{"orpha":765,"name":"Pyruvate dehydrogenase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["PDH","PDHC","Pyruvate dehydrogenase complex deficiency"],"definition":"Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders. Six subtypes related to the affected subunit of the PDH complex have been recognized with significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, and PDH phosphatase deficiency.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-765/","orphanet_url":"https://www.orpha.net/en/disease/detail/765","names":{"fr":{"name":"Déficit en pyruvate déshydrogénase","synonyms":["PDH","PDHC","Déficit en complexe pyruvate déshydrogénase"],"definition":"Le déficit en pyruvate déshydrogénase (DPD) est une maladie neurologique rare caractérisée par des signes cliniques très variés, en association avec des anomalies neurologiques et métaboliques de sévérité variable. Les manifestations varient d'une acidose lactique néonatale sévère, souvent fatale à des présentations neurologiques plus tardives. Selon la sous-unité du complexe PD affectée, six sous-types ont été décrits, dont certains ont des caractéristiques communes : le DPD E1-alpha, le DPD E1-bêta, le DPD E2 et E3, le déficit en protéine de liaison E3 du complexe PD et le déficit en phosphatase du complexe PD."},"de":{"name":"Pyruvat-Dehydrogenase-Mangel","synonyms":["PDHc","Pyruvat-Dehydrogenase-Komplex-Mangel"],"definition":"Der Pyruvat-Dehydrogenase-Mangel (PDHD) ist eine seltene neurometabolische Erkrankung und gekennzeichnet durch einen weiten Bereich klinischer Zeichen mit metabolischen und neurologischen Komponenten unterschiedlichen Schweregrades. Die Manifestationen reichen von schwerer, oft tödlicher neonataler Laktatazidose bis zu später beginnenden neurologischen Störungen. Abhängig von den betroffenen Untereinheiten des PDH-Komplexes wurden 6 Untertypen mit signifikanter klinischer Überschneidung definiert: PDHD durch E1-alpha-, E1-beta-, E2- und E3-Mangel, PDHD durch Mangel des E3-bindenden Proteins und PDH-Phosphatase-Mangel."},"es":{"name":"Deficiencia de piruvato deshidrogenasa","synonyms":["Deficiencia del complejo piruvato deshidrogenasa","PDH","PDHC"],"definition":"El déficit de piruvato deshidrogenasa (PDHD) es un trastorno neurometabólico raro caracterizado por un amplio rango de signos clínicos con componentes metabólicos y neurológicos de gravedad variable. Las manifestaciones van desde una acidosis láctica neonatal, grave, a menudo letal, a trastornos neurológicos de aparición más tardía. Se han identificado 6 subtipos asociados a la subunidad del complejo PDH afectada con un solapamiento clínico significativo: PDHD por déficit de E1-alfa, E1-beta, E2 y E3, PDHD por déficit de la proteína de unión E3, y déficit de PDH fosfatasa."},"it":{"name":"Deficit della piruvato deidrogenasi","synonyms":["Deficit del complesso della piruvato deidrogenasi","PDH","PDHC"],"definition":"Il deficit di piruvato deidrogenasi (PDHD) è una malattia rara neurometabolica con segni neurologici e metabolici di gravità variabile: dall'acidosi lattica neonatale grave, spesso fatali, ai disturbi neurologici a esordio tardivo. Sono stati identificati 6 sottotipi, legati alla subunità del complesso della PDH coinvolta, caratterizzati da una significativa sovrapposizione del fenotipo clinico: PDHD da deficit di E1-alfa, E1-beta, E2 e E3, PDHD da deficit della proteina legante E3 e deficit della PDH fosfatasi."},"nl":{"name":"Pyruvaatdehydrogenasedeficiëntie","synonyms":["Deficiëntie van het pyruvaatdehydrogenasecomplex","PDH","PDHC"],"definition":"Pyruvaatdehydrogenasedeficiëntie (PDHD) is een zeldzame neurometabole aandoening gekenmerkt door een grote waaier aan klinische symptomen met metabole en neurologische componenten van uiteenlopende ernst. Manifestaties variëren van vaak dodelijke, ernstige, neonatale lactaatacidose tot later optredende neurologische stoornissen. Zes subtypes gerelateerd aan de getroffen subeenheid van het PDH-complex zijn erkend met significante klinische overlapping: PDHD door E1-alfa-, E1-bèta-, E2- en E3-deficiëntie, PDHD door E3-bindend proteïnedeficiëntie en PDH-fosfatasedeficiëntie (zie deze termen)."},"pt":{"name":"Deficiência de piruvato desidrogenase","definition":"A deficiência de piruvato desidrogenase (PDHD) é uma doença rara neurometabólica caracterizada por vários sinais clínicos com componentes metabólicos e neurológicos de gravidade variável. As manifestações variam de fatal, grave e neonatal até distúrbios neurológicos de início tardio. Foram reconhecidos, com sobreposição clínica significativa, 6 subtipos relacionados com a subunidade afetada do complexo PDH: PDHD devido à deficiência de alfa-E1, beta-E1, E2 e E3, PDHD devido à deficiência da proteína de ligação da E3 e deficiência da PDH fosfatase (ver estes termos)."},"pl":{"name":"Niedobór dehydrogenazy pirogronianowej","synonyms":["Niedobór kompleksu dehydrogenazy pirogronianowej","PDH","PDHC"]},"cs":{"name":"Deficit pyruvát dehydrogenázy","synonyms":["PDH","PDHC","Deficit komplexu pyruvát dehydrogenázy"]},"uk":{"name":"Дефіцит піруватдегідрогенази","synonyms":["PDH","PDHC","Дефіцит піруватдегідрогеназного комплексу"],"definition":"Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders. Six subtypes related to the affected subunit of the PDH complex have been recognized with significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, and PDH phosphatase deficiency (see these terms)."