{"orpha":3008,"name":"Pyruvate carboxylase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Ataxia with lactic acidosis type 2","Ataxia with lactic acidosis type II","Leigh necrotizing encephalopathy due to pyruvate carboxylase deficiency","Leigh syndrome due to PC deficiency","Leigh syndrome due to pyruvate carboxylase deficiency"],"definition":"Pyruvate carboxylase (PC) deficiency is a rare neurometabolic disorder characterized by metabolic acidosis, failure to thrive, developmental delay, and recurrent seizures at an early age in severely affected patients.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-3008/","orphanet_url":"https://www.orpha.net/en/disease/detail/3008","names":{"fr":{"name":"Déficit en pyruvate carboxylase","synonyms":["Ataxie avec acidose lactique type 2","Ataxie avec acidose lactique type II","Encéphalopathie nécrosante subaiguë de Leigh par déficit en pyruvate carboxylase","Syndrome de Leigh par déficit en PC","Syndrome de Leigh par déficit en pyruvate carboxylase"],"definition":"Le déficit en pyruvate carboxylase (PC) est un trouble neurométabolique caractérisé par une acidose métabolique, un retard de croissance staturo-pondérale, un retard de développement et des convulsions récurrentes dès le plus jeune âge chez les patients sévèrement atteints."},"de":{"name":"Pyruvat-Carboxylase-Mangel","synonyms":["Ataxie mit Laktatazidose Typ 2","Leigh-Syndrom durch Pyruvat-Carboxylase-Mangel","Nekrotisierende Enzephalopathie durch Pyruvat-Carboxylase-Mangel"],"definition":"Der Pyruvatcarboxylase (PC)-Mangel ist eine seltene neurometabolische Erkrankung. Schwere Fälle sind schon in frühem Alter gekennzeichnet durch metabolische Azidose, Gedeihstörung, verzögerte Entwicklung und rezidivierende Krampfanfälle"},"es":{"name":"Deficiencia de piruvato carboxilasa","synonyms":["Ataxia con acidosis láctica tipo 2","Ataxia con acidosis láctica tipo II","Encefalopatía necrosante de Leigh por deficiencia de piruvato carboxilasa","Síndrome de Leigh por deficiencia de PC","Síndrome de Leigh por deficiencia de piruvato carboxilasa"],"definition":"El déficit de piruvato-carboxilasa (PC) es un trastorno neurometabólico raro caracterizado por acidosis metabólica, retraso en el crecimiento y en el desarrollo y convulsiones recurrentes a una edad temprana en pacientes gravemente afectados."},"it":{"name":"Deficit di piruvato carbossilasi","synonyms":["Atassia con acidosi lattica, tipo 2","Atassia con acidosi lattica, tipo II","Encefalopatia necrotizzante di Leigh da deficit di piruvato carbossilasi","Sindrome di Leigh da deficit di PC","Sindrome di Leigh da deficit di piruvato carbossilasi"],"definition":"Il deficit di piruvato carbossilasi (PC) è un disturbo neurometabolico raro caratterizzato da acidosi metabolica, ritardo della crescita, ritardo dello sviluppo, e convulsioni ricorrenti precoci nei pazienti affetti in forma grave."},"nl":{"name":"Deficiëntie van pyruvaatcarboxylase","synonyms":["Ataxie met lactaatacidose type II","Ataxie met melkzuuracidose type 2","Ataxie met melkzuuracidose type II","Necrotiserende encefalopathie van Leigh door deficiëntie van pyruvaatcarboxylase","Syndroom van Leigh door PC-deficiëntie","Syndroom van Leigh door deficiëntie van pyruvaatcarboxylase","Ataxie met lactaatacidose type 2"],"definition":"Pyruvaatcarboxylase (PC)-deficiëntie is een zeldzame neurometabole aandoening gekenmerkt door metabole acidose, slecht gedijen, ontwikkelingsvertraging en terugkerende aanvallen op jonge leeftijd bij ernstig getroffen patiënten."},"pt":{"name":"Deficiência de piruvato carboxilase"},"pl":{"name":"Niedobór karboksylazy pirogronianowej","synonyms":["Ataksja z kwasicą mleczanową typu 2","Ataksja z kwasicą mleczanową typu II","Martwicza encefalopatia Leigha z powodu niedoboru karboksylazy pirogronianowej","Zespół Leigha z powodu niedoboru karboksylazy pirogronianowej","Zespół Leigha z powodu niedoboru PC"],"definition":"Niedobór karboksylazy pirogronianowej to rzadkie schorzenie neurometaboliczne charakteryzujące się kwasicą metaboliczną, niedoborem wzrostu i masy ciała, opóźnieniem rozwoju i nawracającymi drgawkami w młodym wieku u ciężko chorych pacjentów."},"cs":{"name":"Deficit pyruvátkarboxylázy","synonyms":["Ataxie s laktátovou acidózou, typ 2","Ataxie s laktátovou acidózou, typ II","Leighova nekrotizující encefalopatie způsobená deficitem pyruvátkarboxylázy","Leighův syndrom způsobený deficitem PC","Leighův syndrom způsobený deficitem pyruvátkarboxylázy"]},"uk":{"name":"Дефіцит піруваткарбоксилази","synonyms":["Атаксія з молочнокислим ацидозом типу 2","Атаксія з молочнокислим ацидозом II типу","Некротизуюча енцефалопатія Лі внаслідок дефіциту піруваткарбоксилази","Синдром Лі внаслідок дефіциту PC","Синдром Лі через дефіцит піруваткарбоксилази"],"definition":"Pyruvate carboxylase (PC) deficiency is a rare neurometabolic disorder characterized by metabolic acidosis, failure to thrive, developmental delay, and recurrent seizures at an early age in severely affected patients."