction". Scientific Reports. 6: 26113. doi:10.1038/srep26113. ISSN 2045-2322. PMC 4870691. PMID 27189516. ## External links[edit] Classification D * ICD-10: H18.5 * ICD-9-CM: 371.57 * OMIM: 136800 610158 * MeSH: D005642 * DiseasesDB: 31163 External resources * MedlinePlus: 007295 * eMedicine: article/1193591 * Facts About the Cornea and Corneal Disease - The National Eye Institute (United States) * Fuchs' dystrophy at Curlie * v * t * e Types of corneal dystrophy Epithelial and subepithelial * Epithelial basement membrane dystrophy * Gelatinous drop-like corneal dystrophy * Lisch epithelial corneal dystrophy * Meesmann corneal dystrophy * Subepithelial mucinous corneal dystrophy Bowman's membrane * Reis–Bucklers corneal dystrophy * Thiel-Behnke dystrophy Stroma * Congenital stromal corneal dystrophy * Fleck corneal dystrophy * Granular corneal dystrophy * Lattice corneal dystrophy * Macular corneal dystrophy * Posterior amorphous corneal dystrophy * Schnyder crystalline corneal dystrophy Descemet's membrane and endothelial * Congenital hereditary endothelial dystrophy * Fuchs' dystrophy * Posterior polymorphous corneal dystrophy * X-linked endothelial corneal dystrophy * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis * v * t * e Diseases of collagen, laminin and other scleroproteins Collagen disease COL1: * Osteogenesis imperfecta * Ehlers–Danlos syndrome, types 1, 2, 7 COL2: * Hypochondrogenesis * Achondrogenesis type 2 * Stickler syndrome * Marshall syndrome * Spondyloepiphyseal dysplasia congenita * Spondyloepimetaphyseal dysplasia, Strudwick type * Kniest dysplasia (see also C2/11) COL3: * Ehlers–Danlos syndrome, types 3 & 4 * Sack–Barabas syndrome COL4: * Alport syndrome COL5: * Ehlers–Danlos syndrome, types 1 & 2 COL6: * Bethlem myopathy * Ullrich congenital muscular dystrophy COL7: * Epidermolysis bullosa dystrophica * Recessive dystrophic epidermolysis bullosa * Bart syndrome * Transient bullous dermolysis of the newborn COL8: * Fuchs' dystrophy 1 COL9: * Multiple epiphyseal dysplasia 2, 3, 6 COL10: * Schmid metaphyseal chondrodysplasia COL11: * Weissenbacher–Zweymüller syndrome * Otospondylomegaepiphyseal dysplasia (see also C2/11) COL17: * Bullous pemphigoid COL18: * Knobloch syndrome Laminin * Junctional epidermolysis bullosa * Laryngoonychocutaneous syndrome Other * Congenital stromal corneal dystrophy * Raine syndrome * Urbach–Wiethe disease * TECTA * DFNA8/12, DFNB21 see also fibrous proteins * v * t * e Genetic disorder, membrane: Solute carrier disorders 1-10 * SLC1A3 * Episodic ataxia 6 * SLC2A1 * De Vivo disease * SLC2A5 * Fructose malabsorption * SLC2A10 * Arterial tortuosity syndrome * SLC3A1 * Cystinuria * SLC4A1 * Hereditary spherocytosis 4/Hereditary elliptocytosis 4 * SLC4A11 * Congenital endothelial dystrophy type 2 * Fuchs' dystrophy 4 * SLC5A1 * Glucose-galactose malabsorption * SLC5A2 * Renal glycosuria * SLC5A5 * Thyroid dyshormonogenesis type 1 * SLC6A19 * Hartnup disease * SLC7A7 * Lysinuric protein intolerance * SLC7A9 * Cystinuria 11-20 * SLC11A1 * Crohn's disease * SLC12A3 * Gitelman syndrome * SLC16A1 * HHF7 * SLC16A2 * Allan–Herndon–Dudley syndrome * SLC17A5 * Salla disease * SLC17A8 * DFNA25 21-40 * SLC26A2 * Multiple epiphyseal dysplasia 4 * Achondrogenesis type 1B * Recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia * SLC26A4 * Pendred syndrome * SLC35C1 * CDOG 2C * SLC39A4 * Acrodermatitis enteropathica * SLC40A1 * African iron overload see also solute carrier family * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Fuchs' dystrophy	c0016781	7,041	wikipedia	https://en.wikipedia.org/wiki/Fuchs%27_dystrophy	2021-01-18T18:44:30	{"gard": ["10018"], "mesh": ["D005642"], "umls": ["C0016781"], "orphanet": ["98974"], "wikidata": ["Q1464888"]}
A number sign (#) is used with this entry because of evidence that Joubert syndrome-31 (JBTS31) is caused by homozygous or compound heterozygous mutation in the CEP120 gene (613446) on chromosome 5q23. Biallelic mutations in the CEP120 gene have also been reported in patients with short-rib thoracic dysplasia-13 (SRTD13; 616300). For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300). Clinical Features Roosing et al. (2016) reported 4 probands diagnosed with Joubert syndrome who had biallelic mutations in the CEP120 gene, including a 4.5-year-old girl from Italy (COR391), an 11-year-old boy from the United States (MTI-143), a 2-year-old boy from Palestine (MTI-991), and a 2-year-old girl from India (MTI-1516). All 4 patients presented with a neurologic phenotype consisting of hypotonia, developmental delay, and cognitive impairment, and all exhibited the molar tooth sign. Ataxia and neonatal breathing abnormalities were reported in 2 patients (MTI-143 and MTI-1516), and patient MTI-143 also had abnormal ocular movements. None of the 4 showed involvement of other organs such as retina, kidneys, liver, or skeleton. Molecular Genetics Roosing et al. (2016) performed exome sequencing in a cohort of 145 patients with Joubert syndrome, including 15 children diagnosed with orofaciodigital syndrome type VI (OFD6; 277170), and also screened a panel of 120 known and candidate ciliopathy genes, including CEP120, in a cohort of 346 probands with a phenotype consistent with Joubert syndrome or related ciliopathies. In 4 (0.8%) of the 491 JBTS patients, the authors identified homozygous or compound heterozygous mutations in the CEP120 gene (see, e.g., 613446.0004-613446.0008). Noting that all 4 patients had a relatively mild, purely neurologic phenotype, whereas other patients with mutations in CEP120 exhibit a more complex and severe phenotype (see SRTD13, 616300), Roosing et al. (2016) stated that the mechanism through which mutations in the same gene cause such wide phenotypic variability remained unexplained. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Strabismus \- Ocular motor apraxia \- Duane syndrome NEUROLOGIC Central Nervous System \- Hypotonia \- Neonatal breathing abnormalities \- Developmental delay \- Cognitive impairment \- Truncal ataxia \- Molar tooth sign \- Hypoplasia of corpus callosum \- Mild ventriculomegaly MOLECULAR BASIS \- Caused by mutation in the 120-kd centrosomal protein (CEP120, 613446.0004 ) ▲ 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	JOUBERT SYNDROME 31	c4551568	7,042	omim	https://www.omim.org/entry/617761	2019-09-22T15:44:55	{"doid": ["0080277"], "mesh": ["C536293"], "omim": ["213300", "617761"], "orphanet": ["475"], "synonyms": ["CPD IV", "Cerebelloparenchymal disorder IV", "Classic Joubert syndrome", "Joubert syndrome type A", "Joubert-Boltshauser syndrome", "Pure Joubert syndrome"], "genereviews": ["NBK1325"]}
## Summary ### Clinical characteristics. The disorder dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is characterized by the following: * A movement disorder resulting from manganese accumulation in the basal ganglia * Whole-blood manganese concentrations that often exceed 2000 nmol/L (normal: <320 nmol/L) * Polycythemia * Hepatomegaly with variable hepatic fibrosis/cirrhosis Neurologic findings can manifest: in childhood (ages 2-15 years) as four-limb dystonia, leading to a characteristic high-stepping gait ("cock-walk gait"), dysarthria, fine tremor, and bradykinesia or on occasion spastic paraplegia; or in adulthood as parkinsonism (shuffling gait, rigidity, bradykinesia, hypomimia, and monotone speech) unresponsive to L-dopa treatment. Hepatic failure, secondary complications of cirrhosis, and the neurologic disorder shorten life expectancy. ### Diagnosis/testing. The diagnosis is suggested by characteristic clinical and brain MRI findings, elevated whole-blood concentration of manganese, and polycythemia. It is confirmed by identification of biallelic pathogenic variants in SLC30A10. ### Management. Treatment of manifestations: Regular chelation therapy with intravenous disodium calcium edetate improves blood manganese levels and neurologic findings and causes signs of liver disease to disappear. In addition, supplementation with oral iron therapy (despite normal serum iron levels) can reduce blood manganese levels and resolve polycythemia. Liver transplantation should be considered in individuals with end-stage liver disease, although it has not yet been attempted in this disorder. Prevention of primary manifestations: Chelation therapy and iron supplementation may prevent primary disease manifestations in affected asymptomatic sibs. Prevention of secondary complications: Early initiation of physiotherapy and orthopedic management aims to prevent contractures and maintain ambulation. Symptomatic treatment with antispasticity medications (including baclofen and botulinum toxin) and levodopa may be attempted. Swallowing evaluation and regular dietary assessments are indicated to assure adequate nutrition. In order to prevent aspiration pneumonia gastric feeding tube and/or tracheostomy may be required. The potential for complications from chelation therapy and/or iron supplementation can be lessened by careful surveillance Agents/circumstances to avoid: Foods very high in manganese: cloves; saffron; nuts; mussels; dark chocolate; and pumpkin, sesame, and sunflower seeds Evaluation of relatives at risk: Because chelation therapy and iron supplementation could prevent primary disease manifestations in affected asymptomatic individuals, it is recommended that at-risk sibs of a proband be evaluated either by molecular genetic testing (if the pathogenic variants in the family are known) or by periodic monitoring of whole-blood manganese concentration and hemoglobin. ### Genetic counseling. Dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the SLC30A10 pathogenic variants in the family are known. ## Diagnosis ### Suggestive Findings Dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease should be suspected in individuals with typical clinical, brain MRI, and laboratory findings. Clinical findings. An early- and a late-onset form exist: * Childhood-onset form (between ages 2 and 15 years). Usually four-limb dystonia (leading to a characteristic high-stepping gait ("cock-walk gait"), dysarthria, fine tremor, and bradykinesia [Tuschl et al 2012, Quadri et al 2015] or on occasion spastic paraplegia [Gospe et al 2000] * Adult-onset form. Parkinsonism (shuffling gait, rigidity, bradykinesia, hypomimia, and monotone speech) unresponsive to L-dopa treatment [Quadri et al 2012] Brain MRI. See Figure 1. #### Figure 1. Representative brain MRI of an affected individual A. Transaxial T1-weighted images. Note abnormally high signal return from all white matter as well as more prominent signal return from the putamen and globus pallidus bilaterally. * T1-weighted images show characteristic hyperintensity of the basal ganglia including the globus pallidus; putamen; and caudate, subthalamic, and dentate nuclei with sparing of the thalamus and ventral pons. When the disease is extensive, white matter and anterior pituitary involvement can be present. * T2-weighted images show corresponding hypointensity changes. However, these changes are often less pronounced and, hence, may be reported as normal. * Note: Normalization of manganese blood levels (see Management) improves the findings on brain MRI [Quadri et al 2012, Stamelou et al 2012, Tuschl et al 2012]. Laboratory findings. Hypermanganesemia: * Whole-blood manganese concentrations are elevated in all affected individuals. Average in affected individuals is greater than 2000 nmol/L (normal: <320 nmol/L). * In contrast, blood manganese concentration in acquired hypermanganesemia is usually less than 2000 nmol/L. ### Corroborative Features * Polycythemia. Manganese induces expression of the gene encoding erythropoietin [Ebert & Bunn 1999]. Characteristically, affected individuals are polycythemic. Hemoglobin concentrations reported in the literature range from 15.9 to 22.5 g/dL (mean: 18.6 g/dL). Some individuals studied have been found to have elevated erythropoietin levels [Gospe et al 2000, Quadri et al 2012, Tuschl et al 2012]. * Markers of depleted iron stores. Manganese and iron compete for the same serum-binding protein (transferrin) and membranous transporter protein (divalent metal transporter 1). Therefore, affected individuals show low serum ferritin concentration and serum iron levels while total iron binding capacity is elevated [Quadri et al 2012, Tuschl et al 2012]. * Chronic liver disease. Hepatic involvement may be present with variable severity and is not pathognomonic for this disease; when present, however, hepatic involvement should further suggest the diagnosis: * The majority of affected individuals reported to date have evidence of hepatic involvement that includes hepatomegaly, elevated transaminases (alanine transaminase [ALT], aspartate transaminase [AST]), and unconjugated hyperbilirubinemia. * Liver ultrasound examination or MRI can confirm hepatomegaly and features of liver cirrhosis. * Pathologic features on liver biopsy/post-mortem examination in six affected individuals included fibrosis, steatosis, and micronodular cirrhosis. Note: One individual with hepatomegaly and micronodular cirrhosis had no laboratory evidence of hepatic dysfunction [Gospe et al 2000, Tuschl et al 2008, Quadri et al 2012, Tuschl et al 2012, Lechpammer et al 2014]. * Hepatic manganese content is highly elevated. Rhodanine staining confirms deposition of manganese in hepatocytes. Copper and zinc content can also be affected with mild elevation in hepatic levels [Gospe et al 2000, Tuschl et al 2008, Quadri et al 2012, Tuschl et al 2012, Lechpammer et al 2014]. * Family history consistent with autosomal recessive inheritance, including parental consanguinity ### Establishing the Diagnosis The diagnosis of dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is established in a proband with identification of biallelic pathogenic variants of SLC30A10 on molecular genetic testing [Quadri et al 2012, Tuschl et al 2012] (see Table 1). Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Single-gene testing. Sequence analysis of SLC30A10 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. * A multigene panel that includes SLC30A10 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). 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 Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease View in own window Gene 1Test MethodProportion of Probands with Pathogenic Variants 2 Detectable by This Method SLC30A10Sequence analysis 314/15 4 Gene-targeted deletion/duplication analysis 51/15 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. 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\. 24 individuals from 14 families (13 with childhood-onset forms, 1 with the adult-onset form) [Quadri et al 2012, Tuschl et al 2012, Avelino et al 2014, Quadri et al 2015, Mukhtiar et al 2016]. Sequence analysis in affected individuals of 14 families identified homozygous SLC30A10 pathogenic variants. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used 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\. Four affected sibs from one family were homozygous for a large genomic SLC30A10 deletion involving exons 1 and 2 [Tuschl et al 2012]. ## Clinical Characteristics ### Clinical Description Neurologic findings * Childhood onset. In the childhood-onset form of dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease, affected individuals present with neurologic signs between ages two and 15 years. Many become wheelchair bound in their teens. The neurologic signs and symptoms of the childhood-onset form are primarily extrapyramidal and include dystonia, dysarthria, and rigidity. Four-limb dystonia manifests with difficulties walking and a high-stepping gait ("cock walk gait"), dystonic posturing, and painful extensor spasms. Fine motor impairment causes problems with writing and drawing and inability to perform rapid alternating movements of the hands (dysdiadochokinesis). Dystonia of the tongue can lead to dysarthria [Quadri et al 2012, Tuschl et al 2012, Quadri et al 2015]. Isolated corticospinal tract involvement has been described in one affected individual. Typical neurologic signs of spastic paraparesis (e.g., spasticity, hyperreflexia, extensor plantar responses) were found [Gospe et al 2000]. * Adult onset. Quadri et al [2012] reported two brothers who presented at ages 47 years and 57 years with progressive gait disturbance and bradykinesia. Neurologic examination showed features of parkinsonism including hypomimia, monotone speech, mild rigidity, global bradykinesia, wide-based gait with freezing and starting hesitation, and moderate postural instability without evidence of tremor, dystonia, or cerebellar or pyramidal disturbances. Treatment with L-dopa and dopamine agonists did not improve neurologic findings. Sensory-motor axonal polyneuropathy has been described in two affected individuals with the late-onset neurologic presentation [Quadri et al 2012]. Hypermanganesemia: Whole-blood manganese concentrations are elevated in all affected individuals. * Due to limited data, the onset of hypermanganesemia is not accurately known. * Raised whole-blood manganese concentrations have been recorded in affected children as young as age five years. * However, given that clinical manifestations can be apparent in the first two years of life, it is expected that hypermanganesemia develops concurrently or prior to onset of clinical manifestations. * Hypermanganesemia due to environmental overexposure (including parenteral nutrition) and acquired hepatocerebral degeneration in persons with end-stage liver disease must be excluded. See Differential Diagnosis. * Quadri et al [2012] reported one affected individual whose blood manganese concentration was only minimally increased on one occasion; therefore, a single measurement of manganese concentration could be misleading and repeat measurements are recommended when the clinical suspicion is strong. Note: Blood manganese concentrations of heterozygotes (i.e., carriers of one SLC30A10 pathogenic variant) are within normal limits or are mildly elevated. Gospe et al [2000] reported a borderline high blood manganese concentration of 380 nmol/L in an obligate heterozygous parent and Tuschl et al [2012] reported levels between 380 and 649 nmol/L in three heterozygous parents (normal: <320 nmol/L). Polycythemia. All affected individuals reported to date had polycythemia at the time of diagnosis. Polycythemia can precede the onset of neurologic manifestations and, therefore, affected individuals often undergo repeat phlebotomies prior to recognition of the correct diagnosis [Quadri et al 2012, Tuschl et al 2012]. Polycythemia has been described in affected children from age three years; earlier presentation of polycythemia cannot be ruled out because of insufficient data. Individuals in whom neurologic symptoms do not manifest until late adulthood have had polycythemia since as early as the third decade. Polycythemia can resolve upon treatment with chelation therapy or iron. There is evidence from one patient whose polycythemia resolved without treatment during advanced stage of disease [Lechpammer et al 2014]. Liver disease. The spectrum of hepatic involvement ranges from mild hepatomegaly to hepatic failure in early adulthood [Tuschl et al 2012]. However, pure neurologic phenotypes presenting with dystonia alone have been reported [Quadri et al 2012]. In the majority of affected individuals, transaminases are mildly elevated [Quadri et al 2012, Tuschl et al 2012]. To date, three affected individuals died of complications of liver cirrhosis between ages 18 and 46 years. As most of the affected individuals known to the authors are still in their teens or early adulthood, no long-term follow-up data are available. Significant phenotypic variability even within the same family is apparent: The two brothers reported by Quadri et al [2012], who are now in their sixties and severely affected by dystonia, did not show hepatic involvement. Both had normal liver function and liver ultrasound examination throughout their lives. However, while the affected sister had minimal neurologic involvement, she developed liver cirrhosis in the third decade and died of liver failure at age 46 years. Intellect appears normal in all affected individuals. Quadri et al [2012] described one individual who developed cognitive and behavioral problems, thought to be alcohol related. While environmental manganese exposure is known to cause cognitive and psychiatric disturbances (so called "manganese madness") including emotional lability, hallucinations, and compulsive behavior [Racette et al 2012], this has not yet been observed in patients with dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease. Pica. Several affected individuals had pica during early childhood [Brna et al 2011; Brna, unpublished data]. Darker skin tone. Some affected individuals have been described to have a purple or dark skin discoloration to an extent that parents are able to distinguish affected and unaffected children prior to the manifestation of clinical symptoms [Authors, unpublished data]. Pathology. Post-mortem studies in an individual with SLC30A10 deficiency showed yellow-grey mottling of the basal ganglia associated with severe neuronal loss, astrocytosis, myelin loss, spongiosis, and rhodanine-positive deposits particularly in the globus pallidus, while other basal ganglia were affected to a lesser extent. Gliosis of the white matter and axonal loss of the corticospinal tracts were observed [Lechpammer et al 2014]. ### Genotype-Phenotype Correlations Fourteen homozygous SLC30A10 pathogenic variants and one homozygous multiexon deletion have been documented in ten unrelated families with either childhood- or adult-onset disease [Quadri et al 2012, Tuschl et al 2012]. Due to the small number of known cases, no firm genotype-phenotype correlation can be made. However, it is interesting that the pathogenic variant in the sibship presenting with adult-onset parkinsonism is toward the end of the fourth (last) exon of SLC30A10. This pathogenic variant (p.Gln412ArgfsTer26; c.1235delA) is predicted to cause a frameshift that introduces a premature stop codon and the translation of a protein lacking the last 49 amino acids [Quadri et al 2012]. It is possible that this specific allele produces a protein with residual function. ### Prevalence This inborn error of manganese metabolism has only recently been identified. A total of 28 affected individuals from ten families are known worldwide [Quadri et al 2012, Tuschl et al 2012, Avelino et al 2014, Quadri et al 2015, Mukhtiar et al 2016]. The prevalence is yet to be determined. ## Differential Diagnosis The following are included in the differential diagnosis of dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease. SLC39A14 deficiency (SLC39A14-related early-onset parkinsonism-dystonia). This manganese transporter defect is caused by impaired manganese uptake into the liver. Affected individuals also present with hypermanganesemia and rapidly progressive childhood-onset parkinsonism-dystonia due to cerebral manganese deposition. Brain MRI appearances are the same as for dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease. Distinguishing features are the absence of liver disease and polycythemia due to the lack of hepatic manganese deposition, which can be assessed by liver MRI [Tuschl et al 2016]. Acquired hypermanganesemia. Overexposure to manganese is known to be neurotoxic and causes ‘‘manganism’’ – a distinct syndrome of extrapyramidal movement disorder (dystonia/parkinsonism) combined with high signal intensity of the basal ganglia on T1-weighted MR images of the brain resulting from manganese accumulation in the basal ganglia [Racette et al 2012]. * Environmental exposure has been described in workers in mining and welding industries who inhale manganese-laden dust or fumes, in individuals ingesting contaminated drinking water, and in drug addicts who use intravenous methcathinone contaminated with potassium permanganate [Stepens et al 2008, Bouchard et al 2011, Racette et al 2012]. * Total parenteral nutrition has been associated with manganese toxicity because the control mechanisms of manganese absorption in the gut and subsequent hepatic excretion are bypassed [Chalela et al 2011]. * Acquired hepatocerebral degeneration is observed in those with advanced hepatic cirrhosis or portosystemic shunts in which impaired biliary excretion of manganese results in manganese accumulation in the basal ganglia causing a debilitating movement disorder [Meissner & Tison 2011]. Wilson disease Parkinson disease and its differential diagnoses including: * Atypical degenerative parkinsonisms (multiple-system atrophy, progressive supranucleal palsy) * Vascular parkinsonism * Drug-induced parkinsonism * Huntington disease * DRPLA (dentatorubral-pallidoluysian atrophy) * Juvenile Parkinson disease, including parkin type of early-onset parkinsonism Inherited forms of dystonia including: * DYT1 early-onset isolated dystonia (DYT-TOR1A) * Dopa-responsive dystonia (DRD) including disorders of dopamine synthesis / transport and disorder affecting tetrahydrobiopterin synthesis / recycling (see GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia) * Other forms of primary dystonia and dystonia plus disorders (see Dystonia Overview) Neurodegenerative diseases associated with dystonia including: * Pantothenate kinase-associated neurodegeneration (PKAN), a form of neurodegeneration with brain iron accumulation (NBIA) * Other forms of NBIA (see NBIA Overview) caused by pathogenic variants in PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17. * Niemann-Pick disease type C (associated with liver disease) * Organic acidemias (i.e. glutaric, methylmalonic, propionic, 3-hydroxyisobutyryl-CoA hydrolase deficiency) * Mitochondrial respiratory chain disorders * Pyruvate dehydrogenase complex deficiency * Gaucher disease Cerebral palsy. Familial and acquired spastic paraplegia (see Hereditary Spastic Paraplegia Overview) ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease, the following evaluations are recommended: * Neurologic examination for dystonia, parkinsonism, and spasticity, including evaluation of ambulation and speech * Brain MRI * Assessment of the liver including liver function tests, liver ultrasound examination, and liver biopsy if indicated. Consultation with a hepatologist is advised. * Establishment of whole blood manganese levels * Assessment for physiotherapy, occupational therapy, and/or speech therapy * Evaluation of swallowing and nutritional status * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations #### Chelation Therapy with Disodium Calcium Edetate Regular chelation therapy with intravenous disodium calcium edetate can stabilize blood manganese levels, improve neurologic symptoms, and halt liver disease [Tuschl et al 2008, Quadri et al 2012, Tuschl et al 2012]. Short term. The response of an individual to disodium calcium edetate is determined by a single five-day course of twice-daily disodium calcium edetate at 20 mg/kg/dose (made up in 250 mL of 0.9% sodium chloride, given intravenously over 1 hour) and daily measurement of plasma manganese concentration and 24-hour urine manganese levels. Other monitoring includes: serum concentrations of electrolytes, calcium, phosphate, and magnesium; renal and liver function; full blood count; and serum concentrations of trace metals such as zinc, copper, and selenium. Note: To avoid hypocalcemia, disodium calcium edetate infusions need to be administered slowly over at least one hour. If the calcium level (corrected for albumin concentration) is low, infusions should be administered over a longer time span (i.e., >3 hours). Long term. If chelation therapy proves to be effective in the short term, monthly five-day courses of disodium calcium edetate (intravenous 20 mg/kg/dose 2x/day) are expected to lower blood manganese levels and normalize hemoglobin concentration and iron indices [Tuschl et al 2008, Quadri et al 2012, Tuschl et al 2012]. Chelation therapy should be continued lifelong. While on treatment, monitoring once every two months includes: serum concentration of electrolytes, calcium, phosphate, magnesium; renal and liver function; full blood count; and serum concentrations of trace metals such as zinc, copper, and selenium (see Prevention of Secondary Complications). #### Iron Therapy Iron is a competitive inhibitor of intestinal manganese uptake; hence, supplementation with iron given orally (despite normal serum iron levels) can reduce blood manganese levels and resolve polycythemia [Tuschl et al 2008, Tuschl et al 2012]. The high serum transferrin levels seen in affected individuals are thought to reduce the risk of manganese toxicity. Note: Iron indices need to be monitored frequently (every ~3 months) in those receiving iron supplements (see Prevention of Secondary Complications). #### Liver Transplantation Liver transplantation should be considered in individuals with end-stage liver disease; however, it has not been attempted in individuals with this disorder and, hence, no data are available. #### Other Dystonia can result in physical deformities and pain. Physiotherapy, occupational therapy, and/or speech therapy should be provided. Symptomatic treatment with antispasticity medications and L-dopa has been attempted with limited success. ### Prevention of Primary Manifestations Chelation therapy and iron supplementation may prevent primary disease manifestations in affected sibs who are asymptomatic (see Treatment of Manifestations). ### Prevention of Secondary Complications Early initiation of physiotherapy and orthopedic management aims to prevent contractures and maintain ambulation. As needed, individuals should be referred for adaptive aids (e.g., a walker or wheelchair for gait abnormalities) and assistive communication devices. Symptomatic treatment with antispasticity medications including baclofen and botulinum toxin, and levodopa has been attempted with limited success. Swallowing evaluation and regular dietary assessments are indicated to assure adequate nutrition. Once an adequate oral diet can no longer be maintained, gastrostomy tube placement should be considered. In order to prevent aspiration pneumonia gastric feeding tube and/or tracheostomy may be required. The potential for complications from chelation therapy and/or iron supplementation can be lessened by careful surveillance. ### Surveillance Close monitoring of liver function and disease markers such as hemoglobin, iron indices, and whole-blood manganese is required at three-month intervals. Routine follow up with a neurologist and hepatologist should be provided with repeat assessment of MRI brain, and liver ultrasound and biopsy when clinically indicated (e.g., worsening of liver function) and for monitoring of treatment. Adverse effects of chelation therapy with disodium calcium edetate include hypocalcemia, nephrotoxicity, trace metal and vitamin deficiency, and thrombocytopenia and leukopenia [Lamas et al 2012]. Complete blood count and renal function including urinalysis are assessed at baseline and monthly thereafter. Monitoring may be extended to every other month once on a stable dose. Additionally, the following need to be monitored: trace metal levels including manganese, zinc, copper, and selenium; liver function; electrolytes; calcium, magnesium, and phosphate concentrations; and iron status. Trace metal supplements are provided as needed. Treatment may need to be discontinued if: * White blood count <3.5x10^9/L * Neutrophils <2.0x10^9/L * Platelets <150x10^9/L * >2+ proteinuria on >1 occasion (and no evidence of infection) The above cut-off values are based on guidelines for D-penicillamine treatment [Chakravarty et al 2008]. Because chelation treatment with disodium calcium edetate may prevent mortality and morbidity in SLC39A14-related early-onset parkinsonism-dystonia, lower cut-off values may be acceptable. The clinical treatment benefit needs to be carefully weighed against occurring adverse effects for each affected individual. Toxicity of iron supplementation. In order to avoid iron toxicity, serum iron and total iron binding capacity need to be monitored regularly. If serum iron exceeds 80% of total iron binding capacity, iron supplementation should be stopped or reduced. ### Agents/Circumstances to Avoid Foods very high in manganese (cloves; saffron; nuts; mussels; dark chocolate; and pumpkin, sesame and sunflower seeds) should be avoided. ### Evaluation of Relatives at Risk It is appropriate to evaluate apparently asymptomatic sibs of a proband in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures. Chelation therapy and iron supplementation can potentially prevent primary disease manifestations in asymptomatic individuals. Evaluations include: * Molecular genetic testing if the SLC30A10 pathogenic variants in the family are known; * Periodic monitoring of whole-blood manganese concentration and hemoglobin if the pathogenic variants in the family are not known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management For an affected fetus, no prenatal treatment is recommended as the disease does not manifest before early childhood. For an affected mother, no data or information on pregnancy management are available. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease	None	7,043	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK100241/	2021-01-18T21:29:50	{"synonyms": []}
Bohring-Opitz syndrome is a rare condition that affects the development of many parts of the body. Most individuals with Bohring-Opitz syndrome have profound to severe intellectual disability, developmental delay, and seizures. Most affected individuals have a normal head shape and size with no brain abnormalities; however, some have abnormal development of the head. Abnormal development can lead to a small head size (microcephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance. Structural brain abnormalities can occur with or without head abnormalities. For example, the fluid-filled spaces near the center of the brain (ventricles) may be usually large (ventriculomegaly) or the tissue that connects the left and right halves of the brain (the corpus callosum) can be abnormally thin. Eye problems that can affect vision also occur in people with Bohring-Opitz syndrome. People with this disorder may have protruding eyes (exophthalmos), eyes that do not point in the same direction (strabismus), widely spaced eyes (hypertelorism), or outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may have severe nearsightedness (high myopia) or abnormalities in the light-sensitive tissue at the back of the eye (the retina) or the nerves that carry information from the eyes to the brain (optic nerves). Additional facial differences associated with Bohring-Opitz syndrome can include a flat nasal bridge, nostrils that open to the front rather than downward (anteverted nares), a high arch or opening in the roof of the mouth (high arched or cleft palate), a split in the upper lip (cleft lip), a small lower jaw (micrognathia), low-set ears that are rotated backward, a red birthmark (nevus simplex) on the face (usually the forehead), a low frontal hairline often with eyebrows that grow together in the middle (synophrys), and excessive body and facial hair (hirsutism) that increases with age. Some individuals with Bohring-Opitz syndrome have poor growth before birth (intrauterine growth retardation). During infancy, they grow and gain weight slowly and often have severe feeding difficulties with recurrent vomiting. People with this condition often have characteristic body positioning, known as Bohring-Opitz syndrome posture. This posture consists of slouching shoulders, bent elbows and wrists, hands positioned with the wrists or all of the fingers angled outward toward the fifth finger (ulnar deviation), with the legs usually extended straight. Affected individuals usually stop exhibiting the Bohring-Opitz syndrome posture as they get older. Other abnormalities include joint deformities (called contractures) that are apparent at birth in the knees, hips, or other joints and abnormal muscle tone. Affected individuals can have recurrent infections and heart, kidney, or genital abnormalities. In rare cases, a childhood form of kidney cancer known as Wilms tumor can develop. Some individuals with Bohring-Opitz syndrome do not survive past early childhood, while others live into adolescence or early adulthood. The most common causes of death are heart problems, abnormalities of the throat and airways that cause pauses in breathing (obstructive apnea), and lung infections. ## Frequency Bohring-Opitz syndrome is thought to be a rare condition, although its exact prevalence is unknown. More than 40 affected individuals have been described in the scientific literature. ## Causes Bohring-Opitz syndrome is caused by mutations in the ASXL1 gene. This gene provides instructions for making a protein that is involved in a process known as chromatin remodeling. Chromatin is the complex of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Through its role in chromatin remodeling, the ASXL1 gene regulates the activity (expression) of many genes, including a group of genes known as HOX genes, which play important roles in development before birth. The ASXL1 protein can turn on (activate) or turn off (repress) HOX genes depending on when they are needed. ASXL1 gene mutations reduce the amount of functional ASXL1 protein available, which likely disrupts the regulation of the activity of HOX genes and other genes during development. Altered activity of these genes probably leads to the neurological and physical features of this condition. ### Learn more about the gene associated with Bohring-Opitz syndrome * ASXL1 ## Inheritance Pattern Bohring-Opitz syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of the condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family. No one with Bohring-Opitz syndrome has been known to have children. Very rarely, individuals with Bohring-Opitz syndrome inherit the altered gene from their unaffected mother, who has the mutation only in some cells, including egg cells, but not in others. This phenomenon is known as mosaicism. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Bohring-Opitz syndrome	c0796232	7,044	medlineplus	https://medlineplus.gov/genetics/condition/bohring-opitz-syndrome/	2021-01-27T08:25:37	{"gard": ["10140"], "mesh": ["C537419"], "omim": ["605039"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-2 (SCAR2) is caused by homozygous or compound heterozygous mutation in the PMPCA gene (613036) on chromosome 9q34. Description Autosomal recessive spinocerebellar ataxia-2 is an neurologic disorder characterized by onset of impaired motor development and ataxic gait in early childhood. Additional features often include loss of fine motor skills, dysarthria, nystagmus, cerebellar signs, and delayed cognitive development with intellectual disability. Brain imaging shows cerebellar atrophy. Overall, the disorder is non- or slowly progressive, with survival into adulthood (summary by Jobling et al., 2015). Clinical Features Norman (1940) described 3 sibs in 1 family and 2 sibs in another who had cerebellar ataxia and mental deficiency since early life. Postmortem examinations showed severe cerebellar granule cell loss. One child showed delayed motor development and mental deficiency in infancy. Other features included small head, cataracts, increased knee jerks, and intention tremor. He died at age 20 years. Postmortem examination showed marked cerebellar atrophy with complete absence of granule cells in the lateral lobes of the cerebellum and the superior part of the vermis. There were heterotopic Purkinje cells and gliosis (Weiner and Konigsmark, 1971). Scherer (1933) described 2 affected sibs, and Jervis (1950) 3 affected sibs. Jervis (1954) also observed the disorder in monozygotic Italian twin sisters. In many members of an inbred Christian Maronite family originating from a village in the northeast of Lebanon, Megarbane et al. (1999) described hereditary congenital nonprogressive cerebellar ataxia. The 12 affected members were thought to have the autosomal recessive Norman type of cerebellar atrophy, also known as primary granular cell atrophy of the cerebellum. The patients in the Lebanese family were of short stature, varying from 136 cm in a 44-year-old female to 164 cm in a 40-year-old male. Jobling et al. (2015) provided follow-up on the family reported by Megarbane et al. (1999). There were 12 affected individuals, ranging in age from 22 to 46 years, with ataxic gait. All had delayed psychomotor development with delayed speech acquisition and intellectual disability. Additional features included dysarthria, dysmetria, and gaze-evoked nystagmus; brain imaging showed cerebellar atrophy, dilated fourth ventricle, and a large cisterna magna. More variable features included brisk deep tendon reflexes, spasticity, hypotonia, slightly decreased muscle strength, flat feet, and visuospatial deficits. Jobling et al. (2015) also reported 4 patients from 2 additional families of Lebanese descent. These patients had similar ataxic gait, although in some cases the gait abnormalities appeared between 11 and 15 months of age after normal initial development. Features included truncal and gait ataxia, difficulty in fine motor skills, saccadic smooth pursuit, dysmetria, dysdiadochokinesis, and tremor. All but 1 had intellectual disability and delayed speech with dysarthria. A fourth family, of French descent, contained 2 affected sibs, including 1 living 58-year-old man with gait ataxia, dysmetria, gaze-evoked nystagmus, and dysarthria. He had normal intellectual development and his neurologic status was stable over time. An affected sister died at age 29 years. Choquet et al. (2016) reported 2 brothers of French Canadian descent with SCAR2. There was clinical variability: one developed symptoms of impaired gait, dysdiadochokinesis, dysmetria, and mild distal atrophy in adolescence, whereas the other developed more severe symptoms around age 5; the younger brother also had hemidystonia and sensorineural hearing loss. Neither had intellectual disability, but both had mild learning difficulties. The disorder was slowly progressive in these patients. Inheritance The transmission pattern of SCAR2 in the families reported by Jobling et al. (2015) was consistent with autosomal recessive inheritance. Mapping By genomewide analysis of the large consanguineous Lebanese family reported by Megarbane et al. (1999), Delague et al. (2001) found linkage to a 12.1-cM interval on chromosome 9q34-qter between markers D9S67 and D9S312. Molecular Genetics In 16 individuals from 3 unrelated families of Lebanese descent, including the family reported by Megarbane et al. (1999), Jobling et al. (2015) identified a homozygous missense mutation in the PMPCA gene (A377T; 613036.0001). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the families; haplotype analysis indicated a founder effect. Western blot analysis of affected patients showed markedly decreased levels of the mutant protein (range, 25-50% of control values). Patient cells showed some evidence of improper mitochondrial processing of FXN (606829) with abnormal accumulation of the FXN42-210 isoform and decreased levels of the FXN81-210 isoform, as well as evidence of an increased oxidation/reduction ratio in the mitochondria compared to controls. Direct functional studies of the variant were not performed. Direct sequencing of the PMPCA gene in 46 French individuals with a similar phenotype identified compound heterozygous missense mutations (613036.0002 and 613036.0003) in 1 individual. In 2 brothers of French Canadian descent with SCAR2, Choquet et al. (2016) identified a homozygous missense mutation in the PMPCA gene (V256M; 613036.0004). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed abnormal accumulation of the FXN42-210 isoform and decreased levels of the FXN81-210 isoform. Functional studies of the variant were not performed. Nomenclature A form of autosomal recessive spinocerebellar ataxia previously designated SCAR1 has been reclassified as autosomal recessive spinocerebellar ataxia with axonal neuropathy (SCAN2; 606002). A form previously designated SCAR5 has been reclassified as Galloway-Mowat syndrome-1 (GAMOS1; 251300). Animal Model Weiner and Konigsmark (1971) noted that infection of the fetal rat by rat virus (Margolis and Kilham, 1968) and of the fetal kitten by panleukopenia virus (Kilham and Margolis, 1966) can result in granule cell hypoplasia. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Eyes \- Nystagmus \- Saccadic smooth pursuit SKELETAL Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation, moderate to severe \- Intellectual disability \- Visuospatial defects \- Gait ataxia \- Limb ataxia \- Unsteady gait \- Incoordination \- Delayed speech development \- Tremor \- Dysarthria \- Spasticity \- Dysmetria \- Cerebellar hypoplasia \- Atrophy of the granular cell layer of the cerebellum \- Abnormal Purkinje cells \- Reactive gliosis Peripheral Nervous System \- Hyperreflexia \- Hyporeflexia (less common) MISCELLANEOUS \- Onset in infancy or in the first year of life \- Later onset in adolescence has rarely been reported \- Non- or slowly progressive \- Some patients do not achieve independent ambulation MOLECULAR BASIS \- Caused by mutation in the mitochondrial processing peptidase, alpha gene (PMPCA, 613036.0001 ) ▲ 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	SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 2	c1859298	7,045	omim	https://www.omim.org/entry/213200	2019-09-22T16:29:51	{"doid": ["0080061"], "mesh": ["C565865"], "omim": ["213200"], "orphanet": ["1170"], "synonyms": ["Alternative titles", "CEREBELLAR HYPOPLASIA, NONPROGRESSIVE NORMAN TYPE", "CEREBELLAR GRANULAR CELL HYPOPLASIA AND MENTAL RETARDATION, CONGENITAL", "CEREBELLOPARENCHYMAL DISORDER III", "CPD III"]}
