{"orpha":869,"name":"Triple A syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["2A syndrome","3A syndrome","4A syndrome","AAA syndrome","Achalasia-addisonianism-alacrima syndrome","Adrenal insufficiency-achalasia-alacrima syndrome","Allgrove syndrome","Double A syndrome","Quaternary A syndrome"],"definition":"Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-869/","orphanet_url":"https://www.orpha.net/en/disease/detail/869","names":{"fr":{"name":"Syndrome triple A","synonyms":["Syndrome AAA","Syndrome d'Allgrove","Syndrome d'achalasie-addisonisme-alacrymie","Syndrome des 2A","Syndrome des 3A","Syndrome des 4A"],"definition":"Le syndrome triple A est une maladie multisystémique très rare caractérisée par une insuffisance surrénale avec un déficit isolé en glucocorticoïdes, une achalasie, une alacrymie, une dysfonction autonomique et une neurodégénerescence."},"de":{"name":"Triple-A-Syndrom","synonyms":["2A-Syndrom","3A-Syndrom","4A-Syndrom","AAA-Syndrom","Achalasie-Addisonismus-Alakrimie-Syndrom","Allgrove-Syndrom"],"definition":"Das Triple-A-Syndrom (Achalasie-, Addison-, Alakrimie-Syndrom, auch AAA-Syndrom) ist eine sehr seltene Multisystem-Erkrankung. Charakteristische Symptome sind Nebenniereninsuffizienz mit isoliertem Glukokortikoidmangel, Alachasie, Alakrimie, einer vegetativen Funktionsstörungen und Neurodegeneration."},"es":{"name":"Síndrome triple A","synonyms":["Síndrome doble A","Síndrome 2A","Síndrome 3A","Síndrome 4A","Síndrome A cuaternario","Síndrome AAA","Síndrome de Allgrove","Síndrome de acalasia-addisonismo-alacrimia","Síndrome de insuficiencia suprarrenal-acalasia-alacrimia"],"definition":"El síndrome triple A es una enfermedad multisistémica muy poco frecuente, que se caracteriza por insuficiencia suprarrenal con déficit aislado de glucocorticoides, acalasia, alacrimia (ausencia congénita de secreción lagrimal) disfunción autonómica y neurodegeneración."},"it":{"name":"Sindrome della tripla A","synonyms":["Sindrome 2A","Sindrome 3A","Sindrome 4A","Sindrome AAA","Sindrome acalasia-addisonismo-alacrimia","Sindrome della doppia A","Sindrome delle quattro A","Sindrome di Allgrove","Sindrome insufficienza surrenalica-acalasia-alacrimia"],"definition":"La sindrome della tripla A è una malattia multisistemica molto rara caratterizzata da insufficienza surrenalica con deficit isolato di glucocorticoidi, acalasia, alacrimia, disfunzione del sistema autonomo e neurodegenerazione."},"nl":{"name":"Triple A-syndroom","synonyms":["2A-syndroom","3A-syndroom","4A-syndroom","AAA-syndroom","Achalasie - addisonianisme - alacrimie-syndroom","Adrenale insufficiëntie - achalasie - alacrimie-syndroom","Dubbel A-syndroom","Quaternair A-syndroom","Syndroom van Allgrove"],"definition":"Triple A-syndroom is een zeer zeldzame multisystemische ziekte die gekenmerkt wordt door bijnierinsufficiëntie met geïsoleerde glucocorticoïdedeficientie, achalasie, alacrimie, autonome disfunctie en neurodegeneratie."},"pt":{"name":"Síndrome triplo A","synonyms":["Síndrome 2A","Síndrome 3A","Síndrome 4A","Síndrome A quaternário","Síndrome AAA","Síndrome Allgrove","Síndrome de acalasia-addisonianismo-alacrimia","Síndrome de insuficiência supra-renal-acalasia-alacrimia","Síndrome duplo A"]},"pl":{"name":"Zespół potrójnego A","synonyms":["Niedoczynność nadnerczy - achalazja - alakrimia","Zespół 2A","Zespół 3A","Zespół 4A","Zespół AAA","Zespół achalazji, addisonizmu i alakrimii","Zespół Allgrove'a","Zespół poczwórnego A","Zespół podwójnego A"]},"cs":{"name":"Triple A syndrom","synonyms":["2A syndrom","3A syndrom","4A syndrom","AAA syndrom","Achalázie, adrenální insuficience a alakrimie","Syndrom dvojitého A","Double A syndrom","Allgrovův syndrom","Syndrom čtverného A"]},"uk":{"name":"Синдром потрійного А","synonyms":["Синдром 2А","Синдром 3А","Синдром 4А","Синдром ААА","Синдром ахалазії-аддисонізму-алакрими","Синдром надниркової недостатності-ахалазії-алакрими","Синдром Олгроува","Синдром подвійного А","Синдром четвертинного А"],"definition":"Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration."