{"orpha":137681,"name":"Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Hepatoencephalopathy due to COXPD1"],"definition":"A rare, inherited mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by intrauterine growth retardation, metabolic decompensation with recurrent vomiting, persistent severe lactic acidosis, encephalopathy, seizures, failure to thrive, severe global developmental delay, poor eye contact, severe muscular hypotonia or axial hypotonia with limb hypertonia, hepatomegaly and/or liver dysfunction and/or liver failure, leading to fatal outcome in severe cases. Neuroimaging abnormalities may include corpus callosum thinning, leukodystrophy, delayed myelination and basal ganglia involvement.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-137681/","orphanet_url":"https://www.orpha.net/en/disease/detail/137681","names":{"fr":{"name":"Hépatoencéphalopathie par déficit combiné de la phosphorylation oxydative de type 1","synonyms":["Hépatoencéphalopathie par COXPD1"],"definition":"Un trouble mitochondrial héréditaire rare, causé par un déficit de synthèse des protéines mitochondriales. Il se caractérise par un retard de croissance intra-utérin, une décompensation métabolique avec des vomissements récurrents, une acidose lactique persistante sévère, une encéphalopathie, des convulsions, un retard de croissance staturopondérale, un retard sévère du développement global, peu de contact visuel, une hypotonie musculaire ou axiale sévère avec hypertonie des membres, une hépatomégalie et/ou une dysfonction hépatique, et/ou une insuffisance hépatique, pouvant être fatal dans les cas sévères. Les anomalies observées en neuro-imagerie peuvent inclure un corps calleux fin, une leucodystrophie, un retard de la myélinisation et une atteinte des ganglions de la base."},"de":{"name":"Hepatoenzephalopathie durch kombinierten Defekt der oxidativen Phosphorylierung Typ 1","synonyms":["Hepatoenzephalopathie durch COXPD1"],"definition":"Eine seltene hereditäre Mitochondriopathie aufgrund eines Defekts in der mitochondrialen Proteinsynthese. Charakteristische Merkmale sind intrauterine Wachstumsverzögerung, metabolische Dekompensation mit rezidivierendem Erbrechen, persistierende schwere Laktatazidose, Enzephalopathie, Krampfanfälle, Gedeihstörung, schwere globale Entwicklungsverzögerung, schlechter Augenkontakt, schwere muskuläre Hypotonie oder axiale Hypotonie mit Gliedmaßenhypertonie, Hepatomegalie und/oder Leberdysfunktion und/oder Leberversagen, was in schweren Fällen zum Tod führt. Auffälligkeiten im Neuroimaging-Verfahren können eine Ausdünnung des Corpus callosum, Leukodystrophie, verzögerte Myelinisierung und eine Beteiligung der Basalganglien umfassen."},"es":{"name":"Hepatoencefalopatía por deficiencia combinada de la fosforilación oxidativa tipo 1","synonyms":["Hepatoencefalopatía por COXPD1"],"definition":"Es un trastorno mitocondrial hereditario poco frecuente debido a un defecto de la síntesis proteica mitocondrial. Está caracterizado por retraso del crecimiento intrauterino, descompensación metabólica con vómitos recurrentes, acidosis láctica grave persistente, encefalopatía, crisis epilépticas, fallo de medro, grave retraso global del desarrollo, contacto visual pobre, hipotonía muscular grave o hipotonía axial con hipertonía en las extremidades, hepatomegalia y/o disfunción hepática y/o insuficiencia hepática, lo que resulta en un desenlace fatal en casos graves. Las anomalías detectadas en la neuroimagen pueden incluir adelgazamiento del cuerpo calloso, leucodistrofia, retraso de la mielinización y afectación de los ganglios basales."},"it":{"name":"Epatoencefalopatia da difetto combinato della fosforilazione ossidativa, tipo 1","synonyms":["Epatoencefalopatia da COXPD1"],"definition":"L'epatoencefalopatia da difetto combinato della fosforilazione ossidativa tipo 1 è una malattia mitocondriale ereditaria rara, causata da un difetto della sintesi proteica mitocondriale. È caratterizzata da ritardo della crescita intrauterina, scompenso metabolico con vomito ricorrente, acidosi lattica grave persistente, encefalopatia, crisi epilettiche, ritardo della crescita, grave ritardo dello sviluppo globale, scarso contatto visivo, grave ipotonia muscolare o ipotonia assiale con ipertonia degli arti, epatomegalia e/o disfunzione epatica e/o insufficienza epatica che, nei casi più gravi, esita nel decesso. Le neuroimmagini evidenziano l'assottigliamento del corpo calloso, leucodistrofia, ritardo della mielinizzazione e interessamento dei gangli basali."