Selenium deficiency Selenium SpecialtyEndocrinology Causescompromised intestinal function Selenium deficiency occurs when an organism lacks the required levels of selenium, a critical nutrient in many species. Deficiency, although relatively rare in healthy well-nourished individuals,[1] can have significant negative results,[2] affecting the health of the heart and the nervous system; contributing to depression, anxiety, and dementia; and interfering with reproduction and gestation. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Reference ranges * 4 Epidemiology and prevention * 5 In non-human animals * 6 References * 7 External links ## Signs and symptoms[edit] Selenium deficiency in combination with Coxsackievirus infection can lead to Keshan disease, which is potentially fatal. Selenium deficiency also contributes (along with iodine deficiency) to Kashin-Beck disease.[3] The primary symptom of Keshan disease is myocardial necrosis, leading to weakening of the heart. Kashin-Beck disease results in atrophy, degeneration and necrosis of cartilage tissue.[4] Keshan disease also makes the body more susceptible to illness caused by other nutritional, biochemical, or infectious diseases. Selenium is also necessary for the conversion of the thyroid hormone thyroxine (T4) into its more active counterpart triiodothyronine (T3),[3] and as such a deficiency can cause symptoms of hypothyroidism, including extreme fatigue, mental slowing, goiter, cretinism, and recurrent miscarriage.[5] ## Causes[edit] It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, those who have had gastrointestinal bypass surgery, and also in persons of advanced age (i.e., over 90).[6] People dependent on food grown from selenium-deficient soil may be at risk for deficiency.[7][citation needed] Increased risk for developing various diseases has also been noted, even when certain individuals lack optimal amounts of selenium, but not enough to be classified as deficient.[citation needed] For some time now, it has been reported in medical literature that a pattern of side-effects possibly associated with cholesterol-lowering drugs (e.g., statins) may resemble the pathology of selenium deficiency.[8][9] ## Diagnosis[edit] ### Reference ranges[edit] In the US, the Dietary Reference Intake for adults is 55 µg/day. In the UK it is 75 µg/day for adult males and 60 µg/day for adult females. 55 µg/day recommendation is based on full expression of plasma glutathione peroxidase. Selenoprotein P[10] is a better indicator of selenium nutritional status, and full expression of it would require more than 66 µg/day.[11] ## Epidemiology and prevention[edit] These diseases are most common in certain parts of China where the intake is low[12] because the soil is extremely deficient in selenium. Studies in Jiangsu Province of China have indicated a reduction in the prevalence of these diseases by taking selenium supplements.[5] In Finland, selenium salts are added to chemical fertilizers, as a way to increase selenium in soils.[13] Dietary supplements may utilize sodium selenite, L-selenomethionine or selenium-enriched yeast. ## In non-human animals[edit] In some regions (e.g. much of the northeastern and northwestern US and adjacent Canada, and the southeastern US), selenium deficiency in some animal species is common unless supplementation is carried out.[14] Selenium deficiency is responsible (either alone or together with vitamin E deficiency) for many of the cases of WMD ("white muscle disease"), evidenced at slaughter or during necropsy by whitish appearance of striated muscle tissue due to bleaching by peroxides and hydroperoxides.[15] Although this degenerative disease can occur in foals, pigs and other animal species, ruminants are particularly susceptible.[16] In general, absorption of dietary selenium is lower in ruminants than in non-ruminants, and is lower from forages than from grain.[17] Sheep are more susceptible than cattle to WMD, and goats are more susceptible than sheep.[17] Because of selenium's role in certain peroxidases (converting hydroperoxides to alcohols) and because of the antioxidant role of vitamin E (preventing hydroperoxide formation), a low level of Se can be somewhat (but not wholly) compensated by a high level of vitamin E. (In the animal, localization of peroxidases and vitamin E differs, partly because of the fat-solubility of vitamin E.) Some studies have indicated that about 0.12 or 0.23 mg Se per kg of dry matter intake may be sufficient for avoiding Se deficiency in sheep in some circumstances.[14] However, somewhat higher Se intake may be required for avoidance of WMD where certain legumes are consumed.[18] The cyanogenic glycosides in some white clover (Trifolium repens) varieties may influence the Se requirement,[17] presumably because of cyanide from the aglycone released by glucosidase activity in the rumen[19] and inactivation of glutathione peroxidases by the effect of absorbed cyanide on the glutathione moiety.[20] In areas where selenium deficiency in livestock is a concern, selenium (as selenite) may be supplemented in feed. In some countries, e.g. the US and Canada, such supplementation is regulated. Neonate ruminants at risk of WMD may be administered both Se and vitamin E by injection; some of the WMD myopathies respond only to Se, some only to vitamin E, and some to either.[21] ## References[edit] 1. ^ Weeks, Benjamin S.; Hanna, Mirna S.; Cooperstein, Deborah (2012). "Dietary selenium and selenoprotein function". Medical Science Monitor. 18 (8): RA127–RA132. doi:10.12659/msm.883258. PMC 3560698. PMID 22847213. 2. ^ Kieliszek, Marek (3 April 2019). "Selenium–Fascinating Microelement, Properties and Sources in Food". Molecules. 24 (7). doi:10.3390/molecules24071298. PMC 6480557. PMID 30987088. 3. ^ a b "Toxicological Profile for Selenium" (PDF). Agency for Toxic Substances and Disease Registry. U.S. Department of Health and Human Services. September 2003. Retrieved 7 Sep 2015. 4. ^ Moreno-Reyes, Rodrigo; Suetens, Carl; Mathieu, Françoise; Begaux, Françoise; Zhu, Dun; Rivera, Maria T.; Boelaert, Marleen; Nève, Jean; et al. (1998). "Kashin–Beck Osteoarthropathy in Rural Tibet in Relation to Selenium and Iodine Status" (PDF). New England Journal of Medicine. 339 (16): 1112–20. doi:10.1056/NEJM199810153391604. PMID 9770558. S2CID 2485235. 5. ^ a b "Selenium". Office of Dietary Supplements. 6. ^ Ravaglia, Giovanni; Forti, Paola; Maioli, Fabiola; Bastagli, Luciana; Facchini, Andrea; Mariani, Erminia; Savarino, Lucia; Sassi, Simonetta; et al. (2000). "Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged ≥90 y". American Journal of Clinical Nutrition. 71 (2): 590–8. doi:10.1093/ajcn/71.2.590. PMID 10648276. 7. ^ "Selenium Deficiency". Healthline. Retrieved 10 May 2020. 8. ^ Moosmann, B; Behl, C (2004). "Selenoprotein synthesis and side-effects of statins". Lancet. 363 (9412): 892–4. doi:10.1016/S0140-6736(04)15739-5. PMID 15031036. S2CID 43675310. 9. ^ Moosmann, B; Behl, C (2004). "Selenoproteins, cholesterol-lowering drugs, and the consequences: Revisiting of the mevalonate pathway". Trends in Cardiovascular Medicine. 14 (7): 273–81. doi:10.1016/j.tcm.2004.08.003. PMID 15542379. 10. ^ Papp, Laura Vanda; Lu, Jun; Holmgren, Arne; Khanna, Kum Kum (2007). "From Selenium to Selenoproteins: Synthesis, Identity, and Their Role in Human Health" (PDF). Antioxidants & Redox Signaling. 9 (7): 775–806. doi:10.1089/ars.2007.1528. PMID 17508906. 11. ^ Xia, Yiming; Hill, Kristina E; Byrne, Daniel W; Xu, Jiayuan; Burk, Raymond F (1 April 2005). "Effectiveness of selenium supplements in a low-selenium area of China". The American Journal of Clinical Nutrition. 81 (4): 829–834. doi:10.1093/ajcn/81.4.829. PMID 15817859. 12. ^ Johnson, Larry E. (May 2020). "Selenium Deficiency". Merck Manuals Professional Edition. 13. ^ Varo, P; Alfthan, G; Ekholm, P; Aro, A; Koivistoinen, P (1 August 1988). "Selenium intake and serum selenium in Finland: effects of soil fertilization with selenium". The American Journal of Clinical Nutrition. 48 (2): 324–329. doi:10.1093/ajcn/48.2.324. PMID 2841842. 14. ^ a b Nutrient Requirements of Sheep (6th ed.). National Academies Press. 1985. ISBN 978-0-309-03596-5. 15. ^ Jensen, Rue; Swift, Brinton L.; Kimberling, Cleon V. (1988). Jensen and Swift's Diseases of Sheep. Lea & Febiger. ISBN 978-0-8121-1099-9.[page needed] 16. ^ Underwood, Eric John (1999). The Mineral Nutrition of Livestock. CABI. ISBN 978-0-85199-128-3.[page needed] 17. ^ a b c Committee on the Nutrient Requirements of Small Ruminants (2007). Nutrient Requirements of Small Ruminants: Sheep, Goats, Cervids, and New World Camelids. National Academies Press. ISBN 978-0-309-10213-1.[page needed] 18. ^ Whanger, P. D.; Weswig, P. H.; Oldfield, J. E.; Cheeke, P. R.; Muth, O. H. (1972). "Factors influencing selenium and white muscle disease: forage types, salts, amino acids and dimethyl sulfoxide". Nutr. Rep. Int. 6: 21–37. 19. ^ Coop, I. E.; Blakely, R. L. (1949). "The metabolism and toxicity of cyanides and cyanogenic glycosides in sheep". N. Z. J. Sci. Technol. 30: 277–291. 20. ^ Kraus, Richard J.; Prohaska, Joseph R.; Ganther, Howard E. (September 1980). "Oxidized forms of ovine erythrocyte glutathione peroxidase cyanide inhibition of a 4-glutathione:4-selenoenzyme". Biochimica et Biophysica Acta (BBA) - Enzymology. 615 (1): 19–26. doi:10.1016/0005-2744(80)90004-2. PMID 7426660. 21. ^ Kahn, Cynthia M., ed. (2005). The Merck Veterinary Manual (9th ed.). Wiley. ISBN 978-0-911910-50-6.[page needed] ## External links[edit] Classification D * ICD-10: E59 * ICD-9-CM: 269.3 * DiseasesDB: 11941 * v * t * e Malnutrition Protein-energy malnutrition * Kwashiorkor * Marasmus * Catabolysis Vitamin deficiency B vitamins * B1 * Beriberi * Wernicke–Korsakoff syndrome * Wernicke's encephalopathy * Korsakoff's syndrome * B2 * Riboflavin deficiency * B3 * Pellagra * B6 * Pyridoxine deficiency * B7 * Biotin deficiency * B9 * Folate deficiency * B12 * Vitamin B12 deficiency Other * A: Vitamin A deficiency * Bitot's spots * C: Scurvy * D: Vitamin D deficiency * Rickets * Osteomalacia * Harrison's groove * E: Vitamin E deficiency * K: Vitamin K deficiency Mineral deficiency * Sodium * Potassium * Magnesium * Calcium * Iron * Zinc * Manganese * Copper * Iodine * Chromium * Molybdenum * Selenium * Keshan disease Growth * Delayed milestone * Failure to thrive * Short stature * Idiopathic General * Anorexia * Weight loss * Cachexia * Underweight [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Selenium deficiency	c0238421	7,046	wikipedia	https://en.wikipedia.org/wiki/Selenium_deficiency	2021-01-18T18:46:26	{"umls": ["C0238421"], "icd-9": ["269.3"], "icd-10": ["E59"], "wikidata": ["Q1322302"]}
Mucinous adenocarcinoma of the appendix is a very rare, slow growing, well-differentiated epithelial neoplasm of the appendix characterized by abundant mucin production. Clinically, it presents as acute appendicitis (with abdominal pain, fever, leukocytosis) or as pseudomyxoma peritonei (wide-spread presence of mucin within the peritoneal cavity), however some patients may be completely asymptomatic at the time of diagnosis. In many cases, a second gastrointestinal malignancy is present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Mucinous adenocarcinoma of the appendix	c1706832	7,047	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391723	2021-01-23T17:23:16	{"umls": ["C1706832"], "icd-10": ["C18.1"], "synonyms": ["Appendiceal mucinous adenocarcinoma"]}
See also: Perianal gland tumor Cytology of an anal sac adenocarcinoma An anal sac adenocarcinoma is an uncommon and aggressive malignant tumor found in dogs that arises from the apocrine glandular tissue of anal sac. The disease exists in cats as well, but is much less common in that species.[1] They are the second most common cancerous cause of hypercalcaemia (high serum calcium) in dogs, following T-cell lymphoma.[2] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment and prognosis * 4 Commonly affected breeds * 5 References * 6 External links ## Signs and symptoms[edit] Apocrine gland anal sac adenocarcinomas first appear as small lumps associated with one of the anal sacs (rarely bilateral), but they can grow to a large size. Smaller tumors are undetectable without a rectal examination, while larger tumors can cause pain and straining to defecate. Between 25 and 40 percent of dogs with these tumors will also develop hypercalcaemia[3] through secretion of parathyroid hormone-related protein by the tumor.[4] Symptoms of hypercalcaemia include increased drinking and urination, vomiting, loss of appetite, weight loss, and bradycardia (slow heart rate). Apocrine gland anal sac adenocarcinomas also have a tendency to metastasize to the regional lymph nodes, spleen, and eventually lungs and, less commonly, bones.[5] The sublumbar (iliac) lymph nodes are the most common site of metastasis and can become larger than the original tumor.[6] ## Diagnosis[edit] Anal sac adenocarcinomas are often suspected due to location (palpable masse in anal sac) and behavior, but a biopsy and histopathology is necessary for a definitive diagnosis. Fine needle aspiration and cytology is a common first step. Cytopathology reveals clusters of cells with uniform round nuclei. These cells do not have many of the features usually associated with malignancy, such as a high nucleus to cytoplasm ratio or prominent nucleoli.[7] Ultrasonography and radiography are performed to look for metastasis. ## Treatment and prognosis[edit] Aggressive surgical removal of the tumor and any enlarged sublumbar lymph nodes is essential for treatment of the tumor and associated hypercalcaemia. There is a high recurrence rate, although removal of lymph nodes with metastasis may improve survival time.[8] Radiation therapy and chemotherapy may be helpful in treatment. Severe hypercalcaemia is treated with aggressive IV fluid therapy using sodium chloride and medications such as loop diuretics (increased kidney excretion of calcium) and aminobisphosphonates (decreased calcium release from bones).[2] A poorer prognosis is associated with large tumor size (greater than 10 cm), hypercalcaemia, and distante metastasis.[9] Early, incidental diagnosis of small anal sac masses may lead to a better prognosis with surgery alone (ongoing study). ## Commonly affected breeds[edit] Breeds that may be more commonly affected include the English Cocker Spaniel, German Shepherd Dog, Alaskan Malamute, Dachshund, and Springer Spaniel.[10] It is a disease of middle-age to older dogs and even though early reports described spayed females as more commonly affected, multiple recents studies have shown no gender overrepresentation. ## References[edit] 1. ^ Mellanby R, Foale R, Friend E, Woodger N, Herrtage M, Dobson J (2002). "Anal sac adenocarcinoma in a Siamese cat". J Feline Med Surg. 4 (4): 205–7. doi:10.1053/jfms.2002.0174. PMID 12468314. 2. ^ a b Lucas, Pamela; Lacoste, Hugues; de Lorimier, Louis-Phillipe; Fan, Timothy M. (May 2007). "Treating paraneoplastic hypercalcemia in dogs and cats". Veterinary Medicine. Advanstar Communications. 102 (5): 314–331. 3. ^ Kadar E, Rush J, Wetmore L, Chan D (2004). "Electrolyte disturbances and cardiac arrhythmias in a dog following pamidronate, calcitonin, and furosemide administration for hypercalcemia of malignancy". J Am Anim Hosp Assoc. 40 (1): 75–81. PMID 14736909. 4. ^ Gröne A, Werkmeister J, Steinmeyer C, Capen C, Rosol T (1994). "Parathyroid hormone-related protein in normal and neoplastic canine tissues: immunohistochemical localization and biochemical extraction". Vet Pathol. 31 (3): 308–15. doi:10.1177/030098589403100303. PMID 8053125. 5. ^ Morrison, Wallace B. (1998). Cancer in Dogs and Cats (1st ed.). Williams and Wilkins. ISBN 0-683-06105-4. 6. ^ Kessler, Martin (2006). "Anal sac carcinoma in the dog" (PDF). Proceedings of the North American Veterinary Conference. Archived from the original (PDF) on 2007-09-27. Retrieved 2007-03-29. 7. ^ Cronin, Kim L. (December 2007). "Apocrine gland adenocarcinoma of the anal sac". DVM. Advanstar Communications: 2S–6S. 8. ^ Hobson H, Brown M, Rogers K (2006). "Surgery of metastatic anal sac adenocarcinoma in five dogs". Vet Surg. 35 (3): 267–70. doi:10.1111/j.1532-950X.2006.00137.x. PMID 16635006. 9. ^ Kirpensteijn, Jolle (2006). "Treatment of perianal and anal sac tumors" (PDF). Proceedings of the North American Veterinary Conference. Archived from the original (PDF) on 2007-09-29. Retrieved 2007-03-29. 10. ^ "Apocrine Gland Tumors of Anal Sac Origin". The Merck Veterinary Manual. 2006. Retrieved 2007-01-01. ## External links[edit] * Anal Sac Tumors in Cats and Dogs from Pet Cancer Center * Anal sac gland carcinoma: veterinary factsheet from Davies Veterinary Specialists * Bladder and Prostate Cancer: Neutering Male Dogs Increases Risk from Dog Cancer Blog [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Anal sac adenocarcinoma	c3670773	7,048	wikipedia	https://en.wikipedia.org/wiki/Anal_sac_adenocarcinoma	2021-01-18T18:55:53	{"wikidata": ["Q4751004"]}
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: "Total anterior circulation infarct" – news · newspapers · books · scholar · JSTOR (May 2008) (Learn how and when to remove this template message) Total anterior circulation infarct Play media The brain areas supplied by left anterior cerebral artery (represented in green color). An infarct to left anterior cerebral artery can damage these brain areas in part or full. SpecialtyNeurology Total anterior circulation infarct (TACI) is a type of cerebral infarction affecting the entire anterior circulation supplying one side of the brain. Total anterior circulation stroke syndrome (TACS) refers to the symptoms of a patient who clinically appears to have suffered from a total anterior circulation infarct, but who has not yet had any diagnostic imaging (e.g. CT Scan) to confirm the diagnosis. It is diagnosed when it causes all 3 of the following symptoms: * Higher dysfunction * Dysphasia * Visuospatial disturbances * Decreased level of consciousness * Homonymous hemianopia * Motor and Sensory Defects (≥2/3 of face, arm, leg) For more information, see stroke. ## External links[edit] Classification D * ICD-9-CM: 433.1 * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Total anterior circulation infarct	None	7,049	wikipedia	https://en.wikipedia.org/wiki/Total_anterior_circulation_infarct	2021-01-18T19:07:20	{"icd-9": ["433.1"], "wikidata": ["Q524620"]}
A number sign (#) is used with this entry because of evidence that the Paris-Trousseau type of thrombocytopenia (TCPT) is a contiguous gene deletion syndrome. Clinical Features Favier et al. (1993) reported the cases of a 30-year-old woman and her 1-year-old son with chronic thrombocytopenia associated with mild hemorrhagic complications. The platelets contained giant, red-staining granules, and in the bone marrow megakaryocytes were increased with many micromegakaryocytes. Since platelet life span was normal, Favier et al. (1993) interpreted the results as indicative of ineffective platelet production. Both patients had a deletion of band 11q23. The mother showed unusual facial features, including hypertelorism, long philtrum, and low-set ears. Mental retardation was characterized by an inability to count, although she could read and write. At the age of 10 years, she was operated on for aortic isthmic stenosis (coarctation) without hemorrhagic complications. The son showed intrauterine growth retardation and had the same dysmorphologic facial features as the mother but also had hepatomegaly and fifth finger syndactyly. Neither thrombocytopenia nor chromosomal aberrations were found in other members of the family. Psychomotor development at one year was retarded. Favier et al. (1993) noted that Wardinsky et al. (1990) had examined reports of 35 patients with deletion of 11q23. Thrombocytopenia was associated in 47% of the cases. In the mother and son reported by Favier et al. (1993), Breton-Gorius et al. (1995) identified a terminal deletion of 11q. Using electron microscopy to examine the platelets of an infant with an 11q23.3-qter deletion and clinical features of Jacobsen syndrome (147791), Krishnamurti et al. (2001) identified giant alpha-granules identical to those described in Paris-Trousseau syndrome. They suggested that TCPT may be a variant of Jacobsen syndrome and that the thrombocytopenia in all cases of 11q23.3 deletion is due to dysmegakaryopoiesis, with formation of giant alpha-granules during prolonged residence in the bone marrow. Favier et al. (2003) reported 10 unrelated children with deletions of 11q23 who had abnormal platelets with giant alpha-granules on peripheral blood smear and dysmegakaryopoiesis with many micromegakaryocytes on bone marrow examination. Clinical characteristics in addition to thrombocytopenia included mental retardation, facial dysmorphism, clinodactyly, and pyloric stenosis. Nine of the 10 children were found to be heterozygous for a deletion of the FLI1 gene (193067). Favier et al. (2003) noted clinical, hematologic, and cytogenetic similarities between this cohort of patients and patients with Jacobsen syndrome and stated that their findings demonstrated clear overlap between the 2 syndromes. Raslova et al. (2004) showed that lentivirus-mediated overexpression of FLI1 in CD34-positive (142230) cells of patients with TCPT restored megakaryopoiesis in vitro, indicating that FLI1 hemizygous deletion contributes to the hematopoietic defects in the disorder. FISH analysis on pre-mRNA and single-cell RT-PCR revealed FLI1 expression to be mainly monoallelic in CD41-positive (see 607759)/CD42-negative progenitors, whereas it was predominantly biallelic in the other stages of megakaryopoiesis. In TCPT cells, the hemizygous deletion of FLI1 generated a subpopulation of CD41-positive/CD42-negative cells completely lacking FLI1 transcription. Raslova et al. (2004) proposed that the absence of FLI1 expression in those CD41-positive/CD42-negative cells might prevent their differentiation, resulting in the segregation of the TCPT megakaryocytes into 2 subpopulations: one normal and the other composed of small immature megakaryocytes undergoing massive lysis, presumably originating from FLI1-positive and FLI1-negative CD41-positive/CD42-negative cells, respectively. INHERITANCE \- Isolated cases HEAD & NECK Head \- Trigonocephaly Face \- Micrognathia Eyes \- Ptosis ABDOMEN Gastrointestinal \- Pyloric stenosis SKELETAL Hands \- Clinodactyly NEUROLOGIC Central Nervous System \- Mental retardation HEMATOLOGY \- Thrombocytopenia \- Hemorrhagic diathesis, mild \- Increased bleeding time \- Giant platelet alpha granules (peripheral blood) \- Increased megakaryocytes (bone marrow) \- Increased micromegakaryocytes (bone marrow) LABORATORY ABNORMALITIES \- Chromosome 11q23.3 deletion MISCELLANEOUS \- Paris-Trousseau thrombocytopenia can occur in Jacobsen syndrome ( 147791 ) in which similar platelet defects are accompanied by facial dysmorphism, cardiac defects, mental retardation, and deletion at 11q23 MOLECULAR BASIS \- A contiguous gene syndrome caused by deletion of the friend leukemia virus integration 1 gene (FLI1, 193067 ) and perhaps other genes in 11q23 ▲ 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	THROMBOCYTOPENIA, PARIS-TROUSSEAU TYPE	c1956093	7,050	omim	https://www.omim.org/entry/188025	2019-09-22T16:32:46	{"mesh": ["D054868"], "omim": ["188025"], "orphanet": ["851"], "synonyms": ["Alternative titles", "CHROMOSOME 11q23 DELETION SYNDROME"]}
A number sign (#) is used with this entry because of evidence that prune belly syndrome (PBS) is caused by homozygous mutation in the CHRM3 gene (118494) on chromosome 1q43. One such family has been reported. Description In its rare complete form, 'prune belly' syndrome comprises megacystis (massively enlarged bladder) with disorganized detrusor muscle, cryptorchidism, and thin abdominal musculature with overlying lax skin (summary by Weber et al., 2011). Clinical Features This condition was first described by Frolich (1839). The appellation 'prune belly syndrome' is descriptive because the intestinal pattern is evident through the thin, lax, protruding abdominal wall in the infant (Osler, 1901). (Osler did not use the term 'prune belly.' His article on this subject and one 'on a family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes'--see 187300--appeared successively in the November 1901 issue of the Johns Hopkins Hospital Bulletin. Osler wrote: 'In the summer of 1897 a case of remarkable distension of the abdomen was admitted to the wards, with greatly distended bladder, and on my return in September, Dr. Futcher, knowing that I would be interested in it, sent for the child.') The full syndrome probably occurs only in males (Williams and Burkholder, 1967). A possibly related syndrome was described in a single patient by Texter and Murphy (1968). The triad consisted of absence of the right testis, kidney, and rectus abdominis muscle. King and Prescott (1978) presented evidence to support the suggestion that the maldevelopment of the abdominal musculature and abdominal laxity are secondary phenomena, the primary event being marked distention of the abdomen in the fetal period because of obstruction of the urinary tract. Likewise, Pagon et al. (1979) suggested that the abdominal muscle deficiency is secondary to fetal abdominal distention of various causes, most often perhaps, urethral obstruction with enlarged bladder. 'Prune belly' occurs, in the main, as a consequence of posterior urethral valves; thus the predominance as a male-limited multifactorial trait. Gaboardi et al. (1982) reported 2 brothers and a sister with prune belly syndrome with bilateral hydronephrosis, megaureter, and megabladder, but no urethral stenosis. A better prognosis than is usually thought to obtain was suggested by the series of 19 patients reported by Burke et al. (1969). Greskovich and Nyberg (1988) gave a review in which they stated incorrectly that the term prune belly syndrome was coined by Osler. Eagle and Barrett (1950) described 9 cases of congenital deficiency of abdominal musculature with associated genitourinary abnormalities. They pointed out that genitourinary symptoms are often not present and that the obstructive manifestations in the genitourinary tract must be searched for and corrected at the earliest possible moment. Eagle and Barrett (1950) stated that 42 cases had been reported before their report of 9 cases. Every case except 1 was in a male. Smolkin et al. (2008) reported a male infant born with protrusion of both sides of the abdomen, consistent with prune belly; mild scoliosis, unilateral auricular sinus, bilateral cryptorchidism with normal-sized penis, and right-sided congenital hip dislocation were also noted. Chest x-ray showed multiple segmentation defects, including 11 pairs of ribs, bilateral cervical ribs, and T8 to T12 and S3 hemivertebrae with resultant scoliosis. Abdominal ultrasound demonstrated absence of upper abdominal muscles, liver in the right flank protrusion and both spleen and bowel in the left flank protrusion; the right kidney was normal, but the left kidney was absent, and there were normal-appearing intraabdominal testes. Smolkin et al. (2008) noted that their patient with prune belly syndrome had 2 previously unreported malformations, auricular sinus and hemivertebrae, and suggested that on the basis of the heterogeneous phenotype and the as yet unknown etiology, the designation be changed to 'prune belly association.' Weber et al. (2005) reported a consanguineous Turkish family in which 3 brothers had posterior urethral valves (PUVs) and 2 other brothers had PUV in association with prune belly syndrome; 1 of the latter boys died of urosepsis. The affected sibs had dysfunctional or areflexic bladders with vesicoureteral reflux and variably decreased glomerular filtration rates. The most severely affected brother had hydronephrosis, severe dysplasia of the right kidney, cryptorchidism, and prune belly abnormalities of the abdominal wall. There was also a sister who had normal renal function and no urinary tract abnormalities except for minimal left lower pole calyx hypoplasia. Abdominal ultrasound in both parents revealed no abnormalities of the kidneys or urinary tract. No associated extrarenal abnormalities were observed in any of the family members. Weber et al. (2011) restudied the Turkish family originally described by Weber et al. (2005), into which a sixth affected brother with a malformed bladder had been born. Examination of affected individuals also revealed bilaterally impaired pupillary constriction to light and dry mouths. Nomenclature Dorst and Seidel (1982) suggested Eagle-Barrett syndrome as a 'kinder and more appropriate designation' than prune belly syndrome. Inheritance Autosomal recessive inheritance is suggested by some reports. For example, in Lebanon, where the rate of consanguinity is high, Afifi et al. (1972) described an affected offspring of first-cousin parents. Garlinger and Ott (1974) described 2 affected brothers in 1 family and 2 affected male cousins in a second, and found 3 other reports of affected sibs, 2 of affected cousins and 1 of concordant male twins. In the first family the parents were nonconsanguineous. In the second family the affected boys' mothers were half sisters; they had different maternal grandmothers. Ramasamy et al. (2005) reported 2 brothers with deficient abdominal wall musculature and bilateral undescended testes, neither of whom had dilation of the urinary tract. There was no earlier family history of prune belly syndrome. Ramasamy et al. (2005) reviewed reported cases of 'complete' familial prune belly syndrome, in which the full clinical triad was present, noting that 28% of patients were female in the familial form of the syndrome compared to only 5% of nonfamilial cases. They stated that their findings strongly supported an autosomal recessive, sex-influenced mode of inheritance. Population Genetics In British Columbia, Baird and MacDonald (1981) found that the incidence of prune belly syndrome between 1964 and 1978 was 1 in 29,231 live births. Mapping Weber et al. (2005) performed genomewide linkage analysis in a consanguineous Turkish family in which 5 brothers had posterior urethral valve/prune belly syndrome and identified a 35-cM region of homozygosity on chromosome 1q41-q44, with a maximum multipoint lod score of Z(max) = 3.134 (theta = 0) for the SNPs rs158724-rs720163. A second alternative locus was identified on chromosome 11p11 with a lod score of Z(max) = 3.61 (theta = 0). Equal significance for either locus was obtained when the affection status of the sibs' sister was set to 'unknown' (lod score of Z(max) = 3.01; theta = 0). Molecular Genetics In a consanguineous Turkish family with posterior urethral valve/prune belly syndrome, previously studied by Weber et al. (2005), Weber et al. (2011) performed exon capture and massively parallel sequencing and identified a homozygous frameshift mutation in the CHRM3 gene on chromosome 1q43 (118494.0001) that segregated with disease and was not found in 374 Turkish control chromosomes. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Impaired pupillary constriction to light Mouth \- Dry mouth CARDIOVASCULAR Heart \- Congenital heart defect Vascular \- Patent ductus arteriosus CHEST Ribs Sternum Clavicles & Scapulae \- Flared ribs \- Pectus excavatum \- Pectus carinatum ABDOMEN External Features \- Absent abdominal musculature \- Visible intestinal pattern (so-called 'prune belly') \- Thin, lax, protruding abdominal wall Gastrointestinal \- Imperforate anus GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Hydronephrosis Ureters \- Posterior urethral valves \- Hydroureter Bladder \- Distended bladder \- Fetal urinary tract obstruction SKELETAL Pelvis \- Congenital hip dislocation Feet \- Clubfoot SKIN, NAILS, & HAIR Skin \- Wrinkled abdominal skin PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios MOLECULAR BASIS \- Caused by mutation in the muscarinic cholinergic receptor-3 gene (CHRM3, 118494.0001 ) ▲ 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	PRUNE BELLY SYNDROME	c0033770	7,051	omim	https://www.omim.org/entry/100100	2019-09-22T16:45:33	{"doid": ["0060889"], "mesh": ["D011535"], "omim": ["100100"], "icd-9": ["756.71"], "icd-10": ["Q79.4"], "orphanet": ["2970"], "synonyms": ["Alternative titles", "ABDOMINAL MUSCLES, ABSENCE OF, WITH URINARY TRACT ABNORMALITY AND CRYPTORCHIDISM", "EAGLE-BARRETT SYNDROME"]}
A rare, genetic, non-syndromic intestinal transport defect characterized by congenital onset of severe watery diarrhea containing high concentrations of sodium, hyponatremia and metabolic acidosis. ## Epidemiology Less than 50 cases have been described to date. ## Clinical description Presentation is typically prenatal with polyhydramnios, prominent abdominal distension due to dilated fluid-filled loops of the intestine. A watery diarrhea is present after birth, independent of oral feeding (breast or formula) or nil by mouth. The diarrhea can be described as 'non-stopping', and can be mistaken for urine. There are increased bowel sounds at examination, and passing of meconium is never reported. The infants become irritable and eventually apathetic, and develop moderate to severe dehydration. Rarely, there is no watery diarrhea noticed either due to severe dehydration or intestinal paralysis. This pseudo-obstruction is caused by dilated fluid-filled loops of intestine, which may result in volvulus, and the affected neonate typically undergoes abdominal surgery. Laboratory findings include high stool sodium levels (importantly, this can be normal when the depletion of body sodium has progressed for some time) and low serum sodium levels, metabolic acidosis and alkaline fecal pH, and low urinary sodium excretion. Histological findings include a structurally intact epithelium and brush border with a normal villus-to-crypt ratio. ## Etiology The classical (non-syndromic) form of the disorder is due to loss of function of the intestinal sodium/hydrogen exchanger 3 (NHE3; encoded by SLC9A3, 5p15.33), resulting in abrogated sodium absorption, enhanced fluid secretion and diarrhea. Causal mutations have been identified in both SCL9A3 and GUCY2C, encoding an intestinal receptor guanylate cyclase C (GC-C) and for which activating mutations inhibit NHE3. In 40% of patients a genetic mutation has not yet been identified. ## Diagnostic methods Diagnosis is suspected on clinical presentation and exclusion of the differential diagnosis. Initial diagnosis might include determination of fecal sodium, chloride and potassium. Separate sampling of watery stool and urine should be performed. Diagnosis is confirmed by genetic testing. ## Differential diagnosis Differential diagnosis includes the syndromic form of congenital sodium diarrhea (due to SPINT2 mutations) which is typically distinguished by the presence of uni- or bilateral choanal atresia at birth. Other differential diagnoses include anatomical bowel obstruction, congenital chloride diarrhea (distinguished by excessive fecal chloride), glucose-galactose malabsorption (which exhibits a diet-induced dehydrating diarrhea with later onset), microvillus inclusion disease and congenital tufting enteropathy (distinguished by histopathology). ## Antenatal diagnosis Diagnosis may be suspected on presentation of polyhydramnios in the third trimester. Early, targeted genetic prenatal testing is possible after identifying disease-causing variants in an index patient; however, general concerns to sampling fetal material and diagnosing genetic conditions late in pregnancy would apply. ## Genetic counseling The pattern of inheritance is autosomal recessive for SLC9A3 mutations and autosomal dominant for GUCY2C mutations. The risk of disease transmission to offspring for autosmal recessive disease is 25% where both parents are unaffected carriers. GUCY2C mutations are most often of de-novo origin; so far, germline mosaicism in unaffected parents of such patients has not been reported, resulting in a very low recurrence risk for sibs of affected patients. If a parent is affected and carrier of the pathogenic GUCY2C mutation, the risk of transmission is 50%. Of note, a number of individuals with GUCY2C and SLC9A3 mutations developed inflammatory bowel disease. ## Management and treatment After birth, total parenteral nutrition for treatment of dehydration for at least several months is required. Sodium supplementation should be provided for treatment of severe dehydration and to maintain normal body growth by preventing total body sodium depletion. In certain cases, patients may be weaned off total parenteral nutrition. For monitoring adequate sodium supplementation, the fractional excretion of sodium (FENa) should be calculated (normal range reportedly between 0.5%-1.5%). ## Prognosis Affected individuals may continue to have mild watery diarrhea but otherwise tend to lead a normal life. Reported complications include growth delay and hypoaldosteronism. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Congenital sodium diarrhea	c0267663	7,052	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=103908	2021-01-23T18:30:03	{"mesh": ["C562576"], "omim": ["270420", "616868"], "umls": ["C0267663"], "icd-10": ["P78.3"], "synonyms": ["Na-H exchange deficiency", "Non-syndromic congenital sodium diarrhea"]}
An extremely rare association syndrome, described in only two brothers to date (one of which died at 2 months of age), characterized by aplasia cutis congenita of the vertex and generalized edema (as well as hypoproteinemia and lymphopenia) due to intestinal lymphangiectasia. There have been no further descriptions in the literature since 1985. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Aplasia cutis congenita-intestinal lymphangiectasia syndrome	c1859753	7,053	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1116	2021-01-23T18:33:11	{"gard": ["753"], "mesh": ["C537788"], "omim": ["207731"], "umls": ["C1859753"], "synonyms": ["Bronspiegel-Zelnick syndrome"]}
