{"orpha":254925,"name":"Combined oxidative phosphorylation defect type 4","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["COXPD4"],"definition":"Combined oxidative phosphorylation defect type 4 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by a neonatal onset of severe metabolic acidosis and respiratory distress, persistent lactic acidosis with episodes of metabolic crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial hypotonia with limb spasticity and reduced spontaneous movements. Neuroimaging studies reveal polymicrogyria, white matter abnormalities and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy. Decreased activity of complex I and IV have been determined in muscle biopsy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-254925/","orphanet_url":"https://www.orpha.net/en/disease/detail/254925","names":{"fr":{"name":"Déficit combiné de la phosphorylation oxydative type 4","synonyms":["COXPD4"],"definition":"Maladie mitochondriale rare par défaut de synthèse des protéines mitochondriales, caractérisée par une acidose métabolique sévère d'apparition néonatale et une détresse respiratoire, une acidose lactique persistante avec des crises métaboliques, une régression du développement, une microcéphalie, une anomalie de fixation et de poursuite du regard, une hypotonie axiale avec spasticité des membres et une réduction des mouvements spontanés. Les examens par neuro-imagerie révèlent une polymicrogyrie, des anomalies de la substance blanche et de multiples lésions cérébrales kystiques, y compris des ganglions de la base, ainsi qu'une atrophie cérébrale. Les biopsies musculaires révèlent une diminution de l'activité des complexes I et IV."},"de":{"name":"Kombinierter Defekt der oxidativen Phosphorylierung Typ 4","synonyms":["COXPD4"],"definition":"Der kombinierte oxidative Phosphorylierungsdefekt Typ 4 ist eine seltene mitochondriale Störung, die auf einem Defekt in der mitochondrialen Proteinsynthese beruht. Sie ist gekennzeichnet durch eine neonatal einsetzende schwere metabolische Azidose und Atemnot, persistierende Laktatazidose mit Episoden metabolischer Krisen, Entwicklungsrückschritte, Mikrozephalie, abnorme Blickfixierung und Verfolgung, axiale Hypotonie mit Spastizität der Gliedmaßen und reduzierte Spontanbewegungen. Neuroimaging-Untersuchungen zeigen Polymikrogyrien, Anomalien der weißen Substanz und multiple zystische Hirnläsionen, einschließlich der Basalganglien, und zerebrale Atrophie. In der Muskelbiopsie wurde eine verminderte Aktivität von Komplex I und IV festgestellt."},"es":{"name":"Deficiencia combinada de la fosforilación oxidativa tipo 4","synonyms":["COXPD4"],"definition":"Es un trastorno mitocondrial poco frecuente debido a un defecto en la síntesis de proteínas mitocondriales. Está caracterizada por un inicio neonatal de acidosis metabólica grave y dificultad respiratoria, acidosis láctica persistente con episodios de crisis metabólicas, regresión del desarrollo, microcefalia, fijación y seguimiento anómalos de la mirada, hipotonía axial con espasticidad de extremidades y movimientos espontáneos reducidos. Los estudios de neuroimagen revelan polimicrogiria, anomalías de la sustancia blanca y múltiples lesiones cerebrales quísticas, incluyendo los ganglios basales, y atrofia cerebral. En biopsias musculares, se detecta una actividad disminuida de los complejos I y IV."},"it":{"name":"Difetto combinato della fosforilazione ossidativa, tipo 4","synonyms":["COXPD4"],"definition":"Il difetto combinato della fosforilazione ossidativa tipo 4 è una malattia rara dei mitocondri causata da un'alterata sintesi proteica mitocondriale, caratterizzata da acidosi metabolica grave e distress respiratorio ad esordio neonatale, acidosi lattica persistente con episodi di crisi metaboliche, regressione dello sviluppo, microcefalia, anomalie della fissazione dello sguardo e dei movimenti di inseguimento, ipotonia assiale con spasticità degli arti e riduzione dei movimenti spontanei. Le immagini diagnostiche evidenziano polimicrogiria, anomalie della sostanza bianca, lesioni cistiche cerebrali multiple, anche nei gangli basali, e atrofia cerebrale. La biopsia dei muscoli mostra una diminuzione dell'attività dei complessi I e IV."},"nl":{"name":"Gecombineerde oxidatieve fosforylatiedeficiëntie type 4","synonyms":["COXPD4","Gecombineerd defect in oxidatieve fosforylering type 4"],"definition":"Gecombineerde oxidatieve fosforylatiedeficiëntie type 4 is een zeldzame mitochondriale stoornis als gevolg van een defect in de mitochondriale proteïnesynthese, en wordt gekarakteriseerd door een neonatale aanvang van ernstige metabole acidose en ademnood, persisterende lactaatacidose met episodes van metabole crises, ontwikkelingsregressie, microcefalie, abnormale fixatie en volgbewegingen van de ogen, axiale hypotonie met spasticiteit in de ledematen, en verminderde spontane bewegingen. Neurologische beeldvormingsonderzoeken tonen polymicrogyrie, afwijkingen van de witte stof en meervoudige cystische hersenletsels, waaronder atrofie van basale ganglia en de grote hersenen. Er werd een verminderde activiteit van complex I en IV vastgesteld in spierbiopten."},"pt":{"name":"Deficiência combinada da fosforilação oxidativa, tipo 4","synonyms":["COXPD4"]},"pl":{"name":"Złożony defekt fosforylacji oksydacyjnej typu 4","synonyms":["COXPD4"]},"cs":{"name":"Kombinovaný defekt oxidativní fosforylace, typ 4","synonyms":["COXPD4"]},"uk":{"name":"Комбінований дефект окисного фосфорилювання, тип 4","synonyms":["COXPD4"],"definition":"Combined oxidative phosphorylation defect type 4 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by a neonatal onset of severe metabolic acidosis and respiratory distress, persistent lactic acidosis with episodes of metabolic crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial hypotonia with limb spasticity and reduced spontaneous movements. Neuroimaging studies reveal polymicrogyria, white matter abnormalities and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy. Decreased activity of complex I and IV have been determined in muscle biopsy."},"zh":{"name":"结合氧化磷酸化不足4","synonyms":["COXPD4"],"definition":"联合氧化磷酸化缺陷症-4型是一种罕见的线粒体疾病，其特征是线粒体蛋白合成缺陷，表现为新生儿严重代谢性酸中毒和呼吸窘迫，持续性乳酸酸中毒伴代谢危象发作，发育倒退，小头畸形，异常的注视和平滑追踪，轴性肌张力低下伴肢体痉挛和自发活动减少。神经影像检查显示多小脑回、白质异常和多发性囊性脑病灶，包括基底节和脑萎缩。在肌肉活检中发现复合物I和IV的活性降低。"},"tr":{"name":"Kombine oksidatif fosforilasyon defekti tip 4","synonyms":["COXPD4"]}},"xrefs":[{"source":"OMIM","code":"610678","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":"1170105564"},{"source":"MONDO","code":"0012534","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C565690","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1857682","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]}],"children":[],"genes":[{"symbol":"TUFM","name":"Tu translation elongation factor, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"17160893[PMID]","hgnc":"12420","ensembl":"ENSG00000178952","omim":"602389","loci":["16p11.2"]}],"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":"17160893[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_17160893[PMID]"}],"phenotypes":null}