{"orpha":511,"name":"Maple syrup urine disease","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["BCKD deficiency","BCKDH deficiency","Branched-chain 2-ketoacid dehydrogenase deficiency","Branched-chain ketoaciduria","MSUD"],"definition":"A rare inherited disorder of branched-chain amino acid metabolism classically characterized by poor feeding, lethargy, vomiting and a maple syrup odor in the cerumen (and later in urine) noted soon after birth, followed by progressive encephalopathy and central respiratory failure if untreated. The four overlapping phenotypic subtypes are: classic, intermediate, intermittent and thiamine-responsive MSUD.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-511/","orphanet_url":"https://www.orpha.net/en/disease/detail/511","names":{"fr":{"name":"Maladie des urines sirop d'érable","synonyms":["Cétoacidurie à chaînes ramifiées","Déficit en BCKD","Déficit en BCKDH","Déficit en complexe de la déshydrogénase des alpha-cétoacides à chaîne ramifiée","Leucinose","MSUD","Maladie des urines à odeur de sirop d'érable"],"definition":"La maladie du sirop d'érable est un trouble héréditaire et rare du métabolisme des acides aminés à chaîne ramifiée. Elle se caractérise habituellement par des difficultés pour s'alimenter, une léthargie, des vomissements et une odeur de sirop d'érable dans le cérumen (et plus tardivement dans l'urine) observés précocement après la naissance, suivis par une encéphalopathie et une insuffisance respiratoire centrale en l'absence de traitement. Les quatre sous-types phénotypiques se superposant sont : la maladie du sirop d'érable classique, intermédiaire, intermittente et sensible à la thiamine."},"de":{"name":"Ahornsirup-Krankheit","synonyms":["Alpha-Ketosäuredecarboxylase-Mangel","BCKD-Mangel","BCKDH-Mangel","MSUD","Verzweigtkettenketoazidurie"],"definition":"Die Ahornsirupkrankheit (englisch Maple syrup urine disease/MSUD) ist eine seltene genetische Erkrankung im Stoffwechsel verzweigtkettiger Aminosäuren und ist klassischerweise gekennzeichnet durch geringe Nahrungsaufnahme, Lethargie, Erbrechen und einen Ahornsirup-ähnlichen Geruch im Ohrschmalz (und später im Urin) kurz nach der Geburt. Wenn die Krankheit unbehandelt bleibt, dann folgen progressive Enzephalopathie und zentrales Atemversagen. Die vier klinisch überlappenden Subtypen sind: klassische Form, Intermediärform, intermittierende Form und Thiamin-responsive Form (s. diese Termini)."},"es":{"name":"Enfermedad de la orina con olor a jarabe de arce","synonyms":["Cetoaciduria de cadena ramificada","Deficiencia de 2-cetoácido deshidrogenasa de cadena ramificada","Deficiencia de BCKD","Deficiencia de BCKDH","EOOJA","MSUD"],"definition":"Es un trastorno hereditario raro del metabolismo de los aminoácidos de cadena ramificada caracterizado clásicamente por rechazo alimentario, letargo, vómitos y olor a jarabe de arce en el cerumen (y posteriormente en la orina); se detecta nada más nacer y, si no se trata, va seguido de encefalopatía progresiva e insuficiencia respiratoria central. Existen cuatro subtipos fenotípicos solapantes de la enfermedad: clásica, intermedia, intermitente y sensible a tiamina."},"it":{"name":"Malattia delle urine a sciroppo d'acero","synonyms":["Chetoaciduria a catena ramificata","Deficit di 2-chetoacido deidrogenasi a catena ramificata","Deficit di BCKD","Deficit di BCKDH","MSUD"],"definition":"La malattia delle urine a sciroppo d'acero (MSUD) è un difetto raro del metabolismo degli aminoacidi a catena ramificata, caratterizzato tipicamente da difficoltà all'alimentazione, letargia, vomito, ed un cerume, notato subito dopo la nascita (e in seguito le urine), che odora di sciroppo d'acero, seguiti, in assenza di trattamento, da un'encefalopatia progressiva e un'insufficienza respiratoria centrale. I quattro sottotipi fenotipici in sovrapposizione sono la MSUD classica, intermedia, intermittente e tiamina-sensibile (si vedano questi termini)."},"nl":{"name":"Maple syrup urine disease","synonyms":["Ahornsiroopurineziekte","BCKD-deficiëntie","BCKDH-deficiëntie","Esdoornsiroopurineziekte","MSUD","Vertakte keten-ketozuurdehydrogenasedeficiëntie"],"definition":"Een zeldzame, erfelijke stoornis van het vertakte keten-aminozuurmetabolisme, doorgaans gekarakteriseerd door voedingsproblemen, lethargie, braken, en een geur van ahornsiroop in het cerumen (oorsmeer) (en later in de urine) die kort na de geboorte wordt opgemerkt, gevolgd door progressieve encefalopathie en centraal respiratoir falen indien onbehandeld. De vier overlappende fenotypische subtypes zijn klassieke, intermediaire, intermitterende en thiamineresponsieve MSUD."