A rare, axonal hereditary motor and sensory neuropathy characterized by adult onset of slowly progressive distal muscle weakness and atrophy, decreased deep tendon reflexes of lower limbs, and mild distal sensory loss leading to gait difficulties in most patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation	None	7,054	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=435819	2021-01-23T17:30:15	{"icd-10": ["G60.0"], "synonyms": ["CMT2 due to TFG mutation"]}
Autosomal recessive intermediate Charcot-Marie-Tooth disease type D is a rare hereditary motor and sensory neuropathy characterized by childhood onset of unsteady gait, pes cavus, frequent falls and foot dorsiflexor weakness slowly progressing to distal upper and lower limb muscle weakness and atrophy, distal sensory impairment and reduced tendon reflexes. Additional symptoms may include bilateral sensorineural hearing impairment and neuropathic pain. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Autosomal recessive intermediate Charcot-Marie-Tooth disease type D	c4015029	7,055	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=435998	2021-01-23T17:11:02	{"omim": ["616039"], "icd-10": ["G60.0"], "synonyms": ["RI-CMT type D"]}
Coronary artery aneurysm Coronary arteries SpecialtyCardiology Causesatherosclerosis, Kawasaki disease, coronary catheterization. Diagnostic methodcoronary angiography Treatmentmedical management, surgical excision, coronary bypass grafting (CABG), and percutaneous coronary interventions[1] Coronary artery aneurysm is an abnormal dilatation of part of the coronary artery. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 See also * 6 References * 7 External links ## Causes[edit] Acquired causes include atherosclerosis,[2] Kawasaki disease[3] and coronary catheterization. It can also be congenital.[4][5] ## Diagnosis[edit] It is often found coincidentally on coronary angiography.[6] ## Treatment[edit] This section is empty. You can help by adding to it. (September 2017) ## Prognosis[edit] Generally, it has a good prognosis.[6] In Kawasaki's disease, untreated, there is a 1–2% death rate, from cardiac causes. ## See also[edit] * Aneurysm * Coronary artery ectasia ## References[edit] 1. ^ Kawsara, Akram; Núñez Gil, Iván J.; Alqahtani, Fahad; Moreland, Jason; Rihal, Charanjit S.; Alkhouli, Mohamad (2018-07-09). "Management of Coronary Artery Aneurysms". JACC: Cardiovascular Interventions. 11 (13): 1211–1223. doi:10.1016/j.jcin.2018.02.041. ISSN 1936-8798. PMID 29976357. Retrieved 2020-09-19. 2. ^ Nichols L, Lagana S, Parwani A (May 2008). "Coronary artery aneurysm: a review and hypothesis regarding etiology". Arch. Pathol. Lab. Med. 132 (5): 823–8. doi:10.1043/1543-2165(2008)132[823:CAAARA]2.0.CO;2 (inactive 2021-01-10). PMID 18466032.CS1 maint: DOI inactive as of January 2021 (link) 3. ^ Fukazawa R, Ikegam E, Watanabe M, et al. (May 2007). "Coronary artery aneurysm induced by Kawasaki disease in children show features typical senescence". Circ. J. 71 (5): 709–15. doi:10.1253/circj.71.709. PMID 17456996. 4. ^ Seabra-Gomes R, Somerville J, Ross DN, Emanuel R, Parker DJ, Wong M (April 1974). "Congenital coronary artery aneurysms". Br Heart J. 36 (4): 329–35. doi:10.1136/hrt.36.4.329. PMC 1020027. PMID 4842623. 5. ^ Meinert D, Mohammed Z (March 2000). "MRI of congenital coronary artery aneurysm". Br J Radiol. 73 (867): 322–4. doi:10.1259/bjr.73.867.10817051. PMID 10817051. 6. ^ a b Pahlavan PS, Niroomand F (October 2006). "Coronary artery aneurysm: a review". Clin Cardiol. 29 (10): 439–43. doi:10.1002/clc.4960291005. PMC 6654377. PMID 17063947. ## External links[edit] Classification D * ICD-10: I25.4 * ICD-9-CM: 414.11 * MeSH: D003323 * 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 * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension This article about a medical condition affecting the circulatory 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	Coronary artery aneurysm	c0010051	7,056	wikipedia	https://en.wikipedia.org/wiki/Coronary_artery_aneurysm	2021-01-18T19:01:05	{"gard": ["6200"], "mesh": ["D003323"], "umls": ["C0010051"], "wikidata": ["Q5172183"]}
A rare hematologic disease characterized by the presence of 20-29% blasts in the bone marrow, presence of 5-29% blasts in the peripheral blood, and/or presence of Auer rods. Patients show relatively stable peripheral blood counts for weeks or months, with specific cytogenetic and molecular genetic characteristics constituting important prognostic factors. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Refractory anemia with excess blasts in transformation	c0002894	7,057	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168960	2021-01-23T18:00:01	{"mesh": ["D000754"], "umls": ["C0002894", "C0280028"], "icd-10": ["D46.3"], "synonyms": ["RAEB-t"]}
Peeling skin syndrome SpecialtyMedical genetics Peeling skin syndrome (also known as "acral peeling skin syndrome", "continual peeling skin syndrome", "familial continual skin peeling", "idiopathic deciduous skin", and "keratolysis exfoliativa congenita"[1]) is an autosomal recessive disorder characterized by lifelong peeling of the stratum corneum, and may be associated with pruritus, short stature, and easily removed anagen hair.[2]:502 "Acral" refers to the fact that the peeling of the skin is most noticeable on the hands and feet of this state. Peeling happens sometimes on the arms and legs, too. The peeling is typically apparent from birth, although it may start in childhood or later on in life as well. Skin peeling is caused by sun, humidity, moisture, and friction.[3] The acral form can be associated with TGM5.[4][5] ## Contents * 1 Syndromes * 1.1 Peeling Skin Syndrome 1 * 1.2 Peeling Skin Syndrome 2 * 1.3 Peeling Skin Syndrome 3 * 1.4 Peeling Skin Syndrome 4 * 1.5 Peeling Skin Syndrome 5 * 1.6 Peeling Skin Syndrome 6 * 2 Symptoms * 3 Treatment * 4 Frequency * 5 See also * 6 References * 7 External links ## Syndromes[edit] Peeling Skin syndrome is also associated with 6 syndromes that are each caused by a different genetic defect. The various syndromes include peeling skin syndrome 1, 2 , 3, 4, 5, and 6. ### Peeling Skin Syndrome 1[edit] Peeling Skin Syndrome 1 is caused by a genetic defect in the Corneodesmosin(CDSN) gene. This gene localizes to the human epidermis and other epithelia. The protein experiences a chain of cleavages during corneocyte maturation.[6] Its symptoms include short stature, abnormality of metabolism/homeostasis, scaling skin, pruritus, erythema, asthma, brittle hair, and abnormality of hair texture. [7][8] ### Peeling Skin Syndrome 2[edit] Peeling Skin Syndrome 2 is caused by a genetic defect in the TGM5 gene. Transglutaminase 5 is best for catalyzing the cross-linking of proteins and the conjugation of polyamines to proteins. It also adds to the development of the cornified cell envelope of keratinocytes.[9] Its symptoms include excessive wrinkling of palmar skin, skin erosion, hyperpigmentation of the skin, ichthyosis, and allergy.[10][11] ### Peeling Skin Syndrome 3[edit] Peeling Skin Syndrome 3 is caused by a genetic defect in the Carbohydrate sulfotransferase (CHST8) gene. This gene is characterized by a way of asymptomatic lifelong and non-stop dropping of the stratum corneum of the dermis. Its symptoms begin for the duration of the second half of the primary decade of existence and encompass generalized white scaling taking place over the upper and lower extremities. [12] ### Peeling Skin Syndrome 4[edit] Peeling Skin Syndrome 4 is caused by a genetic defect in the Cystatin A (CSTA) gene. This gene is an intracellular thiol proteinase inhibitor. It has an essential role in desmosome-mediated cell-cellular adhesion inside the lower levels of the dermis.[13] Its symptoms include well-circumcised peeling of skin on the extremities and neck, generalized dry skin with fine scaling and sparing of face, hyperkeratosis, and palmoplantar keratoderma[14] ### Peeling Skin Syndrome 5[edit] Peling Skin Syndrome 5 is caused by a genetic defect in the Serpin (Serpin Family Member 8) gene. This gene is produced by platelets and can bind to and inhibit the function of furin, which is a serine protease involved in platelet functions. It is also characterized by superficial peeling of the dorsal and palmar pores and skin of the hands and feet; the pores and skin of the forearms and legs may also be involved. [15] Its symptoms include superficial peeling of small areas of the skin that involve the dorsal and palmar surfaces of the hands and feet, superficial scaling of forearms and legs, and acanthosis.[16] ### Peeling Skin Syndrome 6[edit] Peeling Skin Syndrome 6 is caused by a genetic defect in the Filaggrin (Filaggrin Family Member 2) gene. The function for this gene is vital for normal cellular-cell adhesion within the cornified cell layers. It is also critical for the integrity and mechanical strength of the stratum corneum of the epidermis.[17] Its symptom include dryness of the skin, peeling of the skin. erythema at lesion sites, bullae, and hyper-pigmentation. [18] ## Symptoms[edit] Symptoms: * Abnormal blistering of the skin * Abnormality of hair texture * Dry Skin * Aminoaciduria * Hyperhidrosis * Ichythosis ## Treatment[edit] There is no remedy for peeling skin syndrome. Treatment focuses on avoiding skin damage and treating symptoms as they occur. Ointments are also used to minimize skin peeling and when the blister grows, sterile needles may be activated. The condition can be exacerbated by hot temperatures, humidity, and friction.[19] Individuals should be informed to avoid exacerbating triggers such as trauma, humidity, heat, perspiration, and water. ## Frequency[edit] Only several dozen cases have been reported in the literature, making it rare, but because its symptoms are mild and similar to other disorders it could very well be under-diagnosed.[20] ## See also[edit] * Idiopathic calcified nodules of the scrotum * Keratolysis exfoliativa * List of cutaneous conditions * Corneodesmosin * TGM5 * Carbohydrate sulfotransferase * Cystatin A * Serpin * Filaggrin ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. Chapter 56. ISBN 978-1-4160-2999-1. 2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 3. ^ Reference, Genetics Home. "Acral peeling skin syndrome". Genetics Home Reference. Retrieved 2020-04-29. 4. ^ Online Mendelian Inheritance in Man (OMIM): 609796 5. ^ Cassidy AJ, van Steensel MA, Steijlen PM, et al. (December 2005). "A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome". Am. J. Hum. Genet. 77 (6): 909–17. doi:10.1086/497707. PMC 1285176. PMID 16380904. 6. ^ "CDSN Gene - GeneCards \| CDSN Protein \| CDSN Antibody". www.genecards.org. Retrieved 2020-05-06. 7. ^ "Peeling Skin Syndrome 1 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2020-05-06. 8. ^ "OMIM Entry - * 602593 - CORNEODESMOSIN; CDSN". omim.org. Retrieved 2020-05-06. 9. ^ "TGM5 Gene - GeneCards \| TGM5 Protein \| TGM5 Antibody". www.genecards.org. Retrieved 2020-05-06. 10. ^ "Peeling Skin Syndrome 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2020-05-06. 11. ^ "OMIM Entry - # 609796 - PEELING SKIN SYNDROME 2; PSS2". omim.org. Retrieved 2020-05-06. 12. ^ "OMIM Entry - # 616265 - PEELING SKIN SYNDROME 3; PSS3". omim.org. Retrieved 2020-05-06. 13. ^ "CSTA Gene - GeneCards \| CYTA Protein \| CYTA Antibody". www.genecards.org. Retrieved 2020-05-06. 14. ^ "OMIM Clinical Synopsis - #607936 - PEELING SKIN SYNDROME 4; PSS4". omim.org. Retrieved 2020-05-06. 15. ^ "OMIM Entry - # 617115 - PEELING SKIN SYNDROME 5; PSS5". omim.org. Retrieved 2020-05-06. 16. ^ "OMIM Clinical Synopsis - #617115 - PEELING SKIN SYNDROME 5; PSS5". omim.org. Retrieved 2020-05-06. 17. ^ "FLG2 Gene - GeneCards \| FILA2 Protein \| FILA2 Antibody". www.genecards.org. Retrieved 2020-05-06. 18. ^ "OMIM Clinical Synopsis - #618084 - PEELING SKIN SYNDROME 6; PSS6". omim.org. Retrieved 2020-05-06. 19. ^ "Acral peeling skin syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-04-29. 20. ^ "Acral peeling skin syndrome". Genetics Home Reference. U.S. National Library of Medicine. Retrieved 17 April 2018. * Cabral, Rita M.; Kurban, Mazen; Wajid, Muhammad; Shimomura, Yutaka; Petukhova, Lynn; Christiano, Angela M. (2012-04). "Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome". Genomics. 99 (4): 202–208. doi:10.1016/j.ygeno.2012-01-005. ISSN 1089-8646. PMC 4362535. PMID 22289416. ## External links[edit] Classification D * ICD-10: Q80.8 * OMIM: 270300 External resources * Orphanet: 817 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Peeling skin syndrome	c2751314	7,058	wikipedia	https://en.wikipedia.org/wiki/Peeling_skin_syndrome	2021-01-18T18:50:49	{"gard": ["7347"], "umls": ["C2751314"], "orphanet": ["263543", "817"], "wikidata": ["Q17120550"]}
Liposarcoma (LS), a type of soft tissue sarcoma, describes a group of lipomatous tumors of varying severity ranging from slow-growing to aggressive and metastatic. Liposarcomas are most often located in the lower extremities or retroperitoneum, but they can also occur in the upper extremities, neck, peritoneal cavity, spermatic cord, breast, vulva and axilla. ## Epidemiology Liposarcomas account for approximately 15-20% of all soft tissue sarcomas. The incidence is approximately 1 per 100, 000 persons/years. ## Clinical description They can affect all age groups but are most frequently seen in middle-aged and older adults. Liposarcomas are classified into 4 biological groups (encompassing five histological subtypes): well-differentiated (WDLS), dedifferentiated (DDLS), myxoid /round cell (MRCLS) and pleomorphic (PLS) (see these terms). ## Etiology The etiology is unknown but many chromosomal aberrations are found in liposarcomas. ## Prognosis The prognosis is dependent on the specific subtype, size, stage and location of the disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Liposarcoma	c0023827	7,059	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=69078	2021-01-23T17:37:09	{"gard": ["6913"], "mesh": ["D008080"], "omim": ["613488"], "umls": ["C0023827"], "icd-10": ["C49.9"]}
A rare, genetic proximal spinal muscular atrophy characterized by degeneration of alpha motor neurons in the anterior horns of the spinal cord and lower brain stem manifesting with adult onset, slowly progressive, mild proximal muscle weakness. ## Epidemiology The average prevalence at birth of proximal spinal muscular atrophy (SMA) is estimated between 1/12,000 of which approximately 1% account for type 4. ## Clinical description Disease onset is typically in the second or third decade of life. The muscle weakness predominantly affects the legs and hip muscles and then progresses to the shoulders and arms. Waddling gait is common. Finger trembling, fasciculation and calf hypertrophy may occur. The clinical picture is similar to that seen in SMA type 3 but the motor weakness is less severe. Cognition is unaffected. ## Etiology The disease is a result of degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei. Causal homozygous mutations/deletions in the SMN1 gene (5q12.2-q13.3) are responsible. SMN1encodes the survival motor neuron protein (SMN) which is known to participate in critical pathways related to RNA processing and transport, and it is believed that motor neurons are particularly vulnerable to impairments in these processes. The disease is modified by the gene SMN2 (5q13.2), a homologous centromeric copy of SMN1, (5q13.1), the copy number of which is inversely correlated to disease severity. ## Diagnostic methods The diagnosis is based on clinical history and examination. In patients with SMN1 anomalies, the diagnosis may be confirmed by genetic testing. Electromyography and muscle biopsy may be necessary. ## Differential diagnosis Differential diagnoses include the amyotrophic lateral sclerosis, primary lateral sclerosis, Kennedy disease, myasthenia gravis, and carbohydrate metabolism disorders. ## Antenatal diagnosis Prenatal diagnosis is possible for families in which the mutations in the SMN1 gene have been identified. ## Genetic counseling The SMN1 gene deletions are transmitted in an autosomal recessive manner. Genetic counseling should be provided. ## Management and treatment Management is symptomatic, involves a multidisciplinary approach, and aims to improve quality of life. Physiotherapy and occupational therapies are recommended. Walking aids may be required as the disease progresses. Documenting functional status in SMA is important, since all patients show limitations in daily functioning. Nusinersen, an antisense oligonucleotide, is now approved for treatment of SMA in Europe and the USA. There is no data currently available concerning treatment in SMA type 4; however, it is believed that nusinersen may be most effective when started as soon as possible after diagnosis. Other clinical trials are ongoing to identify other potential treatments. ## Prognosis Affected individuals have a normal life expectancy. The greatest morbidity is on quality of life, with impairment of daily activities. Some patients may lose the ability to walk. * 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	Proximal spinal muscular atrophy type 4	c1838230	7,060	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83420	2021-01-23T17:04:57	{"mesh": ["C563948"], "omim": ["271150"], "umls": ["C1838230"], "icd-10": ["G12.1"], "synonyms": ["SMA type 4", "SMA type IV", "SMA-IV", "SMA4", "Spinal muscular atrophy, adult form"]}
A number sign (#) is used with this entry because of evidence that mitochondrial progressive myopathy with congenital cataract, hearing loss, and developmental delay is caused by homozygous mutation in the GFER gene (600924) on chromosome 16p13. One such family has been reported. Clinical Features Di Fonzo et al. (2009) reported a consanguineous Moroccan family including 3 children with congenital cataract, muscular hypotonia, sensorineural hearing loss, and developmental delay. The first child presented in the first month of life with congenital cataract and axial hypotonia. He did not learn to walk until 2 years of age or speak until 3 years of age. At the age of 12 he developed progressive hearing loss and bilateral ptosis. At age 17, neurologic examination revealed generalized hypotonia and hypotrophy, especially in the lower limbs. He could walk only with assistance and was unable to fix his gaze; rotatory nystagmus was noted. Proximal and distal muscle strength was normal. Upper and lower extremity deep tendon reflexes were weak or absent. Audiologic examination showed severe bilateral hearing loss. ECG and echocardiography were normal. Ferritin was low. Amylase and serum lactate were somewhat elevated. MRI showed a thin corpus callosum. His 2 brothers had similar manifestations. Muscle biopsies from the first 2 sibs showed scattered COX-negative fibers. Biochemical studies revealed a constant moderate reduction (30 to 50% of normal mean values) of complex IV activity in multiple tissues from both probands. Interestingly, the older proband displayed a multicomplex alteration including a complex I and II defect in both muscle and myoblasts, whereas an analysis of the younger proband's fibroblasts revealed only reduced complex IV activity. Ultrastructural analysis of muscle tissue showed abnormally enlarged mitochondria with electron-dense vacuolizations and thickened cristae. In addition, all manifested accelerated time-dependent accumulation of multiple mitochondrial DNA deletions. Molecular Genetics In 3 sibs from a consanguineous Moroccan family with a combined mitochondrial complex deficiency, Di Fonzo et al. (2009) detected homozygosity for a missense mutation in the GFER gene (600924.0001). The consequences of the mutation at the level of the patients' muscle tissues and fibroblasts were a reduction in complex I, II, and IV activity, a lower cysteine-rich protein content, and abnormal ultrastructural morphology of the mitochondria with enlargement of the mitochondrial intermembrane space. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	MYOPATHY, MITOCHONDRIAL PROGRESSIVE, WITH CONGENITAL CATARACT, HEARING LOSS, AND DEVELOPMENTAL DELAY	c2751320	7,061	omim	https://www.omim.org/entry/613076	2019-09-22T15:59:46	{"mesh": ["C567769"], "omim": ["613076"], "orphanet": ["330054"], "synonyms": ["Alternative titles", "MYOPATHY WITH CATARACT AND COMBINED RESPIRATORY CHAIN DEFICIENCY", "MITOCHONDRIAL COMPLEX DEFICIENCY, COMBINED"]}
A number sign (#) is used with this entry because Aland Island eye disease is caused by mutation in the CACNA1F gene (300110). X-linked incomplete congenital stationary night blindness (CSNB2A; 300071), which has a similar phenotype, is caused by mutations in the same gene. Description Aland Island eye disease (AIED) is an X-linked recessive retinal disease characterized by fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect (303900), progressive myopia, and defective dark adaptation. Although AIED has been referred to as a form of albinism, there is no misrouting of the optic nerves, which excludes it from the formal diagnosis of classic albinism (King et al., 2001). Clinical Features Forsius and Eriksson (1964) reported X-linked tapetoretinal degeneration in a family described in a family from the Aland Islands in the Sea of Bothnia. Males in 6 generations were affected with hypopigmentation of the fundus, foveal hypoplasia, marked impairment of vision, nystagmus, myopia, astigmatism, and protan colorblindness. Female carriers showed slight disturbances of color discrimination and electromyographically demonstrable nystagmus. Warburg (1964) described ocular albinism and protanopia in the same Aland Island kindred family. Only 2 of 4 males with ocular albinism showed dyschromatopsia. The absence of characteristic fundus pigmentary pattern in female carriers in the family of Forsius and Eriksson suggested that they had a distinct entity from X-linked Nettleship-Falls ocular albinism (OA1; 300500). Scialfa (1967) reported another family with this disorder. By electron microscopic study of skin biopsies obtained by Forsius in the Island of Aland, O'Donnell and Green (1978) and O'Donnell et al. (1980) concluded that the Forsius-Eriksson type is morphologically distinct from the Nettleship-Falls type of ocular albinism; no macromelanosomes were present. By electrophysiologic studies, van Dorp et al. (1985) showed that there is no misrouting of the optic pathways in Aland Eye disease, thus distinguishing it from true albinism. Other differences from albinism, not commented on earlier, included differences in the spontaneous and optokinetic nystagmus. Maumenee (1986) expressed the opinion that this disorder may be a variety of achromatopsia. Weleber et al. (1989) pointed out that newer electrophysiologic techniques, including electroretinography, show many differences between this disorder and OA1; however, the disorder showed some similarities to X-linked incomplete congenital stationary night blindness (300071). Glass et al. (1991, 1993) reported studies of a 6-generation family with 9 affected males and 14 obligatory carriers. Clinical features included severely reduced visual acuity, nystagmus, high axial myopia, foveal hypoplasia, and protanomalous color vision deficiency associated with minor fundal depigmentation. Although impaired night vision was not a symptom, psychophysical and electrophysiologic testing showed that both rod and cone function were abnormal in all affected males. No abnormality was detected in carrier females. The findings were similar to those previously reported in both CSNB2A and AIED. Jalkanen et al. (2007) stated that although AIED and CSNB2A are allelic disorders, there are a few distinct differences between the symptoms of the patients in the original AIED family and those described as having CSNB2A. AIED has progressive myopic refraction, foveal dysplasia with no foveal reflex, and a protan defect in color vision (303900), whereas CSNB2A is apparently stationary with a normal fovea and mostly normal color vision, with tritan (190900) or mixed defects in some cases. They suggested that the differences my be attributable to differences in genetic background (i.e., other genes or genetic modifiers). Hawksworth et al. (1995) studied a Welch kindred in which congenital nystagmus and moderate-to-high refractive error segregated as an X-linked trait, with manifestation in some female carriers. Affected males demonstrated myopia, but a high proportion of female carriers and some of the possibly affected males showed hypermetropia. Clinical ophthalmologic examination and electrodiagnostic studies of retinal function were compatible with a diagnosis of either incomplete congenital stationary night blindness or Aland island eye disease. Hawksworth et al. (1995) raised the question of whether the 2 entities are the same. Mapping By linkage analysis, Waardenburg et al. (1969) found a recombination fraction of about 0.12 with the Xg blood group locus (Race and Sanger, 1968), suggesting that Aland Island disease and OA1 may be allelic or due to genes at adjacent loci. However, Waardenburg et al. (1969) concluded that the disorder was distinct from X-linked OA1. From multilocus linkage analysis, Alitalo et al. (1991) concluded that the most probable location of the AIED gene is in the pericentromeric region between DXS7 and DXS72. These results ruled out the more distal localization on Xp proposed by others. The findings did not exclude the possibility that AIED and incomplete congenital stationary night blindness could be allelic. From studies of a large Danish family with AIED, Schwartz and Rosenberg (1991) likewise located the gene to the proximal part of Xp: proximal to DXS7 and tightly linked to the following cluster of loci--DXS255, TIMP (305370), DXS146, and DXS14. By linkage analysis in an affected family, Glass et al. (1991, 1993) indicated location of the gene in proximal Xp. Several loci in the Xp11.4-p11.23 region showed positive 2-point lod scores. For example, PFC (300383) showed a maximum lod score of 3.56 at theta = 0.00. Cytogenetics Pillers et al. (1988, 1990) described a 6-year-old adopted boy with an interstitial Xp21 deletion and Aland Island disease plus DMD (310200), GK deficiency (307030), and congenital adrenal hypoplasia (300200). By molecular analysis, including PCR amplification and Southern blotting, Pillers et al. (1989, 1990) defined the deletion in this patient as Xp21.3-p21.2. Weleber et al. (1989) described the ophthalmologic findings in this patient and discussed the similarities to incomplete congenital stationary night blindness as defined by Miyake et al. (1986, 1987). Molecular Genetics Wutz et al. (2002) identified mutations in the CACNA1F gene (300110), which is also mutated in the incomplete form of X-linked congenital stationary night blindness (CSNB2A), in a Finnish family and a sporadic Swiss case with an AIED-like phenotype. Reevaluation indicated full compatibility of the patients' ophthalmologic phenotypes with CSNB2A. No CACNA1F mutation by complete DNA sequencing of all 48 exons could be found in a classic AIED family previously shown to map to the pericentromeric region of the X chromosome (Alitalo et al., 1991). Due to similar clinical features of AIED and CSNB2A, Wutz et al. (2002) speculated that the mutation in this family may be located in an intron or in the promoter region. In affected members of the original family with Aland Island eye disease described by Forsius and Eriksson (1964), Jalkanen et al. (2007) identified homozygosity for a 425-bp deletion mutation encompassing exon 30 and portions of adjacent introns of the CACNA1F gene (300110.0008). The mutation was found in heterozygous state in carrier females of this family and was not found in samples from 121 Finnish male control subjects. Eyes \- Fundus albinism \- Foveal hypoplasia \- Marked vision impairment \- Nystagmus \- Myopia \- Astigmatism \- Protanomalous colorblindness Misc \- Slightly decreased color discrimination, and nystagmus by EMG in carrier females Lab \- No macromelanosomes on EM Inheritance \- X-linked ▲ 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	ALAND ISLAND EYE DISEASE	c0268505	7,062	omim	https://www.omim.org/entry/300600	2019-09-22T16:20:04	{"doid": ["0050630"], "mesh": ["C562664"], "omim": ["300600"], "orphanet": ["178333"], "synonyms": ["Alternative titles", "FORSIUS-ERIKSSON TYPE OCULAR ALBINISM"]}
A rare, virus associated tumor due to human T-cell leukemia virus type 1 or human T-cell lymphotropic virus type 1 (HTLV-1) and is characterized by the presence of anti-HTLV-1 antibodies, and malignant, mature, medium-sized T cells with condensed chromatin and polylobated nuclei. The malignant cells exhibit a mature CD4+ T cells phenotype and express CD2, CD5, CD25, CD45RO, HLA-DR, and T-cell receptor αβ. Presentation is heterogeneous and is typically of aggressive leukemia or lymphoma, variable skin eruptions, and visceral organ involvement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Adult T-cell leukemia/lymphoma	c0023493	7,063	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86875	2021-01-23T18:11:41	{"mesh": ["D015459"], "umls": ["C0023493"], "icd-10": ["C91.5"], "synonyms": ["ATLL"]}
Talaromycosis SpecialtyInfectious disease Talaromycosis (formerly known as penicilliosis or penicillosis) is an infection caused by Talaromyces marneffei.[1][2][3] ## Contents * 1 Symptoms * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 References * 6 External links ## Symptoms[edit] The most common symptoms are fever, skin lesions, anemia, generalized lymphadenopathy, and hepatomegaly. ## Diagnosis[edit] Diagnosis is usually made by identification of the fungus from clinical specimens. Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology. ## Treatment[edit] Talaromyces marneffei demonstrates in vitro susceptibility to multiple antifungal agents including ketoconazole, itraconazole,[4] miconazole, flucytosine, and amphotericin B. Without treatment patients have a poor prognosis; death occur by liver failure as the fungus releases toxins in the bloodstream. The elevation of liver enzyme in the blood helps to establish a diagnosis. ## Epidemiology[edit] Once considered rare, its occurrence has increased due to AIDS. It is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.[5] ## References[edit] 1. ^ Desakorn V, Smith MD, Walsh AL, et al. (January 1999). "Diagnosis of Penicillium marneffei infection by quantitation of urinary antigen by using an enzyme immunoassay". Journal of Clinical Microbiology. 37 (1): 117–21. PMC 84182. PMID 9854074. 2. ^ Ning, Chuanyi; Lai, Jingzhen; Wei, Wudi; Zhou, Bo; Huang, Jiegang; Jiang, Junjun; Liang, Bingyu; Liao, Yanyan; Zang, Ning (2018). "Accuracy of rapid diagnosis of Talaromyces marneffei: A systematic review and meta-analysis". PLOS ONE. 13 (4): e0195569. Bibcode:2018PLoSO..1395569N. doi:10.1371/journal.pone.0195569. ISSN 1932-6203. PMC 5886574. PMID 29621346. 3. ^ Chastain, Daniel B.; Henao-Martínez, Andrés F.; Franco-Paredes, Carlos (2017-08-22). "Opportunistic Invasive Mycoses in AIDS: Cryptococcosis, Histoplasmosis, Coccidiodomycosis, and Talaromycosis". Current Infectious Disease Reports. 19 (10): 36. doi:10.1007/s11908-017-0592-7. ISSN 1523-3847. PMID 28831671. 4. ^ Wu TC, Chan JW, Ng CK, Tsang DN, Lee MP, Li PC (April 2008). "Clinical presentations and outcomes of Penicillium marneffei infections: a series from 1994 to 2004". Hong Kong Med J. 14 (2): 103–9. PMID 18382016. 5. ^ Chastain, Daniel B.; Henao-Martínez, Andrés F.; Franco-Paredes, Carlos (2017-08-22). "Opportunistic Invasive Mycoses in AIDS: Cryptococcosis, Histoplasmosis, Coccidiodomycosis, and Talaromycosis". Current Infectious Disease Reports. 19 (10): 36. doi:10.1007/s11908-017-0592-7. ISSN 1523-3847. PMID 28831671. ## External links[edit] Classification D * ICD-10: B48.4 * ICD-9-CM: 117.3 * DiseasesDB: 9802 * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Talaromycosis	None	7,064	wikipedia	https://en.wikipedia.org/wiki/Talaromycosis	2021-01-18T18:36:25	{"icd-9": ["117.3"], "icd-10": ["B48.4"], "wikidata": ["Q3080319"]}
A rare subtype of pyoderma gangrenosum disease characterized by a solitary, erythematous, ulcerated plaque, which lacks the violaceous border typically present in classic pyoderma gangrenosum, usually affecting individuals who are otherwise healthy. Histologically, the lesion presents a central layer containing neutrophilic inflamation, surrounded by a palisade of histiocytes, which are rimmed by a lymphocytic infiltrate. In comparison with the other variants of pyoderma gangrenosum, this subtype usually shows a good response to less aggressive treatments and underlying systemic disorders are less frequently associated. It is considered the most benign and uncommon clinical variant of pyoderma gangrenosum. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Vegetative pyoderma gangrenosum	None	7,065	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=538872	2021-01-23T18:00:42	{"icd-10": ["L88"], "synonyms": ["Granulomatous pyoderma gangrenosum"]}
A number sign (#) is used with this entry because Stormorken syndrome (STRMK) is caused by heterozygous mutation in the STIM1 gene (605921) on chromosome 11p15. Heterozygous mutation in the STIM1 gene can also cause isolated tubular aggregate myopathy-1 (TAM1; 160565). Description Stormorken syndrome is an autosomal dominant disorder characterized by mild bleeding tendency due to platelet dysfunction, thrombocytopenia, anemia, asplenia, tubular aggregate myopathy, congenital miosis, and ichthyosis. Additional features may include headache or recurrent stroke-like episodes (summary by Misceo et al., 2014). Clinical Features Stormorken et al. (1985) described a curious syndrome of thrombocytopathy with bleeding diathesis, asplenia evidenced by Howell-Jolly bodies in the red cells of the blood smear and absence of spleen by computerized tomography, striking miosis, muscle fatigue, migraine, dyslexia, and ichthyosis. The syndrome was observed in 3 generations--a grandmother, mother, and son--but was reliably reported in 3 members of the next earlier generation. There was no male-to-male transmission. Misceo et al. (2014) reported follow-up of the family reported by Stormorken et al. (1985) and demonstrated that the grandmother was not affected. The affected son had dysmorphic features, including deep-set eyes, hypotelorism, and a prominent nose. Misceo et al. (2014) reported a Japanese mother and daughter and 2 unrelated Caucasian men with Stormorken syndrome. The Japanese women, previously described by Mizobuchi et al. (2000), had nasal hemorrhage in childhood or adolescence, miosis, ichthyosis, splenic hypoplasia, and mild limb muscle weakness. Laboratory studies showed increased serum creatine kinase consistent with myopathy, anemia, and thrombocytopenia. Muscle biopsy of the daughter showed myogenic changes and tubular aggregates. A Caucasian male presented with a subarachnoid hemorrhage at age 20, and later developed additional intracranial aneurysms. He also had recurrent extreme headaches associated with neurologic signs. Additional findings included anemia, thrombocytopenia, asplenia, increased serum creatine kinase, and miosis. An unrelated Caucasian man presented with adult-onset diffuse myalgia. He had had a therapeutic splenectomy due to purpura and also showed miosis. Both men had deep-set eyes, hypotelorism, and a large nose. None of the patients had immunologic abnormalities. White (2003, 2003) and White and Ahlstrand (2003, 2003) reported detailed platelet studies of a mother and son with prolonged thrombocytopenia. These initial reports stated that they had no clinical bleeding problems, no hemorrhagic episodes, and no need for transfusional support. Laboratory studies showed low platelet numbers and moderately increased platelet volume. Electron microscopic studies showed that the platelets contained 2 types of giant organelles present in platelets and in megakaryocytes in the bone marrow. These organelles, which were electron-opaque, appeared to arise from fragments of the endoplasmic reticulum. The authors determined that the organelles were not aberrant dense bodies and that they contained high levels of calcium and phosphorus as well as peroxidase and acid phosphatase activity, suggestive of a lysosomal disorder. Markello et al. (2015) reported follow-up of this family (family A), which now included an affected son of the previously studied son. This report stated that the original mother and son both had bruising in early childhood; the mother had epistaxis, heavy menstrual periods, and postpartum hemorrhage requiring transfusions. Both patients also had a myopathy affecting the proximal and distal muscles, upgaze palsy, impaired pupillary reactions, and increased serum creatine kinase. Muscle biopsies showed myopathic changes, including marked variation in fiber size, endomysial fibrosis, fatty infiltration, and internalized nuclei; there was no evidence of a mitochondrial disorder. White and Gunay-Aygun (2011) reported a 4-year-old girl with thrombocytopenia since birth and a proximal myopathic disorder. Electron microscopy of patient platelets showed 2 types of organelles: giant electron-opaque organelles and huge target organelles, similar to those observed in the patients reported by White (2003, 2003) and White and Ahlstrand (2003, 2003). The abnormal organelles appeared to develop in the rough and smooth endoplasmic reticulum of parent megakaryocytes and to mature in the dense tubular system of circulating platelets. The disorder was designated York platelet syndrome (YPS). White et al. (2013) reported a 4-year-old boy with YPS and a mitochondrial myopathy. Platelets in this child showed the characteristic electron-opaque organelles, but not the target type; the platelets were also nearly devoid of alpha granules. Morin et al. (2014) reported a French father and son and a German mother and daughter with Stormorken syndrome. In the first family, a newborn presented with thrombocytopenia and skin rash. At age 6 years, he had deep-set eyes with miosis and muscle weakness. Laboratory studies showed increased creatine kinase, mild hypocalcemia, and thrombocytopenia. The patient had moderate learning difficulties. The father had short stature, severe miosis, hypotelorism, asplenia, increased serum creatine kinase, and thrombocytopenia. Muscle biopsy of both patients showed findings consistent with tubular aggregates that stained with antibodies against STIM1, STIM2 (610841), ORAI1 (610277) and ORAI2 (610929). In the German family, the 19-year-old mother had miosis, thrombocytopenia, asplenia, mild muscle weakness, low serum calcium, and urticarial skin eruptions. She also had impaired cognition. The 2.5-year-old daughter had miosis and thrombocytopenia, but no evidence of muscle weakness. Markello et al. (2015) reported 4 additional patients from 3 unrelated families with YPS. Three had onset of easy bruising associated with thrombocytopenia in infancy; 1 had abnormal platelet morphology on electron microscopy. All patients had walking difficulties due to myopathy as well as increased levels of serum creatine kinase. Platelet aggregation studies, performed on 2 unrelated patients, showed impaired responses to ADP, collagen, arachidonic acid, and epinephrine, but normal responses to thrombin. Inheritance The transmission pattern of Stormorken syndrome in the families reported by Misceo et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In 6 patients from 4 unrelated families with Stormorken syndrome, including the families reported by Stormorken et al. (1985) and Mizobuchi et al. (2000), Misceo et al. (2014) identified a heterozygous missense mutation in the STIM1 gene (R304W; 605921.0008). The mutation was found in the first 2 families by exome sequencing. Patient platelets showed increased calcium content and lack of induction of store-operated calcium entry (SOCE), suggesting that the mutation results in constitutive activation of the ORAI1 (610277) calcium channel with resultant inhibition of further activation. Simultaneously and independently, Nesin et al. (2014) identified a heterozygous R304W mutation in the STIM1 gene in 2 unrelated patients with Stormorken syndrome. Patient cells showed constitutive activation of the CRAC calcium channel as well as suppression of fast calcium-dependent inactivation, consistent with a gain of function. Nesin et al. (2014) postulated that disordered and sustained calcium entry over long periods of time results in an environment in the sarcoplasmic reticulum that is hostile to protein folding, thus initiating the formation of tubular aggregates. In 4 patients from 2 unrelated families with Stormorken syndrome, Morin et al. (2014) identified a heterozygous R304W mutation in the STIM1 gene. Patient fibroblasts and HEK293 cells transfected with the mutation showed an increase in resting cytosolic calcium levels and a modest increase in store-operated calcium entry compared to controls, consistent with a gain-of-function effect. Molecular modeling predicted that the mutation caused a structural defect that may affect the conformation and disrupt the inhibitory state. In 7 patients from 4 unrelated families with Stormorken syndrome, referred to as York platelet syndrome, Markello et al. (2015) identified 2 different heterozygous missense mutations in the STIM1 gene (I115F, 605921.0009 and R304W). Each of these mutations had previously been reported, I115F in a patient with tubular aggregate myopathy-1 (TAM1; 160565) and R304W in patients with Stormorken syndrome. Markello et al. (2015) did not perform functional studies of the variants, but they noted that the R304W mutation had been shown to cause a gain of function. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Eyes \- Miosis \- Deep-set eyes \- Hypotelorism Nose \- Prominent nose \- Epistaxis CARDIOVASCULAR Vascular \- Intracranial bleeding (in some patients) ABDOMEN Spleen \- Asplenia \- Splenic aplasia \- Functional asplenia SKIN, NAILS, & HAIR Skin \- Ichthyosis MUSCLE, SOFT TISSUES \- Proximal muscle weakness \- Muscle pain \- Myopathy \- Tubular aggregates seen on biopsy NEUROLOGIC Central Nervous System \- Learning difficulties (in some patients) \- Headache \- Stroke-like episodes (in some patients) HEMATOLOGY \- Increased bleeding tendency due to platelet dysfunction \- Thrombocytopenia \- Anemia \- Howell-Jolly bodies LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Decreased serum calcium MISCELLANEOUS \- Onset of bleeding symptoms in childhood or young adulthood \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the stromal interaction molecule 1 gene (STIM1, 605921.0008 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake 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	STORMORKEN SYNDROME	c1861451	7,066	omim	https://www.omim.org/entry/185070	2019-09-22T16:34:07	{"doid": ["0060354"], "mesh": ["C566108"], "omim": ["185070"], "orphanet": ["3204"], "synonyms": ["Alternative titles", "THROMBOCYTOPATHY, ASPLENIA, AND MIOSIS", "YORK PLATELET SYNDROME"]}
