{"orpha":565624,"name":"Combined oxidative phosphorylation defect type 39","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["COXPD39","GFM2-related combined oxidative phosphorylation defect"],"definition":"A rare mitochondrial oxidative phosphorylation disorder characterized by early onset of severe developmental delay (sometimes with regression of developmental milestones) and intellectual disability, poor or absent speech, and hypotonia. Other features include movement disorder, seizures, or microcephaly, among others. Brain imaging may show features of Leigh syndrome with signal abnormalities in the basal ganglia or mid brain, cerebellar atrophy, or thin corpus callosum.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-565624/","orphanet_url":"https://www.orpha.net/en/disease/detail/565624","names":{"fr":{"name":"Déficit combiné de la phosphorylation oxydative type 39","synonyms":["COXPD39","Déficit combiné de la phosphorylation oxydative associé à GFM2"],"definition":"Myopathie congénitale rare lentement progressive, caractérisée par une faiblesse généralisée et/ou une atrophie des muscles proximaux et distaux. Certains patients présentent une faiblesse scapulopéronière et un décollement des omoplates. La maladie se déclare généralement dans la petite enfance ou l'enfance, mais des cas d'apparition à l'âge adulte ont également été rapportés. Les patients peuvent présenter des problèmes respiratoires et/ou une cardiomyopathie. Des inclusions de corps hyalins dans les fibres de type&#160;I sont visibles à la biopsie musculaire."},"de":{"name":"Kombinierter Defekt der oxidativen Phosphorylierung Typ 39","synonyms":["COXPD39","GFM2-assoziierter Kombinierter Defekt der oxidativen Phosphorylierung"],"definition":"Eine seltene mitochondriale Störung der oxidativen Phosphorylierung, die durch eine schwere frühkindliche Entwicklungsverzögerung (manchmal mit Rückschritten in der Entwicklung), Intelligenzminderung, schlechte oder fehlende Sprache und Hypotonie gekennzeichnet ist. Weitere Merkmale sind Bewegungsstörungen, Krampfanfälle und Mikrozephalie. Die zerebrale Bildgebung kann Merkmale des Leigh-Syndroms mit Signalanomalien in den Basalganglien oder im Mittelhirn, Kleinhirnatrophie oder dünnem Corpus callosum zeigen."},"es":{"name":"Deficiencia combinada de la fosforilación oxidativa tipo 39","synonyms":["COXPD39","Deficiencia combinada de la fosforilación oxidativa asociada a GFM2"],"definition":"Es un trastorno poco frecuente de la fosforilación oxidativa mitocondrial caracterizado por la aparición temprana de un retraso grave del desarrollo (en ocasiones con regresión de los hitos del desarrollo) y discapacidad intelectual, ausencia/ deficiencia del habla e hipotonía. Las características adicionales incluyen trastornos del movimiento, crisis o microcefalia, entre otras. Las neuroimágenes pueden mostrar características del síndrome de Leigh con alteración de la señal de los ganglios basales o del mesencéfalo, atrofia cerebelosa o adelgazamiento del cuerpo calloso."},"it":{"name":"Difetto combinato della fosforilazione ossidativa tipo 39","synonyms":["COXPD39","Difetto combinato della fosforilazione ossidativa correlato a GFM2"]},"nl":{"name":"Gecombineerde oxidatieve fosforylatiedeficiëntie type 39","synonyms":["COXPD39","GFM2-gerelateerde gecombineerde oxidatieve fosforylatiedeficiëntie"],"definition":"Een zeldzame stoornis van mitochondriale oxidatieve fosforylatie, gekenmerkt door vroeg optreden van ernstige ontwikkelingsachterstand (soms met regressie van ontwikkelingsmijlpalen) en intellectuele achterstand, ondermaatse of afwezige spraak, en hypotonie. Overige kenmerken zijn onder meer bewegingsstoornis, insulten, of microcefalie. Beeldvorming van hersenen toont mogelijk kenmerken van syndroom van Leigh met afwijkende signalen in basale ganglia of middenhersenen, cerebellaire atrofie, of dun corpus callosum."},"pt":{"name":"Defeito combinado da fosforilação oxidativa tipo 39","definition":"Doença rara da fosforilação oxidativa mitocondrial caracterizada por início precoce de atraso do desenvolvimento grave (por vezes com regressão das etapas do desenvolvimento) e perturbação do desenvolvimento intelectual, linguagem pobre ou ausente e hipotonia. Outras características incluem distúrbios do movimento, convulsões ou microcefalia, entre outros. Os exames de neuroimagem cerebral podem demostrar características da síndrome Leigh com alterações de sinal nos gânglios da base ou no mesencéfalo, atrofia cerebelar ou corpo caloso fino."},"pl":{"name":"Złożony defekt fosforylacji oksydacyjnej typu 39","synonyms":["COXPD39","GFM2-related combined oxidative phosphorylation defect"]},"cs":{"name":"Kombinovaný defekt oxidativní fosforylace typu 39","synonyms":["COXPD39","GFM2-related combined oxidative phosphorylation defect"]},"uk":{"name":"Комбінований дефект окисного фосфорилювання, тип 39","synonyms":["COXPD39","Комбінований дефект окислювального фосфорилювання, повязаний з GFM2"],"definition":"A rare mitochondrial oxidative phosphorylation disorder characterized by early onset of severe developmental delay (sometimes with regression of developmental milestones) and intellectual disability, poor or absent speech, and hypotonia. Other features include movement disorder, seizures, or microcephaly, among others. Brain imaging may show features of Leigh syndrome with signal abnormalities in the basal ganglia or mid brain, cerebellar atrophy, or thin corpus callosum."},"zh":{"name":"复合氧化磷酸化缺陷39型","synonyms":["GFM2基因相关复合氧化磷酸化缺陷"]},"tr":{"name":"Kombine oksidatif fosforilasyon defekti tip 39","synonyms":["COXPD39","GFM2-ilişkili kombine oksidatif fosforilasyon defekti"]}},"xrefs":[{"source":"OMIM","code":"618397","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":"attributed","validated":true},{"source":"MONDO","code":"0032726","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5193075","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"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":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"GFM2","name":"GTP dependent ribosome recycling factor mitochondrial 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22700954[PMID]_26016410[PMID]_29075935[PMID]","hgnc":"29682","ensembl":"ENSG00000164347","omim":"606544","loci":["5q13.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Antenatal","Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"22700954[PMID]_26016410[PMID]_29075935[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_22700954[PMID]_26016410[PMID]_29075935[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-08-27","source":"26016410[PMID]_29075935[PMID]","terms":[{"hpo":"HP:0001317","label":"Abnormal cerebellum morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001273","label":"Abnormal corpus callosum morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012379","label":"Abnormal enzyme/coenzyme activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001662","label":"Bradycardia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007321","label":"Deep white matter hypodensities","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002505","label":"Loss of ambulation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008763","label":"No social interaction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000543","label":"Optic disc pallor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000817","label":"Reduced eye contact","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011448","label":"Ankle clonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007366","label":"Atrophy/Degeneration affecting the brainstem","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005745","label":"Congenital foot contractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007371","label":"Corpus callosum atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000762","label":"Decreased nerve conduction velocity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002521","label":"Hypsarrhythmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004305","label":"Involuntary movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006956","label":"Lateral ventricle dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031959","label":"Leg dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002509","label":"Limb hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002061","label":"Lower limb spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003394","label":"Muscle spasm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002058","label":"Myopathic facies","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011470","label":"Nasogastric tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001998","label":"Neonatal hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000194","label":"Open mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012428","label":"Prominent calcaneus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null}]}}