},"zh":{"name":"丙酮酸羧化酶缺乏","synonyms":["丙酮酸羧化酶缺乏所致Leigh坏死性脑病"]},"tr":{"name":"Piruvat karboksilaz eksikliği","synonyms":["Tip 2 laktik asidozlu ataksi","Tip II laktik asidozlu ataksi","PC eksikliğine bağlı Leigh sendromu","Piruvat karboksilaz eksikliğine bağlı Leigh sendromu","Piruvat karboksilaz eksikliğine bağlı Leigh nekrotizan ensefalopatisi"]}},"xrefs":[{"source":"OMIM","code":"266150","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E74.4","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C53.03","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"2047948460"},{"source":"MONDO","code":"0009949","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D015324","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0034341","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"7512","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10077944","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79177,"name":"Gluconeogenesis disorder","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[{"orpha":353320,"name":"Pyruvate carboxylase deficiency, benign type","type":"Clinical subtype"},{"orpha":353308,"name":"Pyruvate carboxylase deficiency, infantile type","type":"Clinical subtype"},{"orpha":353314,"name":"Pyruvate carboxylase deficiency, severe neonatal type","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"PC","name":"pyruvate carboxylase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301764[PMID]","hgnc":"8636","ensembl":"ENSG00000173599","omim":"608786","loci":["11q13.2"],"via":{"orpha":353308,"name":"Pyruvate carboxylase deficiency, infantile type"}},{"symbol":"PC","name":"pyruvate carboxylase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301764[PMID]","hgnc":"8636","ensembl":"ENSG00000173599","omim":"608786","loci":["11q13.2"],"via":{"orpha":353314,"name":"Pyruvate carboxylase deficiency, severe neonatal type"}},{"symbol":"PC","name":"pyruvate carboxylase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301764[PMID]","hgnc":"8636","ensembl":"ENSG00000173599","omim":"608786","loci":["11q13.2"],"via":{"orpha":353320,"name":"Pyruvate carboxylase deficiency, benign type"}}],"inheritance":["Autosomal recessive","Not applicable"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.4,"area":"Europe","status":"Validated","source":"ISBN:79130356[OTHER]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"[EXPERT]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-01-07","source":"30870574[PMID]_20301764[PMID]","terms":[{"hpo":"HP:0032653","label":"Elevated lactate:pyruvate ratio","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:0500231","label":"Abnormal CSF pyruvate family amino acid concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500198","label":"Decreased CSF glutamine concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012706","label":"Elevated brain choline level by MRS","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012707","label":"Elevated brain lactate level by MRS","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011966","label":"Elevated plasma citrulline","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003348","label":"Hyperalaninemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500149","label":"Hyperglutamatemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0410175","label":"Hyperketonemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002161","label":"Hyperlysinemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008358","label":"Hyperprolinemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500181","label":"Hypertaurinemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500147","label":"Hypoglutaminemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500233","label":"Increased CSF alanine concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500246","label":"Increased CSF citrulline concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500200","label":"Increased CSF glutamate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012644","label":"Increased caudate lactate level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003542","label":"Increased circulating pyruvate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003648","label":"Lacticaciduria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001942","label":"Metabolic acidosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012708","label":"Reduced brain N-acetyl aspartate level by MRS","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002793","label":"Abnormal pattern of respiration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025160","label":"Abnormal temper tantrums","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002039","label":"Anorexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000741","label":"Apathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006999","label":"Basal ganglia gliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003429","label":"CNS hypomyelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012698","label":"Cerebellar gliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012762","label":"Cerebral white matter atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000722","label":"Compulsive behaviors","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001944","label":"Dehydration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025336","label":"Delayed ability to sit","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100660","label":"Dyskinesia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001262","label":"Excessive daytime somnolence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011169","label":"Generalized clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003074","label":"Hyperglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003228","label":"Hypernatremia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003265","label":"Neonatal hyperbilirubinemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007109","label":"Periventricular cysts","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000817","label":"Reduced eye contact","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002416","label":"Subependymal cysts","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002789","label":"Tachypnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001259","label":"Coma","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100023","label":"Recurrent hand flapping","frequency":"Very rare (<4-1%)","criteria":null}]}}