Postoperative nausea and vomiting SpecialtyAnesthesia Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the postanesthesia care unit (PACU) or within 24 hours following a surgical procedure. It is an unpleasant complication that affects about 10% of the population undergoing general anaesthesia each year. ## Contents * 1 Cause * 1.1 Risk factors * 2 Management * 2.1 Preoperative fasting * 2.2 Medications[4] * 2.3 Alternative medicine * 3 Epidemiology * 4 References * 5 Further reading * 6 External links ## Cause[edit] Emetogenic drugs commonly used in anaesthesia include nitrous oxide, physostigmine, and opioids. The intravenous anaesthetic propofol is currently the least emetogenic general anaesthetic. These medications are thought to stimulate the chemoreceptor trigger zone. This area is on the floor of the fourth ventricle and is effectively outside of the blood-brain barrier, which makes it incredibly sensitive to toxin and pharmacological stimulation. Several neurotransmitters are known, such as histamine, dopamine, serotonin, acetylcholine, and the more recently discovered neurokinin-1 (substance P). ### Risk factors[edit] A 2008 study compared 121 Japanese patients who experienced PONV after being given the general anesthetic propofol to 790 people who were free of postoperative nausea after receiving it. Those with a G at both copies of rs1800497 were 1.6 times more likely to experience PONV within six hours of surgery compared to those with the AG or AA genotypes, but they were not significantly more likely to experience PONV more than six hours after surgery.[1] PONV results from patient, surgical, and anesthetic factors. Surgical factors that confer increased risk for PONV include procedures of increased length and gynecological, abdominal, laparoscopic and ENT procedures, and strabismus procedures in children. Anesthetic risk factors include the use of volatile anesthetics, nitrous oxide (N2O), opioids, and longer duration of anesthesia. Patient factors that confer increased risk for PONV include female gender, obesity, age less than 16 years, past history of motion sickness or chemotherapy-induced nausea, high levels of preoperative anxiety, and patients with history of PONV. Smokers and the elderly often have a decreased risk for PONV. A risk-stratification method created by Apfel et al has been developed to determine a patient's risk for PONV. The presence of 0, 1, 2, 3, or 4 of any of the following risk factors corresponds to a PONV respective risk of 10, 20, 40, 60, and 80%.[2] \- Female gender \- Non-smoking \- History of PONV or motion sickness \- Expectant use of postoperative opioid medications ## Management[edit] Because currently no single antiemetic available is especially effective on its own, experts recommend a multimodal approach. Anesthetic strategies to prevent vomiting include using regional anesthesia whenever possible and avoiding medications that cause vomiting. Medications to treat and prevent PONV are limited by both cost and the adverse effects. People with risk factors likely warrant preventive medication, whereas a "wait and see" strategy is appropriate for those without risk factors. ### Preoperative fasting[edit] Fasting guidelines often restrict the intake of any oral fluid 2-6 hours preoperatively, but in a large retrospective analysis in Torbay Hospital, unrestricted clear oral fluids until transfer to theatre could significantly reduce the incidence of postoperative nausea and vomiting without an increased risk in the adverse outcomes for which such conservative guidance exists.[3] ### Medications[4][edit] A multimodal approach to treating a patient with PONV can be efficacious. Numerous patient factors and medication adverse effects must be taken into consideration when selecting a treatment regimen. * Serotonin (5-HT3) receptor antagonists can be administered as a single dose at the end of surgery. Adverse effects include prolongation of the QT interval on electrocardiogram (EKG). Medications include ondansetron, granisetron, and dolasetron. * Anticholinergics can be used as a long-acting patch placed behind the patient's ear. Adverse effects include dry mouth and blurry vision. Care must be taken when handling the patch, as transfer of medication to the eye can induce pupillary dilation. Avoid use in elderly patients. Medications include scopolamine. * Glucocorticoids have direct antiemetic effects and can reduce need for postoperative opioids. Adverse effects include a transient increase in serum glucose level, and poor wound healing (controversial). Medications include dexamethasone. * Butyrophenones are typically administered as a single injection at the end of surgery. Adverse effects include prolongation of the QT interval on EKG. Medications include droperidol and haloperidol. * Phenothiazines are particularly effective in treating opioid-induced PONV. Adverse effects are dose-dependent and include sedation and extrapyramidal symptoms. Medications include promethazine and prochlorperazine. * Neurokinin 1 (NK1) receptor antagonists prevent an emetic signal from being transmitted. Medications include aprepitant and rolapitant. * Histamine receptor antagonists can be administered by multiple routes, including orally, intramuscularly, or rectally. Adverse effects include dry mouth, sedation, and urinary retention. Medications include dimenhydrinate and diphenhydramine. * Propofol, an anesthetic medication, confers its own antiemetic properties. ### Alternative medicine[edit] In conjunction with antiemetic medications, at least one study has found that application to the pericardium meridian 6 acupressure point produced a positive effect in relieving PONV.[5] Another study found no statistically significant difference.[6] The two general types of alternative pressure therapy are sham acupressure and the use of the P6 point. A 2015 study found no significant difference between the use of either therapy in the treatment or prevention of PONV. In a review of 59 studies, both therapies significantly affected the nausea aspect, but had no significant effect on vomiting. Cannabinoids have also been used for treatment of PONV, but its safety and efficacy are controversial. ## Epidemiology[edit] Typically, the incidence of nausea or vomiting after general anesthesia ranges between 25 and 30%.[7] Nausea and vomiting can be extremely distressing for patients, and so is one of their major concerns.[8] Vomiting has been associated with major complications, such as pulmonary aspiration of gastric content, and might endanger surgical outcomes after certain procedures, for example after maxillofacial surgery with wired jaws. Nausea and vomiting can delay discharge, and about 1% of patients scheduled for day surgery require unanticipated overnight admission because of uncontrolled PONV. ## References[edit] 1. ^ [1] 2. ^ Apfel CC, Läärä E, Koivuranta M, et al. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology 1999; 91:693. 3. ^ McCracken, Graham C.; Montgomery, Jane (2017-11-06). "Postoperative nausea and vomiting after unrestricted clear fluids before day surgery: A retrospective analysis". European Journal of Anaesthesiology. Publish Ahead of Print (5): 337–342. doi:10.1097/EJA.0000000000000760. ISSN 0265-0215. PMID 29232253. 4. ^ Gibbison, B; Spencer, R (December 2009). "Post-operative nausea and vomiting". Anesthesia & Intensive Care Medicine. 10 (12): 583–585. doi:10.1016/j.mpaic.2009.09.006. 5. ^ "Acupressure Treatment For The Prevention Of Postoperative Nausea And Vomiting". 6. ^ "Effect of acupressure on postoperative nausea and vomiting in laparoscopic cholecystectomy". Archived from the original on 2012-02-13. Retrieved 2009-02-18. 7. ^ Cohen 1994 8. ^ Macario 1999 ## Further reading[edit] * Blackburn, J., Spencer, R. (2015). Postoperative nausea and vomiting. * Pleuvry, B. (2015). Physiology and pharmacology of nausea and vomiting. ## External links[edit] Classification D * MeSH: D020250 * v * t * e Anesthesia and anesthesiology Types * General * Sedation * Twilight anesthesia * Local * Topical * Intercostal nerve block * Neuraxial blockade * Spinal * Epidural * Dental * Inferior alveolar nerve Techniques * Airway management * Anesthesia provision in the US * Arterial catheter * Bronchoscopy * Capnography * Dogliotti's principle * Drug-induced amnesia * Intraoperative neurophysiological monitoring * Nerve block * Penthrox inhaler * Tracheal intubation Scientific principles * Blood–gas partition coefficient * Concentration effect * Fink effect * Minimum alveolar concentration * Second gas effect Measurements * ASA physical status classification system * Baricity * Bispectral index * Entropy monitoring * Fick principle * Goldman index * Guedel's classification * Mallampati score * Neuromuscular monitoring * Thyromental distance Instruments * Anaesthetic machine * Anesthesia cart * Boyle's machine * Gas cylinder * Laryngeal mask airway * Laryngeal tube * Medical monitor * Odom's indicator * Relative analgesia machine * Vaporiser * Double-lumen endotracheal tube * Endobronchial blocker Complications * Emergence delirium * Allergic reactions * Anesthesia awareness * Local anesthetic toxicity * Malignant hyperthermia * Perioperative mortality * Postanesthetic shivering * Postoperative nausea and vomiting * Postoperative residual curarization Subspecialties * Cardiothoracic * Critical emergency medicine * Geriatric * Intensive care medicine * Obstetric * Oral sedation dentistry * Pain medicine Professions * Anesthesiologist * Anesthesiologist assistant * Nurse anesthetist * Operating department practitioners * Certified Anesthesia Technician * Certified Anesthesia Technologist * Anaesthetic technician * Physicians' assistant (anaesthesia) History * ACE mixture * Helsinki Declaration for Patient Safety in Anaesthesiology * History of general anesthesia * History of neuraxial anesthesia * History of tracheal intubation Organizations * American Association of Nurse Anesthetists * American Society of Anesthesia Technologists & Technicians * American Society of Anesthesiologists * Anaesthesia Trauma and Critical Care * Association of Anaesthetists of Great Britain and Ireland * Royal College of Anaesthetists * Association of Veterinary Anaesthetists * Australian and New Zealand College of Anaesthetists * Australian Society of Anaesthetists * International Anesthesia Research Society * Category * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Postoperative nausea and vomiting	c0520909	7,067	wikipedia	https://en.wikipedia.org/wiki/Postoperative_nausea_and_vomiting	2021-01-18T18:30:26	{"mesh": ["D020250"], "wikidata": ["Q1658731"]}
Char syndrome is a condition that affects the development of the face, heart, and limbs. It is characterized by a combination of three major features: a distinctive facial appearance, a heart defect called patent ductus arteriosus, and hand abnormalities. Char syndrome is caused by mutations in the TFAP2B gene and is inherited in an autosomal dominant fashion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Char syndrome	c1868570	7,068	gard	https://rarediseases.info.nih.gov/diseases/1237/char-syndrome	2021-01-18T18:01:32	{"mesh": ["C566815"], "omim": ["169100"], "umls": ["C1868570"], "orphanet": ["46627"], "synonyms": ["CHAR", "Patent ductus arteriosus with facial dysmorphism and abnormal fifth digits"]}
Autophony Other namesTympanophony Autophony is the unusually loud hearing of a person's own voice. Possible causes are: * The "occlusion effect", caused by an object, such as an unvented hearing aid or a plug of ear wax, blocking the ear canal and reflecting sound vibration back towards the eardrum.[1] * Serous otitis media * Open or patulous Eustachian tube, allowing vocal or breathing sounds to be conducted into the middle ear * Superior canal dehiscence, which can lead to an abnormally amplified bone conduction of sound into the inner ear. Persons with superior canal dehiscence syndrome (SCDS) typically hear not only their own voice but also heartbeat, footsteps, chewing, intestinal sounds and possibly even the sound of their eye movements when reading. ## References[edit] 1. ^ The "Occlusion Effect" Archived August 6, 2007, at the Wayback Machine ## External links[edit] Classification D * ICD-9-CM: 388.40 * O'Connor, A. F; Shea, J. J (1981). "Autophony and the patulous eustachian tube". The Laryngoscope. 91 (9 Pt 1): 1427–35. PMID 7346684. * Definition of Autophony * Painhealth.com - Definition of Autophony * emedicine Patulous Eustachian Tube * SCDS with Autophony * SCDS with Autophony - animation * "Doctor, I can hear my eyes" - W Albuquerque, A M Bronstein * ABC News - Health - The Musician Who Heard Too Much [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Autophony	c0877395	7,069	wikipedia	https://en.wikipedia.org/wiki/Autophony	2021-01-18T18:44:27	{"umls": ["C0877395"], "icd-9": ["388.40"], "wikidata": ["Q684088"]}
A number sign (#) is used with this entry because of evidence that susceptibility to hereditary essential tremor-1 (ETM1) is conferred by variation in the DRD3 gene (126451) on chromosome 3q13. Description Essential tremor may be the most common human movement disorder. The main feature of essential tremor is postural tremor of the arms, but the head, legs, trunk, voice, jaw, and facial muscles also may be involved. Aggravated by emotions, hunger, fatigue, and temperature extremes, the condition may cause a functional disability or even incapacitation. Autosomal dominant inheritance can be demonstrated in most families (summary by Higgins et al., 1997). Deng et al. (2007) provided a detailed review of the genetics of essential tremor. ### Genetic Heterogeneity of Essential Tremor Other forms of hereditary essential tremor include ETM2 (602134), mapped to chromosome 2p25-p22; ETM3 (611456), mapped to chromosome 6p23; ETM4 (614782), caused by mutation in the FUS gene (137070) on chromosome 16p11; and ETM5 (616736), caused by mutation in the TENM4 gene (610084) on chromosome 11q14. Clinical Features Louis (2001) reviewed the clinical features of essential tremor and therapeutic options. Critchley (1949) gave a classic review of this subject. Larsson and Sjogren (1960) did a thorough study of hereditary essential tremor in a parish of Sweden. In all, 210 cases were ascertained. The age of onset, which showed high intrafamilial correlation, was on the average about 50 years and somewhat later in women than in men. 'Anticipation' (progressively earlier age of onset in successive generations) was not observed. Fine rapid tremor of the hands was usually the first symptom. Tremor of the arms, tongue (with dysarthria), head, legs, and trunk developed later, usually in the order listed. Mild extrapyramidal symptoms in the form of rigidity and stiffness of gait occurred frequently, but the clinical picture was easily distinguishable from parkinsonism (see 168600). Mental deterioration was not a feature. With 2 exceptions, all 210 cases could be traced back to 4 ancestral couples. The inheritance was autosomal dominant. From observation of about 15 presumed homozygous individuals, it was concluded that there is no difference from the disease in heterozygotes. It was estimated that more than 9% of the males and 6 to 6.5% of females of the parish carry the gene for essential tremor. The authors could find no reason to suspect selective fertility, selective mortality, or assortative mating as factors in the high gene frequency observed. Rather, chance variations that occurred when the population was small--about 150 persons in the late 1700s--seem to have been responsible. Kehrer (1965) described a family in which members of 3 successive generations had tremor of the hands and face and in 2 patients studied in detail, cerebral atrophy demonstrable by pneumoencephalography. He suggested that this represents a distinct entity. Busenbark et al. (1991) reported the results of a self-administered questionnaire concerning sickness-related dysfunction in 753 patients with essential tremor and compared the results with those in 87 controls and 145 patients with Parkinson disease. They concluded that although the disability with essential tremor is significant and may cause relatively greater psychosocial dysfunction, it tends to be less severe than in parkinsonism. Garcia-Albea et al. (1993) reported a 24-year-old man with paroxysmal episodes of tremor lasting from 10 to 60 minutes and occurring once every 3 to 6 weeks without apparent precipitating factors. The episodes were accompanied by a 9- to 10-Hz tremor electromyographically. A similar pattern was present in the patient's mother and in 2 of his 4 brothers. The authors proposed that this was a distinct variant. Bain and Findley (1994) believed that classic familial essential tremor typically begins with intermittent symptoms and that the observation of Garcia-Albea et al. (1993) should not be considered a novel variant. Bain et al. (1994) studied 93 first-degree relatives and 38 more distant relatives of 20 index patients with hereditary essential tremor. The age of onset was bimodally distributed with a median at 15 years, and penetrance was virtually complete at the age of 65 years. Approximately 50% of the cases were alcohol responsive. In most families, alcohol responsiveness or its absence was a consistent feature, but in 20% there was heterogeneity of alcohol response within the family. Head tremor was invariably mild and in 75% of cases was of a 'no-no' type. There was no association with Parkinson disease or dystonia, although classical migraine (see 157300) occurred in 26% of cases and cosegregated with tremor. Gulcher et al. (1997) quoted Jankovic et al. (1995) as finding that the average life expectancy of essential tremor patients is greater than that of unaffected members of their families. However, the disorder has a significant effect on the lives of the persons involved. Essential tremor may not appear until after 65 years of age. Current treatments using beta blockers or primidone have only limited efficacy and frequently become ineffective as the disease progresses. The tremor usually begins between adolescence and 40 years of age. Farrer et al. (1999) studied a family that raised the question of whether postural tremor (essential tremor) can be an alternative phenotype of the same pathogenic mutation that causes Lewy body parkinsonism (168601). They investigated a large family with levodopa-responsive Lewy body parkinsonism in which the disease segregated as an apparent autosomal dominant trait. After performing a genome screen, they identified a chromosome 4p haplotype that segregated with the disorder; however, this haplotype also occurred in individuals in the pedigree who did not have clinical Lewy body parkinsonism but rather suffered from postural tremor, consistent with essential tremor. In a population-based study of cognitive function among 232 Spanish patients with essential tremor and 696 control individuals, Benito-Leon et al. (2006) found that patients with essential tremor scored lower than controls on most neuropsychologic tests and global cognitive performance tests. In addition, a complaint of forgetfulness was marginally more common among essential tremor patients. Inheritance Busenbark et al. (1996) mailed a screening questionnaire to first-degree relatives of patients with essential tremor who denied a positive family history. Even though only 67.7% of patients had previously reported a positive family history, this more direct assessment demonstrated that 96% of essential tremor patients had a positive family history, suggesting that essential tremor is primarily a hereditary disease. In a study of relatives of patients with essential tremor, in comparison with relatives of control subjects, Louis et al. (2001) found mild tremor in many relatives of the former group. Even among case relatives 60 years of age or older, there was an increased prevalence of higher tremor scores, suggesting that in that age group, subclinical essential tremor may be present and penetrance may still not be complete. Louis et al. (2001) examined 59 patients with essential tremor, 72 controls, and over 200 relatives of each group and determined that relatives of patients with essential tremor are 5 times more likely to develop the disease than are members of the general population and 10 times more likely if the proband's tremor began before age 50. Severity of tremor in the proband was an important determinant of tremor severity among relatives. Lorenz et al. (2004) conducted a twin study in Denmark to assess the relative contribution of genetic and environmental factors in essential tremor and to explore the effect of different diagnostic criteria. A total of 2,448 twins aged 70 years or more were screened for essential tremor by an interview and an Archimedes spiral test. All 162 twin pairs with a positive screening test of at least 1 of the twins were recontacted, and 218 individuals (109 pairs) were interviewed and examined by a movement disorder specialist. The probandwise concordance rate for the broadest definition of essential tremor was 77% for monozygotic twins and 59% for dizygotic twins. However, in an analysis restricted to cases of probable and definite essential tremor, the concordance rates were 93% and 29%. The heritability for the liability to essential tremor ranged from 93% to 99% using a general population prevalence of 1.2% for white persons 70 years of age and older. Population Genetics Rautakorpi et al. (1982) reported a remarkably high frequency of essential tremor in a Finnish population: 55.5% of persons over 40 years of age. Benito-Leon et al. (2005) estimated an annual incidence of essential tremor of 616 per 100,000 among Spanish individuals aged 65 years and older. Sixty-four (77.1%) of 83 incident cases were diagnosed only during a follow-up, suggesting that many patients may never seek medical attention. The prevalence and incidence of essential tremor did not differ between men and women. Pathogenesis Tanner et al. (2001) performed a study of essential tremor in twins who were members of the National Academy of Sciences and National Research Council World War II Veteran Twins Registry. When patients with Parkinson disease and incidences of incomplete data were excluded, 16 twin pairs were found in which at least 1 twin had essential tremor. Pairwise concordance in monozygotic twins was approximately 2 times that in dizygotic twins (0.60 for monozygotic, 0.27 for dizygotic). The results indicated that environmental factors may play a role in the cause of the disease. In a review, Louis (2009) presented evidence that essential tremor may represent a family of diseases rather than a single disease entity. He noted that a broad variety of clinical features have been described in patients with essential tremor, including additional motor, cognitive, and psychiatric impairments. These features are heterogeneously distributed across patients with ET. In addition, there is a heterogeneity of response to common treatments, such as propranolol and primidone. Pathologic reports have identified 2 main, yet distinct, types: one with cerebellar degenerative changes and significant Purkinje cell loss, and another with Lewy bodies confined to the locus ceruleus. Finally, essential tremor is age-associated, shows an insidious onset, is progressive, and in some cases has shown cell loss and structural brain changes, suggesting that it may be considered a neurodegenerative disorder. Clinical Management Higgins et al. (1997) stated that beta-adrenergic blocking agents and primidone, established treatments for essential tremor, are only partially effective and have significant side effects. Mapping Since hereditary essential tremor is often associated with dystonia, a pathologic connection between it and idiopathic torsion dystonia (DYT1; 128100), which maps to chromosome 9, has been suggested. Durr et al. (1993) excluded this possibility by ruling out linkage to 9q32-q34. Gulcher et al. (1997) reported the results of a genomewide scan in 16 Icelandic families with 75 individuals affected with essential tremor. A locus, which they symbolized FET1 for familial essential tremor 1, was mapped to 3q13 when the data were analyzed either parametrically, assuming an autosomal dominant model (lod score = 3.71), or nonparametrically (lod score = 4.70). Shortly after the publication of the study of Gulcher et al. (1997) mapping an essential tremor gene to chromosome 3, Higgins et al. (1997, 1998) reported mapping an essential tremor gene to 2p25-p22 (ETM2; 602134). Kovach et al. (2001) described a 38-member, 6-generation Midwestern family with essential tremor. This family did not map to either the ETM1 or ETM2 loci; a candidate locus for parkinsonism and postural tremor on chromosome 4p was also excluded, showing further heterogeneity of autosomal dominant essential tremor. Heterogeneity In a genomewide association study including 452 Icelandic patients with essential tremor and 14,394 controls, Stefansson et al. (2009) found linkage to 2 SNPs in the LINGO1 gene (609791) on chromosome 15q24.3 (p less than 1.0 x 10(-5)). Replication studies in samples from Austria, Germany, the United States, and Iceland confirmed a significant association with the G allele of 1 of these SNPS (rs9652490), yielding a combined odds ratio of 1.55 and p value of 1.2 x 10(-9). The SNP is located within intron 3 of the LINGO1 gene, which the authors noted is exclusively expressed in the central nervous system. In a study of 190 Asian patients with essential tremor and 733 controls, Tan et al. (2009) observed an association between essential tremor and the G allele of rs9652490 in the LINGO1 gene. Seventy-five (39.5%) of 190 patients had a positive family history of ET. In the whole cohort, the population attributable risk of the GG genotype was 18.8%. However, the most robust association was with familial ET for the GG genotype (OR, 3.26; p = 0.005). Analysis of sporadic ET did not show any association with this SNP. By genotyping of 15 SNPs in the LINGO1 gene in 257 ET patients and 265 controls from northern Manhattan, Clark et al. (2010) found a marginally significant association between ET and the G allele of rs9652490 (OR of 1.33, p = 0.0569). The association with this SNP strengthened in a subset of cases with 'definite' or 'probable' ET (OR of 1.41, p = 0.03). Subsequent analysis of early-onset ET (less than 40 years) showed an association between ET and 3 SNPs: rs177008, rs13313467, and rs8028808 (OR of 1.52, p = 0.028; OR of 1.54, p = 0.0238; and OR of 1.55, p = 0.0391, respectively). These 3 SNPs represented a 2.3-kb haplotype. The study independently suggested that variation in the LINGO1 gene may be a risk factor for ET in a Caucasian population in North America, particularly for those with early onset. Molecular Genetics In 23 of 30 unrelated French families, Lucotte et al. (2006) found significant association between hereditary essential tremor and a BalI polymorphism in the DRD3 gene (S9G; 126451.0001) on chromosome 3q13. Parametric linkage analysis and transmission disequilibrium testing also showed significant positive association between the polymorphism and essential tremor. Among probands, gly9 homozygotes had significantly younger age at onset and more severe symptoms compared to heterozygotes, suggesting a gene dosage effect. Lucotte et al. (2006) noted that the polymorphism occurs in the extracellular N terminus of the protein, which may increase dopamine affinity and efficacy. The authors hypothesized that essential tremor may result from a gain-of-function mechanism. ### Associations Pending Confirmation For discussion of a possible association between essential tremor and variation in the SCN4A gene, see 603967.0033. History Dominantly inherited essential tremor was recognized by Dana (1887). Louis (2001) reviewed evidence related to the progressive tremor from which Samuel Adams (1722-1803), the American Revolutionist and brewer, suffered. The tremor affected his hands, head, and voice. Although mild, the tremor was already manifest when Adams was in his early forties. A prolific writer, Adams experienced progressive difficulty with writing in his fifties and early sixties. By age 71, he was forced to dictate all of his correspondence. His tremor was familial, affecting his daughter Hannah and her children. Louis (2001) concluded that he suffered from one of the earliest documented cases of essential tremor. Animal Model Kralic et al. (2005) generated alpha-1 gamma-aminobutyric acid receptor (GABRA1; 137160) -/- mice and observed postural and kinetic tremor and motor incoordination characteristic of essential tremor disease. Drugs used to treat essential tremor patients were efficacious in reducing tremor in Gabra1-null mice, as were several candidate drugs. Electrophysiologic studies revealed that cerebellar Purkinje cells in Gabra1-null mice had a profound loss of all responses to synaptic or exogenous GABA, but there were no differences in abundance, gross morphology, or spontaneous synaptic activity. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Tremor, action (arms, tongue, head, legs and trunk) \- Tremor, postural (arms, tongue, head, legs and trunk) \- Fine rapid hand tremor, 4-12 Hz \- Dysarthria MISCELLANEOUS \- Age at onset ranges from 50 to 70 years \- Penetrance is usually complete by age 65 years \- Progressive disorder \- Favorable response to alcohol in about 50% \- Prevalence of essential tremor ranges from 0.4 to 6% in the general population MOLECULAR BASIS \- Susceptibility conferred by mutation in the dopamine receptor D3 gene (DRD3, 126451.0001 ) ▲ 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	TREMOR, HEREDITARY ESSENTIAL, 1	c1860861	7,070	omim	https://www.omim.org/entry/190300	2019-09-22T16:32:28	{"mesh": ["C536545"], "omim": ["190300"], "synonyms": ["Alternative titles", "TREMOR, FAMILIAL ESSENTIAL, 1"]}
Septal panniculitis Septal panniculitis is a condition of the subcutaneous fat affecting the layer of adipose tissue that lies between the dermis and underlying fascia, of which there are two forms: acute erythema nodosum and chronic erythema nodosum.[1]:487–9 ## See also[edit] * Erythema nodosum * List of cutaneous conditions * Panniculitis * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. * v * t * e Disorders of subcutaneous fat Panniculitis Lobular * without vasculitis * Cold * Cytophagic histiocytic * Factitial * Gouty * Pancreatic * Traumatic * needle-shaped clefts * Subcutaneous fat necrosis of the newborn * Sclerema neonatorum * Post-steroid panniculitis * Lipodermatosclerosis * Weber–Christian disease * Lupus erythematosus panniculitis * Sclerosing lipogranuloma * with vasculitis: Nodular vasculitis/Erythema induratum Septal * without vasculitis: Alpha-1 antitrypsin deficiency panniculitis * Erythema nodosum * Acute * Chronic * with vasculitis: Superficial thrombophlebitis Lipodystrophy Acquired * generalized: Acquired generalized lipodystrophy * partial: Acquired partial lipodystrophy * Centrifugal abdominal lipodystrophy * HIV-associated lipodystrophy * Lipoatrophia annularis * localized: Localized lipodystrophy Congenital * Congenital generalized lipodystrophy * Familial partial lipodystrophy * Marfanoid–progeroid–lipodystrophy syndrome * Poland syndrome 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	Septal panniculitis	c0263011	7,071	wikipedia	https://en.wikipedia.org/wiki/Septal_panniculitis	2021-01-18T18:54:59	{"umls": ["C0263011"], "wikidata": ["Q7452045"]}
Gyrate atrophy of the choroid and retina is an inherited disorder of protein metabolism characterized by progressive vision loss. Symptoms such as nearsightedness (myopia), difficulty seeing in low light (night blindness), and loss of side (peripheral) vision develop during childhood. Over time, the field of vision progressively narrows, resulting in tunnel vision. Cataracts may also develop. These vision changes may lead to blindness by about the age of 50. While most people with gyrate atrophy of the choroid and retina have no symptoms other than vision loss, neonatal hyperammonemia (excess ammonia in the blood in the newborn period), neurological abnormalities, intellectual disability, peripheral nerve problems, and muscle weakness may occur. This condition is caused by mutations in the OAT gene and is inherited in an autosomal recessive manner. Treatment may include dietary supplements and/or a specialized diet. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Gyrate atrophy of choroid and retina	c0599035	7,072	gard	https://rarediseases.info.nih.gov/diseases/6556/gyrate-atrophy-of-choroid-and-retina	2021-01-18T18:00:11	{"mesh": ["D015799"], "omim": ["258870"], "orphanet": ["414"], "synonyms": ["Ornithine aminotransferase deficiency", "Ornithine ketoacid aminotransferase deficiency", "Gyrate atrophy", "OAT deficiency", "OKT deficiency", "Hyperornithinemia with gyrate atrophy of choroid and retina", "HOGA", "Girate atrophy of the retina", "Hyperornithinemia", "Hyperornithinemia-gyrate atrophy of choroid and retina syndrome", "Fuchs atrophia gyrata chorioideae et retinae"]}
Condition in which an individual cannot voluntarily visualize imagery Aphantasia is a condition characterized by an inability to voluntarily visualize mental imagery.[1] Many people with aphantasia also report an inability to recall sounds, smells, or sensations of touch. Some also report prosopagnosia, the inability to recognize faces.[2] The phenomenon was first described by Francis Galton in 1880[3] but has since remained relatively unstudied. Interest in the phenomenon renewed after the publication of a study in 2015 conducted by a team led by Professor Adam Zeman of the University of Exeter,[4] which also coined the term aphantasia.[5] Research on the condition is still scarce.[6][7] The term "aphantasia" is derived from the Greek word "phantasia", which translates to "imagination", and the prefix "a-", which means "without".[8] ## Contents * 1 History * 2 Assessment * 3 Research * 4 Notable aphantasiacs * 5 See also * 6 References * 7 Further reading * 8 External links ## History[edit] The phenomenon was first described by Francis Galton in 1880 in a statistical study about mental imagery,[3] describing it as a common phenomenon among his peers.[9] It remained largely unstudied until 2005, when Professor Adam Zeman of the University of Exeter was approached by MX, a man who seemed to have lost the ability to visualize after undergoing minor surgery.[10] Following the publication of MX's case in 2010,[11] a number of people approached Zeman reporting a lifelong inability to visualise. In 2015, Zeman's team published a paper on what they termed "congenital aphantasia",[4] sparking renewed interest in the phenomenon.[5] In April 2016 Blake Ross, co-creator of Firefox, published an essay describing his own aphantasia and his realization that not everyone experiences it.[12] The essay gained wide circulation on social media and in a variety of news sources.[13][14] In May 2018, in collaboration with Zeman, The Aphantasia Network was launched to create a community of people exploring life with aphantasia, and share stories and strategies to learn more about its effects.[15] ## Assessment[edit] In Zeman's original paper,[4] the Vividness of Visual Imagery Questionnaire (VVIQ) is used to evaluate the quality of the mental image of 21 self-diagnosed and self-selected participants. This questionnaire invites the person to visualize a series of images (a relative, a rising sun, a shop they know, etc.) and rank how vivid the image is, from "perfectly clear and lively as real seeing" (5 points) to "no image at all, you only know that you are thinking of the object" (1 point). A total of 20 or less across 16 questions qualifies as aphantasia.[16] ## Research[edit] Zeman's paper[4] identified that aphantasia characterizes only voluntary visualizations; the aphantasiacs were still able to have involuntary visualizations (i.e. dreams). Another study[17] posited that frontal engagement driving feedback connections activates sensory representations in the visual cortex; people with aphantasia could have a deficit with these feedback connections such that the visual cortex cannot be activated to produce an image. A 2020 study concluded that those who experience aphantasia also experience reduced imagery in other senses, and have less vivid autobiographical memories.[18] In addition to congenital aphantasia there have been cases reported of acquired aphantasia, due either to brain injury or psychological causes.[19][20] ## Notable aphantasiacs[edit] * Ed Catmull, co-founder of Pixar and former president of Walt Disney Animation Studios. Catmull surveyed 540 colleagues from Pixar about their mental visualization and found that the production managers tended to have stronger visualizations than the artists.[21] * Derek Parfit, British philosopher. His aphantasia may have influenced his long interest in photography.[22][23] * Blake Ross, co-creator of the web browser Mozilla Firefox.[24] * Richard Herring, British comedian and podcaster.[25] * Yoon Ha Lee, science fiction author.[26] * Michelle Sagara, fantasy author.[27] * James Harkin, co-host of podcast No Such Thing as a Fish, researcher for television show QI.[28] ## See also[edit] * Creative visualization * Engineering and the Mind's Eye * Number form * Prefrontal Synthesis ## References[edit] 1. ^ Larner, A. J. (2016). A Dictionary of Neurological Signs. Springer. p. 29–30. ISBN 978-3319298214. Archived from the original on 2016-12-24. Retrieved 2016-09-04. 2. ^ Kendle, Alan (2017). Aphantasia: Experiences, Perceptions, and Insights. Dark River. p. 11,17. 3. ^ a b Galton, Francis (19 July 1880). "Statistics of Mental Imagery". Mind. os–V (19): 301–318. doi:10.1093/mind/os-V.19.301. Archived from the original on 16 April 2016. Retrieved 26 April 2016. 4. ^ a b c d Zeman, Adam; Dewar, Michaela; Della Sala, Sergio (3 June 2015). "Lives without imagery – Congenital aphantasia" (PDF). Cortex. 73: 378–380. doi:10.1016/j.cortex.2015.05.019. hdl:10871/17613. ISSN 0010-9452. PMID 26115582. S2CID 19224930. 5. ^ a b Gallagher, James (26 August 2015). "Aphantasia: A life without mental images". BBC News Online. Archived from the original on 26 August 2015. Retrieved 26 August 2015. 6. ^ Zimmer, Carl (22 June 2015). "Picture This? Some Just Can't". The New York Times. ISSN 0362-4331. Archived from the original on 23 June 2015. Retrieved 24 June 2015. 7. ^ Grinnell, Dustin (20 April 2016). "My mind's eye is blind – so what's going on in my brain?". New Scientist (2070). Archived from the original on 18 September 2016. Retrieved 9 July 2016. 8. ^ Clemens, Anna (1 August 2018). "When the Mind's Eye is Blind". Scientific American. 9. ^ "To my astonishment, I found that the great majority of the men of science to whom I first applied, protested that mental imagery was unknown to them, and they looked on me as fanciful and fantastic in supposing that the words 'mental imagery' really expressed what I believed everybody supposed them to mean. They had no more notion of its true nature than a colour-blind man who has not discerned his defect has of the nature of colour." (Galton, 1880) 10. ^ "You might not be able to imagine things, and not know it". The Independent. 2016-04-25. Archived from the original on 2016-12-20. Retrieved 2016-12-16. 11. ^ Zeman, Adam Z. J.; Della Sala, Sergio; Torrens, Lorna A.; Gountouna, Viktoria-Eleni; McGonigle, David J.; Logie, Robert H. (2010-01-01). "Loss of imagery phenomenology with intact visuo-spatial task performance: A case of 'blind imagination'". Neuropsychologia. 48 (1): 145–155. doi:10.1016/j.neuropsychologia.2009.08.024. PMID 19733188. S2CID 207235666. 12. ^ "Aphantasia: How It Feels To Be Blind In Your Mind \| Facebook". www.facebook.com. 13. ^ Cabral-Isabedra, Catherine (27 April 2016). "Mozilla Firefox Co-Creator Says He Can't Visualize Images: What You Need To Know About Aphantasia". Tech Times. Retrieved 25 June 2019. 14. ^ Clemens, Anna (1 August 2018). "When the Mind's Eye Is Blind". Scientific American. Retrieved 25 June 2019. 15. ^ "The Aphantasia Network". aphantasia.com. 4 September 2017. 16. ^ "Vividness of Visual Imagery Quiz". The Aphantasia Network. 23 June 2019. Retrieved 10 May 2020. 17. ^ Keogh, Rebecca; Pearson, Joel (August 2018). "The blind mind: No sensory visual imagery in aphantasia" (PDF). Cortex. 105: 53–60. doi:10.1016/j.cortex.2017.10.012. PMID 29175093. S2CID 9138613. Archived (PDF) from the original on 2019-03-16. Retrieved 2019-03-30 – via Elsevier Science Direct. 18. ^ Dawes, Alexei J.; Keogh, Rebecca; Andrillon, Thomas; Pearson, Joel (2020-06-22). "A cognitive profile of multi-sensory imagery, memory and dreaming in aphantasia". Scientific Reports. 10 (1): 10022. doi:10.1038/s41598-020-65705-7. ISSN 2045-2322. PMC 7308278. PMID 32572039. 19. ^ de Vito, Stefania; Bartolomeo, Paolo (January 2016). "Refusing to imagine? On the possibility of psychogenic aphantasia. A commentary on Zeman et al. (2015)". Cortex. 74: 334–335. doi:10.1016/j.cortex.2015.06.013. PMID 26195151. S2CID 40642476. 20. ^ Zeman, Adam; Dewar, Michaela; Della Sala, Sergio (January 2016). "Reflections on aphantasia". Cortex. 74: 336–337. doi:10.1016/j.cortex.2015.08.015. hdl:20.500.11820/b67449c9-1804-4a8f-95ee-c320928c7eeb. PMID 26383091. S2CID 206985920. Archived from the original on 2017-08-28. 21. ^ Gallagher, James (9 April 2019). "Aphantasia: Ex-Pixar chief Ed Catmull says 'my mind's eye is blind'". BBC News. Archived from the original on 9 April 2019. Retrieved 9 April 2019. 22. ^ Appleyard, Bryan (6 June 2018). "Derek Parfit's quest for perfection". NewStatesman. Retrieved 2020-04-16. 23. ^ MacFarquhar, Larissa (29 October 2011). "How To Be Good". The New Yorker. Retrieved 2020-04-16. 24. ^ Cabral-Isabedra, Catherine (27 April 2016). "Mozilla Firefox Co-Creator Says He Can't Visualize Images: What You Need To Know About Aphantasia". Tech Times. 25. ^ "Warming Up \| RichardHerring.com". February 8, 2020. Retrieved 2020-07-01. 26. ^ "Raven Strategem author Yoon Ha Lee on how his spaceships became bags of holding". SciFiNow. 2017-05-31. Retrieved 2020-07-02. 27. ^ "Aphantasia: when the mental image is missing". Canadian Broadcasting Corporation. June 24, 2016. 28. ^ "No Such Thing As A Jigsaw For The Queen". No Such Thing as a Fish. January 19, 2018. ## Further reading[edit] * Kendle, Alan (2017). Aphantasia: Experiences, Perceptions, and Insights. Bennion Kearny Limited. ISBN 978-1-911121-42-8. (foreword by Adam Zeman) * Faw, Bill (2009). "Conflicting Intuitions May Be Based on Differing Abilities: Evidence From Mental Imaging Research". Journal of Consciousness Studies. 16 (4): 45–68. ## External links[edit] Wikimedia Commons has media related to Aphantasia. * "Aphantasia: When The Mental Image Is Missing". Quirks and Quarks. Episode Part 1. CBC Radio. 2016-06-25. * Paul Aflalo (2019-09-14). "Can you picture things in your head? Well, this guy can't". The Doc Project. Episode Part 1. CBC Radio. * Carly Cassella: People With This Rare Brain Condition Can't 'Count Sheep' in Their Mind. On: sciencealert. 4 January 2021 * v * t * e Nervous system Central nervous system * Meninges * Spinal cord * Brain * Hindbrain * Medulla * Pons * Cerebellum * Midbrain * Forebrain * Diencephalon * Retina * Optic nerve * Cerebrum * Limbic system Peripheral nervous system Somatic * Sensory nerve * Motor nerve * Cranial nerve * Spinal nerve Autonomic * Sympathetic * Parasympathetic * Enteric [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Aphantasia	None	7,073	wikipedia	https://en.wikipedia.org/wiki/Aphantasia	2021-01-18T18:56:05	{"wikidata": ["Q20707611"]}
