{"orpha":56,"name":"Alkaptonuria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Hereditary ochronosis","Homogentisic acid oxidase deficiency"],"definition":"A rare inborn error of metabolism disorder characterized by homogentisic acid accumulation causing dark urine.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-56/","orphanet_url":"https://www.orpha.net/en/disease/detail/56","names":{"fr":{"name":"Alcaptonurie","synonyms":["Déficit en homogentisicase","Déficit en oxydase de l'acide homogentisique","Ochronose héréditaire"],"definition":"Trouble rare du métabolisme de la phénylalanine ou de la tyrosine caractérisé par l'accumulation d'acide homogentisique (AHG) et de son produit d'oxydation, acide benzoquinone acétique (ABQA), dans divers tissus (par exemple, cartilage, tissu conjonctif) et dans les fluides corporels (urine, sueur), conduisant à une coloration foncée des urines au contact de l'air, une pigmentation gris-bleue des sclérotiques et de l'hélix (ochronose) et par une maladie articulaire invalidante avec atteinte axiale et périphérique (arthropathie ochronotique)."},"de":{"name":"Alkaptonurie","synonyms":["Homogentisin(säure)oxigenase-Mangel","Ochronose, hereditäre"],"definition":"Eine seltene Störung des Phenylalanin- und Tyrosin-Stoffwechsels, die durch die Anhäufung von Homogentisinsäure (HGA) und ihrem Oxidationsprodukt, der Benzochinon-Essigsäure (BQA), in verschiedenen Geweben (z. B. Knorpel, Bindegewebe) und Körperflüssigkeiten (Urin, Schweiß) gekennzeichnet ist. Die Folgen sind: Dunkelfärbung des Urins an der Luft, grau-blaue Färbung der Skleren und der Ohrmuscheln (Ochronose) und eine invalidisierende Erkrankung der axialen und peripheren Gelenke (ochronotische Arthropathie)."},"es":{"name":"Alcaptonuria","synonyms":["Deficiencia de homogentisico oxidasa","Ocronosis hereditaria"],"definition":"Un trastorno poco frecuente del metabolismo de la fenilalanina y la tirosina caracterizado por el acúmulo de ácido homogentísico (HGA) y su producto oxidado, el ácido benzoquinona acético (BQA), en diversos tejidos (cartílago, tejido conectivo) y fluidos corporales (orina, sudor), provocando el oscurecimiento de la orina cuando se expone al aire así como una coloración gris-azulada de la esclerótica y de la hélix de la oreja (ocronosis), y una enfermedad articular incapacitante que afecta tanto a las articulaciones axiales como a las periféricas (artropatía ocronótica)."},"it":{"name":"Alcaptonuria","synonyms":["Deficit di acido omogentisico ossidasi","Ocronosi ereditaria"],"definition":"Si tratta di un difetto raro del metabolismo della fenilalanina e della tirosina, caratterizzato dall'accumulo di acido omogentisico (HGA) e del prodotto della sua ossidazione, l'acido benzochinone acetico (BQA), in diversi tessuti (ad es. cartilagini, tessuti connettivi) e nei liquidi corporei (urine, sudore), con la conseguente colorazione scura delle urine al contatto con l'aria, una colorazione grigio-blu della sclera e dell'elice dell'orecchio (ocronosi) e una patologia invalidante a livello delle articolazioni assiali e periferiche (artropatia ocronotica)."},"nl":{"name":"Alkaptonurie","synonyms":["Endogene ochronose","Erfelijke ochronose","Homogenisaatoxidasedeficiëntie","Homogenistinezuuroxidasedeficiëntie"],"definition":"Een zeldzame stoornis van het fenylalanine- en tyrosinemetabolisme gekarakteriseerd door de accumulatie van homogentisinezuur (HGA) en het geoxideerde product ervan, benzochinon azijnzuur (BQA), in verschillende weefsels (e.g. kraakbeen, bindweefsel) en lichaamsvloeistoffen (urine, zweet), wat leidt tot verdonkering van de urine bij blootstelling aan lucht alsook blauwgrijze verkleuring van het oogwit en de helices van de oren (ochronose), en een invaliderende gewrichtsziekte met betrokkenheid van zowel de axiale als perifere gewrichten (ochronotische artropathie)."},"pt":{"name":"Alcaptonúria","synonyms":["Deficiência de ácido homogentísico oxidase","Ocronose hereditária"]},"pl":{"name":"Alkaptonuria","synonyms":["Dziedziczna ochronoza","Niedobór oksydazy kwasu homogentyzynowego"],"definition":"Alkaptonuria jest chorobą metaboliczną, charakteryzującą się nagromadzeniem kwasu homogentyzynowego (HGA) i jego produktu utleniania, benzochinonu kwasu octowego (BQA) w różnych tkankach (np. chrząstkach, tkance łącznej) i płynach ustrojowych (moczu, pocie), co powoduje ciemnienie moczu na powietrzu, jak również szaroniebieskie zabarwienie twardówki i obrąbka małżowiny usznej (ochronoza) oraz zmiany zwyrodnieniowe stawów, obejmujące zarówno osiowe jak i stawy obwodowe (artropatia ochronotyczna)."},"cs":{"name":"Alkaptonurie","synonyms":["Deficit oxidázy homogentisové kyseliny","Dědičná ochronóza"]},"uk":{"name":"Алкаптонурія","synonyms":["Спадковий охроноз","Дефіцит оксидази гомогентизинової кислоти"],"definition":"A rare disorder of phenylalanine and tyrosine metabolism characterized by the accumulation of homogentisic acid (HGA) and its oxidized product, benzoquinone acetic acid (BQA), in various tissues (e.g. cartilage, connective tissue) and body fluids (urine, sweat), causing urine to darken when exposed to air as well as grey-blue coloration of the sclera and ear helix (ochronosis), and a disabling joint disease involving both the axial and peripheral joints (ochronotic arthropathy)."},"zh":{"name":"黑酸尿症","synonyms":["尿黑酸氧化酶缺乏症"]},"tr":{"name":"Alkaptonüri","synonyms":["Kalıtsal okronoz","Homojentisik asit oksidaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"203500","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E70.2","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C50.10","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"1761652827"},{"source":"MONDO","code":"0008753","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D000474","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0002066","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"5775","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10001689","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":284818,"name":"Disorder of tyrosine metabolism","classifications":[150,156]},{"orpha":79387,"name":"Metabolic disease with skin involvement","classifications":[156]},{"orpha":79217,"name":"Other metabolic disease with skin involvement","classifications":[187]},{"orpha":519296,"name":"Rare disorder with pigmented sclera","classifications":[156,189]}],"children":[],"genes":[{"symbol":"HGD","name":"homogentisate 1,2-dioxygenase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301627[PMID]","hgnc":"4892","ensembl":"ENSG00000113924","omim":"607474","loci":["3q13.