},"zh":{"name":"丙酮酸脱氢酶缺乏症","synonyms":["丙酮酸脱氢酶复合物缺乏症"]},"tr":{"name":"Piruvat dehidrojenaz eksikliği","synonyms":["PDH","PDHC","Piruvat dehidrojenaz kompleks eksikliği"]}},"xrefs":[{"source":"OMIM","code":"245348","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"245349","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"246900","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"312170","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"608782","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614111","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E74.4","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C53.02","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"1124597954"},{"source":"MONDO","code":"0019169","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D015325","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0034345","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"7513","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10084109","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":225700,"name":"Mitochondrial disease with epilepsy","classifications":[156,181]},{"orpha":225703,"name":"Mitochondrial disease with peripheral neuropathy","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":254746,"name":"Pyruvate metabolism disorder","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[{"orpha":79243,"name":"Pyruvate dehydrogenase E1-alpha deficiency","type":"Clinical subtype"},{"orpha":255138,"name":"Pyruvate dehydrogenase E1-beta deficiency","type":"Clinical subtype"},{"orpha":79244,"name":"Pyruvate dehydrogenase E2 deficiency","type":"Clinical subtype"},{"orpha":2394,"name":"Pyruvate dehydrogenase E3 deficiency","type":"Clinical subtype"},{"orpha":255182,"name":"Pyruvate dehydrogenase E3-binding protein deficiency","type":"Clinical subtype"},{"orpha":79246,"name":"Pyruvate dehydrogenase phosphatase deficiency","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"DLAT","name":"dihydrolipoamide S-acetyltransferase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"16049940[PMID]","hgnc":"2896","ensembl":"ENSG00000150768","omim":"608770","loci":["11q23.1"],"via":{"orpha":79244,"name":"Pyruvate dehydrogenase E2 deficiency"}},{"symbol":"DLD","name":"dihydrolipoamide dehydrogenase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24777537[PMID]","hgnc":"2898","ensembl":"ENSG00000091140","omim":"238331","loci":["7q31.1"],"via":{"orpha":2394,"name":"Pyruvate dehydrogenase E3 deficiency"}},{"symbol":"PDP1","name":"pyruvate dehydrogenase phosphatase catalytic subunit 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"15855260[PMID]","hgnc":"9279","ensembl":"ENSG00000164951","omim":"605993","loci":["8q22.1"],"via":{"orpha":79246,"name":"Pyruvate dehydrogenase phosphatase deficiency"}},{"symbol":"LONP1","name":"lon peptidase 1, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"30304514[PMID]","hgnc":"9479","ensembl":"ENSG00000196365","omim":"605490","loci":["19p13.2"],"via":{"orpha":79243,"name":"Pyruvate dehydrogenase E1-alpha deficiency"}},{"symbol":"PDHA1","name":"pyruvate dehydrogenase E1 subunit alpha 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"10679936[PMID]_15384102[PMID]_20002461[PMID]","hgnc":"8806","ensembl":"ENSG00000131828","omim":"300502","loci":["Xp22.12"],"via":{"orpha":79243,"name":"Pyruvate dehydrogenase E1-alpha deficiency"}},{"symbol":"PDHB","name":"pyruvate dehydrogenase E1 subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"15138885[PMID]","hgnc":"8808","ensembl":"ENSG00000168291","omim":"179060","loci":["3p14.3"],"via":{"orpha":255138,"name":"Pyruvate dehydrogenase E1-beta deficiency"}},{"symbol":"PDHX","name":"pyruvate dehydrogenase complex component X","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"9399911[PMID]","hgnc":"21350","ensembl":"ENSG00000110435","omim":"608769","loci":["11p13"],"via":{"orpha":255182,"name":"Pyruvate dehydrogenase E3-binding protein deficiency"}}],"inheritance":["Autosomal recessive","Not applicable","X-linked dominant"],"onset":["Childhood","Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2015[OTHER]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000496","label":"Abnormality of eye movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007370","label":"Aplasia/Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001266","label":"Choreoathetosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100453","label":"Osteolytic defects of the middle phalanx of the 4th toe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002789","label":"Tachypnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100021","label":"Cerebral palsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002094","label":"Dyspnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001012","label":"Multiple lipomas","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000275","label":"Narrow face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000243","label":"Trigonocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null}]}}