Brown et al. (1972) described a physically and mentally retarded child with dibasicaminoaciduria and hyperammonemia. Oral loading tests showed diminished capacity for absorbing lysine. Fasting blood arginine and lysine concentrations were low. Postprandial hyperammonemia was thought to be due to deficiency of arginine to serve as substrate for urea cycle activity. The defect in intestinal absorption distinguishes this disorder from familial protein intolerance (222690, 222700). In periodic hyperlysinemia, normal protein intake results in hyperlysinemia and high protein intake or administration of a lysine load precipitates severe hyperammonemia and coma. Hyperammonemia is thought to result from the elevated levels of lysine competitively inhibiting arginase, which catalyzes the last step in urea formation. A partial deficiency (25% of normal) of L-lysine dehydrogenase, the enzyme that converts lysine to an alpha-keto-epsilon aminocaproic acid, has been demonstrated in a liver biopsy from a single patient (a 3-month-old girl) (Ghadimi, 1978). No information is available on the genetics of this disorder. Growth \- Retarded growth Neuro \- Mental retardation \- Lethargy \- Coma Lab \- Hyperlysinuria \- Hyperlysinemia \- Hyperammonemia \- Dibasicaminoaciduria \- Low fasting blood arginine and lysine \- L-lysine dehydrogenase partial deficiency GI \- Protein intolerance \- Lysine malabsorption Inheritance \- ? Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	HYPERLYSINURIA WITH HYPERAMMONEMIA	c0268555	7,074	omim	https://www.omim.org/entry/238750	2019-09-22T16:26:51	{"mesh": ["D020167"], "omim": ["238750"], "synonyms": ["Alternative titles", "HYPERLYSINEMIA, PERIODIC"]}
## Cloning and Expression From a rat genomic library, Ingvarsson et al. (1988) isolated a new member of the MYC family, designated BMYC because its highest expression was found in brain and because it was highly homologous to MYC (190080). Mapping Ingvarsson et al. (1988) used a fragment of the cloned BMYC gene to map the corresponding rat locus by Southern blotting of DNA prepared from rat/mouse somatic cell hybrids; BMYC mapped to rat chromosome 3, whereas MYC maps to rat chromosome 7 and NMYC and LMYC to rat chromosomes 6 and 5, respectively. The partial sequence of BMYC had extensive sequence homology to the MYC protein-coding region, and intron homology was also detected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	ONCOGENE BMYC	c1833829	7,075	omim	https://www.omim.org/entry/165210	2019-09-22T16:37:06	{"omim": ["165210"]}
Rare, extreme form of the movement disorder chorea This article may need to be rewritten to comply with Wikipedia's quality standards. You can help. The talk page may contain suggestions. (May 2009) Hemiballismus Other namesBallismus or Ballism SpecialtyNeurology Hemiballismus or hemiballism is a basal ganglia syndrome resulting from damage to the subthalamic nucleus in the basal ganglia.[1] Hemiballismus is a rare hyperkinetic movement disorder,[2] that is characterized by violent involuntary limb movements,[1][3] on one side of the body,[4] and can cause significant disability.[5] Ballismus affects both sides of the body and is much rarer.[4] Symptoms can decrease during sleep.[6] Hemiballismus differs from chorea in that the movements occur in the proximal limbs whereas in chorea the limb movements are in the distal limbs.[4] Also in chorea the movements are more dance-like, flowing from one region to another.[7] ## Contents * 1 Presentation * 2 Causes * 3 Anatomy * 4 Diagnosis * 5 Treatments * 6 Prognosis * 7 History * 8 See also * 9 References * 10 External links ## Presentation[edit] Ballism was defined by Meyers in 1968[8] as "Repetitive, but constantly varying, large amplitude involuntary movements of the proximal parts of the limbs. This activity is almost ceaseless and movements are often complex and combined". Hemiballismus is usually characterized by involuntary flinging motions of the extremities.[2] The movements are often violent and have wide amplitudes of motion.[9] They are continuous and random and can involve proximal or distal muscles on one side of the body. Some cases even include the facial muscles.[6] It is common for arms and legs to move together. The more a patient is active, the more the movements increase. With relaxation comes a decrease in movements.[10] Physicians can measure the severity of the disorder by having the patient perform a series of basic, predetermined tasks and counting the hemiballistic movements during a set time session.[11] The physicians then rate the patient on a severity scale. This scale gives scientists and clinicians a way to compare patients and determine the range of the disorder.[citation needed] The name hemiballismus literally means "half ballistic", referring to the violent, flailing movements observed on one side of the body. ## Causes[edit] In examining the causes of hemiballismus, it is important to remember that this disorder is extremely rare. While hemiballismus can result from the following list, just because a patient suffers from one of these disorders does not mean they will also suffer from hemiballismus.[citation needed] Stroke Hemisballismus as a result of stroke occurs in only about 0.45 cases per hundred thousand stroke victims.[2] Even at such a small rate, stroke is by far the most common cause of hemiballismus.[12] A stroke causes tissue to die due to a lack of oxygen resulting from an impaired blood supply. In the basal ganglia, this can result in the death of tissue that helps to control movement. As a result, the brain is left with damaged tissue that sends damaged signals to the skeletal muscles in the body. The result is occasionally a patient with hemiballismus.[citation needed] Traumatic Brain Injury Hemiballismus can also occur as a result of a traumatic brain injury. There are cases in which victims of assault or other forms of violence have developed hemiballismus.[5] Through these acts of violence, the victim’s brain has been damaged and the hemiballistic movements have developed.[citation needed] Amyotrophic Lateral Sclerosis This disease causes neuronal loss and gliosis, which can include the subthalamic nucleus and other areas of the brain.[13] Essentially any disorder that causes some form of neuronal loss or gliosis in the basal ganglia has the potential to cause hemiballismus.[citation needed] Play media Hyperglycemia-induced involuntary movements (in this case, not hemiballismus, but hemichorea (chorea of one side of the body) and bilateral dystonia) in a 62-year-old Japanese woman with type 1 diabetes. Nonketotic Hyperglycemia Patients with nonketotic hyperglycemia can develop hemiballismus as a complication to the disease through the development of a subthalamic nucleus lesion.[14] This is the second most common reported cause of hemiballismus. It can be found primarily in the elderly and many of the reported cases have come from East Asian origin, which suggests that there may be some genetic disposition to development of hemiballismus as a result of hyperglycemia. Hemiballistic movements appear when blood glucose levels get too high and then subside once glucose levels return to normal. This time scale for this is usually several hours. In patients with this type of hemiballismus, imaging reveals abnormalities in the putamen contralateral to the movements as well as the globus pallidus and caudate nucleus. While the hyperglycemia itself is not the cause of the hemiballistic movements, it has been suggested that petechial hemorrhage or a decreased production of GABA and acetylcholine could result secondary to the hyperglycemia. One of these issues could be responsible for the hemiballistic movements.[10] Neoplasms A neoplasm is an abnormal growth of cells. Cases have shown that if this occurs somewhere in the basal ganglia, hemiballismus can result.[10] Vascular malformations Vascular malformations can cause abnormal blood flow to areas of the brain. If too little blood is delivered to the basal ganglia, a stroke can occur.[10] Tuberculomas This is another form of tumor that can result in the brain as a result of a tuberculous meningitis infection. This type of tumor can also damage parts of the basal ganglia, sometimes resulting in hemiballismus.[10] Demyelinating plaques Demyelinating plaques attack the myelin sheaths on neurons. This decreases the conduction velocity of the neurons, making the signals received by the basal ganglia garbled and incomplete. This disorganized signal can also cause the chaotic movements characterized by hemiballismus.[10] Complications from HIV infection Patients with HIV often have complications that arise along with AIDS. Hypoglycemia due to pentamidine use in patients with AIDS has been known to cause hemiballismus. In some patients, hemiballismus has been the only visible symptom to alert the physician that the patients may have AIDS. It is typically a result of a secondary infection that occurs due to the compromised immune system and the most common infection causing hemiballismus is cerebral toxoplasmosis. Most of the lesions that result from this infection are found in the basal ganglia. As long as the diagnosis is not missed, this type of hemiballismus can be treated just as well as in patients without HIV.[10] ## Anatomy[edit] Basal ganglia The basal ganglia are a collection of nuclei that connects to several other areas of the brain. Due to the diverse nuclei that they contain, the basal ganglia are involved in numerous functions, including motor control. It is within this structure that hemiballismus primarily occurs in the brain.[citation needed] Subthalamic nucleus This structure within the basal ganglia innervates other structures, including a very important connection to the internal globus pallidus. The subthalamic nucleus essentially provides the excitement needed to drive the globus pallidus.[10] Injury to this area or its efferent or afferent connections can induce this disorder contralateral to the side of the lesion.[9] The structure itself is a regulator of motor function and is also involved in associative and limbic functions.[15] It was traditionally thought that the disorder was only caused by injury to the subthalamic nucleus, but later studies have shown that damage to other basal ganglia regions can also be responsible for causing this disorder.[12] Hemiballismus caused by lesions in the subthalamic nucleus is more severe than other forms of the disorder.[10] Globus pallidus From recent studies, it is now thought that hemiballismus can be associated with a decreased output of the globus pallidus. This is because studies have shown that firing rates decrease from 70/s to 40/s.[10] In addition to a decreased firing rate, degenerative neurological disorders that cause patients to exhibit hemiballistic movements show a marked decrease in the globus pallidus mass as well.[13] Increases in activity in this area causes there to be an inhibition of the motor thalamus. This causes cortical activation and thus a movement inhibition. In the case of hemiballismus, the opposite occurs, leading to the characteristic large, irregular movements.[10] Putamen The putamen is also part of the basal ganglia and can be involved in hemiballismus due to the fact that it projects to the premotor cortex through the globus pallidus. As a result, damage to this area can also cause hemiballistic movements to be seen as it is also part of the chain in movement.[6] Caudate nucleus The caudate nucleus is the portion of the basal ganglia that helps control voluntary movement. Damage to this area can also result in hemiballismus as it is directly related to voluntary movement.[6] Cortical structures While the majority of damage that causes hemiballismus occurs within the basal ganglia, there are still cases that have been documented on which damage to cortical structures has caused hemiballistic movements.[10] ## Diagnosis[edit] Diagnosis of hemiballismus is a clinical one, made with observation during clinical examination. Hemiballismus is a clinical sign with a number of different causes. Therefore a diagnosis underlying this clinical sign should be sought. The observer should note sudden, flinging movements of a limb(s) and occasionally the face. This is commonly unilateral ("Hemiballismus"). The movements must be distinguished from other hyperkinetic movement disorders such as tremor (generally more rhythmic, and smaller amplitude) and chorea, akathisia and athetosis (all are often of lower amplitude and less violent)[citation needed] ## Treatments[edit] When treating hemiballismus, it is first important to treat whatever may be causing the manifestation of this disorder. This could be hyperglycemia, infections, or neoplastic lesions. Some patients may not even need treatment because the disorder is not severe and can be self – limited.[10] Dopamine Blockers When pharmacological treatment is necessary, the most standard type of drug to use is an antidopaminergic drug. Blocking dopamine is effective in about ninety percent of patients. Perphenazine, pimozide, haloperidol, and chlorpromazine are standard choices for treatment. Scientists are still unsure as to why this form of treatment works, as dopamine has not been directly linked to hemiballismus.[10] Anticonvulsants An anticonvulsant called topiramate has helped patients in three cases and may be a viable treatment for the future.[16] ITB Therapy Intrathecal baclofen (ITB) therapy is used to treat a variety of movement disorders such as cerebral palsy and multiple sclerosis. It can also be a possibility to help treat hemiballismus.[5] In one case, before ITB the patient had an average of 10-12 ballism episodes of the right lower limb per hour. During episodes, the right hip would flex up to about 90 degrees, with a fully extended knee. After an ITB pump was implanted and the correct dosage was found, the frequency of ballistic right leg movements decreased to about three per day, and the right hip flexed to only 30 degrees. The patient was also able to better isolate individual distal joint movements in the right lower limb. The patient currently receives 202.4 microg/day of ITB and continues to benefit almost 6 years after the ITB pump was implanted.[5] Botulinum Injections New uses for botulinum toxin have included treatment of hemiballismus. However, this is still in the early stages of testing. This treatment deals with the muscular manifestations of hemiballismus as opposed to the neurological causes.[5][10] Tetrabenazine Tetrabenazine has been used to treat other movement disorders, but is now being used to treat hemiballismus. Patients using this medication have had a dramatic response. However, lowering the dosage leads to a return of symptoms. This drug works by depleting dopamine.[6] Antipsychotics In one case, a patient had not been responding to haloperidol, thus the physician tried olanzapine. The patient made a significant recovery. More research is being performed on the use of these types of drugs in treating hemiballismus.[11] Functional Neurosurgery Surgery as a treatment should only be used on patients with severe hemiballismus that has not responded to treatment. Lesioning of the globus pallidus or deep brain stimulation of the globus pallidus are procedures that can be used on humans. Usually, lesioning is favored over deep brain stimulation because of the maintenance required to continue stimulating the brain correctly and effectively.[10] ## Prognosis[edit] In the past, the prognosis for patients with this disease had been very poor; with many patients suffering from severe disability or death. Now, patients are responding remarkably well to current treatments and the majority of patients go into spontaneous remission. For those that do not go into remission, the symptoms of hemiballismus can generally be very well controlled with medication.[10] Due to the rarity of this disorder, scientists know very little about the details of hemiballismus. •There appears to be a discrepancy between this disorder in humans and animals that has yet to be explained.[10] •Hemiballismus can also be induced by damage to other areas of the basal ganglia besides the subthalamic nucleus. Research is being done in these areas in order to give scientists and clinicians a better model for this disease that will ultimately lead to better diagnosis and treatment of this disorder.[10] •Research is also being done on why certain treatments seem to help hemiballistic patients when they should seemingly do more harm. An example of this is why lesioning the globus pallidus seems to reduce hemiballistic movements.[10] •The mechanism behind the effect of dopamine on patients’ symptoms remains unknown.[10] ## History[edit] The work of J.R. Whittier, F.A. Mettler, and M.B. Carpenter in the mid 1900s helped scientists and clinicians form a more complete picture of hemiballismus. In their experiments, several lesions were made in the basal ganglia structures in monkeys and then they monitored the results. They noticed that the majority of the time, the monkeys did not have any unusual movements. However, when at least twenty percent of the subthalamic nucleus was damaged, abnormal movements were seen in the limbs opposite to the side of the brain that was damaged. This observation caused scientists to believe that hemiballismus outside the subthalamic nucleus did not occur. It was not until much later that this classical model began to expand to include other areas of the basal ganglia and even some cortical structures. They also noticed that unlike human patients, the unusual movements in the monkeys were mainly in the lower extremities. In about half of the monkeys, the hemiballismus continued until the monkey died.[10] Other scientists have also worked on this perplexing disorder and have found that the symptoms can be induced by injecting kainic acid or ibotenic acid into the subthalamic nucleus. I. Hamada and M.R. DeLong found that by using these chemicals, they could destroy only four percent of the subthalamic nucleus and still see hemiballistic movements. However, the abnormal movements would usually disappear within four to five hours even though it did not appear as though the damaged tissue had healed. This suggests that the subthalamic nucleus is plastic enough to adapt to small amounts of damage in order to resume normal function.[10] ## See also[edit] * Movement disorders ## References[edit] 1. ^ a b Purves, Dale (2012). Neuroscience (5th ed.). Sunderland, Mass. pp. 411–412. ISBN 9780878936953. 2. ^ a b c Das RR, Romero JR, Mandel A (2005). "Hemiballismus in a patient with Contralateral Carotid Artery Occlusion". Journal of the Neurological Sciences. 238: S392. doi:10.1016/S0022-510X(05)81507-2. S2CID 54398493. 3. ^ Gale J. T., Amirnovin R., Wiliams Z., Flaherty A. W. & Eskandar, E. N. (2008). "Symphony to cacophony: Pathophysiology of the human Basal Ganglia in Parkinson disease". Neuroscience and Biobehavioral Reviews. 32 (3): 378–387. doi:10.1016/j.neubiorev.2006.11.005. PMID 17466375. S2CID 14612243.CS1 maint: multiple names: authors list (link) 4. ^ a b c "Chorea, Athetosis, and Hemiballismus - Neurologic Disorders". MSD Manual Professional Edition. Retrieved 9 October 2020. 5. ^ a b c d e Francisco GE (2006). "Successful treatment of posttraumatic hemiballismus with intrathecal baclofen therapy". American Journal of Physical Medicine & Rehabilitation. 85 (9): 779–782. doi:10.1097/01.phm.0000233173.32432.6f. PMID 16924190. 6. ^ a b c d e Sitburana O, Ondo W (2006). "Tetrabenazine in hyperglycemic-induced hemichorea-hemiballismus". Movement Disorders. 21 (11): S353–S354. doi:10.1002/mds.21100. PMID 16986158. 7. ^ Haines, Duane; Mihailoff, Gregory (2018). Fundamental neuroscience for basic and clinical applications (Fifth ed.). Philadelphia, PA: Elsevier. p. 387. ISBN 9780323396325. 8. ^ Meyer, R. (1968) Ballismus. In: Vinken, P.J. and Bruyn, G.W. (Eds.), Handbook of Clinical Neurology, Vol. 6, North-Holland Publishing Co., Amsterdam, pp. 476-490. 9. ^ a b Gimenez-Munoz A, Alarcia R, Ledesma L, Ara JR (2008). "Pseudoballism secondary to spinal trauma". Neurologia. 23 (5): 315–318. PMID 18247185. 10. ^ a b c d e f g h i j k l m n o p q r s t u v w Postuma RB, Lang AE (2003). "Hemiballism: revisiting a classic disorder". Lancet Neurology. 2 (11): 661–668. doi:10.1016/S1474-4422(03)00554-4. PMID 14572734. S2CID 33892692. 11. ^ a b Mukand JA, Fitzsimmons C, Wennemer HK, Carrillo A, Cai CB, Bailey KM (2005). "Olanzapine for the treatment of hemiballismus: A case report". Archives of Physical Medicine and Rehabilitation. 86 (3): 587–590. doi:10.1016/j.apmr.2004.05.012. PMID 15759249. 12. ^ a b Grandas, F (2011). "Hemiballismus". Handbook of clinical neurology. 100: 249–60. doi:10.1016/B978-0-444-52014-2.00017-3. PMID 21496584. 13. ^ a b Gamez J, Corbera-Bellalta M, Mila M, Lopez-Lisbona R, Boluda S, Ferrer I (2008). "Chorea-ballism associated with familial amyotrophic lateral sclerosis. A clinical, genetic, and neuropathological study". Movement Disorders. 23 (3): 434–438. doi:10.1002/mds.21856. PMID 18072201. 14. ^ Kim HJ, Moon WJ, Oh J, Lee IK, Kim HY, Han SH (2008). "Subthalamic lesion on MR imaging in a patient with nonketotic hyperglycemia-induced hemiballism". American Journal of Neuroradiology. 29 (3): 526–527. doi:10.3174/ajnr.A0927. PMID 18184834. 15. ^ Temel Y, Blokland A, Steinbusch HW, Visser-Vandewalle V (2005). "The functional role of the subthalamic nucleus in cognitive and limbic circuits". Progress in Neurobiology. 76 (6): 393–413. doi:10.1016/j.pneurobio.2005.09.005. PMID 16249050. S2CID 12222747. 16. ^ Driver-Dunckley E, Evidente VG (2005). "Hemichorea-hemiballismus may respond to topiramate". Clinical Neuropharmacology. 28 (3): 142–144. doi:10.1097/01.wnf.0000164160.71206.a3. PMID 15965315. ## External links[edit] Classification D * ICD-10: G25.5 * ICD-9-CM: 333.5 * MeSH: D020820 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis * v * t * e Symptoms and signs relating to movement and gait Gait * Gait abnormality * CNS * Scissor gait * Cerebellar ataxia * Festinating gait * Marche à petit pas * Propulsive gait * Stomping gait * Spastic gait * Magnetic gait * Truncal ataxia * Muscular * Myopathic gait * Trendelenburg gait * Pigeon gait * Steppage gait * Antalgic gait Coordination * Ataxia * Cerebellar ataxia * Dysmetria * Dysdiadochokinesia * Pronator drift * Dyssynergia * Sensory ataxia * Asterixis Abnormal movement * Athetosis * Tremor * Fasciculation * Fibrillation Posturing * Abnormal posturing * Opisthotonus * Spasm * Trismus * Cramp * Tetany * Myokymia * Joint locking Paralysis * Flaccid paralysis * Spastic paraplegia * Spastic diplegia * Spastic paraplegia * Syndromes * Monoplegia * Diplegia / Paraplegia * Hemiplegia * Triplegia * Tetraplegia / Quadruplegia * General causes * Upper motor neuron lesion * Lower motor neuron lesion Weakness * Hemiparesis Other * Rachitic rosary * Hyperreflexia * Clasp-knife response [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake 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	Hemiballismus	c0221169	7,076	wikipedia	https://en.wikipedia.org/wiki/Hemiballismus	2021-01-18T19:10:06	{"mesh": ["D020820"], "umls": ["C0221169"], "icd-9": ["333.5"], "icd-10": ["G25.5"], "wikidata": ["Q946041"]}
This article is written like a personal reflection, personal essay, or argumentative essay that states a Wikipedia editor's personal feelings or presents an original argument about a topic. Please help improve it by rewriting it in an encyclopedic style. (April 2014) (Learn how and when to remove this template message) Emotional eating is defined as the "propensity to eat in response to positive and negative emotions."[1] While the term "emotional eating" often refers to eating as a means of coping with negative emotions, it also includes eating for positive emotions such as eating foods when celebrating an event or eating to enhance an already good mood. In these situations, emotions are still driving the eating but not in a negative way. ## Contents * 1 Background * 2 Characteristics * 3 Major theories behind eating to cope * 4 Contributing factors * 4.1 Negative affect * 4.2 Childhood development * 4.3 Related disorders * 4.4 Biological and environmental factors * 4.5 Positive Affect * 5 Impact * 6 Treatment * 7 Stress fasting * 8 See also * 9 References ## Background[edit] Emotional eating includes eating in response to any emotion, whether that be positive or negative. Most frequently, people refer to emotional eating as "eating to cope with negative emotions." In these situations, emotional eating can be considered a form of disordered eating which is defined as "an increase in food intake in response to negative emotions" and can be considered a maladaptive strategy. More specifically, emotional eating in order to relieve negative emotions would qualify as a form of emotion-focused coping, which attempts to minimize, regulate, and prevent emotional distress. A study found that emotional eating sometimes does not reduce emotional distress but instead enhances emotional distress by sparking feelings of intense guilt after an emotional eating session.[2] Those that eat as a coping strategy are at an especially high risk of developing binge-eating disorder, and those with eating disorders are at a higher risk to engage in emotional eating as a means to cope. In a clinical setting, emotional eating can be assessed by the Dutch Eating Behavior Questionnaire which contains a scale for restrained, emotional and external eating. Other questionnaires such as the Palatable Eating Motives Scale can determine reasons why a person eats tasty foods when they are not hungry; sub-scales include eating for reward enhancement, coping, social, and conformity.[3] ## Characteristics[edit] Emotional eating usually occurs when one is attempting to satisfy his or her hedonic drive, or the drive to eat palatable food to obtain pleasure in the absence of an energy deficit but can also occur when one is seeking food as a reward, eating for social reasons (such as eating at a party), or eating to conform (which involves eating because friends or family wants the individual to). When one is engaging in emotional eating, they are usually seeking out palatable foods (such as sweets) rather than just food in general. In some cases, emotional eating can lead to something called "mindless eating" during which the individual is eating without being mindful of what or how much they are consuming; this can occur during both positive and negative settings. Emotional hunger does not originate from the stomach, such as with a rumbling or growling stomach, but tends to start when a person thinks about a craving or wants something specific to eat. Emotional responses are also different. Giving in to a craving or eating because of stress can cause feelings of regret, shame, or guilt, and these responses tend to be associated with emotional hunger. On the other hand, satisfying a physical hunger is giving the body the nutrients or calories it needs to function and is not associated with negative feelings. ## Major theories behind eating to cope[edit] Current research suggests that certain individual factors may increase one's likelihood of using emotional eating as a coping strategy. The inadequate affect regulation theory posits that individuals engage in emotional eating because they believe overeating alleviates negative feelings.[4] Escape theory builds upon inadequate affect regulation theory by suggesting that people not only overeat to cope with negative emotions, but they find that overeating diverts their attention away from a stimuli that is threatening self-esteem to focus on a pleasurable stimuli like food. Restraint theory suggests that overeating as a result of negative emotions occurs among individuals who already restrain their eating. While these individuals typically limit what they eat, when they are faced with negative emotions they cope by engaging in emotional eating.[4] Restraint theory supports the idea that individuals with other eating disorders are more likely to engage in emotional eating. Together these three theories suggest that an individual's aversion to negative emotions, particularly negative feelings that arise in response to a threat to the ego or intense self-awareness, increase the propensity for the individual to utilize emotional eating as a means of coping with this aversion. The biological stress response may also contribute to the development of emotional eating tendencies. In a crisis, corticotropin-releasing hormone (CRH) is secreted by the hypothalamus, suppressing appetite and triggering the release of glucocorticoids from the adrenal gland.[5] These steroid hormones increase appetite and, unlike CRH, remain in the bloodstream for a prolonged period of time, often resulting in hyperphagia. Those who experience this biologically instigated increase in appetite during times of stress are therefore primed to rely on emotional eating as a coping mechanism. ## Contributing factors[edit] ### Negative affect[edit] Overall, high levels of the negative affect trait are related to emotional eating. Negative affectivity is a personality trait involving negative emotions and poor self-concept. Negative emotions experienced within negative affect include anger, guilt, and nervousness. It has been found that certain negative affect regulation scales predicted emotional eating.[6] An inability to articulate and identify one's emotions made the individual feel inadequate at regulating negative affect and thus more likely to engage in emotional eating as a means for coping with those negative emotions.[6] Further scientific studies regarding the relationship between negative affect and eating find that, after experiencing a stressful event, food consumption is associated with reduced feelings of negative affect (i.e. feeling less bad) for those enduring high levels of chronic stress. This relationship between eating and feeling better suggests a self-reinforcing cyclical pattern between high levels of chronic stress and consumption of highly palatable foods as a coping mechanism.[7] Contrarily, a study conducted by Spoor et al.[4] found that negative affect is not significantly related to emotional eating, but the two are indirectly associated through emotion-focused coping and avoidance-distraction behaviors. While the scientific results differed somewhat, they both suggest that negative affect does play a role in emotional eating but it may be accounted for by other variables.[4][6] ### Childhood development[edit] For some people, emotional eating is a learned behavior. During childhood, their parents give them treats to help them deal with a tough day or situation, or as a reward for something good. Over time, the child who reaches for a cookie after getting a bad grade on a test may become an adult who grabs a box of cookies after a rough day at work. In an example such as this, the roots of emotional eating are deep, which can make breaking the habit extremely challenging.[8] In some cases, individuals may eat in order to conform; for example, individuals may be told "you have to finish your plate" and the individual may eat past the point in which they feel satisfied. ### Related disorders[edit] Emotional eating as a means to cope may be a precursor to developing eating disorders such as binge eating or bulimia nervosa. The relationship between emotional eating and other disorders is largely due to the fact that emotional eating and these disorders share key characteristics. More specifically, they are both related to emotion focused coping, maladaptive coping strategies, and a strong aversion to negative feelings and stimuli. It is important to note that the causal direction has not been definitively established, meaning that while emotional eating is considered a precursor to these eating disorders, it also may be the consequence of these disorders. The latter hypothesis that emotional eating happens in response to another eating disorder is supported by research that has shown emotional eating to be more common among individuals already suffering from bulimia nervosa.[6] ### Biological and environmental factors[edit] Stress affects food preferences. Numerous studies — granted, many of them in animals — have shown that physical or emotional distress increases the intake of food high in fat, sugar, or both, even in the absence of caloric deficits.[9] Once ingested, fat- and sugar-filled foods seem to have a feedback effect that damps stress-related responses and emotions, as these foods trigger dopamine and opioid releases, which protect against the negative consequences of stress.[10] These foods really are "comfort" foods in that they seem to counteract stress, but rat studies demonstrate that intermittent access to and consumption of these highly palatable foods creates symptoms that resemble opioid withdrawal, suggesting that high-fat and high-sugar foods can become neurologically addictive [10] A few examples from the American diet would include: hamburgers, pizza, French fries, sausages and savory pasties. The most common food preferences are in decreasing order from: sweet energy-dense food, non-sweet energy-dense food then, fruits and vegetables.[11] This may contribute to people's stress-induced craving for those foods.[12] The stress response is a highly-individualized reaction and personal differences in physiological reactivity may also contribute to the development of emotional eating habits. Women are more likely than men to resort to eating as a coping mechanism for stress,[13] as are obese individuals and those with histories of dietary restraint.[14] In one study, women were exposed to an hour-long social stressor task or a neutral control condition. The women were exposed to each condition on different days. After the tasks, the women were invited to a buffet with both healthy and unhealthy snacks. Those who had high chronic stress levels and a low cortisol reactivity to the acute stress task consumed significantly more calories from chocolate cake than women with low chronic stress levels after both control and stress conditions.[15] High cortisol levels, in combination with high insulin levels, may be responsible for stress-induced eating, as research shows high cortisol reactivity is associated with hyperphagia, an abnormally increased appetite for food, during stress.[16] Furthermore, since glucocorticoids trigger hunger and specifically increase one's appetite for high-fat and high-sugar foods, those whose adrenal glands naturally secrete larger quantities of glucocorticoids in response to a stressor are more inclined toward hyperphagia.[5] Additionally, those whose bodies require more time to clear the bloodstream of excess glucocorticoids are similarly predisposed. These biological factors can interact with environmental elements to further trigger hyperphagia. Frequent intermittent stressors trigger repeated, sporadic releases of glucocorticoids in intervals too short to allow for a complete return to baseline levels, leading to sustained and elevated levels of appetite. Therefore, those whose lifestyles or careers entail frequent intermittent stressors over prolonged periods of time thus have greater biological incentive to develop patterns of emotional eating, which puts them at risk for long-term adverse health consequences such as weight gain or cardiovascular disease. Macht (2008) [17] described a five-way model to explain the reasoning behind stressful eating: (1) emotional control of food choice, (2) emotional suppression of food intake, (3) impairment of cognitive eating controls, (4) eating to regulate emotions, and (5) emotion-congruent modulation of eating. These break down into subgroups of: Coping, reward enhancement, social and conformity motive. Thus, providing an individual with are stronger understanding of personal emotional eating. ### Positive Affect[edit] Geliebter and Aversa (2003) conducted a study comparing individuals of three weight groups: underweight, normal weight and overweight. Both positive and negative emotions were evaluated. When individuals were experiencing positive emotional states or situations, the underweight group reporting eating more than the other two groups. As an explanation, the typical nature of underweight individuals is to eat less and during times of stress to eat even less. However, when positive emotional states or situations arise, individuals are more likely to indulge themselves with food.[18] ## Impact[edit] Emotional eating may qualify as avoidant coping and/or emotion-focused coping. As coping methods that fall under these broad categories focus on temporary reprieve rather than practical resolution of stressors, they can initiate a vicious cycle of maladaptive behavior reinforced by fleeting relief from stress.[19] Additionally, in the presence of high insulin levels characteristic of the recovery phase of the stress-response, glucocorticoids trigger the creation of an enzyme that stores away the nutrients circulating in the bloodstream after an episode of emotional eating as visceral fat, or fat located in the abdominal area.[5] Therefore, those who struggle with emotional eating are at greater risk for abdominal obesity, which is in turn linked to a greater risk for metabolic and cardiovascular disease. ## Treatment[edit] There are numerous ways in which individuals can reduce emotional distress without engaging in emotional eating as a means to cope. The most salient choice is to minimize maladaptive coping strategies and to maximize adaptive strategies. A study conducted by Corstorphine et al. in 2007 investigated the relationship between distress tolerance and disordered eating.[20] These researchers specifically focused on how different coping strategies impact distress tolerance and disordered eating. They found that individuals who engage in disordered eating often employ emotional avoidance strategies. If an individual is faced with strong negative emotions, they may choose to avoid the situation by distracting themselves through overeating. Discouraging emotional avoidance is thus an important facet to emotional eating treatment. The most obvious way to limit emotional avoidance is to confront the issue through techniques like problem solving. Corstorphine et al. showed that individuals who engaged in problem solving strategies enhance one's ability to tolerate emotional distress.[20] Since emotional distress is correlated to emotional eating, the ability to better manage one's negative affect should allow an individual to cope with a situation without resorting to overeating. One way to combat emotional eating is to employ mindfulness techniques.[21] For example, approaching cravings with a nonjudgmental inquisitiveness can help differentiate between hunger and emotionally-driven cravings. An individual may ask his or herself if the craving developed rapidly, as emotional eating tends to be triggered spontaneously. An individual may also take the time to note his or her bodily sensations, such as hunger pangs, and coinciding emotions, like guilt or shame, in order to make conscious decisions to avoid emotional eating. Emotional eating can also be improved by evaluating physical facets like hormone balance. Female hormones, in particular, can alter cravings and even self-perception of one's body. Additionally, emotional eating can be exacerbated by social pressure to be thin. The focus on thinness and dieting in our culture can make young girls, especially, vulnerable to falling into food restriction and subsequent emotional eating behavior.