},"zh":{"name":"三联A综合征","synonyms":["肾上腺功能减退-贲门失弛缓-无泪综合征"]},"tr":{"name":"Triple A sendromu","synonyms":["2A sendromu","3A sendromu","4A sendromu","AAA sendromu","Allgrove sendromu","Çift A sendromu","Kuaterner A sendromu","Akalazya-addisonyanizm-alakrima sendromu","Adrenal yetersizlik-akalazya-alakrima sendromu"]}},"xrefs":[{"source":"OMIM","code":"231550","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"615510","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E27.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5A74.Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"180128195"},{"source":"MONDO","code":"0009279","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536008","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0271742","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"457","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10073592","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":99777,"name":"Achalasia-alacrimia syndrome","status":"inactive"}],"preferential_parent":{"orpha":97978,"name":"Rare endocrine disease"},"parents":[{"orpha":98604,"name":"Congenital alacrima","classifications":[156,189]},{"orpha":101960,"name":"Genetic chronic primary adrenal insufficiency","classifications":[156,193]},{"orpha":371445,"name":"Genetic syndromic esophageal malformation","classifications":[156]},{"orpha":207015,"name":"Rare hereditary disease with peripheral neuropathy","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":108961,"name":"Syndromic esophageal malformation","classifications":[147,182]}],"children":[],"genes":[{"symbol":"GMPPA","name":"GDP-mannose pyrophosphorylase A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24035193[PMID]","hgnc":"22923","ensembl":"ENSG00000144591","omim":"615495","loci":["2q35"]},{"symbol":"AAAS","name":"aladin WD repeat nucleoporin","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11159947[PMID]_20674935[PMID]_11815731[PMID]","hgnc":"13666","ensembl":"ENSG00000094914","omim":"605378","loci":["12q13.13"]},{"symbol":"TRAPPC11","name":"trafficking protein particle complex subunit 11","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27707803[PMID]","hgnc":"25751","ensembl":"ENSG00000168538","omim":"614138","loci":["4q35.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":100.0,"area":"Worldwide","status":"Validated","source":"14723589[PMID]_[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-10-02","source":"32533814[PMID]_32809536[PMID]_36763264[PMID]_32481456[PMID]_78049[PMID]_27707803[PMID]","terms":[{"hpo":"HP:0002571","label":"Achalasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000846","label":"Adrenal insufficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000522","label":"Alacrima","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007440","label":"Generalized hyperpigmentation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012735","label":"Cough","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008163","label":"Decreased circulating cortisol level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001611","label":"Hypernasal speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002173","label":"Hypoglycemic seizures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002615","label":"Hypotension","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031078","label":"Impaired cortisol response to corticotropin releasing hormone stimulation test","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003154","label":"Increased circulating ACTH level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000982","label":"Palmoplantar keratoderma","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001824","label":"Weight loss","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010486","label":"Abnormality of the hypothenar eminence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012804","label":"Corneal ulceration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001097","label":"Keratoconjunctivitis sicca","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007002","label":"Motor axonal neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007556","label":"Plantar hyperkeratosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004319","label":"Decreased circulating aldosterone level","frequency":"Very rare (<4-1%)","criteria":null}]}}