},"pt":{"name":"Doença da urina xarope de bordo","synonyms":["Cetoaciduria de cadeia ramificada","Deficiência de BCKD","Deficiência de BCKDH","Deficiência de desidrogenase de 2-cetoácido de cadeia ramificada","MSUD"],"definition":"Doença hereditária rara do metabolismo dos aminoácidos de cadeia ramificada, classicamente caracterizada por dificuldades alimentares, letargia, vómitos e odor a xarope de ácer no cerúmen (e posteriormente na urina) observada logo após o nascimento, seguida de encefalopatia progressiva e insuficiência respiratória central se não tratada. Os quatro subtipos fenotípicos sobrepostos são: MSUD clássica, intermédia, intermitente e responsiva à tiamina."},"pl":{"name":"Choroba syropu klonowego","synonyms":["Ketoaciduria łańcuchów rozgałęzionych","MSUD","Niedobór BCKD","Niedobór BCKDH","Niedobór dehydrogenazy 2-ketokwasów łańcuchów rozgałęzionych"]},"cs":{"name":"Leucinóza","synonyms":["Nemoc javorového sirupu","Deficit BCKD","Deficit BCKDH","Deficit dehydrogenázy 2-ketokyselin s větveným řetězcem"]},"uk":{"name":"Хвороба кленового сиропу","synonyms":["Дефіцит BCKD","Дефіцит BCKDH","Дефіцит дегідрогенази 2-кетокислот з розгалуженим ланцюгом","Розгалужена кетоацидурія","MSUD"],"definition":"A rare inherited disorder of branched-chain amino acid metabolism classically characterized by poor feeding, lethargy, vomiting and a maple syrup odor in the cerumen (and later in urine) noted soon after birth, followed by progressive encephalopathy and central respiratory failure if untreated. The four overlapping phenotypic subtypes are: classic, intermediate, intermittent and thiamine-responsive MSUD."},"zh":{"name":"枫糖尿病","synonyms":["支链酮酸尿症"]},"tr":{"name":"Akçaağaç şurubu idrar hastalığı","synonyms":["MSUD","BCKD eksikliği","BCKDH eksikliği","Dallı zincirli ketoasidüri","Dallı zincirli 2-ketoasit dehidrojenaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"248600","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615135","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620698","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620699","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.0","qualifier":"E","icd_relation":"specific","validated":true},{"source":"ICD-11","code":"5C50.D0","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"1623706568"},{"source":"MONDO","code":"0009563","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D008375","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0024776","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3228","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10026817","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79197,"name":"Disorder of branched-chain amino acid metabolism","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[{"orpha":268145,"name":"Classic maple syrup urine disease","type":"Clinical subtype"},{"orpha":268162,"name":"Intermediate maple syrup urine disease","type":"Clinical subtype"},{"orpha":268173,"name":"Intermittent maple syrup urine disease","type":"Clinical subtype"},{"orpha":268184,"name":"Thiamine-responsive maple syrup urine disease","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"BCKDHB","name":"branched chain keto acid dehydrogenase E1 subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"987","ensembl":"ENSG00000083123","omim":"248611","loci":["6q14.1"],"via":{"orpha":268145,"name":"Classic maple syrup urine disease"}},{"symbol":"BCKDHB","name":"branched chain keto acid dehydrogenase E1 subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"987","ensembl":"ENSG00000083123","omim":"248611","loci":["6q14.1"],"via":{"orpha":268162,"name":"Intermediate maple syrup urine disease"}},{"symbol":"BCKDHB","name":"branched chain keto acid dehydrogenase E1 subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"987","ensembl":"ENSG00000083123","omim":"248611","loci":["6q14.1"],"via":{"orpha":268173,"name":"Intermittent maple syrup urine disease"}},{"symbol":"DBT","name":"dihydrolipoamide