[22] Emotional eating disorder predisposes individuals to more serious eating disorders and physiological complications. Therefore, combatting disordered eating before such progression takes place has become the focus of many clinical psychologists. ## Stress fasting[edit] In a lesser percentage of individuals, emotional eating may conversely consist of reduced food intake, or stress fasting.[23] This is believed to result from the fight-or-flight response.[24] In some individuals, depression and other psychological disorders can also lead to emotional fasting or starvation. ## See also[edit] * Comfort food * Food addiction * Overeating * Social determinants of health ## References[edit] 1. ^ Turton, Robert; Chami, Rayane; Treasure, Janet (2017-04-22). "Emotional Eating, Binge Eating and Animal Models of Binge-Type Eating Disorders". Current Obesity Reports. 6 (2): 217–228. doi:10.1007/s13679-017-0265-8. ISSN 2162-4968. PMID 28434108. S2CID 3973000. 2. ^ Bennett, Jessica; Greene, Geoffrey; Schwartz-Barcott, Donna (January 28, 2013). "Perceptions of emotional eating behavior. A qualitative study of college students". Appetite. 60 (1): 187–192. doi:10.1016/j.appet.2012.09.023. PMID 23046706. S2CID 5720881. 3. ^ Boggiano, M.M.; Burgess, E.E.; Turan, B.; Soleymani, T.; Daniel, S.; Vinson, L.D.; Lokken, K.L.; Wingo, B.C.; Morse, A. (December 2014). "Motives for eating tasty foods associated with binge-eating. Results from a student and a weight-loss seeking population". Appetite. 83: 160–166. doi:10.1016/j.appet.2014.08.026. ISSN 0195-6663. PMC 4962333. PMID 25169880. 4. ^ a b c d Spoor, S. T.; Bekker, M. H.; van Strien, T.; van Heck, G. L. (2007). "Relations between negative affect, coping, and emotional eating" (PDF). Appetite. 48 (3): 368–376. doi:10.1016/j.appet.2006.10.005. PMID 17145096. S2CID 2017758. 5. ^ a b c Sapolsky, Robert M. (1998). Why Zebras Don't Get Ulcers. W. H. Freeman. pp. 39–42. ISBN 978-0716732105. 6. ^ a b c d Spence, S.; Courbasson, C. (2012). "The role of emotional dysregulation in concurrent eating disorders and substance use disorders". Eating Behaviors. 13 (4): 382–385. doi:10.1016/j.eatbeh.2012.05.006. PMID 23121793. 7. ^ Klatzkin, R.; Baldassaro, A.; Hayden (2018). "The impact of chronic stress on the predictors of acute stress-induced eating in women". Appetite. 123: 343–351. doi:10.1016/j.appet.2018.01.007. PMID 29309852. S2CID 3622058. 8. ^ Galan, Nicole (15 February 2018). "Emotional eating: How to overcome stress eating". Medical News Today. Retrieved 2018-10-11. 9. ^ Yau, Yvonne H. C.; Potenza, Marc N. (2013). "Stress and Eating Behaviors". Minerva Endocrinologica. 38 (3): 255–267. ISSN 0391-1977. PMC 4214609. PMID 24126546. 10. ^ a b Adam, Tanja C.; Epel, Elissa S. (July 2007). "Stress, eating and the reward system". Physiology & Behavior. 91 (4): 449–458. doi:10.1016/j.physbeh.2007.04.011. PMID 17543357. S2CID 4845263. 11. ^ Konttinen, Hanna; Männistö, Satu; Sarlio-Lähteenkorva, Sirpa; Silventoinen, Karri; Haukkala, Ari (June 2010). "Emotional eating, depressive symptoms and self-reported food consumption. A population-based study". Appetite. 54 (3): 473–479. doi:10.1016/j.appet.2010.01.014. ISSN 1095-8304. PMID 20138944. S2CID 27554287. 12. ^ "Why stress causes people to overeat - Harvard Health". Harvard Health. February 2012. Retrieved 2018-10-11. 13. ^ "Gender and Stress". American Psychological Association. 2010. Retrieved 7 April 2020. 14. ^ Yau, Yvonne H. C.; Potenza, Marc N. (2003). "Stress and Eating Behaviors". Minerva Endocrinologica. 38 (3): 255–267. ISSN 0391-1977. PMC 4214609. PMID 24126546. 15. ^ Tryon, M.S.; DeCant, Rashel; Laugero, K.D. (April 2013). "Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness". Physiology & Behavior. 114–115: 32–37. doi:10.1016/j.physbeh.2013.02.018. PMID 23500173. S2CID 24971720. 16. ^ Epel, Elissa; Lapidus, Rachel; McEwen, Bruce; Brownell, Kelly (January 2001). "Stress may add bite to appetite in women: a laboratory study of stress-induced cortisol and eating behavior". Psychoneuroendocrinology. 26 (1): 37–49. doi:10.1016/S0306-4530(00)00035-4. PMID 11070333. S2CID 4889400. 17. ^ Macht, Michael (2008). "How emotions affect eating: A five-way model". Appetite. 50 (1): 1–11. doi:10.1016/j.appet.2007.07.002. PMID 17707947. S2CID 2820934. 18. ^ Geliebter, Allan; Aversa, Angela (January 2003). "Emotional eating in overweight, normal weight, and underweight individuals". Eating Behaviors. 3 (4): 341–347. doi:10.1016/S1471-0153(02)00100-9. ISSN 1471-0153. PMID 15000995. 19. ^ "Emotional Eating as a Coping Mechanism". The Huffington Post. 2013-03-19. Retrieved 2016-04-18. 20. ^ a b Corstorphine, E.; Mountford, V.; Tomlinson, S.; Waller, G.; Meyer, C. (2007). "Distress tolerance in the eating disorders". Eating Behaviors. 8 (1): 91–97. doi:10.1016/j.eatbeh.2006.02.003. PMID 17174856. 21. ^ "Comfort Foods: Men Vs Women & 3 Ways to Curb Your Cravings". factfindersteph.com. Retrieved 2016-04-18. 22. ^ Johnson, Brynn. "How to Stop Binge Eating". Brynn Johnson Emotional Eating Coach. Retrieved 13 September 2018. 23. ^ Glowatz, Elana (2016-10-05). "Stress Eating vs. Stress Fasting: Dangers And Effects On The Mind And Body". Medical Daily. Retrieved 2020-05-07. 24. ^ Strutner, Suzy (2017-02-15). "Why You Lose Your Appetite When You're Upset". Huffington Post. Retrieved 2020-05-07. * v * t * e Emotions (list) Emotions * Acceptance * Adoration * Aesthetic emotions * Affection * Agitation * Agony * Amusement * Anger * Angst * Anguish * Annoyance * Anticipation * Anxiety * Apathy * Arousal * Attraction * Awe * Boredom * Calmness * Compassion * Confidence * Contempt * Contentment * Courage * Cruelty * Curiosity * Defeat * Depression * Desire * Despair * Disappointment * Disgust * Distrust * Ecstasy * Embarrassment * Vicarious * Empathy * Enthrallment * Enthusiasm * Envy * Euphoria * Excitement * Fear * Flow (psychology) * Frustration * Gratification * Gratitude * Greed * Grief * Guilt * Happiness * Hatred * Hiraeth * Homesickness * Hope * Horror * Hostility * Humiliation * Hygge * Hysteria * Indulgence * Infatuation * Insecurity * Inspiration * Interest * Irritation * Isolation * Jealousy * Joy * Kindness * Loneliness * Longing * Love * Limerence * Lust * Mono no aware * Neglect * Nostalgia * Outrage * Panic * Passion * Pity * Self-pity * Pleasure * Pride * Grandiosity * Hubris * Insult * Vanity * Rage * Regret * Social connection * Rejection * Remorse * Resentment * Sadness * Melancholy * Saudade * Schadenfreude * Sehnsucht * Self-confidence * Sentimentality * Shame * Shock * Shyness * Sorrow * Spite * Stress * Suffering * Surprise * Sympathy * Tenseness * Trust * Wonder * Worry World views * Cynicism * Defeatism * Nihilism * Optimism * Pessimism * Reclusion * Weltschmerz Related * Affect * consciousness * in education * measures * in psychology * Affective * computing * forecasting * neuroscience * science * spectrum * Affectivity * positive * negative * Appeal to emotion * Emotion * and art * and memory * and music * and sex * classification * evolution * expressed * functional accounts * group * homeostatic * perception * recognition * in conversation * in animals * regulation * interpersonal * work * Emotional * aperture * bias * blackmail * competence * conflict * contagion * detachment * dysregulation * eating * exhaustion * expression * intelligence * and bullying * intimacy * isolation * lability * labor * lateralization * literacy * prosody * reasoning * responsivity * security * selection * symbiosis * well-being * Emotionality * bounded * Emotions * and culture * in decision-making * in the workplace * in virtual communication * history * moral * self-conscious * social * social sharing * sociology * Feeling * Gender and emotional expression * Group affective tone * Interactions between the emotional and executive brain systems * Meta-emotion * Pathognomy * Pathos * Social emotional development * Stoic passions * Theory * affect * appraisal * discrete emotion * somatic marker * constructed emotion [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Emotional eating	None	7,077	wikipedia	https://en.wikipedia.org/wiki/Emotional_eating	2021-01-18T18:36:05	{"wikidata": ["Q17010564"]}
A number sign (#) is used with this entry because the papillorenal syndrome (PAPRS) is caused by heterozygous mutation in the PAX2 gene (167409) on chromosome 10q24. Description Papillorenal syndrome is an autosomal dominant disorder characterized by both ocular and renal anomalies. Less common findings include high frequency hearing loss, central nervous system anomalies, soft skin, ligamentous laxity, and/or genital anomalies, consistent with the expression of PAX2 in these tissues during development (summary by Eccles and Schimmenti, 1999; Negrisolo et al., 2011). The disorder shows wide inter- and intrafamilial variability. The renal features are part of a spectrum of malformations termed congenital anomalies of the kidney and urinary tract (CAKUT; see, e.g., 610805), and some patients with PAX2 mutations may present with CAKUT without obvious ocular abnormalities. In these patients, ocular abnormalities may be subtle and difficult to detect without advanced screening methods or may be normal (summary by Negrisolo et al., 2011; Iatropoulos et al., 2012). Eye anomalies associated with PAX2 mutations consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, designated optic nerve 'coloboma' or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease (summary by Schimmenti, 2011). Clinical Features Rieger (1977) reported a family in which the father showed bilateral optic disc anomalies and died of chronic nephritis; his son showed macular and retinal abnormalities but renal function was normal, whereas his daughter had normal eyes but suffered from renal failure. This is a variability not unexpected for an autosomal dominant syndrome. Karcher (1979) described a father and son with the 'morning glory' optic disc anomaly and renal disease. Weaver et al. (1988) reported 2 brothers with optic nerve colobomas associated with renal disease. There is uncertainty as to whether the 'morning glory' syndrome represents a colobomatous defect or an abnormality of regression of mesodermal structures of the embryonic optic disc (Kindler, 1970; Dempster et al., 1983). Under the designation papillorenal syndrome, Bron et al. (1989) described the same disorder. Parsa (1998) also concluded that this is a condition of dysplastic discs rather than coloboma and that papillorenal syndrome is a more appropriate designation. Schimmenti et al. (1995) and Sanyanusin et al. (1995) described a father and 3 sons had optic nerve colobomas, vesicoureteral reflux, and renal anomalies. The 35-year-old father was more mildly affected than the sons. He had bilateral optic nerve colobomas but no renal problems recognized during childhood. An evaluation prompted by the renal problems in his sons demonstrated hypertension, mild proteinuria, and an elevated serum creatinine, but normal renal ultrasound. Ophthalmologic examination showed severe bilateral myopia, scleral staphyloma, and bilateral colobomas. Mild sensorineural hearing loss of unknown cause was also present. The oldest affected son, aged 15 years, had chronic renal failure and severe visual impairment. He first presented at 18 months for investigation of short stature. He already had renal insufficiency and showed a nonfunctioning right kidney and bilateral grade IV vesicoureteral reflux. The last ureteral reimplantation was performed at age 2. Hearing was normal. The second affected son, aged 10 years, had severe visual impairment, optic nerve colobomas, and mild renal dysfunction. He had grade II vesicoureteral reflux and small hypoplastic kidneys with poor corticomedullary differentiation. The third affected son, aged 6 years, had progressive renal failure for which he underwent renal transplantation at the age of 5 years. Sanyanusin et al. (1995) reported further on 2 brothers with 'typical renal-coloboma syndrome without associated vesicoureteric reflux' who were originally described by Weaver et al. (1988). The younger brother had presented with severe progressive renal failure leading to renal transplantation and had a bilateral visual field defect with optic nerve colobomas. The older brother presented with chronic mild renal failure, a visual field defect, and optic nerve colobomas. The 2 brothers were the only affected family members and both parents had normal ophthalmologic examinations. Amiel et al. (2000) described a family in which 3 affected sibs showed striking ocular phenotypic variability. One sib had bilateral renal hypoplasia and 'morning glory' syndrome, whereas the other 2 presented with isolated unilateral cystic renal hypoplasia with no obvious ocular manifestation. Careful ophthalmologic examination of the latter 2 sibs showed an optic disc anomaly in both: bilateral papillary dysplasia in one and bilateral optic nerve coloboma in the other. Schimmenti et al. (1999) described a severely affected girl and a mildly affected mother and daughter, all of whom had PAX2 homoguanine tract (7G) missense mutations. The mother and daughter had optic nerve colobomas and the daughter had vesicoureteral reflux. The severely affected girl developed renal failure and had bilateral colobomatous eye defects. Additionally, this girl developed hydrocephalus associated with platybasia and a Chiari-1 malformation. Thus, the phenotype associated with PAX2 mutations must be expanded to include brain malformations. Amiel et al. (2000) described a family in which 3 affected sibs showed striking ocular phenotypic variability. One sib had bilateral renal hypoplasia and 'morning glory' syndrome, whereas the other 2 presented with isolated unilateral cystic renal hypoplasia with no obvious ocular manifestation. Careful ophthalmologic examination of the latter 2 sibs showed an optic disc anomaly in both: bilateral papillary dysplasia in one and bilateral optic nerve coloboma in the other. To define better the characteristics of the papillorenal syndrome, Parsa et al. (2001) studied 2 unrelated probands and 11 family members via Doppler imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations. Affected individuals had numerous cilioretinal vessels with rudimentary or absent central retinal vessels. Static superonasal visual field defects, typical of papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in 2 affected members of 1 family (with previously unsuspected renal failure in 1 case), and recurrent pyelonephritis was discovered in 4 affected members of the other family. No PAX2 mutations were detected in either family. In the papillorenal syndrome, the hereditary absence of the central retinal vessels may be missed, leading to confusion with isolated optic nerve coloboma, low-tension glaucoma, and morning glory anomaly. Parsa et al. (2001) suggested that greater awareness of this syndrome would avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and facilitate genetic counseling. They proposed that the papillorenal syndrome is a primary vascular dysgenesis affecting the optic nerve, kidney, and urinary tract, causing hypoplasia of these structures. The authors concluded that the absence of mutations in the PAX2 gene in these families suggests that defects in other genes may also result in this syndrome. ### Clinical Variability Weber et al. (2006) identified heterozygous PAX2 mutations in 7 patients from 6 unrelated families ascertained for renal hypodysplasia. The families were part of a larger cohort of 99 index patients with renal hypodysplasia screened for mutations in 5 genes. Ocular abnormalities, including coloboma and optic disc dysplasia, were found in 5 of the 7 patients and in 1 of 2 affected parents. In most of these patients, the ocular alterations were so subtle that they had not been diagnosed before the detection of the PAX2 mutation. In 2 of 20 unrelated children and young adults with CAKUT resulting in renal failure and renal transplantation but with no apparent ocular abnormalities, Negrisolo et al. (2011) identified 2 different de novo heterozygous mutations in the PAX2 gene: a nonsense mutation and a splice site mutation respectively. One of the patients was later found to have myopia and isotropy of the right eye. The other patients showed bilateral excavation of the optic disc on optic fundus reexamination. Negrisolo et al. (2011) concluded that patients with CAKUT without apparent ocular abnormalities should be screened for mutations in the PAX2 gene, and that ocular abnormalities may be underdiagnosed in patients with PAX2 mutations. Thomas et al. (2011) identified heterozygous pathogenic PAX2 mutations in 3 of 73 children with chronic kidney disease due to renal hypodysplasia. It was not known if the patients with PAX2 mutations had subtle ocular findings, and Thomas et al. (2011) concluded that they should be followed for extrarenal manifestations. The findings also had implications for genetic counseling. Iatropoulos et al. (2012) reported a pair of monozygotic twin sisters with papillorenal syndrome confirmed by genetic analysis who were discordant for the phenotype. The proband was found to have multicystic kidneys antenatally and she had poor renal function after birth. Renal examination showed a nonfunctional multicystic right kidney and a hyperechogenic left kidney with poor corticomedullary differentiation. She had chronic renal disease and underwent successful kidney graft at age 23. Dilated eye examination showed no ocular abnormalities. Her sister showed renal insufficiency at birth associated with hyperechoic renal pyramids, but this resolved rapidly. At age 10 years, dipstick showed mild proteinuria. At age 2 years, she had complete loss of visual acuity in the left eye due to optic nerve coloboma; the right eye was normal. At age 20 years, she had overt nephropathy with normal renal function. Both sisters had joint laxity and skin hyperextensibility. There was no evidence of somatic mosaicism for the mutation among tissues from the sisters, and Iatropoulos et al. (2012) postulated environmental or epigenetic modifiers to explain the discordant phenotype. Barua et al. (2014) reported 7 unrelated individuals with CAKUT diagnosed in early childhood. Features were variable, and included solitary kidney with hydronephrosis or hydrocele, horseshoe kidney, ureteropelvic junction obstruction (UPJO), ureterovesical junction obstruction (UVJO), and vesicoureteral reflux (VUR). Two patients had additional nonrenal manifestations, including dysmorphic features. No ocular or auditory abnormalities were documented. Pathogenesis Parsa et al. (2002) noted that the dysplastic discs seen in papillorenal syndrome are not true colobomas: defective angiogenesis, rather than abnormal fissure closure, underlies the anomalous disc morphology as well as the retinal and choroidal hypoplasia with corresponding visual field defects. Affected individuals show multiple cilioretinal vessels and a variable attenuation or absence of the central retinal vessels. Alterations in vascular development also explain observed abnormalities of the renal cortex, the second most perfused tissue per gram of weight in the human body (after the choroid). Molecular Genetics In a father and 3 sons with coloboma of the optic nerve and renal disease, Sanyanusin et al. (1995) identified a mutation in the PAX2 gene (167409.0001). In 2 brothers with optic nerve coloboma and renal disease originally described by Weaver et al. (1988), Sanyanusin et al. (1995) identified a heterozygous mutation in the PAX2 gene (619insG; 167409.0002). Cunliffe et al. (1998) studied 99 patients with isolated colobomas or colobomas and urogenital abnormalities. A gene mutation in the PAX2 gene was found in only 1 individual who had typical renal-coloboma syndrome. Tellier et al. (1998) reported patients with isolated renal hypoplasia and mutation in the PAX2 gene (e.g., 167409.0005). In a severely affected girl and a mildly affected mother and daughter, Schimmenti et al. (1999) identified mutations in the PAX2 gene. The mother and daughter had a contraction in a string of 7 G's to 6 G's on one allele of PAX2, leading to a premature stop codon 2 amino acids downstream. The severely affected girl, who also had a brain malformation, had an expansion to 8 G's on one allele, leading to a premature stop codon 27 amino acids downstream. The 8G expansion had been found in other patients without brain anomalies and had occurred spontaneously in a mouse model, PAX2(1Neu). In 3 sibs with papillorenal syndrome who showed striking ocular variability, Amiel et al. (2000) identified the PAX2 619insG mutation (167409.0002). The unaffected parents did not carry the mutation, suggesting the presence of germline mosaicism. The study of a PAX2 intragenic DNA microsatellite marker showed that the mutation was of paternal origin (false paternity was excluded by the study of polymorphic markers). Ford et al. (2001) described a family in which at least 7 members had manifestations of renal-coloboma syndrome. Two of these had renal disease due to oligohydramnios and renal hypoplasia, diagnosed prenatally by ultrasound examination. All affected members had the PAX2 619insG mutation (167409.0002). There was remarkable variability in both the ocular and renal manifestations. In a child with atypical bilateral optic nerve coloboma and congenital renal hypoplasia, Chung et al. (2001) identified a novel heterozygous PAX2 mutation leading to premature termination of the protein. The mutation was not found in the parents. The authors concluded that the causal relationship between PAX2 gene mutations and the renal-coloboma syndrome was further supported by this novel mutation. In a mother and daughter previously reported by Naito et al. (1989) with macular abnormalities accompanied by anomalies of the optic disc and kidney consistent with the diagnosis of renal-coloboma syndrome, Higashide et al. (2005) identified a mutation in the PAX2 gene (167409.0012). Higashide et al. (2005) suggested that this mutation might also cause foveal hypoplasia and pigmented macular atrophy in addition to anomalies of the optic disc and kidney. Because the daughter also had polydactyly, Naito et al. (1989) had made the diagnosis of acrorenoocular syndrome (607323). To investigate whether PAX2 mutations occur in patients with isolated renal hypoplasia, Nishimoto et al. (2001) analyzed DNA from 20 patients with bilateral renal hypoplasia associated with decreased renal function. Heterozygous PAX2 mutations were detected in 2 patients (167409.0010 and 167409.0011, respectively). Ophthalmologic examination revealed very mild, asymptomatic coloboma in the second patient, whereas the fundus was normal in the first. The mutation cosegregated with renal hypoplasia in the family of the first patient, appearing de novo in the patient's mother. Nishimoto et al. (2001) concluded that isolated renal hypoplasia can be part of the spectrum of the renal-coloboma syndrome. Martinovic-Bouriel et al. (2010) analyzed the PAX2 gene in 2 fetuses with renal anomalies and optic nerve colobomas and in 18 fetuses with isolated renal disease, of which 10 had uni- or bilateral renoureteral agenesis, 6 had enlarged dysplastic kidneys, and 2 had small dysplastic kidneys. In the 2 fetuses with papillorenal syndrome, the authors identified a frameshift and a splice site mutation in the PAX2 gene, respectively, but no mutations were detected in the 18 fetuses with isolated renal disease. Barua et al. (2014) identified 8 different missense mutations in the PAX2 gene in 7 (8%) of 85 individuals with CAKUT. Seven patients had a heterozygous mutation, whereas 1 patient with a more severe phenotype and extrarenal abnormalities was compound heterozygous. Parental DNA available from 3 of the patients showed that the mutations occurred de novo. Functional studies of the variants were not performed, but 6 occurred in the transactivation domain. ### Reviews Eccles and Schimmenti (1999) reviewed the clinical features of patients with renal-coloboma syndrome and PAX2 mutations, and the specific mutations reported to that time. Bower et al. (2012) reviewed published cases of PAX2 mutations as well as data from a consortium of 3 laboratories, and identified a total of 53 unique PAX2 mutations and 12 other PAX2 variants in 173 individuals from 86 families. The most frequently reported recurring mutation was 76dup (167409.0002). Renal disease was the most highly penetrant feature in this series, being identified in 159 (92%) of 173 mutation-positive individuals. The most common renal findings were renal hypodysplasia (114 patients; 65%), vesicoureteral reflux (25 patients; 14%), renal cysts (13 patients; 8%), and multicystic dysplastic kidneys (7 patients; 6%). Nineteen individuals (13%) were reported to have 'renal failure' without further details. In this series, 134 (77%) of 173 mutation-positive individuals were reported to have ophthalmologic abnormalities, whereas 12 (7%) had a normal eye exam and 37 (21%) did not have an eye exam. Abnormalities of the optic nerve were noted in 125 cases, with the most common findings described as optic nerve coloboma (84 patients), optic disc dysplasia (21), excavation of the optic disc or 'pits' (14), optic disc hyperplasia (11), morning glory optic discs (10), and hypoplastic optic discs (7). Additional findings included gliosis of the optic nerve and absent optic nerve head; several patients had more than 1 finding involving the optic nerve. Many patients had involvement outside the optic nerve, with retinal findings in 23 patients that included retinal coloboma (6), abnormal retinal pigment epithelium (6), abnormal retinal vessels (8), chorioretinal degeneration (3), and 1 report each of retinal detachment, retinal staphyloma, and retinal edema. Macular abnormalities were reported in 6 patients: macular degeneration, papillomacular detachment, hyperpigmentation of the macula, and cystic degeneration of the macula. Lens abnormalities were reported in 2 cases (posterior lens luxation and lens opacity), and microphthalmia was reported in 3 cases. Bower et al. (2012) noted that iris coloboma did not appear to be a feature in the renal coloboma syndrome, as it was not found in any of the mutation-positive individuals. Additional nonrenal, nonophthalmologic findings included hearing loss in 12 (7%) of the 173 patients. No clear genotype/phenotype correlations emerged from this study, and the authors commented that the tremendous intrafamilial variability described in renal coloboma syndrome suggests that factors other than PAX2 genotype play a significant role. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Sensorineural hearing loss (rare) Eyes \- Retinal coloboma \- Optic nerve coloboma \- Optic disc dysplasia \- Excavation of optic disc (pits) \- Optic disc hyperplasia \- Morning glory optic disc \- Hypoplastic optic disc \- Orbital cysts \- Microphthalmia \- Gliosis of optic nerve \- Absent optic nerve head \- Abnormal retinal pigment epithelium \- Abnormal retinal vessels \- Chorioretinal degeneration \- Retinal detachment (rare) \- Retinal staphyloma (rare) \- Retinal edema (rare) \- Macular degeneration (rare) \- Papillomacular detachment (rare) \- Hyperpigmentation of the macula (rare) \- Cystic degeneration of the macula (rare) \- Posterior lens luxation (rare) \- Lens opacity (rare) GENITOURINARY Kidneys \- Congenital anomalies of the kidney and urinary tract (CAKUT) \- Renal hypoplasia \- End stage renal failure \- Renal cysts \- Multicystic dysplastic kidneys \- Medullary sponge kidney (rare) \- Horseshoe kidney (rare) \- Nephrolithiasis (rare) \- Renal malrotation (rare) \- Anomalous renal pelvis (rare) Ureters \- Vesicoureteral reflux \- Pyeloureteral duplication (rare) SKELETAL \- Joint laxity SKIN, NAILS, & HAIR Skin \- Hyperextensible skin \- Soft skin NEUROLOGIC Central Nervous System \- Normal intelligence \- Mental retardation (one patient) \- Seizure disorder \- Arnold Chiari type I malformation LABORATORY ABNORMALITIES \- Proteinuria MISCELLANEOUS \- Onset in infancy \- Variable phenotype \- Ocular abnormalities may be very mild \- End-stage renal disease (CKD Stage 5) requiring kidney transplantation is commonly reported MOLECULAR BASIS \- Caused by mutation in the paired box homeotic gene 2 (PAX2, 167409.0001 ) ▲ 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	PAPILLORENAL SYNDROME	c1852759	7,078	omim	https://www.omim.org/entry/120330	2019-09-22T16:43:06	{"doid": ["0090006"], "mesh": ["C537168"], "omim": ["120330"], "orphanet": ["1475"], "synonyms": ["Alternative titles", "RENAL-COLOBOMA SYNDROME", "OPTIC NERVE COLOBOMA WITH RENAL DISEASE", "COLOBOMA OF OPTIC NERVE WITH RENAL DISEASE", "OPTIC COLOBOMA, VESICOURETERAL REFLUX, AND RENAL ANOMALIES", "RENAL-COLOBOMA SYNDROME WITH MACULAR ABNORMALITIES", "CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT WITH OR WITHOUT OCULAR ABNORMALITIES", "CAKUT WITH OR WITHOUT OCULAR ABNORMALITIES"], "genereviews": ["NBK1451"]}
A number sign (#) is used with this entry because of evidence that poikiloderma with neutropenia (PN) is caused by homozygous or compound heterozygous mutation in the C16ORF57 gene (USB1; 613276) on chromosome 16q21. Clinical Features Erickson (1999) provided a review of an apparently unique genodermatosis first described by Clericuzio et al. (1991). The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectases. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. That the disorder is not limited to skin is indicated by the fact that patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. Neutropenia has been variably present and may be cyclical. Autosomal recessive inheritance seemed clear because 8 of the 14 initial patients were sibs and none of the parents were affected. All of the patients were Navajo. There are some similarities to Rothmund-Thomson syndrome (RTS; 268400); however, the skin lesions of RTS primarily occur in sun-exposed areas, and the patients usually show marked alopecia of the head and eyebrows. In addition, RTS patients have skeletal manifestations, cataracts, and predisposition to malignancy, specifically osteosarcoma (Wang et al., 2001). Wang et al. (2003) reported 2 Navajo sisters, ascertained in their teens, who had the classic rash of PN and neutropenia. They also reported a 2-year-old Turkish British girl who carried an initial diagnosis of probable RTS; however, her clinical findings were more consistent with PN. Her rash started at age 3 months on her lower legs, then spread to involve the arms, and eventually more centrally to involve her trunk and face. It began as a mottled pink/red rash with an eczematous component and over time became more hyperpigmented and poikilodermatous. She had pachyonychia, especially of the toenails. At age 20 months, she was found to have severe neutropenia that persisted and was noncyclical. Bone marrow exam was normal. In a Scottish kindred, 2-year-old male and female fraternal twins, born to nonconsanguineous parents, developed an eczematous rash on the arms and legs and subsequently on the face beginning at the age of 2 months. Gradually the eczema cleared and was replaced by poikiloderma; nail dystrophy started at 3 weeks of age with subungual hyperkeratosis. The nails were markedly thickened and difficult to cut. Both children had recurrent respiratory infections with prominent wheezing and recurrent otitis media. At age 20 months, they were both found to have isolated severe neutropenia. Van Hove et al. (2005) reported 2 sibs from a consanguineous Turkish family with poikiloderma of the limbs and face, plantar keratoderma, toenail pachyonychia, and neutropenia and neutrophil dysfunction resulting in frequent respiratory infections. The proband died at 2 years of age from respiratory failure due to a bronchocentric granulomatous pneumonia. His brother had previously been diagnosed with RTS. Linkage analysis excluded the RECQL4 gene (603780) on chromosome 8q24. Van Hove et al. (2005) suggested that previously reported cases of RTS with myelodysplasia and neutropenia might represent PN rather than RTS. Mostefai et al. (2008) reported 3 sibs from a consanguineous Moroccan family who presented with cutaneous poikiloderma following postnatal ichthyosiform lesions, associated with papillomatous lesions, palmoplantar keratoderma, pachyonychia of toenails, fragile carious teeth, and lachrymal duct obstruction. Photosensitivity and blistering improved with age. Atrophic scars were prominent on the limbs. Neutropenia developed in the first year secondary to dysmyelopoiesis affecting the granulocyte lineage, associated with a polyclonal hypergammaglobulinemia. Studies of neutrophils from 1 patient showed impaired production of reactive oxygen species. All patients had bronchopulmonary infections. The phenotype matched that described originally as poikiloderma with neutropenia-Clericuzio type in Navajo Indians. Mostefai et al. (2008) noted the phenotypic overlap with the group of the major hereditary poikiloderma disorders, including Rothmund-Thomson syndrome, dyskeratosis congenita (127550), and Kindler syndrome (173650). Concolino et al. (2010) provided clinical details on a brother and 2 sisters with poikiloderma and neutropenia from the highly consanguineous Italian family previously studied by Volpi et al. (2010). All 3 sibs had poikiloderma, neutropenia, short stature, dystrophic nails, and hypermobile fingers with a 'beak of swan' appearance. The sibs also displayed facial dysmorphism, including hypoplasia of eyebrows, frontal bossing, widely spaced eyes, midface hypoplasia, small nose, depressed nasal bridge, and prognathism. Concolino et al. (2010) reviewed previously reported cases and noted that although dysmorphic features have not always been described, the male patient studied by Van Hove et al. (2005) showed photographic evidence of midface hypoplasia very similar to their male patient. Concolino et al. (2019) reported a 10-year follow-up on the brother and 2 sisters reported by Volpi et al. (2010) and Concolino et al. (2010). The authors noted the stability of the intrafamilial heterogeneity of clinical manifestations. None of the patients, currently in their second and third decades of life, had developed skin cancer or myelodysplastic disorders. In both sisters, a small posterior lens opacity was seen; these were not visually significant. The frequency of acute sinopulmonary infections decreased during later years, despite a persistent noncyclic neutropenia. In one of the patients, normal neutrophil values and an absence of signs or symptoms of acute infection were seen. A substantially elevated ferritin value was noted in one of the sisters; no specific cause of the increased level was identified. Mapping In a highly consanguineous Italian family with poikiloderma and neutropenia, Volpi et al. (2010) performed linkage analysis and identified a 3.4-Mb candidate region on 16q between rs16954293 and rs9939133, containing more than 80 known and predicted genes. Using array capture-mediated next-generation sequencing, Volpi et al. (2010) identified an A-C SNP at 56,608,737 Mb within the highly conserved C16ORF57 gene (613276) that appeared to be a strong candidate. Molecular Genetics In 3 affected sibs from a highly consanguineous Italian family with poikiloderma and neutropenia, who were known to be negative for mutation in the Rothmund-Thomson syndrome (RTS; 268400)-associated gene RECQL4 (603780), Volpi et al. (2010) identified homozygosity for a splice site mutation in the C16ORF57 gene (613276.0001). Analysis of the C16ORF57 gene in 5 patients diagnosed with 'atypical' RTS revealed compound heterozygosity for mutations in C16ORF57 (613276.0002-613276.0003) in an unrelated Italian female patient with neutropenia, who had previously been reported by Pianigiani et al. (2001) with a diagnosis of RTS and myelodysplasia but who was found to be negative for mutation in the RECQL4 gene by Volpi et al. (2010). In 3 affected sibs from the consanguineous Moroccan family with poikiloderma and neutropenia, previously studied by Mostefai et al. (2008), Tanaka et al. (2010) identified homozygosity for a 1-bp deletion in the C16ORF57 gene (613276.0004). The unaffected parents were heterozygous for the mutation, which was not found in an unaffected sister. ### Exclusion Studies Because of phenotypic overlap between PN and RTS, Wang et al. (2003) performed a mutation screen of the RECQL4 gene, which is mutant in RTS, in 1 Navajo and 2 non-Navajo kindreds with the PN phenotype. No mutations were found in any of the patients. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Midface hypoplasia (in some patients) Ears \- Otitis media, recurrent Eyes \- Hypertelorism (in some patients) \- Eyebrow hypoplasia (in some patients) RESPIRATORY Lung \- Pulmonary infections, recurrent ABDOMEN Spleen \- Splenomegaly SKELETAL Hands \- Hypermobile fingers - 'beak of swan' appearance (in some patients) SKIN, NAILS, & HAIR Skin \- Poikiloderma \- Keratoderma of palms and soles Nails \- Pachyonychia HEMATOLOGY \- Neutropenia IMMUNOLOGY \- Recurrent infections at variable sites (sinusitis, otitis media, facial cellulitis, adenitis, blepharitis, conjunctivitis, gastroenteritis) LABORATORY ABNORMALITIES \- Neutropenia MOLECULAR BASIS \- Caused by mutation in the chromosome 16 open reading frame 57 gene (C16ORF57, 613276.0001 ) ▲ 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	POIKILODERMA WITH NEUTROPENIA	c1858723	7,079	omim	https://www.omim.org/entry/604173	2019-09-22T16:12:26	{"doid": ["0060551"], "mesh": ["C565820"], "omim": ["604173"], "orphanet": ["221046"], "synonyms": ["Alternative titles", "POIKILODERMA WITH NEUTROPENIA, CLERICUZIO-TYPE"], "genereviews": ["NBK459118"]}
Rimoin (1969) and Fox et al. (1976) described 2 sisters with an identical malformation of the nose consisting mainly of hypoplasia and coloboma of the alar cartilages. Both also showed telecanthus. The parents and other relatives were unaffected and no parental consanguinity was reported. This remains a unique observation (Gorlin, 1982). Eyes \- Telecanthus Nose \- Alar cartilage hypoplasia \- Alar clefts Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	FRONTONASAL DYSPLASIA WITH ALAR CLEFTS	c1859964	7,080	omim	https://www.omim.org/entry/203000	2019-09-22T16:31:21	{"mesh": ["C535967"], "omim": ["203000"], "orphanet": ["2007"], "synonyms": ["Alternative titles", "ALAR-NASAL CARTILAGES, COLOBOMA OF, WITH TELECANTHUS"]}
Kairo cancer SpecialtyDermatology/oncology Kairo cancer is a cutaneous condition that may develop due to hydrocarbon-fueled heat exposure from coal-fired clothing warmers.[1] ## See also[edit] * Kangri ulcer * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1356. ISBN 978-1-4160-2999-1. 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	Kairo cancer	None	7,081	wikipedia	https://en.wikipedia.org/wiki/Kairo_cancer	2021-01-18T18:29:54	{"wikidata": ["Q6348271"]}
Otopalatodigital syndrome spectrum disorder is a primary bone dysplasia and encompasses a group of congenital anomalies that are characterized by skeletal dysplasia of varying clinical severity and an X linked dominant pattern of inheritance. This group includes otopalatodigital syndrome type 1 and 2 (OPD1, OPD2) which are characterized in affected males by cleft palate, conductive hearing loss, craniofacial abnormalities and skeletal dysplasia; Melnick-Needles syndrome (MNS) which displays skeletal deformities in females and embryonic or perinatal lethality in most males; frontometaphyseal dysplasia (FMD); and terminal osseous dysplasia - pigmentary defects. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Otopalatodigital syndrome spectrum disorder	c2748918	7,082	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=364541	2021-01-23T18:07:44	{"mesh": ["C567577"], "umls": ["C2748918"], "synonyms": ["OPD spectrum disorder", "OPSD"]}
Glutaric acidemia type I (also called glutaric aciduria type I) is an inherited disorder in which the body is unable to process certain proteins properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems. People with glutaric acidemia type I have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these amino acids and their intermediate breakdown products can accumulate and cause damage to the brain, particularly the basal ganglia, which are regions that help control movement. Intellectual disability may also occur. The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood. Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery. ## Frequency Glutaric acidemia type I occurs in approximately 1 in 100,000 individuals. It is much more common in the Amish community and in the Ojibwa population of Canada, where up to 1 in 300 newborns may be affected. ## Causes Mutations in the GCDH gene cause glutaric acidemia type I. The GCDH gene provides instructions for making the enzyme glutaryl-CoA dehydrogenase. This enzyme is involved in processing the amino acids lysine, hydroxylysine, and tryptophan. Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme that cannot function. A shortage (deficiency) of this enzyme allows lysine, hydroxylysine and tryptophan and their intermediate breakdown products to build up to abnormal levels, especially at times when the body is under stress. The intermediate breakdown products resulting from incomplete processing of lysine, hydroxylysine, and tryptophan can damage the brain, particularly the basal ganglia, causing the signs and symptoms of glutaric acidemia type I. ### Learn more about the gene associated with Glutaric acidemia type I * GCDH ## 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	Glutaric acidemia type I	c0268595	7,083	medlineplus	https://medlineplus.gov/genetics/condition/glutaric-acidemia-type-i/	2021-01-27T08:25:50	{"gard": ["6522"], "mesh": ["C536833"], "omim": ["231670"], "synonyms": []}
