{"orpha":289504,"name":"Combined malonic and methylmalonic acidemia","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CMAMMA","Combined malonic and methylmalonic aciduria"],"definition":"A rare inborn error of metabolism characterized by elevation of malonic acid (MA) and methylmalonic acid (MMA) in body fluids, with higher levels of MMA than MA. CMAMMA presents in childhood with metabolic acidosis, developmental delay, dystonia and failure to thrive or in adulthood with seizures, memory loss and cognitive decline.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-289504/","orphanet_url":"https://www.orpha.net/en/disease/detail/289504","names":{"fr":{"name":"Acidémie combinée malonique et méthylmalonique","synonyms":["Acidurie combinée malonique et méthylmalonique","CMAMMA"],"definition":"Erreur innée du métabolisme rare caractérisée par une élévation des taux de l'acide malonique (AM) et de l'acide méthylmalonique (AMM) dans les fluides corporels, les taux d'AMM étant plus élevés que ceux d'AM. La CMAMMA (pour <i> combined malonic and methylmalonic acidemia</i>) se manifeste dans l'enfance par une acidose métabolique, un retard de développement, une dystonie et un retard de croissance staturo-pondérale. Chez l'adulte, elle se manifeste par des convulsions, une perte de la mémoire et un déclin cognitif."},"de":{"name":"Malon- und Methylmalonazidurie, kombinierte","synonyms":["CMAMMA"],"definition":"Die kombinierte Malon- und Methylmalonsäure-Azidämie (CMAMMA) ist eine seltene angeborene Stoffwechselstörung, die durch eine Erhöhung von Malonsäure (MA) und Methylmalonsäure (MMA) in den Körperflüssigkeiten gekennzeichnet ist, wobei die MMA-Werte höher sind als die MA-Werte. CMAMMA zeigt sich in der Kindheit mit metabolischer Azidose, Entwicklungsverzögerung, Dystonie und Gedeihstörung oder im Erwachsenenalter mit Krampfanfällen, Gedächtnisverlust und kognitivem Abbau."},"es":{"name":"Acidemia malónica y metilmalónica combinada","synonyms":["Aciduria malónica y metilmalónica combinada","CMAMMA"],"definition":"La acidemia malónica y metilmalónica combinada es un error congénito del metabolismo poco frecuente caracterizado por elevación de los niveles de ácido malónico (AM) y ácido metilmalónico (AMM) en los fluidos corporales, con valores más altos de AMM que de AM. La CMAMMA se presenta en la infancia con acidosis metabólica, retraso del desarrollo, distonía y retraso del crecimiento, o en la edad adulta con crisis, pérdida de memoria y deterioro cognitivo."},"it":{"name":"Acidemia combinata malonica e metilmalonica","synonyms":["Aciduria metilmalonica e malonica combinata","CMAMMA"],"definition":"L'acidemia combinata malonica e metilmalonica (CMAMMA) è un raro errore congenito del metabolismo, caratterizzato da livelli elevati di acido malonico (MA) e metilmalonico (MMA) nei liquidi corporei; i livelli li MMA sono più elevati rispetto a quelli di MA. La malattia esordisce durante l'infanzia con acidosi metabolica, ritardo dello sviluppo e della crescita e distonia; ma può esordire anche nell'età adulta con crisi epilettiche, perdita della memoria e declino cognitivo."},"nl":{"name":"Gecombineerde malon- en methylmalonacidurie","synonyms":["CMAMMA","Gecombineerde malon- en methylmalonacidemie","Gecombineerde malonzuur- en methylmalonzuuracidemie","Gecombineerde malonzuur- en methylmalonzuuracidurie"],"definition":"Een zeldzaam aangeboren defect van stofwisseling, gekenmerkt door toename van malonzuur (MA) en methylmalonzuur (MMA) in lichaamsvloeistoffen, met hogere gehaltes van MMA dan MA. De aandoening presenteert zich in de kindertijd met metabole acidose, ontwikkelingsachterstand, dystonie, en niet-gedijen, of in de volwassenheid met insulten, geheugenverlies, en cognitieve achteruitgang."},"pt":{"name":"Acidemia combinada malónica e metilmalónica","synonyms":["Acidúria combinada malónica e metilmalónica","CMAMMA"]},"pl":{"name":"Złożona kwasica malonowa i metylomalonowa","synonyms":["CMAMMA","Złożona acyduria malonowa i metylomalonowa"]},"cs":{"name":"Kombinovaná malonová a methylmalonová acidémie","synonyms":["CMAMMA","Kombinovaná malonová a methylmalonová acidurie"]},"uk":{"name":"Поєднання малонової та метилмалонової ацидемії","synonyms":["CMAMMA","Поєднання малонової та метилмалонової ацидурії"],"definition":"A rare inborn error of metabolism characterized by elevation of malonic acid (MA) and methylmalonic acid (MMA) in body fluids, with higher levels of MMA than MA. CMAMMA presents in childhood with metabolic acidosis, developmental delay, dystonia and failure to thrive or in adulthood with seizures, memory loss and cognitive decline."},"zh":{"name":"丙二酸血症和甲基丙二酸血症","synonyms":["丙二酸血症合并甲基丙二酸血症"],"definition":"丙二酸血症合并甲基丙二酸血症（CMAMMA)是一种罕见的先天性代谢异常，其特点是体液中丙二酸（MA）和甲基丙二酸（MMA）升高，MMA水平高于MA。CMAMMA在儿童期表现为代谢性酸中毒、发育迟缓、肌张力障碍和发育障碍，成年期表现为癫痫、记忆丧失和认知能力下降。"},"tr":{"name":"Kombine malonik ve metilmalonik asidemi","synonyms":["CMAMMA","Kombine malonik ve metilmalonik asidüri"]}},"xrefs":[{"source":"OMIM","code":"614265","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.E0","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0013661","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C580002","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3280314","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10818","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79163,"name":"Classic organic aciduria","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"ACSF3","name":"acyl-CoA synthetase family member 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21841779[PMID]","hgnc":"27288","ensembl":"ENSG00000176715","omim":"614245","loci":["16q24.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":3.3,"area":"United States","status":"Validated","source":"21841779[PMID]"},{"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":"2019-10-22","source":"9700595[PMID]_21785126[PMID]_21841779[PMID]","terms":[{"hpo":"HP:0040145","label":"Dicarboxylic acidemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003215","label":"Dicarboxylic aciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002912","label":"Methylmalonic acidemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012120","label":"Methylmalonic aciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001941","label":"Acidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001944","label":"Dehydration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002384","label":"Focal impaired awareness seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011169","label":"Generalized clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031064","label":"Impaired continence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002254","label":"Intermittent diarrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001993","label":"Ketoacidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002354","label":"Memory impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002076","label":"Migraine","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040288","label":"Nasogastric tube feeding","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null}]}}