{"orpha":506,"name":"Leigh syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Infantile subacute necrotizing encephalopathy","Leigh disease"],"definition":"A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-506/","orphanet_url":"https://www.orpha.net/en/disease/detail/506","names":{"fr":{"name":"Syndrome de Leigh","synonyms":["Encéphalomyopathie nécrosante subaiguë","Maladie de Leigh"],"definition":"Le syndrome de Leigh ou encéphalomyopathie nécrosante subaiguë est une maladie neurologique progressive caractérisée par des lésions neuropathologiques associant en particulier une atteinte du tronc cérébral et des ganglions de la base."},"de":{"name":"Leigh-Syndrom","synonyms":["Infantile subakute nekrotisierende Enzephalomyelopathie","Leigh-Krankheit"],"definition":"Eine progressive neurologische Erkrankung, die durch spezifische neuropathologische Merkmale definiert ist, die mit Läsionen des Hirnstamms und der Basalganglien einhergehen."},"es":{"name":"Síndrome de Leigh","synonyms":["Encefalopatia necrotizante subaguda infantil"],"definition":"Es una enfermedad neurológica progresiva definida por unos hallazgos neuropatológicos específicos asociados a lesiones del tronco cerebral y de los ganglios basales."},"it":{"name":"Sindrome di Leigh","synonyms":["Encefalomiopatia necrosante infantile subacuta","Malattia di Leigh"]},"nl":{"name":"Syndroom van Leigh","synonyms":["Infantiele subacute necrotiserende encefalopathie","Ziekte van Leigh"],"definition":"Een progressieve, neurologische ziekte, gekarakteriseerd door specifieke neuropathologische kenmerken geassocieerd met laesies aan hersenstam en basale ganglia."},"pt":{"name":"Síndrome Leigh","synonyms":["Encefalopatia necrotizante sub-aguda infantil"]},"pl":{"name":"Zespół Leigha","synonyms":["Choroba Leigha","Dziecięca podostra encefalopatia martwicza"],"definition":"Postępująca choroba neurologiczna charakteryzująca się specyficznymi cechami neuropatologicznymi, związanymi ze zmianami w pniu mózgu i zwojach podstawy mózgu."},"cs":{"name":"Leighův syndrom","synonyms":["Leighova choroba","Subakutní nekrotizující encefalopatie u kojenců"]},"uk":{"name":"Синдром Лея","synonyms":["Підгостра інфантильна некротична енцефалопатія","Хвороба Лі"],"definition":"A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions."},"zh":{"name":"Leigh综合征","synonyms":["婴儿亚急性坏死性脑病"]},"tr":{"name":"Leigh sendromu","synonyms":["Leigh hastalığı","İnfantil subakut nekrotizan ensefalopati"]}},"xrefs":[{"source":"OMIM","code":"256000","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G31.8","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C53.24","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"672871576"},{"source":"MONDO","code":"0009723","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D007888","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0023264","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6877","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10062950","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":70474,"name":"Leigh syndrome with cardiomyopathy","status":"inactive"},{"type":"Moved to","orpha":255241,"name":"Leigh syndrome with leukodystrophy","status":"inactive"},{"type":"Moved to","orpha":255249,"name":"Leigh syndrome with nephrotic syndrome","status":"inactive"}],"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":2443,"name":"Mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":98687,"name":"Supranuclear eye movement disorder","classifications":[156,189]}],"children":[],"genes":[{"symbol":"IARS2","name":"isoleucyl-tRNA synthetase 2, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"39169373[PMID]","hgnc":"29685","ensembl":"ENSG00000067704","omim":"612801","loci":["1q41"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive","Mitochondrial inheritance","X-linked recessive"],"onset":["All ages"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":2.8,"area":"Europe","status":"Validated","source":"[EXPERT]"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":1.3,"area":"Australia","status":"Validated","source":"8602753[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":2.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2011[OTHER]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-02-05","source":"23772060[PMID]_26506407[PMID]_26425749[PMID]","terms":[{"hpo":"HP:0012379","label":"Abnormal enzyme/coenzyme activity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100022","label":"Abnormality of movement","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003648","label":"Lacticaciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012751","label":"Abnormal basal ganglia MRI signal intensity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012747","label":"Abnormal brainstem MRI signal intensity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000587","label":"Abnormal optic nerve morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012696","label":"Abnormal thalamic MRI signal intensity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100321","label":"Abnormality of the dentate nucleus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0410263","label":"Brain imaging abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008336","label":"Complex organic aciduria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011923","label":"Decreased activity of mitochondrial complex I","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008972","label":"Decreased activity of mitochondrial respiratory chain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002928","label":"Decreased activity of the pyruvate dehydrogenase complex","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006943","label":"Diffuse spongiform leukoencephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012707","label":"Elevated brain lactate level by MRS","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007183","label":"Focal T2 hyperintense basal ganglia lesion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012748","label":"Focal T2 hyperintense brainstem lesion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002171","label":"Gliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000998","label":"Hypertrichosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004305","label":"Involuntary movements","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000602","label":"Ophthalmoplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002344","label":"Progressive neurologic deterioration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031691","label":"Severe viral infection","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002493","label":"Upper motor neuron dysfunction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003535","label":"3-Methylglutaconic aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002793","label":"Abnormal pattern of respiration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000924","label":"Abnormality of the skeletal system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002305","label":"Athetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002072","label":"Chorea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001266","label":"Choreoathetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011924","label":"Decreased activity of mitochondrial complex III","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008347","label":"Decreased activity of mitochondrial complex IV","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410145","label":"Decreased biotinidase activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002460","label":"Distal muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003219","label":"Ethylmalonic aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002909","label":"Generalized aminoaciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003348","label":"Hyperalaninemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002487","label":"Hyperkinetic movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","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:0001993","label":"Ketoacidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012120","label":"Methylmalonic aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002828","label":"Multiple joint contractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003198","label":"Myopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0200147","label":"Neuronal loss in basal ganglia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002542","label":"Olivopontocerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003390","label":"Sensory axonal neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001264","label":"Spastic diplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001596","label":"Alopecia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0008314","label":"Decreased activity of mitochondrial complex II","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001875","label":"Decreased total neutrophil count","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100660","label":"Dyskinesia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000964","label":"Eczematoid dermatitis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0040197","label":"Encephalomalacia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011335","label":"Frontal hirsutism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002579","label":"Gastrointestinal dysmotility","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000348","label":"High forehead","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000100","label":"Nephrotic syndrome","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001947","label":"Renal tubular acidosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000124","label":"Renal tubular dysfunction","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002133","label":"Status epilepticus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Very rare (<4-1%)","criteria":null}]}}