Nodular sclerosis Nodular sclerosis. The distinct nodules on the cut surface of this lymph node strongly suggest the diagnosis. SpecialtyOncology Nodular sclerosis (or "NSHL") is a form of Hodgkin's lymphoma[1] that is the most common subtype of HL in developed countries. It affects females slightly more than males and has a median age of onset at ~28 years. It is composed of large tumor nodules with lacunar Reed–Sternberg cell (RS cells) surrounded by fibrotic collagen bands. The British National Lymphoma Investigation further categorized NSHL based upon Reed-Sternberg cells into "nodular sclerosis type I" (NS I) and "nodular sclerosis type II" (NS II), with the first subtype responding better to treatment.[2] ## References[edit] 1. ^ Falchi L, Capello D, Palumbo B, et al. (November 2007). "A case of nodular sclerosis Hodgkin's lymphoma repeatedly relapsing in the context of composite plasma cell-hyaline vascular Castleman's disease: successful response to rituximab and radiotherapy". Eur. J. Haematol. 79 (5): 455–61. doi:10.1111/j.1600-0609.2007.00952.x. PMC 2121125. PMID 17908180. 2. ^ Mauch, Peter; James Armitage; Volker Diehl; Richard Hoppe; Laurence Weiss (1999). Hodgkin's Disease. Lippincott Williams & Wilkins. p. 107. ISBN 978-0-7817-1502-7. ## External links[edit] * PubMed \- use of Erythropoietin * Subtypes * Lymphoma Association information on nodular sclerosing Classification D * ICD-10: C81.1 * ICD-9-CM: 201.5 * ICD-O: M9663/3-9667/3 * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias This article about a neoplasm 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	Nodular sclerosis	c0152268	7,084	wikipedia	https://en.wikipedia.org/wiki/Nodular_sclerosis	2021-01-18T19:07:10	{"umls": ["C0152268"], "icd-10": ["C81.1"], "wikidata": ["Q17126784"]}
A number sign (#) is used with this entry because of evidence that this form of congenital defect in bile acid synthesis with delta(4)-3-oxosteroid 5-beta-reductase deficiency, referred to here as CBAS2, is caused by homozygous or compound heterozygous mutation in the AKR1D1 gene (604741) on chromosome 7q33. For a general description and a discussion of genetic heterogeneity of congenital bile acid synthesis defects, see 607765. Clinical Features Setchell et al. (1988) reported monozygotic male twins who presented at birth with cholestatic jaundice due to severe intrahepatic cholestasis. A previously born sib had died at the age of 4 months of hepatic failure following an identical course. Using fast atom bombardment ionization-mass spectrometry, the authors found increased urinary excretion and predominance of taurine-conjugated unsaturated hydroxy-oxo-bile acids. The biochemical findings indicated a defect in bile acid synthesis involving the delta(4)-3-oxosteroid 5-beta-reductase enzyme which converts delta(4)-3-oxo-C27 bile acid intermediates into the corresponding 3-alpha-hydroxy-5-beta(H) structures. The inheritance suggested an autosomal recessive disorder. On follow-up studies of the patients reported by Setchell et al. (1988), Daugherty et al. (1993) found defective primary bile acid synthesis and markedly increased levels of atypical oxo and allo bile acids in urine and serum. Liver biopsy showed hepatocellular cholestasis and giant-cell transformation which resolved in parallel with clinical and biochemical recovery during oral bile acid administration. In the twins, 5 years old at the time of report, portal fibrosis stabilized at a mild level. Follow-up biopsy in another brother at 8 months was normal, and he was doing well at 3 years of age. Daugherty et al. (1993) identified 8 additional patients by urine screening; all were boys. Shneider et al. (1994) and Siafakas et al. (1997) reported a total of 5 infants with delta(4)-3-oxosteroid 5-beta-reductase deficiency who also had neonatal hemochromatosis (231100). Kimura et al. (1998) studied a 5-month-old Japanese boy with severe neonatal cholestasis associated with hypertyrosinemia. A liver sample was examined by immunoblot analysis using monoclonal antibodies against 5-beta-reductase. Although an indistinct band of 5-beta-reductase was seen in the analysis, it remained uncertain as to whether this represented a primary or inherited 5-beta-reductase deficiency. It may have been a secondary deficiency due to severe liver damage, even though 3-oxo-delta(4) bile acids constituted more than 70% of the total urinary bile acids. Clayton et al. (1996) and Lemonde et al. (2003) reported a Sardinian girl who presented at age 3 weeks with hyperbilirubinemia, elevated liver enzymes, and prolonged prothrombin time consistent with cholestasis. She also had steatorrhea, failure to thrive, and rickets. Liver biopsy showed extensive giant cell transformation and steatosis. Gamma-GGT (see 612346) was normal. By age 9 years, she was doing well on bile replacement therapy with chenodeoxycholic acid and cholic acid. Lemonde et al. (2003) described 2 additional unrelated patients with neonatal cholestatic jaundice. Both patients were born of consanguineous parents. Other clinical features included coagulopathy, giant cell hepatitis, and almost complete absence of chenodeoxycholic and cholic acids. Both patients developed liver failure necessitating liver transplantation. Molecular Genetics In 3 unrelated patients with progressive familial intrahepatic cholestasis due to delta(4)-3-oxosteroid 5-beta-reductase deficiency, Lemonde et al. (2003) identified 3 different homozygous mutations in the AKR1D1 gene (604741.0001-604741.0003). Urinary profile of all 3 patients showed almost complete absence of chenodeoxycholic and cholic acids. One of the patients had been reported by Clayton et al. (1996). ### Exclusion Studies In an infant with clinical and biochemical features of 5-beta-reductase deficiency, including urinary bile salts with a 3-oxo-delta(4) content greater than 94%, Sumazaki et al. (1997) excluded a pathogenic mutation in the AKR1D1 gene. Genotype/Phenotype Correlations Drury et al. (2010) noted that a patient with a homozygous truncating mutation in the ARK1D1 gene (604741.0002; Lemonde et al., 2003) had a more severe phenotype necessitating liver transplantation compared to 2 sibs with compound heterozygous missense mutations resulting in some residual protein function (605741.0004 and 604741.0005; Gonzales et al., 2004) who responded well to oral cholic acid supplementation and did not need liver transplantation. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive ABDOMEN Liver \- Intrahepatic cholestasis \- Jaundice \- Hepatomegaly \- Giant cell transformation on biopsy \- Canalicular cholestasis \- Hepatocyte necrosis \- Liver failure before adulthood \- Septal fibrosis Spleen \- Splenomegaly Gastrointestinal \- Diarrhea \- Steatorrhea \- Malabsorption of fat and fat-soluble vitamins SKIN, NAILS, & HAIR Skin \- Jaundice HEMATOLOGY \- Coagulopathy secondary to liver disease LABORATORY ABNORMALITIES \- Hyperbilirubinemia \- Abnormal liver function tests \- Increased serum alkaline phosphatase \- Normal serum levels of gamma-GGT ( 231950 ) \- Decreased or absent serum and urinary chenodeoxycholic acid and cholic acid MISCELLANEOUS \- Neonatal onset \- Caused by inborn error in bile acid synthesis \- Favorable response to oral bile acid therapy MOLECULAR BASIS \- Caused by mutation in the delta-4-3-oxosteroid 5-beta-reductase gene (AKR1D1, 604741.0001 ) ▲ 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	BILE ACID SYNTHESIS DEFECT, CONGENITAL, 2	c1856127	7,085	omim	https://www.omim.org/entry/235555	2019-09-22T16:27:09	{"doid": ["0111069"], "mesh": ["C535443"], "omim": ["235555"], "orphanet": ["79303"], "synonyms": ["Alternative titles", "CHOLESTASIS WITH DELTA(4)-3-OXOSTEROID 5-BETA-REDUCTASE DEFICIENCY"]}
Biotinidase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. If this condition is not recognized and treated, its signs and symptoms typically appear within the first few months of life, although it can also become apparent later in childhood. Profound biotinidase deficiency, the more severe form of the condition, can cause seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis. Affected children also have delayed development. Lifelong treatment can prevent these complications from occurring or improve them if they have already developed. Partial biotinidase deficiency is a milder form of this condition. Without treatment, affected children may experience hypotonia, skin rashes, and hair loss, but these problems may appear only during illness, infection, or other times of stress. ## Frequency Profound or partial biotinidase deficiency occurs in approximately 1 in 60,000 newborns ## Causes Mutations in the BTD gene cause biotinidase deficiency. The BTD gene provides instructions for making an enzyme called biotinidase. This enzyme recycles biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Biotinidase removes biotin that is bound to proteins in food, leaving the vitamin in its free (unbound) state. Free biotin is needed by enzymes called biotin-dependent carboxylases to break down fats, proteins, and carbohydrates. Because several of these enzymes are impaired in biotinidase deficiency, the condition is considered a form of multiple carboxylase deficiency. Mutations in the BTD gene reduce or eliminate the activity of biotinidase. Profound biotinidase deficiency results when the activity of biotinidase is reduced to less than 10 percent of normal. Partial biotinidase deficiency occurs when biotinidase activity is reduced to between 10 percent and 30 percent of normal. Without enough of this enzyme, biotin cannot be recycled. The resulting shortage of free biotin impairs the activity of biotin-dependent carboxylases, leading to a buildup of potentially toxic compounds in the body. If the condition is not treated promptly, this buildup damages various cells and tissues, causing the signs and symptoms described above. ### Learn more about the gene associated with Biotinidase deficiency * BTD ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the BTD gene in each cell have mutations. The parents of an individual with biotinidase deficiency each carry one copy of the mutated gene, but they typically do not have any health problems associated with 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	Biotinidase deficiency	c0220754	7,086	medlineplus	https://medlineplus.gov/genetics/condition/biotinidase-deficiency/	2021-01-27T08:25:34	{"gard": ["894"], "mesh": ["D028921"], "omim": ["253260"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that primary lymphedema with myelodysplasia is caused by heterozygous mutation in the GATA2 gene (137295) on chromosome 3q21. Immunodeficiency-21 (IMD21; 614172) is an allelic disorder with overlapping clinical features. Clinical Features Emberger et al. (1979) reported a family in which 3 individuals over 2 generations, who had severe congenital deafness, also developed lower limb lymphedema in childhood and hematologic abnormalities, including pancytopenia in 2 of them and acute myeloblastic leukemia in 1 individual. The male proband was born deaf and developed bilateral lymphedema of the lower extremities at 4 years of age. At age 12 years, he was found to have acute myeloblastic leukemia, and died 1 year later. His older sister, who also had profound congenital deafness, developed lymphedema of her right leg at age 13 years and was found to have anemia with leukopenia at age 21 years. Hematologic evaluation at age 26 years for anemia showed increased hemolysis, with a red cell half-life of 17.5 days; bone marrow function was normal with only slightly reduced daily hemoglobin synthesis. A younger brother had only congenital deafness, without edema or hematologic abnormalities. The older sister had a son who was born with profound bilateral deafness and at the age of 3 years developed edema of the left leg; transient granulocytopenia was noted at that time. A distant relative developed lymphedema of the left lower extremity at age 26 years, but did not have hearing loss or hematologic abnormalities. At 48 years of age, during a hospitalization for macronodular cirrhosis, mitral sclerosis, and cerebellar atrophy, 'elephantiasis-like' edema of the left leg was also noted. She died of hematuria at 51 years of age. The proband's parents were clinically unaffected and had no hematologic abnormalities. Drony et al. (1983) reported a 23-year-old woman who underwent surgery at 19 years of age for lymphedema of both lower extremities; she also had bilateral syndactyly of the second and third toes. During a febrile episode she was noted to be pancytopenic and was diagnosed with acute myeloblastic leukemia. She achieved complete remission with chemotherapy, but relapsed 3 months later and died within 1 year. Drony et al. (1983) also reported a 20-year-old man who underwent surgery for lymphedema of the right lower extremity at 12 years of age. He was later noted to have granulocytopenia; 2 years later he was anemic and bone marrow examination showed 60% undifferentiated cells of erythroblastic lineage, suggestive of acute myeloblastic leukemia. Chemotherapy was complicated by infections and hemorrhage, and he died suddenly 5 months after diagnosis of apparent cardiac complications. Attal et al. (1985) reported a male patient who at 18 years of age developed bilateral lymphedema that was complicated by streptococcal erysipelas and other infections over the next 3 years. At 21 years of age, he was noted to have pancytopenia with a cellular marrow, which was attributed to early myelodysplasia with refractory cytopenia; bone marrow karyotype showed 47 chromosomes (monosomy unspecified). A year later, he developed acute myeloblastic leukemia and died 18 months later without ever achieving remission. A sister had died at 13 years of age from acute myeloblastic leukemia, and a brother had cytopenic myelodysplasia with a cellular marrow; neither had lymphedema, and none of the 3 sibs had hearing loss. Attal et al. (1985) reviewed 4 previously reported cases, noting that all were young patients and that in 3 of the 4 cases, there was a preceding prolonged cytopenia suggestive of early acquired myelodysplasia. Mansour et al. (2010) described 7 unrelated patients with primary lymphedema associated with myelodysplasia, 1 of whom had a significant family history. The authors noted that the lymphedema typically presented in 1 or both lower limbs, before the hematologic abnormalities, with onset between infancy and puberty and frequently involved the genitalia. Acute myeloid leukemia was often preceded by pancytopenia or myelodysplasia with a high incidence of monosomy 7 in the bone marrow (5 probands and 2 relatives). Associated anomalies included hypotelorism, epicanthic folds, long tapering fingers and/or neck webbing (4 patients), recurrent cellulitis in the affected limb (4 patients), generalized warts (2 patients), and congenital high-frequency sensorineural deafness (1 patient). Mansour et al. (2010) concluded that children with lower limb and genital lymphedema should be screened for hematologic abnormalities and immunodeficiency. Molecular Genetics Ostergaard et al. (2011) performed whole-exome sequencing in 3 unrelated individuals with primary lymphedema and myelodysplasia, 2 with familial disease who were previously studied by Mansour et al. (2010) and 1 with sporadic disease, and identified a different heterozygous truncating mutation in the GATA2 gene (137295.0009-137295.0011) in each proband. The 2 variants identified in the familial cases were shown to be transmitted across generations between affected individuals within the kindred. Sanger sequencing of GATA2 in 5 additional probands, 3 of whom had previously been studied by Mansour et al. (2010), revealed heterozygous mutations in each (see, e.g., 137295.0012 and 137295.0013). None of the 8 GATA2 variants was found in 300 unrelated control chromosomes. ### Exclusion Studies Mansour et al. (2010) analyzed various candidate genes in 5 unrelated patients with primary lymphedema and myelodysplasia from whom DNA was available, but did not identify any pathogenic mutations. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Deafness, congenital sensorineural, profound (in some patients) Eyes \- Hypotelorism (in some patients) \- Epicanthic folds (in some patients) Neck \- Webbed neck (in some patients) GENITOURINARY External Genitalia (Male) \- Lymphedema External Genitalia (Female) \- Lymphedema SKELETAL Hands \- Long, tapering fingers (in some patients) SKIN, NAILS, & HAIR Skin \- Cellulitis, recurrent \- Warts, generalized (in some patients) MUSCLE, SOFT TISSUES \- Lymphedema, lower extremities HEMATOLOGY \- Pancytopenia \- Myelodysplasia \- Bone marrow monosomy 7 NEOPLASIA \- Leukemia, acute myeloid MOLECULAR BASIS \- Caused by mutation in the GATA-binding protein-2 gene (GATA2, 137295.0009 ) ▲ 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	LYMPHEDEMA, PRIMARY, WITH MYELODYSPLASIA	c3279664	7,087	omim	https://www.omim.org/entry/614038	2019-09-22T15:56:43	{"mesh": ["D000077428"], "omim": ["614038"], "orphanet": ["3226"], "synonyms": ["Emberger syndrome", "Alternative titles", "EMBERGER SYNDROME"]}
Heijbel and Jagell (1981) described 3 sibs (2 males, 1 female) with what they considered to be a new syndrome of spastic paraplegia, glaucoma, and mental retardation. Another related female was also affected. The 3 sibs had 4 other sibs with essential myoclonus. Chenevix-Trench et al. (1986) described a second sibship from a consanguineous marriage in which 3 brothers were affected with the triad of spastic paresis, mental retardation, and glaucoma. The parents were first cousins once removed. Eyes \- Glaucoma Neuro \- Spastic paraplegia \- Mental retardation Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	SPASTIC PARESIS, GLAUCOMA, AND MENTAL RETARDATION	c1849113	7,088	omim	https://www.omim.org/entry/270850	2019-09-22T16:22:13	{"mesh": ["C564809"], "omim": ["270850"], "orphanet": ["2818"]}
Hemochromatosis type 4 (also called ferroportin disease) is a form of rare hereditary hemochromatosis (HH; see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin. ## Epidemiology HH type 4 is less rare than the other rare forms of HH, hemochromatosis type 2 or type 3 (see these terms). Fewer than 200 cases have been reported in the literature. It has a worldwide distribution. ## Clinical description The disease is phenotypically heterogeneous with two sub-types. Ferroportin disease form A is the usual form and is generally asymptomatic with no tissue damage and further complications. With age, tissue damage in the liver can occur which in some cases can lead to fibrosis. Ferroportin disease form B is rarer and resembles hemochromatosis type 1, but can affect children. ## Etiology Ferroportin disease is due to mutations in the SLC40A1 gene located on chromosome 2, which encodes for ferroportin (FPN), an iron exporter negatively regulated by the hepcidin hormone. In form A, the ferroportin loss of function mutants are unable to export iron from cells leading to cellular (especially macrophage) iron accumulation with decreased availability of iron for serum transferrin, which is reflected in low transferrin saturation. In form B, ferroportin mutations are responsible for a gain of function with full iron export capability but insensitivity to down-regulation by hepcidin (resistance to hepcidin), which leads to a phenotype similar to hepcidin deficiency-related HH (i.e. types 1, 2, and 3). ## Diagnostic methods Ferroportin disease form A displays high serum ferritin levels associated with normal or low transferrin saturation and iron accumulation within splenic and hepatic (Kupffer cells) macrophages. MRI shows iron excess mainly in the spleen and, to a lesser degree, in the liver. Ferroportin disease form B displays elevated transferrin saturation associated with tissue iron accumulation, preferentially within hepatocytes. Due to the dominant pattern of inheritance, the diagnosis is facilitated by the frequent finding of similar cases of hyperferritinemia among family members. Molecular genetic blood testing allows, in most cases, the diagnosis to be established in a non invasive way (i.e. without a liver biopsy). For form A, the diagnosis must rule out other causes of hyperferritinemia with low transferrin saturation such as inflammation, metabolic syndrome, aceruloplasminemia (see this term) and L-ferritin mutations. For form B, the diagnosis must rule out hemochromatosis types 1 and 3, but also type 2 since form B ferroportin disease can also affect children. ## Genetic counseling Transmission is autosomal dominant. Genetic counseling should be offered to affected families, informing them of the 50% risk of inheriting the disease-causing mutation. ## Management and treatment Unlike patients with ferroportin disease form B, patients with form A may not tolerate phlebotomies well, with a risk for developing anemia. ## Prognosis Ferroportin disease form A has a benign course. Ferroportin disease form B is expected to have a good prognosis provided that patients are treated early, before the development of visceral complications. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Hemochromatosis type 4	c1853733	7,089	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139491	2021-01-23T18:32:17	{"gard": ["10094"], "mesh": ["C537249"], "omim": ["606069"], "umls": ["C1853733"], "icd-10": ["E83.1"], "synonyms": ["Autosomal dominant hereditary hemochromatosis", "Ferroportin disease", "Hemochromatosis due to defect in ferroportin"]}
Startle epilepsy is a rare neurologic disease characterized by frequent and spontaneous epileptic seizures (frequently with symmetrical or asymmetrical tonic features) triggered by a normal startle in response to a sudden and unexpected somatosensory (most frequently auditory) stimulus. Falls are common and can be traumatic. In most cases, the disease is associated with spastic hemi-, di-, or tetraplegia and intellectual disability. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Startle epilepsy	c4706527	7,090	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166427	2021-01-23T16:56:49	{"icd-10": ["G40.5"]}
Schistosomiasis is an infectious disease caused by parasitic trematodes of the genus Schistosoma that colonize human blood vessels and release eggs that can cause granulomatous reactions leading to acute (swimmer's itch or acute schistosomiasis syndrome) or chronic disease. Depending on where the eggs lodge, manifestations of chronic schistosomiasis can include diarrhea, abdominal pain, loss of appetite, anemia (intestines), hepatosplenism, periportal fibrosis with portal hypertension (liver), urogenital inflammation and scarring, hematuria and dysuria (genitourinary system). Other patients may be asymptomatic. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Schistosomiasis	c0036323	7,091	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1247	2021-01-23T18:53:27	{"gard": ["9687"], "mesh": ["D012552"], "omim": ["181460"], "umls": ["C0036323"], "icd-10": ["B65.0", "B65.1", "B65.2", "B65.3", "B65.8", "B65.9"], "synonyms": ["Bilharziasis"]}
A transfusion transmitted infection (TTI) is a virus, parasite, or other potential pathogen that can be transmitted in donated blood through a transfusion to a recipient. The term is usually limited to known pathogens, but also sometimes includes agents such as Simian foamy virus which are not known to cause disease. Preventing the spread of these diseases by blood transfusion is addressed in several ways. In many cases, the blood is tested for the pathogen, sometimes with several different methodologies. Donors of blood are also screened for signs and symptoms of disease and for activities that might put them at risk for infection. If a local supply is not safe, blood may be imported from other areas. Human immunodeficiency virus (HIV) leads to the best known of the transfusion transmitted diseases, acquired immune deficiency syndrome (AIDS). Blood that is processed into medications by fractionation is treated in a multi-step process called pathogen inactivation that is analogous to pasteurization: it destroys most viruses and bacteria in the blood. Donors are still screened and tested. ## Contents * 1 Viruses * 1.1 HIV * 1.2 Hepatitis A * 1.3 Hepatitis B * 1.4 Hepatitis C * 1.4.1 Alanine transaminase (ALT) * 1.5 Human T-Lymphotropic Virus (HTLV I/II) * 1.6 Cytomegalovirus (CMV) * 1.7 West Nile virus * 1.8 Simian foamy virus (SFV) * 1.9 SARS * 2 Parasites and specific bacteria * 2.1 Malaria (Plasmodia spp.) * 2.2 Babesiosis * 2.3 Chagas disease * 2.4 Leishmaniasis * 2.5 Syphilis * 2.6 Lyme disease * 3 Other bacteria * 3.1 Skin flora * 3.2 Bacteremia and platelets * 4 Variant Creutzfeldt–Jakob disease (vCJD) * 5 See also * 6 References * 7 External links ## Viruses[edit] Many of these viruses are controlled through laboratory screening tests. These fall into three basic varieties: antibody tests, nucleic acid tests (NAT), and surrogate tests. Antibody tests look for the immune system's response to the infection. Nucleic acid tests look for the genetic material of the virus itself. The third variety are tests that are not specific to the disease but look for other related conditions. High risk activities for transfusion transmitted infections vary, and the amount of caution used for screening donors varies based on how dangerous the disease is. Most of the viral diseases are spread by either sexual contact or by contact with blood, usually either drug use, accidental needle injuries among health care workers, unsterilized tattoo and body piercing equipment, or through a blood transfusion or transplant. Other vectors exist. Whether a donor is considered to be at "too high" of a risk for a disease to be allowed to donate is sometimes controversial, especially for sexual contact. High risk sexual activity usually includes: * Sex in exchange for money or drugs. * Men who have sex with men, the most controversial criterion. * A recent history of sexually transmitted disease. * Sex with a person who has had a positive test or was at high risk for a disease that can be spread in blood transfusions. ### HIV[edit] See also: HIV test The virus that causes AIDS is the best known of the transfusion-transmitted infections because of high-profile cases such as Ryan White, a haemophiliac who was infected through factor VIII, a blood-derived medicine used to treat the disease. Another person who died of medically acquired HIV/AIDS was Damon Courtenay, who died in 1991 due to a bad batch of factor VIII. The standard test for HIV is an enzyme immunoassay test that reacts with antibodies to the virus. This test has a window period where a person will be infected but not yet have an immune response. Other tests are used to look for donors during this period, specifically the p24 antigen test and nucleic acid testing. In addition to the general risk criteria for viruses, blood donors are sometimes excluded if they have lived in certain parts of Africa where subtypes of HIV that are not reliably detected on some tests are found, specifically HIV group O. People who have been in prison for extended periods are also excluded for HIV risk. ### Hepatitis A[edit] * Not a major concern, viremic donors are often obviously ill, not a chronic disease. * Recipients of blood-derived clotting factor concentrates have become ill with Hepatitis A, but there are no documented cases of the disease being transmitted in transfused blood.[1] ### Hepatitis B[edit] * The first virus routinely screened in blood donations. * Delta agent not screened for, since it is a superinfection of Hepatitis B and cannot exist alone. ### Hepatitis C[edit] * Often silent infection * Most likely significant TTI in developed countries #### Alanine transaminase (ALT)[edit] * Used as a surrogate for other Hepatitis testing, losing favor now that HCV tests have improved ### Human T-Lymphotropic Virus (HTLV I/II)[edit] * "HTLV III" ### Cytomegalovirus (CMV)[edit] * Not relevant unless recipient's immune system is compromised (i.e. infants). ### West Nile virus[edit] * is Japanese encephalitis a possible TTI? * Pool vs. individual testing. ### Simian foamy virus (SFV)[edit] * Not known to cause disease, recent studies ### SARS[edit] * Donors screened * No demonstrated transmission, hypothetical risk * No resurgence of disease ## Parasites and specific bacteria[edit] ### Malaria (Plasmodia spp.)[edit] * Tests exist, but they're not very good. * Endemic in many areas of the world. * Only relevant for red blood cell transfusions. ### Babesiosis[edit] Babesia microti is transmitted by ixodes ticks. There are few studies which documents transmission of babesiosis through blood transfusion.[2] ### Chagas disease[edit] * New test in use ### Leishmaniasis[edit] * Donors screened, problem for donors who have been to Iraq. ### Syphilis[edit] * Does not survive at refrigerated temperatures * Used as test for high risk sexual behavior ### Lyme disease[edit] * Theoretical risk only ## Other bacteria[edit] ### Skin flora[edit] ### Bacteremia and platelets[edit] * Testing * Part of the reason that platelet shelf life is so short ## Variant Creutzfeldt–Jakob disease (vCJD)[edit] * "Mad Cow" * UK imported plasma for transfusion[3] ## See also[edit] * Osborn v. Irwin Memorial Blood Bank ## References[edit] 1. ^ "Transfusion transmitted injuries". Public Health Agency of Canada. Retrieved 2009-01-16. 2. ^ Transfusion-acquired, autochthonous human babesiosis in Japan: isolation of Babesia microti-like parasites with hu-RBC-SCID mice. 3. ^ "UK buys "safe" blood supply for NHS". British Broadcasting Corporation. 2002-12-17. Retrieved 2008-06-01. ## External links[edit] * [1] AABB list of TTIs. * v * t * e Blood transfusion and transfusion medicine Blood products * Whole blood * Platelets * Platelet transfusion * Red blood cells * Plasma * Fresh frozen plasma * PF24 * Cryoprecipitate * Cryosupernatant * White blood cells * Granulocyte transfusion * Blood substitutes General concepts * Blood donation * Methods * Apheresis (plasmapheresis, plateletpheresis, leukapheresis) * Exchange transfusion * Intraoperative blood salvage * Tests * Blood typing * Cross-matching * Coombs test * Blood bank * International Society of Blood Transfusion * ISBT 128 Transfusion reactions and adverse effects * Transfusion hemosiderosis * Transfusion related acute lung injury * Transfusion associated circulatory overload * Transfusion-associated graft versus host disease * Febrile non-hemolytic transfusion reaction * Hemolytic reaction * acute * delayed * Serum sickness * Transfusion transmitted infection Blood group systems * Blood types * ABO * Secretor status * Augustine * CD59 * Chido-Rodgers * Colton * Cromer * Diego * Dombrock * Duffy * Er * FORS * Gerbich * GIL * GLOB * Hh * Ii * Indian * JR * JMH * KANNO * Kell (Xk) * Kidd * Knops * Lan * Lewis * Lutheran * LW * MNS * OK * P * Raph * Rh and RHAG * Scianna * Sid * T-Tn * Vel * Xg * Yt * Other [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Transfusion transmitted infection	c4505499	7,092	wikipedia	https://en.wikipedia.org/wiki/Transfusion_transmitted_infection	2021-01-18T18:40:20	{"mesh": ["D065227"], "wikidata": ["Q7834211"]}
A number sign (#) is used with this entry because pseudo-von Willebrand disease is caused by mutation in the gene encoding the alpha subunit (GP1BA; 606672) of the GP Ib platelet membrane von Willebrand factor (VWF; 613160) receptor. Mutations in the GP Ib receptor also cause Bernard-Soulier syndrome (231200). Description Platelet-type von Willebrand disease, also known as pseudo-von Willebrand disease, is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by the platelet glycoprotein Ib (GP Ib) receptor complex. Hemostatic function is impaired due to the removal of VWF multimers from the circulation (Murata et al., 1993). Miller (1996) gave a comprehensive review of the disorder. Clinical Features Weiss et al. (1982) demonstrated that the clinical and laboratory findings of von Willebrand disease (VWD; see 193400) can be mimicked by an intrinsic platelet defect, which they observed in 4 generations of a Puerto Rican kindred: great-grandmother, grandmother, father, and 2 daughters. Either X-linked or autosomal dominant inheritance was suggested by the pedigree. There was increased ristocetin-induced platelet aggregation and decreased plasma levels of FVIII-VWF, such as found in type IIB von Willebrand disease. But whereas the physiologic change in VWD type IIB is due to an abnormality in FVIII-VWF, the defect in pseudo-von Willebrand disease resides in the platelets that remove FVIII-VWF at an abnormal rate. Thrombocytopenia occurred in the patients of Weiss et al. (1982) and is observed also in type II von Willebrand disease. Hoyer (1982) speculated that transient neonatal thrombocytopenia observed in the 2 children in the fourth generation of this family may have been due to mother-to-fetus transfer of normal von Willebrand factor. Miller and Castella (1982) described 5 patients in 3 generations, including one instance of male-to-male transmission, and concluded that the defect involved an intrinsic platelet abnormality affecting FVIII-VWF interactions. Takahashi et al. (1984) studied 4 patients from 2 Japanese families with pseudo-von Willebrand disease. The patients' platelets aggregated at lower concentrations of ristocetin than those required for normal platelets and demonstrated an increased capacity to bind normal von Willebrand factor. In some cases, normal VWF induced aggregation of these platelets in the absence of ristocetin. Administration of dDAVP (1-desamino-8-D-arginine vasopressin; desmopressin acetate) caused an immediate increase in VWF multimers, followed by a rapid disappearance of VWF multimers in plasma. The authors found that VWF in the form of cryoprecipitate could be given, provided quantities do not exceed those that produce thrombocytopenia. Analysis of platelet membrane glycoproteins from the patients showed 2 distinct bands in the GP I region that migrated differently than normal GP I, and the authors suggested that the defect lies in the GP Ib platelet receptor. Molecular Genetics In 7 affected members of a family with pseudo-VWD, Miller et al. (1991) identified a heterozygous mutation in the GP1BA gene (606672.0003). The mutation was absent in 6 unaffected family members. In a father and 2 daughters with pseudo-VWD, Russell and Roth (1993) identified a mutation in the GP1BA gene (606672.0005). The abnormal receptor displayed increased affinity for von Willebrand factor. INHERITANCE \- Autosomal dominant ENDOCRINE FEATURES \- Intermittent thrombocytopenia LABORATORY ABNORMALITIES \- Prolonged bleeding time \- Increased platelet aggregation with ristocetin \- Decreased high molecular weight plasma factor VIII/ vWF multimers MISCELLANEOUS \- Allelic to Giant Platelet Syndrome ( 231200 ) and Bernard-Soulier Syndrome, benign, autosomal dominant ( 153670 ) MOLECULAR BASIS \- Caused by mutation in glycoprotein 1b, platelet, alpha polypeptide (GP1BA, 606672.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake 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	PSEUDO-VON WILLEBRAND DISEASE	c1280798	7,093	omim	https://www.omim.org/entry/177820	2019-09-22T16:35:31	{"doid": ["0111056"], "mesh": ["C536458"], "omim": ["177820"], "orphanet": ["52530"], "synonyms": ["Alternative titles", "BLEEDING DISORDER, PLATELET-TYPE, 3", "VON WILLEBRAND DISEASE, PLATELET-TYPE"]}
Craniofacial-deafness-hand syndrome is characterized by distinctive facial features, profound hearing loss, and hand abnormalities. The distinctive facial features of people with craniofacial-deafness-hand syndrome result from a variety of developmental abnormalities involving the skull (cranium) and face. Affected individuals often have underdeveloped or absent nasal bones resulting in a small nose, thin nostrils, and a flattened mid-face with a flat nasal bridge. Individuals with this condition typically also have widely spaced eyes (ocular hypertelorism), narrowed openings of the eyes (narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips. People with this condition also have profound hearing loss that is caused by abnormalities in the inner ear (sensorineural deafness). Hearing loss in these individuals is present from birth. In affected individuals, a common abnormality of the muscles in the hand is a malformation in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). People with craniofacial-deafness-hand syndrome may also have permanently bent third, fourth, and fifth fingers (camptodactyly), which can limit finger movement and lead to joint deformities called contractures. Contractures in the wrist can further impair hand movements. ## Frequency Craniofacial-deafness-hand syndrome is an extremely rare condition. Only a few cases have been reported in the scientific literature. ## Causes Craniofacial-deafness-hand syndrome is caused by mutations in the PAX3 gene. The PAX3 gene plays a critical role in the formation of tissues and organs during embryonic development. To perform this function, the gene provides instructions for making a protein that attaches (binds) to specific areas of DNA to help control the activity of particular genes. During embryonic development, the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo. The protein produced from the PAX3 gene directs the activity of other genes that signal neural crest cells to form specialized tissues or cell types. These include some nerve tissues, bones in the face and skull (craniofacial bones), and muscle tissue. At least one PAX3 gene mutation has been identified in individuals with craniofacial-deafness-hand syndrome. This mutation appears to affect the ability of the PAX3 protein to bind to DNA. As a result, the PAX3 protein cannot control the activity of other genes and cannot regulate the differentiation of neural crest cells. A lack of specialization of neural crest cells leads to the impaired growth of craniofacial bones, nerve tissue, and muscles seen in craniofacial-deafness-hand syndrome. ### Learn more about the gene associated with Craniofacial-deafness-hand syndrome * PAX3 ## 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	Craniofacial-deafness-hand syndrome	c1852510	7,094	medlineplus	https://medlineplus.gov/genetics/condition/craniofacial-deafness-hand-syndrome/	2021-01-27T08:24:59	{"gard": ["1571"], "mesh": ["C536453"], "omim": ["122880"], "synonyms": []}
Brain-lung-thyroid syndrome is a rare disorder characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC; see these terms). ## Epidemiology Prevalence is unknown but to date about 50 cases have been reported in the literature. ## Clinical description The clinical spectrum varies from the complete triad of brain-lung-thyroid syndrome (50%), to brain and thyroid disease (30%), or isolated BHC (13%), which is the mildest expression of the syndrome. In addition, the severity of symptoms varies widely, even in families with the same disease-causing mutation. The thyroid form can present with overt or, more commonly, subclinical hypothyroidism / hyper-thyrotropinemia at birth, in infancy or in early childhood. There is significant correlation between thyroid morphology (55% normal, 35% hemiagenesis or hypoplasia, and 10% athyreosis in 46 published cases) and the commonly mild elevation of thyroid-stimulating hormone (TSH). The lung form presents most commonly as IRDS at term, suggestive for congenital surfactant protein deficiency. In a subgroup of patients, the disease progresses to chronic interstitial lung disease. In other patients, recurrent mild to severe pulmonary infections may be the initial sign of lung disease. The neurological form presents during the first year of life with hypotonia and psychomotor delay, which progresses to BHC between 1 and 5 years of age. Non-progressive BHC after the age of 5 years is the most common and specific sign of the syndrome. Additional non-classical symptoms including hypo- or oligodontia, microcephaly, intellectual deficit, failure to thrive, growth retardation, dysmorphism, hypoparathyroidism and malabsorption have been reported only in patients with large deletions on chromosome 14 including the NKX2-1 gene. Mild intellectual deficit may be present in some patients. ## Etiology Brain-lung-thyroid syndrome is caused by mutations in the thyroid transcription factor 1 gene (NKX2-1/TITF1; 14q13.3). ## Diagnostic methods Diagnosis is based on neonatal screening rather than clinical presentation of overt hypothyroidism such as feeding difficulty, prolonged jaundice, or large fontanels. Congenital hypothyroidism is screened systematically in many countries and raises suspicion of NKX2-1 defects when found in combination with neurological or respiratory problems. Diagnosis of BHC is based on clinical observation. Cerebral MRI may reveal malformations in about 20% of patients (e.g. dysgenetic basal ganglia, or cerebral atrophy). Diagnosis of brain-lung-thyroid syndrome is confirmed by genetic testing showing mutations in the NKX2-1 gene. ## Differential diagnosis Differential diagnoses include other forms of congenital hypothyroidism, other causes of infant respiratory distress syndrome, genetic forms of surfactant protein deficiency, and other causes of chorea. ## Genetic counseling Genetic counseling of families is essential in the context of autosomal dominant transmission due to life-long morbidity. ## Management and treatment Treatment of congenital hypothyroidism is based on life-long levothyroxin substitution according to international guidelines (starting dose 10-15 mcg/kg/day). Treatment of compensated hypothyroidism / hyperthyrotropinemia should be considered as early as possible. Patients with IRDS at term may require mechanical ventilation for up to several weeks. Treatment options for BHC are not well established. ## Prognosis Prognosis varies considerably depending on the severity of symptoms. BHC causes life-long morbidity of varying degrees. Lung disease, if present, can cause mortality in a subgroup of patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Brain-lung-thyroid syndrome	c1970269	7,095	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=209905	2021-01-23T18:37:20	{"gard": ["12163"], "mesh": ["C567034"], "omim": ["610978"], "umls": ["C1970269"], "icd-10": ["E03.1"], "synonyms": ["Choreoathetosis-hypothyroidism-neonatal respiratory distress syndrome"]}