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adult","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2003[OTHER]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.15,"area":"France","status":"Validated","source":"21927854[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"France","status":"Not yet validated","source":"21927854[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.25,"area":"United States","status":"Not yet validated","source":"20301627[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"United States","status":"Not yet validated","source":"20301627[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":5.3,"area":"Slovakia","status":"Validated","source":"12051967[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 100 000","value":0.0,"area":"Slovakia","status":"Validated","source":"12051967[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2023-10-10","source":"20301627[PMID]_37268334[PMID]_37395296[PMID]_32809406[PMID]_35015405[PMID]_24479547[PMID]","terms":[{"hpo":"HP:0001000","label":"Abnormality of skin pigmentation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000504","label":"Abnormality of vision","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003355","label":"Aminoaciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002829","label":"Arthralgia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001369","label":"Arthritis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100593","label":"Calcification of cartilage","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001717","label":"Coronary artery calcification","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0033704","label":"Elevated urinary homogentisic acid","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000364","label":"Hearing abnormality","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005645","label":"Intervertebral disk calcification","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007400","label":"Irregular hyperpigmentation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001373","label":"Joint dislocation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001387","label":"Joint stiffness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001386","label":"Joint swelling","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030764","label":"Ochronosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002758","label":"Osteoarthritis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001654","label":"Abnormal heart valve morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001597","label":"Abnormal nail morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000366","label":"Abnormality of the nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004380","label":"Aortic valve calcification","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001650","label":"Aortic valve stenosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003418","label":"Back pain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100773","label":"Cartilage destruction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040319","label":"Dark urine","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004382","label":"Mitral valve calcification","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000787","label":"Nephrolithiasis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:6000027","label":"Oil-drop brown pigmentation of the corneal limbus","frequency":"Frequent (79-30%)","criteria":"Pathognomonic sign"},{"hpo":"HP:0007832","label":"Pigmentation of the sclera","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000024","label":"Prostatitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100550","label":"Tendon rupture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004690","label":"Thickened Achilles tendon","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011034","label":"Amyloidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004942","label":"Aortic aneurysm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002621","label":"Atherosclerosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011982","label":"Black pigment gallstones","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025612","label":"Corneal astigmatism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:6000025","label":"Dark cerumen","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000501","label":"Glaucoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001878","label":"Hemolytic anemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000822","label":"Hypertension","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000821","label":"Hypothyroidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002659","label":"Increased susceptibility to fractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012119","label":"Methemoglobinemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001653","label":"Mitral regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001718","label":"Mitral stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001658","label":"Myocardial infarction","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007906","label":"Ocular hypertension","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0034882","label":"Prostatic calculus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004349","label":"Reduced bone mineral density","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null}]}}