branched chain transacylase E2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"2698","ensembl":"ENSG00000137992","omim":"248610","loci":["1p21.2"],"via":{"orpha":268145,"name":"Classic maple syrup urine disease"}},{"symbol":"DBT","name":"dihydrolipoamide branched chain transacylase E2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"2698","ensembl":"ENSG00000137992","omim":"248610","loci":["1p21.2"],"via":{"orpha":268162,"name":"Intermediate maple syrup urine disease"}},{"symbol":"DBT","name":"dihydrolipoamide branched chain transacylase E2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"2698","ensembl":"ENSG00000137992","omim":"248610","loci":["1p21.2"],"via":{"orpha":268173,"name":"Intermittent maple syrup urine disease"}},{"symbol":"DBT","name":"dihydrolipoamide branched chain transacylase E2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301495[PMID]","hgnc":"2698","ensembl":"ENSG00000137992","omim":"248610","loci":["1p21.2"],"via":{"orpha":268184,"name":"Thiamine-responsive maple syrup urine disease"}},{"symbol":"BCKDHA","name":"branched chain keto acid dehydrogenase E1 subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301495[PMID]","hgnc":"986","ensembl":"ENSG00000248098","omim":"608348","loci":["19q13.2"],"via":{"orpha":268145,"name":"Classic maple syrup urine disease"}},{"symbol":"BCKDHA","name":"branched chain keto acid dehydrogenase E1 subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301495[PMID]","hgnc":"986","ensembl":"ENSG00000248098","omim":"608348","loci":["19q13.2"],"via":{"orpha":268162,"name":"Intermediate maple syrup urine disease"}},{"symbol":"BCKDHA","name":"branched chain keto acid dehydrogenase E1 subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301495[PMID]","hgnc":"986","ensembl":"ENSG00000248098","omim":"608348","loci":["19q13.2"],"via":{"orpha":268173,"name":"Intermittent maple syrup urine disease"}},{"symbol":"PPM1K","name":"protein phosphatase, Mg2+/Mn2+ dependent 1K","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23086801[PMID]","hgnc":"25415","ensembl":"ENSG00000163644","omim":"611065","loci":["4q22.1"],"via":{"orpha":268162,"name":"Intermediate maple syrup urine disease"}}],"inheritance":["Autosomal recessive"],"onset":["Childhood","Infancy","Neonatal"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.67,"area":"Worldwide","status":"Validated","source":"[EXPERT]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.78,"area":"United States","status":"Validated","source":"20307994[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.79,"area":"Italy","status":"Validated","source":"11953730[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":7.3,"area":"Tunisia","status":"Validated","source":"22481200[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.19,"area":"Japan","status":"Validated","source":"6468444[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.15,"area":"Portugal","status":"Validated","source":"20466570[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.6,"area":"Australia","status":"Validated","source":"12788994[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.86,"area":"Taiwan, Province of China","status":"Validated","source":"2056791[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2018[OTHER]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.396,"area":"China","status":"Validated","source":"34103049[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.34,"area":"Czech Republic","status":"Validated","source":"31241292[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":4.8,"area":"Israel","status":"Validated","source":"33239050[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-5 / 10 000","value":10.2,"area":"Specific population","status":"Validated","source":"33239050[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0000600","label":"Abnormality of the pharynx","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001608","label":"Abnormality of the voice","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008344","label":"Elevated plasma branched chain amino acids","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001315","label":"Reduced tendon reflexes","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004374","label":"Hemiplegia/hemiparesis","frequency":"Frequent (79-30%)","criteria":null}]}}