Devi et al. (1995) reported the cases of 2 unrelated male infants with similar findings of communicating hydrocephalus, endocardial fibroelastosis (EFE), and congenital cataracts. Both mothers reported an upper respiratory infection during the first trimester of pregnancy, which was further complicated by polyhydramnios in the third trimester. Bilateral congenital nuclear cataracts were present at birth. Serologic tests for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis, as well as galactosemia screen, were negative. Chromosome analyses were normal. Both children developed communicating hydrocephalus between 1 and 3 months after birth. Patient 1 died suddenly at 4 months of age following an upper respiratory infection. Patient 2 developed congestive heart failure and also died at 4 months. At autopsy, both infants had enlarged hearts with endocardial fibroelastosis. No identifiable organism could be isolated. Devi et al. (1995) favored a genetic etiology, although they admitted that viral etiology could not be excluded. Cardiac \- Endocardial fibroelastosis (EFE) Misc \- Polyhydramnios \- Infantile death Eyes \- Congenital cataracts Neuro \- Communicating hydrocephalus Inheritance \- Genetic vs. viral ▲ 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	HYDROCEPHALUS, ENDOCARDIAL FIBROELASTOSIS, AND CATARACTS	c1833607	7,096	omim	https://www.omim.org/entry/600559	2019-09-22T16:16:03	{"mesh": ["C535855"], "omim": ["600559"], "orphanet": ["2119"], "synonyms": ["Alternative titles", "HEC SYNDROME"]}
Vesiculobullous disease Diagram showing cross section of vesicles (left) and bullae (right) on skin. SpecialtyDermatology A vesiculobullous disease is a type of mucocutaneous disease characterized by vesicles and bullae (i.e. blisters). Both vesicles and bullae are fluid-filled lesions, and they are distinguished by size (vesicles being less than 5–10 mm and bulla being larger than 5–10 mm, depending upon which definition is used). In the case of vesiculobullous diseases which are also immune disorders, the term immunobullous[1] is sometimes used. Examples of vesiculobullous diseases include: * Infectious: (viral) * Herpes simplex * Varicella-Zoster infection * Hand, foot and mouth disease * Herpangina * Measles (Rubeola) * Immunobullous: * Pemphigus vulgaris[2] * Pemphigoid * Dermatitis herpetiformis[1] * Linear immunoglobulin-A disease (linear IgA disease) * Genetic: * Epidermolysis bullosa[3] Some features are as follows: Name Acantholysis? Ig epidermolysis bullosa yes mostly IgG bullous pemphigoid no mostly IgG dermatitis herpetiformis no IgA ## References[edit] 1. ^ Magro, C. M.; Roberts-Barnes, J.; Crowson, A. N. (2012). "Direct Immunofluorescence Testing in the Diagnosis of Immunobullous Disease, Collagen Vascular Disease, and Vascular Injury Syndromes". Dermatologic Clinics. 30 (4): 763–798, viii. doi:10.1016/j.det.2012.06.008. PMID 23021058. 2. ^ Williams DM (December 1989). "Vesiculobullous mucocutaneous disease: pemphigus vulgaris". J. Oral Pathol. Med. 18 (10): 544–53. doi:10.1111/j.1600-0714.1989.tb01551.x. PMID 2695619. 3. ^ Rao R, Prabhu SS, Sripathi H, Gupta S (2008). "Vesiculobullous lesions in lipoid proteinosis: a case report". Dermatol. Online J. 14 (7): 16. PMID 18718200. ## External links[edit] Classification D * ICD-10: L10-L14 * ICD-9-CM: 694 * MeSH: D012872 * v * t * e Vesiculobullous disease Acantholysis (epidermis) Pemphigus * Pemphigus vulgaris: Pemphigus vegetans * of Hallopeau * of Neumann * Pemphigus foliaceus: Pemphigus erythematosus * Endemic pemphigus * Paraneoplastic pemphigus * IgA pemphigus * Subcorneal pustular * Intraepidermal neutrophilic Other * Transient acantholytic dermatosis Pemphigoid (dermis) IgG: * Bullous pemphigoid * Cicatricial pemphigoid * Localised * Gestational pemphigoid * Pemphigoid nodularis * Epidermolysis bullosa acquisita IgA: * Linear IgA bullous dermatosis * Childhood * Adult Other bullous * Dermatitis herpetiformis In diseases classified elsewhere * Porphyria cutanea tarda * Bullous lupus erythematosus * PUVA-induced acrobullous 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	Vesiculobullous disease	c0037275	7,097	wikipedia	https://en.wikipedia.org/wiki/Vesiculobullous_disease	2021-01-18T19:10:07	{"mesh": ["D012872"], "umls": ["C0037275"], "wikidata": ["Q7923229"]}
Rare neurodegenerative disease Parts of this article (those related to see PMID 27042904 and PMID 28410663) need to be updated. Please update this article to reflect recent events or newly available information. (March 2018) Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia.[1] CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is characterized by marked disorders in movement and cognition, and is classified as one of the Parkinson plus syndromes. Diagnosis is difficult, as symptoms are often similar to those of other disorders, such as Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and a definitive diagnosis of CBD can only be made upon neuropathologic examination. ## Contents * 1 Signs and symptoms * 1.1 Motor and associated cortical dysfunctions * 1.1.1 Parkinsonism * 1.1.2 Alien hand syndrome * 1.1.3 Apraxia * 1.1.4 Aphasia * 1.2 Psychiatric and cognitive disorders * 2 Molecular features * 2.1 Astroglial inclusions * 2.2 Tauopathy * 3 Diagnosis * 3.1 Criteria * 3.1.1 Possible corticobasal syndrome subtype * 3.1.2 Frontal behavioural-spatial syndrome subtype * 3.1.3 NAV of primary progressive aphasia subtype * 3.1.4 Progressive supranuclear palsy syndrome subtype * 3.1.5 Exclusion criteria * 3.2 Clinical vs. postmortem * 3.3 Overlap with other diseases * 3.4 Neuroimaging * 3.4.1 MRI * 3.4.2 SPECT * 3.4.3 FDOPA PET * 3.5 Corticobasal syndrome * 4 Treatment * 5 Epidemiology * 6 History * 7 Society and culture * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] Because CBD is progressive, a standard set of diagnostic criteria can be used, which is centered on the disease's evolution. Included in these fundamental features are problems with cortical processing, dysfunction of the basal ganglia, and a sudden and detrimental onset.[2] Psychiatric and cognitive dysfunctions, although present in CBD, are much less prevalent and lack establishment as common indicators of the presence of the disease.[3] Although corticobasal degeneration has a plethora of symptoms, some are more prevalent than others. In a study of 147 patients with CBD, it was found that all of them had at least one Parkinsonian sign, 95% having two and 93% had some higher order dysfunction (cognitive impairments like acalculia, sensory loss, dementia, neglect, etc.). In a separate study of 14 patients recorded 3 years after the onset of symptoms, many patients had high numbers of motor symptoms. 71% had bradykinesia (slow movements), 64% showed apraxia, 43% reported limb dystonia, and although more cognitive 36% had dementia. In another study of 36, over half had a useless/alien arm and 27% had a gait impediment[21]. From this we can see why CBD is hard to diagnose. Even if it can be distinguished as different from one of the other similar diseases, the varying combinations of symptoms creates a difficult path to diagnosis.[citation needed] ### Motor and associated cortical dysfunctions[edit] Some of the most prevalent symptom types in people exhibiting CBD pertain to identifiable movement disorders and problems with cortical processing. These symptoms are initial indicators of the presence of the disease. Each of the associated movement complications typically appear asymmetrically and the symptoms are not observed uniformly throughout the body. For example, a person exhibiting an alien hand syndrome (explained later) in one hand, will not correspondingly display the same symptom in the other hand. Predominant movement disorders and cortical dysfunctions associated with CBD include:[citation needed] * Parkinsonism * Alien hand syndrome * Apraxia (ideomotor apraxia and limb-kinetic apraxia) * Aphasia[3] #### Parkinsonism[edit] The presence of parkinsonism as a clinical symptom of CBD is largely responsible for complications in developing unique diagnostic criteria for the disease.[4] Other such diseases in which parkinsonism forms an integral diagnostic characteristic are Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Parkinsonism in CBD is largely present in an extremity such as the arm, and is always asymmetric. It has been suggested that non-dominant arm is involved more often.[5] Common associated movement dysfunctions that comprise parkinsonism are rigidity, bradykinesia, and gait disorder, with limb rigidity forming the most typical manifestation of parkinsonism in CBD. Despite being relatively indistinct, this rigidity can lead to disturbances in gait and correlated movements. Bradykinesia in CBD occurs when there is notable slowing in the completion of certain movements in the limbs. In an associated study, it was determined that, three years following first diagnosis, 71% of persons with CBD demonstrate the presence of bradykinesia.[3] #### Alien hand syndrome[edit] Alien hand syndrome has been shown to be prevalent in roughly 60% of those people diagnosed with CBD.[6] This disorder involves the failure of an individual to control the movements of their hand, which results from the sensation that the limb is "foreign".[2] The movements of the alien limb are a reaction to external stimuli and do not occur sporadically or without stimulation. The presence of an alien limb has a distinct appearance in CBD, in which the diagnosed individual may have a "tactile mitgehen". This mitgehen (German, meaning "to go with") is relatively specific to CBD, and involves the active following of an experimenter's hand by the subject's hand when both hands are in direct contact. Another, rarer form of alien hand syndrome has been noted in CBD, in which an individual's hand displays an avoidance response to external stimuli. Additionally, sensory impairment, revealed through limb numbness or the sensation of prickling, may also concurrently arise with alien hand syndrome, as both symptoms are indicative of cortical dysfunction. Like most of the movement disorders, alien hand syndrome also presents asymmetrically in those diagnosed with CBD.[7] #### Apraxia[edit] Ideomotor apraxia (IMA), although clearly present in CBD, often manifests atypically due to the additional presence of bradykinesia and rigidity in those individuals exhibiting the disorders. The IMA symptom in CBD is characterized by the inability to repeat or mimic particular movements (whether significant or random) both with or without the implementation of objects. This form of IMA is present in the hands and arms, while IMA in the lower extremities may cause problems with walking. Those with CBD that exhibit IMA may appear to have trouble initiating walking, as the foot may appear to be fixed to floor. This can cause stumbling and difficulties in maintaining balance.[3] IMA is associated with deterioration in the premotor cortex, parietal association areas, connecting white matter tracts, thalamus, and basal ganglia. Some individuals with CBD exhibit limb-kinetic apraxia, which involves dysfunction of more fine motor movements often performed by the hands and fingers.[6] #### Aphasia[edit] Aphasia in CBD is revealed through the inability to speak or a difficulty in initiating spoken dialogue and falls under the non-fluent (as opposed to fluent or flowing) subtype of the disorder. This may be related to speech impairment such as dysarthria, and thus is not a true aphasia, as aphasia is related to a change in language function, such as difficulty retrieving words or putting words together to form meaningful sentences. The speech and/or language impairments in CBD result in disconnected speech patterns and the omission of words. Individuals with this symptom of CBD often lose the ability to speak as the disease progresses.[3] ### Psychiatric and cognitive disorders[edit] Psychiatric problems associated with CBD often present as a result of the debilitating symptoms of the disease. Prominent psychiatric and cognitive conditions cited in individuals with CBD include dementia, depression, and irritability, with dementia forming a key feature that sometimes leads to the misdiagnosis of CBD as another cognitive disorder such as Alzheimer's disease (AD). Frontotemporal dementia can be an early feature.[8] ## Molecular features[edit] Neuropathological findings associated with CBD include the presence of astrocytic abnormalities within the brain and improper accumulation of the protein tau (referred to as tauopathy).[9] ### Astroglial inclusions[edit] Postmortem histological examination of the brains of individuals diagnosed with CBD reveal unique characteristics involving the astrocytes in localized regions.[10] The typical procedure used in the identification of these astroglial inclusions is the Gallyas-Braak staining method.[11] This process involves exposing tissue samples to a silver staining material which marks for abnormalities in the tau protein and astroglial inclusions.[12] Astroglial inclusions in CBD are identified as astrocytic plaques, which present as annularly displays of blurry outgrowths from the astrocyte. A recent study indicated that produces a high density of astrocytic plaques in the anterior portion of the frontal lobe and in the premotor area of the cerebral cortex.[13] ### Tauopathy[edit] The protein tau is an important microtubule-associated protein (MAP), and is typically found in neuronal axons. However, malfunctioning of the development of the protein can result in unnatural, high-level expression in astrocytes and glial cells. As a consequence, this is often responsible for the astrocytic plaques prominently noted in histological CBD examinations. Although they are understood to play a significant role in neurodegenerative diseases such as CBD, their precise effect remains a mystery.[12] In recent years Corticobasal Degeneration is seen to be a tauopathy[22]. This is believed due to the most common indicator of CBD being a faulty tau protein. Tau proteins are integral in keeping microtubules stable and these defective cells create 4 microtubule-binding repeats[23]. These 4 binding repeats have increased affinity in binding with microtubules[25]. Because of this increased affinity, they form insoluble fibers (also called "paired helical filaments). Microtubules themselves keep the cell and cytoskeletal structure stable[24]. Thus, when Tau proteins create unnatural configurations, microtubules become unstable, and eventually leads to cell death.[citation needed] ## Diagnosis[edit] New diagnostic criteria known as the Armstrong criteria were proposed in 2013, although the accuracy of these is limited and further research is needed.[14] ### Criteria[edit] * Insidious onset and gradual progression * Lasts 1 year or more * Meets one of the four subtypes: * Possible CBS * FBS or NAV * PSPS plus at least one CBS feature other than limb rigidity or akinesia * No exclusion criteria present * More likely if onset is after age 50 * More likely if no family history (2 or more relatives) * More likely if no genetic mutation affecting T[clarification needed] (e.g., MAPT)[15] #### Possible corticobasal syndrome subtype[edit] Symptoms may be symmetric or asymmetric. One or more of:[citation needed] 1. limb rigidity or akinesia 2. limb dystonia 3. limb myoclonus, plus one of: 4. orobuccal or limb apraxia 5. cortical sensory deficit 6. alien limb phenomena (more than simple levitation) More likely (probable sporadic CBS) if:[citation needed] * Asymmetric presentation * Onset after age 50 * No family history (2 or more relatives) * No genetic mutation affecting T (e.g. MAPT) * plus two of: 1. limb rigidity or akinesia 2. limb dystonia 3. limb myoclonus * plus two of: 1. orobuccal or limb apraxia, 2. cortical sensory deficit 3. alien limb phenomena (more than simple levitation)[15] #### Frontal behavioural-spatial syndrome subtype[edit] Two of:[citation needed] 1. executive dysfunction 2. behavioural or personality changes 3. visuospatial deficits #### NAV of primary progressive aphasia subtype[edit] Effortful, agrammatic speech plus at least one of:[citation needed] 1. impaired grammar/sentence comprehension with relatively preserved single word comprehension or 2. groping, distorted speech production (apraxia of speech) #### Progressive supranuclear palsy syndrome subtype[edit] Three of:[citation needed] 1. axial or symmetric limb rigidity or akinesia 2. postural instability or falls 3. urinary incontinence 4. behavioural changes 5. supranuclear vertical gaze palsy or decreased vertical saccade velocity #### Exclusion criteria[edit] These apply to all types of CBD. * Evidence of Lewy body disease * multiple system atrophy * Alzheimer's disease * ALS * semantic or logopenic variant primary progressive aphasia * structural lesion suggestive of focal cause * granulin mutation or reduced plasma progranulin levels * TDP-43 or fused in sarcoma (FUS) mutations[15] The diagnostic criteria for clinical use may result in a misdiagnosis of other tau-based diseases.[14] The probable criteria are proposed for clinical research.[14] ### Clinical vs. postmortem[edit] One of the most significant problems associated with CBD is the inability to perform a definitive diagnosis while an individual exhibiting the symptoms associated with CBD is still alive. A clinical diagnosis of CBD is performed based upon the specified diagnostic criteria, which focus mainly on the symptoms correlated with the disease. However, this often results in complications as these symptoms often overlap with numerous other neurodegenerative diseases.[16] Frequently, a differential diagnosis for CBD is performed, in which other diseases are eliminated based on specific symptoms that do not overlap. However, some of the symptoms of CBD used in this process are rare to the disease, and thus the differential diagnosis cannot always be used.[3] Postmortem diagnosis provides the only true indication of the presence of CBD. Most of these diagnoses utilize the Gallyas-Braak staining method, which is effective in identifying the presence of astroglial inclusions and coincidental tauopathy.[citation needed] ### Overlap with other diseases[edit] Progressive supranuclear palsy (PSP) is frequently the disease most often confused with CBD. Both PSP and CBD result in similar symptoms, and both display tauopathies upon histological inspection.[17] However, it has been noted that tauopathy in PSP results in tuft-shaped astrocytes in contrast with the ring-shaped astrocytic plaques found as a result of CBD.[13] Individuals diagnosed with PD often exhibit similar movement dysfunction as those diagnosed with CBD, which adds complexity to its diagnosis. Some other neurodegenerative diseases including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), chronic traumatic encephalopathy (CTE) and frontotemporal dementia (FTD) also show commonalities with CBD.[3][18][8] ### Neuroimaging[edit] The types of imaging techniques that are most prominently utilized when studying and/or diagnosing CBD are:[citation needed] * magnetic resonance imaging (MRI) * single-photon emission computed tomography (SPECT) * fluorodopa positron emission tomography (FDOPA PET) Developments or improvements in imaging techniques provide the future possibility for definitive clinical diagnosis prior to death. However, despite their benefits, information learned from MRI and SPECT during the beginning of CBD progression tend to show no irregularities that would indicate the presence of such a neurodegenerative disease.[3] FDOPA PET is used to study the efficacy of the dopamine pathway.[19] Despite the undoubted presence of cortical atrophy (as determined through MRI and SPECT) in individuals experiencing the symptoms of CBD, this is not an exclusive indicator for the disease. Thus, the utilization of this factor in the diagnosis of CBD should be used only in combination with other clinically present dysfunctions.[4] #### MRI[edit] MRI images are useful in displaying atrophied portions of neuroanatomical positions within the brain. As a result, it is especially effective in identifying regions within different areas of the brain that have been negatively affected due to the complications associated with CBD. To be specific, MRI of CBD typically shows posterior parietal and frontal cortical atrophy with unequal representation in corresponding sides. In addition, atrophy has been noted in the corpus callosum.[19] Functional MRI (fMRI) has been used to evaluate the activation patterns in various regions of the brain of individuals affected with CBD. Upon the performance of simple finger motor tasks, subjects with CBD experienced lower levels of activity in the parietal cortex, sensorimotor cortex, and supplementary motor cortex than those individuals tested in a control group.[19] #### SPECT[edit] SPECT is currently being used to try to detect CBD. With many patients of CBD, there are areas in the basal ganglia which have difficulties receiving dopamine, typically asymmetrically. Specifically affected, are dopamine transporters which are presynaptic on the nigrostriatal cells. SPECT is used to detect these abnormalities in Dopamine transporters. Given that many patients have asymmetrical loss of function and metabolism this can help differentiate patients with CBD and those with Alzheimer's.[citation needed] SPECT studies of individuals diagnosed with CBD involve perfusion analysis throughout the parts of the brain. SPECT evaluation through perfusion observation consists of monitoring blood release into different locations in tissue or organ regions, which, in the case of CBD, pertains to localized areas within the brain. Tissue can be characterized as experiencing overperfusion, underperfusion, hypoperfusion, or hyperperfusion. Overperfusion and underperfusion relate to a comparison with the overall perfusion levels within the entire body, whereas hypoperfusion and hyperperfusion are calculated in comparison to the blood flow requirements of the tissue in question. In general, the measurements taken for CBD using SPECT are referred to as regional cerebral blood flow (rCBF).[19] In general, SPECT reveals hypoperfusion within both the posterior regions of the frontal and parietal lobes. As in images gathered through MRI, SPECT images indicated asymmetry in the presentation of abnormalities throughout the brain.[4] Additional studies have revealed the presence of perfusion anomalies in the thalamus, temporal cortex, basal ganglia, and pontocerebellar (from the pons to the cerebellum) locations within subjects' brains.[19] #### FDOPA PET[edit] Research has suggested that the integrity of the dopamine system in the striatum has been damaged as an effect of CBD. Current studies employing the use of FDOPA PET scanning (FDOPA PET) as a possible method for identifying CBD have focused on analyzing the efficiency of neurons in the striatum that utilize the neurotransmitter dopamine. These studies have concluded that, in general, dopamine uptake was diminished in the caudate and the putamen. This characteristic also has the potential to be useful in distinguishing CBD from the similar PD, as individuals having been diagnosed with PD were more likely to have a lower uptake of dopamine than in individuals with CBD.[19] Other clinical tests or procedures that monitor the presence of dopamine within the brain (β-CIT SPECT and IBZM SPECT) have shown similar findings. β-CIT serves as an indicator for presynaptic dopaminergic neurons, whereas IBZM is a tracer that shows an affinity for the postsynaptic neurons of the same type. Despite agreement with other imaging studies, these two SPECT methods suffer some scrutiny due to better accuracy in other imaging methods. However, β-CIT SPECT has proven to be helpful in distinguishing CBD from PSP and multiple system atrophy (MSA).[19] ### Corticobasal syndrome[edit] Main article: Corticobasal syndrome All of the disorders and dysfunctions associated with CBD can often be categorized into a class of symptoms that present with the disease of CBD. These symptoms that aid in clinical diagnosis are collectively referred to as corticobasal syndrome (CBS) or corticobasal degeneration syndrome (CBDS). Alzheimer's disease, Pick's disease, FTDP-17 and progressive supranuclear palsy can display a corticobasal syndrome.[20][21] It has been suggested that the nomenclature of corticobasal degeneration only be used for naming the disease after it has received verification through postmortem analysis of the neuropathology.[4] CBS patients with greater temporoparietal degeneration are more likely to have AD pathology as opposed to frontotemporal lobar degeneration.[22] ## Treatment[edit] Because the exact cause of CBD is unknown, there exists no formal treatment for the disease. Instead, treatments focus on minimizing the appearance or effect of the symptoms resulting from CBD. The most easily treatable symptom of CBD is parkinsonism, and the most common form of treatment for this symptom is the application of dopaminergic drugs. However, in general only moderate improvement is seen and the relief from the symptom is not long-lasting. In addition, palliative therapies, including the implementation of wheelchairs, speech therapy, and feeding techniques, are often used to alleviate many of the symptoms that show no improvement with drug administration.[23] There is no consensus on what causes CBD and so most of the treatment goes in helping symptoms. Unfortunately, many treatments are typically low in their success rates or have not been tested thoroughly or produced frequently. For example, in relation to the motor aspect of disability, CBD has a high resistance against treatments to help the dopamine intake like levodopa. A number of studies have reported no real levels of improvement based with the use of similar drugs/dopaminergic agonists. Because of the brains levels of inhibition, some medications have focused on creating an inhibition that would negate the effect. Many of these relaxants and anticonvulsants have some success but also have unwanted side effects[21]. Cognitive and associative effects of CBD are also hard to treat as we are still unsure of many of the treatments for the symptomatic diseases that ensue like dementia, aphasia, neglect, apraxia and others.[citation needed] ## Epidemiology[edit] Clinical presentation of CBD usually does not occur until age 60, with the earliest recorded diagnosis and subsequent postmortem verification being age 28.[19] Although men and women present with the disease, some analysis has shown a predominant appearance of CBD in women. Current calculations suggest that the prevalence of CBD is approximately 4.9 to 7.3 per 100,000 people. The prognosis for an individual diagnosed with CBD is death within approximately eight years, although some patients have been diagnosed over 17 years ago (2017) and are still in relatively good standing, but with serious debilitation such as dysphagia, and overall limb rigidity. The partial (or total) use of a feeding tube may be necessary and will help prevent aspiration pneumonia, primary cause of death in CBD. Incontinence is common, as patients often can't express their need to go, due to eventual loss of speech. Therefore, proper hygiene is mandatory to prevent urinary tract infections.[3] CBD research has been limited by the rarity of the disease and the lack of research criteria. It is estimated to affect 0.6-0.9 per 100,000 per year.[citation needed] Progressive supranuclear palsy (PSP) without CBD is estimated to be ten times more common. CBD represents roughly 4–6% of patients with Parkinsonism. Average age at disease onset is about 64, with the youngest confirmed onset being at age 43. There may be a slight female predominance.[24] ## History[edit] Corticobasal syndrome was first recognized in 1967 when Rebeiz, Kolodny, and Richardson Jr described three people with a progressive asymmetric akinetic-rigid syndrome combined with apraxia, which they named corticodentatonigral degeneration with neuronal achromasia.[24][25] The condition was "mostly forgotten" until 1989, when Marsden et al. used the name corticobasal degeneration.[24] In 1989 Gibb and colleagues provided detailed clinical and pathological descriptions in a further three cases adopting the name corticobasal degeneration,[26] after which various other names included "corticonigral degeneration with nuclear achromasia" and "cortical basal ganglionic degeneration".[2] Although the underlying cause of CBD is unknown, the disease occurs as a result of damage to the basal ganglia, specifically marked by neuronal degeneration or depigmentation (loss of melanin in a neuron) in the substantia nigra.[17] Additional distinguishing neurological features of those diagnosed with CBD consist of asymmetric atrophy of the frontal and parietal cortical regions of the brain.[2] Postmortem studies of patients diagnosed with CBD indicate that histological attributes often involve ballooning of neurons, gliosis, and tauopathy.[17] Much of the pioneering advancements and research performed on CBD has been completed within the past decade or so, due to the relatively recent formal recognition of the disease.[citation needed] The Office of Rare Diseases in the United States created the first criteria in 2002, and the Armstrong clinical diagnostic criteria were created in 2013.[24] ## Society and culture[edit] The Salt Path by Raynor Winn is an inspiring account of walking England's 630 mile South West Coast Path with her husband who had corticobasal degeneration.[27] ## See also[edit] * Frontotemporal lobar degeneration ## References[edit] 1. ^ "Corticobasalganglionic Degeneration Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". Archived from the original on 2009-03-23. Retrieved 2009-03-20. 2. ^ a b c d Wadia PM, Lang AE (2007). "The many faces of corticobasal degeneration". Parkinsonism & Related Disorders. 13: S336–S40. doi:10.1016/s1353-8020(08)70027-0. PMID 18267261. 3. ^ a b c d e f g h i Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP (2004). "Corticobasal degeneration". Lancet Neurology. 3 (12): 736–43. doi:10.1016/s1474-4422(04)00936-6. PMID 15556806. S2CID 15324889. 4. ^ a b c d Koyama M, Yagishita A, Nakata Y, helloHayashi M, Bandoh M, et al. (2007). "Imaging of corticobasal degeneration syndrome". Neuroradiology. 49 (11): 905–12. doi:10.1007/s00234-007-0265-6. PMID 17632713. S2CID 35778587. 5. ^ Rana AQ, Ansari H, Siddiqui I (2012). "The relationship between arm dystonia in corticobasal degeneration and handedness". Journal of Clinical Neuroscience. 19 (8): 1134–6. doi:10.1016/j.jocn.2011.10.012. PMID 22705141. S2CID 2233432. 6. ^ a b Belfor N, Amici S, Boxer AL, Kramer JH, Gorno-Tempini ML, et al. (2006). "Clinical and neuropsychological features of corticobasal degeneration". Mechanisms of Ageing and Development. 127 (2): 203–7. doi:10.1016/j.mad.2005.09.013. PMID 16310834. S2CID 35169781. 7. ^ FitzGerald DB, Drago V, Jeong Y, Chang YL, White KD, et al. (2007). "Asymmetrical alien hands in corticobasal degeneration". Movement Disorders. 22 (4): 581–4. doi:10.1002/mds.21337. PMID 17230447. S2CID 41998716. 8. ^ a b Lee SE, Rabinovici GD, Mayo MC, Wilson SM, Seeley WW, et al. (August 2011). "Clinicopathological correlations in corticobasal ganglionic degeneration". Annals of Neurology. 70 (2): 327–340. doi:10.1002/ana.22424. PMC 3154081. PMID 21823158. 9. ^ Rizzo G, Martinelli P, Manners D, Scaglione C, Tonon C, et al. (October 2008). "Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease". Brain. 131 (Pt 10): 2690–700. doi:10.1093/brain/awn195. PMID 18819991. 10. ^ Zhu MW, Wang LN, Li XH, Gui QP (April 2004). "Glial abnormalities in progressive supranuclear palsy and corticobasal degeneration". Zhonghua Bing Li Xue Za Zhi. 33 (2): 125–9. doi:10.3760/j.issn:0529-5807.2004.02.008. PMID 15132848. 11. ^ "CBD Identification - Chemistry and Toxicology". The Drug Store. 2020-08-26. Retrieved 2020-10-17. 12. ^ a b Komori T (1999). "Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick's disease". Brain Pathology. 9 (4): 663–79. doi:10.1111/j.1750-3639.1999.tb00549.x. PMID 10517506. S2CID 3142586. 13. ^ a b Hattori M, Hashizume Y, Yoshida M, Iwasaki Y, Hishikawa N, et al. (2003). "Distribution of astrocytic plaques in the corticobasal degeneration brain and comparison with tuft-shaped astrocytes in the progressive supranuclear palsy brain". Acta Neuropathologica. 106 (2): 143–9. doi:10.1007/s00401-003-0711-4. PMID 12732936. S2CID 25741692. 14. ^ a b c Shimohata T, Aiba I, Nishizawa M (2016). "[Diagnoses of corticobasal syndrome and corticobasal degeneration]". Rinsho Shinkeigaku (in Japanese). 56 (3): 149–57. doi:10.5692/clinicalneurol.cn-000841. PMID 26876110. 15. ^ a b c Alexander SK, Rittman T, Xuereb JH, Bak TH, Hodges JR, Rowe JB (August 2014). "Validation of the new consensus criteria for the diagnosis of corticobasal degeneration" (PDF). J. Neurol. Neurosurg. Psychiatry. 85 (8): 925–29. doi:10.1136/jnnp-2013-307035. PMC 4112495. PMID 24521567. 16. ^ Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, et al. (January 1997). "Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study" (PDF). Neurology. 48 (1): 119–25. doi:10.1212/wnl.48.1.119. PMID 9008506. S2CID 30401542. Archived from the original (PDF) on 2011-07-16. Retrieved 2010-11-21. 17. ^ a b c Scaravilli T, Tolosa E, Ferrer I (2005). "Progressive supranuclear palsy and corticobasal degeneration: Lumping versus splitting". Movement Disorders. 20: S21–S8. doi:10.1002/mds.20536. PMID 16092076. S2CID 21358152. 18. ^ Jendroska K, Rossor MN, Mathias CJ, Daniel SE (January 1995). "Morphological overlap between corticobasal degeneration and Pick's disease: a clinicopathological report". Movement Disorders. 10 (1): 111–4. doi:10.1002/mds.870100118. PMID 7885345. S2CID 43288223. 19. ^ a b c d e f g h Seritan AL, Mendez MF, Silverman DH, Hurley RA, Taber KH (2004). "Functional imaging as a window to dementia: Corticobasal degeneration". Journal of Neuropsychiatry and Clinical Neurosciences. 16 (4): 393–9. doi:10.1176/jnp.16.4.393. PMID 15616165. 20. ^ Hassan A, Whitwell JL, Josephs KA (November 2011). "The corticobasal syndrome-Alzheimer's disease conundrum". Expert Review of Neurotherapeutics. 11 (11): 1569–78. doi:10.1586/ern.11.153. PMC 3232678. PMID 22014136. 21. ^ Alladi S, Xuereb J, Bak T, Nestor P, Knibb J, et al. (October 2007). "Focal cortical presentations of Alzheimer's disease". Brain. 130 (10): 2636–45. doi:10.1093/brain/awm213. PMID 17898010. 22. ^ Sha SJ, Ghosh PM, Lee SE, Corbetta-Rastelli C, Jagust WJ, et al. (March 2015). "Predicting amyloid status in corticobasal syndrome using modified clinical criteria, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography". Alzheimer's Research & Therapy. 7 (1): 8. doi:10.1186/s13195-014-0093-y. PMC 4346122. PMID 25733984. 23. ^ Lang AE (2005). "Treatment of progressive supranuclear palsy and corticobasal degeneration". Movement Disorders. 20: S83–S91. doi:10.1002/mds.20545. PMID 16092096. S2CID 45848876. 24. ^ a b c d Constantinides VC, Paraskevas GP, Paraskevas PG, Stefanis L, Kapaki E (August 2019). "Corticobasal degeneration and corticobasal syndrome: A review". Clinical Parkinsonism & Related Disorders. 1: 66–71. doi:10.1016/j.prdoa.2019.08.005. ISSN 2590-1125. 25. ^ Fredericks CA, Lee SE (2016). "The cognitive neurology of corticobasal degeneration and progressive supranuclear palsy". In Miller, Bruce L.; Boeve, Bradley F. (eds.). The Behavioral Neurology of Dementia (Second ed.). Cambridge, United Kingdom: Cambridge University Press. pp. 203–6. ISBN 9781107077201. OCLC 934020279. "[CBD is] reminiscent of classic CBS but with executive function deficits" 26. ^ Gibb WR, Luthert PJ, Marsden CD (1989). "Corticobasal degeneration". Brain. 112 (5): 1171–1192. doi:10.1093/brain/112.5.1171. PMID 2478251.CS1 maint: multiple names: authors list (link) 27. ^ Raynor Winn (2018) The Salt Path, Penguin Books. * Boeve BF (2011). "The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: Implications for further study". Journal of Molecular Neuroscience. 45 (3): 350–3. doi:10.1007/s12031-011-9624-1. PMID 21853287. S2CID 30307394. * Hassan A, Whitwell JL, Josephs KA (2011). "The corticobasal syndrome-alzheimer's disease conundrum". Expert Review of Neurotherapeutics. 11 (11): 1569–78. doi:10.1586/ern.11.153. PMC 3232678. PMID 22014136.CS1 maint: multiple names: authors list (link) * Goode BL, Chau M, Denis PE, Feinstein SC (2000). "Structural and Functional Differences between 3-Repeat and 4-Repeat Tau Isoforms". Journal of Biological Chemistry. 275 (49): 38182–38189. doi:10.1074/jbc.m007489200. PMID 10984497. S2CID 30896096.CS1 maint: multiple names: authors list (link) * Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP (2004). "Corticobasal degeneration". The Lancet Neurology. 3 (12): 736–43. doi:10.1016/s1474-4422(04)00936-6. PMID 15556806. S2CID 15324889. ProQuest 201513368.CS1 maint: multiple names: authors list (link) * Avila J (1992). "Microtubule functions". Life Sci. 50 (5): 327–334. doi:10.1016/0024-3205(92)90433-p. PMID 1732704. * ## External links[edit] Classification D * ICD-9-CM: 331.6 * DiseasesDB: 33284 External resources * eMedicine: neuro/77 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-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	Corticobasal degeneration	c0393570	7,098	wikipedia	https://en.wikipedia.org/wiki/Corticobasal_degeneration	2021-01-18T18:49:29	{"gard": ["46"], "umls": ["C0393570"], "icd-9": ["331.6"], "orphanet": ["454887"], "wikidata": ["Q1755684"]}
A number sign (#) is used with this entry because of evidence that short-rib thoracic dysplasia-8 with or without polydactyly (SRTD8) is caused by compound heterozygous mutation in the WDR60 gene (615462) on chromosome 7q36. Description Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500). Clinical Features McInerney-Leo et al. (2013) studied a nonconsanguineous Australian family of British and Maori descent in which the healthy parents had 2 offspring with short-rib polydactyly syndrome, clinically classified as SRPS type III (SRTD3; 613091). The first child presented with short long bones on ultrasound at 6 weeks' gestation. Follow-up ultrasound at 31 weeks' showed polyhydramnios, severe shortening of long bones with bowed femurs, macrocephaly, short ribs, and ambiguous genitalia. Born at 32 weeks' gestation, the baby died at 2 hours of life. Autopsy confirmed the above findings and in addition revealed postaxial polydactyly of both hands, syndactyly of some fingers and toes, acetabular spurs, pancreatic fibrosis, mild dilation of renal tubules, and enlarged liver with ductal plate malformation. A second pregnancy was terminated at 17 weeks' gestation after ultrasound showed short ribs and short bowed limbs. Autopsy further revealed brachydactyly (not polydactyly), conical epiphyses, hypoplastic trabecular bone, depressed nasal bridge, ventricular septal defect (VSD), focal cystic changes in the kidneys, prominent bile ducts, and early evidence of pulmonary hypoplasia. Molecular Genetics In the deceased proband from a nonconsanguineous Australian family of British and Maori descent segregating autosomal recessive short rib-polydactyly syndrome, McInerney-Leo et al. (2013) performed whole-exome sequencing and identified compound heterozygosity for a nonsense (Q631X; 615462.0001) and a missense (T749M; 615462.0002) mutation in the WDR60 gene. An affected fetus in the family was also compound heterozygous for the mutations, whereas the unaffected parents were each heterozygous for 1 of the mutations. The authors reviewed exome sequencing data from 1,985 unrelated individuals but found no compound heterozygotes carrying WDR60 mutations. However, a review of exome sequencing data from 54 patients with skeletal ciliopathies revealed a 5-year-old Spanish boy, originally diagnosed with Jeune syndrome (see 208500), who was compound heterozygous for mutations in WDR60: the T749M missense mutation and a splice site mutation (615462.0003). In the Spanish boy, prenatal ultrasound had shown short femurs, and at birth he was noted to have narrow chest, preaxial polydactyly on the right hand, and a clinically insignificant VSD. At 1 year of age, he showed signs of failure to thrive, and at 5.25 years of age, his height and weight were below the 5th centile for age. X-rays showed mildly narrowed thorax, 'handlebar' clavicles, and acetabular spurs. He had no evidence of renal, hepatic, retinal, neurologic, or developmental problems. Haplotype analysis excluded a common founder for the shared missense mutation. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Failure to thrive HEAD & NECK Head \- Macrocephaly Nose \- Depressed nasal bridge CARDIOVASCULAR Heart \- Ventricular septal defect RESPIRATORY Lung \- Pulmonary hypoplasia CHEST External Features \- Narrow thorax Ribs Sternum Clavicles & Scapulae \- Short ribs \- Handlebar clavicles (in some patients) ABDOMEN Liver \- Enlarged liver with ductal plate malformation \- Prominent bile duct plates Pancreas \- Pancreatic fibrosis GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia Kidneys \- Dilation of renal tubules, mild \- Focal cystic changes SKELETAL Skull \- Macrocephaly Pelvis \- Acetabular spurs Limbs \- Short long bones on prenatal ultrasound \- Bowed femurs \- Conical epiphyses \- Hypoplastic trabecular bone Hands \- Postaxial polydactyly \- Preaxial polydactyly \- Syndactyly \- Brachydactyly Feet \- Syndactyly PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios MOLECULAR BASIS \- Caused by mutation in the WD repeat-containing protein 60 gene (WDR60, 615462.0001 ) ▲ 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	SHORT-RIB THORACIC DYSPLASIA 8 WITH OR WITHOUT POLYDACTYLY	c0432197	7,099	omim	https://www.omim.org/entry/615503	2019-09-22T15:51:53	{"doid": ["0110094"], "mesh": ["C537602"], "omim": ["615503"], "orphanet": ["93271"], "synonyms": ["Alternative titles", "SHORT RIB-POLYDACTYLY SYNDROME, TYPE VI"]}

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