},"nl":{"name":"Hepato-encefalopathie door gecombineerde oxidatieve fosforylatiedeficiëntie type 1","synonyms":["Hepato-encefalopathie door COXPD1"],"definition":"Een zeldzame, erfelijke mitochondriale aandoening door een defect in mitochondriale eiwitsynthese, gekenmerkt door intra-uteriene groeiretardatie, metabole decompensatie met recidiverend braken, aanhoudende ernstige lactaatacidose, encefalopathie, insulten, niet-gedijen, ernstige algehele ontwikkelingsachterstand, weinig oogcontact, ernstige spierhypotonie of axiale hypotonie met hypertonie van ledematen, hepatomegalie en/of leverdisfunctie en/of leverfalen, met in ernstige gevallen een fatale uitkomst tot gevolg. Mogelijke afwijkingen bij beeldvorming van hersenen zijn onder meer verdunning van corpus callosum, leukodystrofie, vertraagde myelinisatie en betrokkenheid van basale ganglia."},"pt":{"name":"Hepatoencefalopatia por deficiência combinada da fosforilação oxidativa, tipo 1"},"pl":{"name":"Encefalopatia wątrobowa z powodu złożonego niedoboru fosforylacji oksydacyjnej typu 1","synonyms":["Encefalopatia wątrobowa z powodu COXPD1"],"definition":"Rzadkie, dziedziczne zaburzenie mitochondrialne spowodowane defektem syntezy białek mitochondrialnych, charakteryzujące się opóźnieniem wzrostu wewnątrzmacicznego, dekompensacją metaboliczną z nawracającymi wymiotami, uporczywą ciężką kwasicą mleczanową, encefalopatią, drgawkami, brakiem prawidłowego rozwoju, poważnym globalnym opóźnieniem rozwoju, słabym kontaktem wzrokowym, ciężką hipotonią lub hipotonią osiowa ze wzmożonym napięciem w kończynach, hepatomegalią i/lub dysfunkcją wątroby i/lub niewydolnością wątroby, prowadzące w ciężkich przypadkach do zgonu. Nieprawidłowości w badaniach obrazowych to ścieńczenie ciała modzelowatego, leukodystrofia, opóźniona mielinizacja i zajęcie zwojów podstawy."},"cs":{"name":"Hepatoencefalopatie způsobená kombinovaným deficitem oxidativní fosforylace, typ 1","synonyms":["Hepatoencefalopatie způsobená COXPD1"]},"uk":{"name":"Гепатоенцефалопатія внаслідок комбінованого дефекту окисного фосфорилювання типу 1","synonyms":["Гепатоенцефалопатія внаслідок COXPD1"],"definition":"A rare, inherited mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by intrauterine growth retardation, metabolic decompensation with recurrent vomiting, persistent severe lactic acidosis, encephalopathy, seizures, failure to thrive, severe global developmental delay, poor eye contact, severe muscular hypotonia or axial hypotonia with limb hypertonia, hepatomegaly and/or liver dysfunction and/or liver failure, leading to fatal outcome in severe cases. Neuroimaging abnormalities may include corpus callosum thinning, leukodystrophy, delayed myelination and basal ganglia involvement."},"zh":{"name":"复合性氧化磷酸化缺陷所致肝性脑病1型","synonyms":["联合氧化磷酸化缺陷1型所致肝性脑病"],"definition":"结合氧化磷酸化不足1型所致肝性脑病是一种罕见的遗传性线粒体疾病由于线粒体蛋白质合成缺乏导致宫内生长迟缓、代谢代谢失调与复发性呕吐,持续严重乳酸酸中毒,脑病,癫痫,未能茁壮成长,严重的全身发育迟缓,眼神接触少,严重的肌张力减退或躯干张力减退和四肢张力亢进,肝肿大和/或肝功能障碍和/或肝功能衰竭，严重时可导致死亡。神经影像学异常可能包括胼胝体变薄、脑白质营养不良、髓鞘形成延迟和基底节受累。"},"tr":{"name":"Tip 1 kombine oksidatif fosforilasyon defektine bağlı hepatoensefalopati","synonyms":["COXPD1'e bağlı hepatoensefalopati"]}},"xrefs":[{"source":"OMIM","code":"609060","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.23","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1373381208"},{"source":"MONDO","code":"0012191","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4707239","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":35696,"name":"Mitochondrial disorder due to a defect in mitochondrial protein synthesis","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":101940,"name":"Rare metabolic liver disease","classifications":[156,183]}],"children":[],"genes":[{"symbol":"GFM1","name":"G elongation factor mitochondrial 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23430926[PMID]","hgnc":"13780","ensembl":"ENSG00000168827","omim":"606639","loci":["3q25.32"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"21119709[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_21119709[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2025-11-21","source":"38204316[PMID]_34919756[PMID]","terms":[{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008972","label":"Decreased activity of mitochondrial respiratory chain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003073","label":"Hypoalbuminemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001622","label":"Premature birth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0033725","label":"Thin corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null}]}}