{"orpha":17,"name":"Fatal infantile lactic acidosis with methylmalonic aciduria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"Fatal infantile lactic acidosis with methylmalonic aciduria is a rare neurometabolic disease characterized by infantile onset of severe encephalomyopathy, lactic acidosis and elevated methylmalonic acid urinary excretion. Clinically it manifests with severe psychomotor delay, hypotonia, failure to thrive, feeding difficulties and dystonia. Epilepsy and multiple congenital anomalies may be associated.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-17/","orphanet_url":"https://www.orpha.net/en/disease/detail/17","names":{"fr":{"name":"Acidose lactique infantile fatale avec acidurie méthylmalonique","definition":"L'acidose lactique infantile fatale avec acidurie méthylmalonique est une maladie neurométabolique rare survenant pendant la petite enfance. Elle se caractérise par une encéphalomyopathie sévère, une acidose lactique et une excrétion urinaire élevée d'acide méthylmalonique. Sur le plan clinique, elle se manifeste par un retard psychomoteur sévère, une hypotonie, un retard de croissance staturo-pondérale, des difficultés pour s'alimenter et une dystonie. De multiples anomalies congénitales et une épilepsie peuvent être associées."},"de":{"name":"Fatale infantile Laktatazidose mit Methylmalonazidurie","definition":"Die tödliche infantile Laktatazidose mit Methylmalonsäureurie ist eine seltene neurometabolische Erkrankung, die durch einen infantilen Beginn einer schweren Enzephalomyopathie, Laktatazidose und erhöhte Methylmalonsäureausscheidung im Urin gekennzeichnet ist. Klinisch manifestiert sie sich mit schwerer psychomotorischer Verzögerung, Hypotonie, Gedeihstörung, Ernährungsschwierigkeiten und Dystonie. Epilepsie und multiple kongenitale Anomalien können assoziiert sein."},"es":{"name":"Acidosis láctica letal del lactante con aciduria metilmalónica","definition":"La acidosis láctica infantil letal con aciduria metilmalónica es una enfermedad neurometabólica poco frecuente caracterizada por un inicio infantil de encefalomiopatía grave, acidosis láctica y una excreción urinaria elevada de ácido metilmalónico. Clínicamente se manifiesta con retraso psicomotor grave, hipotonía, falta de crecimiento, dificultades para alimentarse y distonia. Puede estar asociada a epilepsia y anomalías congénitas múltiples."},"it":{"name":"Acidosi lattica infantile fatale con aciduria metilmalonica","definition":"L'acidosi lattica infantile letale con aciduria metilmalonica è una malattia neurometabolica rara, ad esordio nell'infanzia, caratterizzata da encefalomiopatia grave, acidosi lattica ed elevati livelli di acido metilmalonico nelle urine. Di solito esordisce con grave ritardo psicomotorio, ipotonia, ritardo della crescita, difficoltà alimentari e distonia. Possono associarsi epilessia ed anomalie congenite multiple."},"nl":{"name":"Fatale infantiele melkzuuracidose met methylmalonacidurie","synonyms":["Fatale infantiele lactaatacidose met methylmalonzuuracidurie","Mitochondriaal DNA-depletiesyndroom 9"],"definition":"Fatale infantiele melkzuuracidose met methylmalonacidurie is een zeldzame neurometabole ziekte die gekarakteriseerd wordt door ernstige encefalomyopathie, lactaatacidose en verhoogde excretie van methylmalonzuur in de urine, met aanvang in de zuigelingentijd. Klinisch manifesteert de ziekte zich met ernstige psychomotorische achterstand, hypotonie, groeiachterstand, moeilijkheden met voeden, en dystonie. Epilepsie en meervoudige congenitale anomalieën kunnen geassocieerd zijn."},"pt":{"name":"Acidose láctica congénita infantil"},"pl":{"name":"Noworodkowa kwasica mleczanowa z acydurią metylomalonową"},"cs":{"name":"Fatální kojenecká laktátová acidóza s methylmalonovou acidurií"},"uk":{"name":"Фатальний молочнокислий ацидоз немовлят з метилмалоновою ацидурією","definition":"Fatal infantile lactic acidosis with methylmalonic aciduria is a rare neurometabolic disease characterized by infantile onset of severe encephalomyopathy, lactic acidosis and elevated methylmalonic acid urinary excretion. Clinically it manifests with severe psychomotor delay, hypotonia, failure to thrive, feeding difficulties and dystonia. Epilepsy and multiple congenital anomalies may be associated."},"zh":{"name":"致死性婴儿乳酸性酸中毒伴甲基丙二酸尿症"},"tr":{"name":"Metilmalonik asitüri ile letal infantil laktik asidoz"}},"xrefs":[{"source":"OMIM","code":"245400","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.20","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1314742423"},{"source":"MONDO","code":"0009504","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4275183","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3163","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":254803,"name":"Mitochondrial DNA depletion syndrome, encephalomyopathic form","classifications":[150,156,181]}],"children":[],"genes":[{"symbol":"SUCLG1","name":"succinate-CoA ligase GDP/ADP-forming subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19526370[PMID]_21639866[PMID]","hgnc":"11449","ensembl":"ENSG00000163541","omim":"611224","loci":["2p11.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-07-07","source":"31240156[PMID]_28358460[PMID]","terms":[{"hpo":"HP:0002912","label":"Methylmalonic acidemia","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0012120","label":"Methylmalonic aciduria","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0003535","label":"3-Methylglutaconic aciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012751","label":"Abnormal basal ganglia MRI signal intensity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012379","label":"Abnormal enzyme/coenzyme activity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011923","label":"Decreased activity of mitochondrial complex I","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011924","label":"Decreased activity of mitochondrial complex III","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008347","label":"Decreased activity of mitochondrial complex IV","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","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:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001397","label":"Hepatic steatosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012087","label":"Abnormal mitochondrial shape","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002104","label":"Apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001266","label":"Choreoathetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000975","label":"Hyperhidrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002487","label":"Hyperkinetic movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002045","label":"Hypothermia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012240","label":"Increased intramyocellular lipid droplets","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003557","label":"Increased variability in muscle fiber diameter","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002352","label":"Leukoencephalopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003200","label":"Ragged-red muscle fibers","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003201","label":"Rhabdomyolysis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000736","label":"Short attention span","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002317","label":"Unsteady gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004742","label":"Abnormal renal collecting system morphology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001680","label":"Coarctation of aorta","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003219","label":"Ethylmalonic aciduria","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011611","label":"Interrupted aortic arch","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000202","label":"Orofacial cleft","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001655","label":"Patent foramen ovale","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0010442","label":"Polydactyly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003097","label":"Short femur","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0005792","label":"Short humerus","frequency":"Very rare (<4-1%)","criteria":null}]}}