{"orpha":289307,"name":"Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Developmental delay due to ALDH6A1 deficiency","Developmental delay due to MMSDH deficiency"],"definition":"A rare, genetic, inborn error of branched-chain amino acid metabolism disorder, with a highly variable clinical and biochemical phenotype, typically characterized by mild to severe global developmental delay, elevated methylmalonic acid and, occasionally, lactic acid plasma levels, and chronic methylmalonic aciduria, which may be accompanied by elevation of additional organic or amino acids in urine (e.g. beta-alanine, methionine, 3-hydroxypropionic, 3-aminoisobutyric and/or 3-hydroxyisobutyric acid). Microcephaly, mild craniofacial dysmorphism, axial hypotonia, liver failure, and central nervous system abnormalities on MRI have also been reported.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-289307/","orphanet_url":"https://www.orpha.net/en/disease/detail/289307","names":{"fr":{"name":"Retard de développement par déficit en méthylmalonate semialdéhyde déshydrogénase","synonyms":["Retard de développement par déficit en ALDH6A1","Retard de développement par déficit en MMSDH"],"definition":"Trouble inné rare, d'origine génétique, du métabolisme des acides aminés à chaînes ramifiées, au phénotype biochimique et clinique très variable, généralement caractérisé par un retard de développement global léger à sévère, des taux élevés d'acide méthylmalonique et parfois d'acide lactique plasmatique, une acidurie méthylmalonique chronique, qui peut s'accompagner d'une hausse du taux d'autres acides aminés ou organiques dans les urines (par ex., bêta-alanine, méthionine, acide 3-hydroxypropanoïque, acide 3-aminoisobutyrique et/ou acide 3-hydroxyisobutyrique). Des cas de microcéphalie, de légère dysmorphie craniofaciale, d'hypotonie axiale, d'insuffisance hépatique et d'anomalies du système nerveux central à l'IRM ont également été rapportés."},"de":{"name":"Entwicklungsverzögerung durch Methylmalonat-Semialdehyd-Dehydrogenase-Mangel","synonyms":["Entwicklungsverzögerung durch ALDH6A1-Mangel","Entwicklungsverzögerung durch MMSDH-Mangel"]},"es":{"name":"Retraso del desarrollo por deficiencia de metilmalonato semialdehído deshidrogenasa","synonyms":["Retraso del desarrollo por deficiencia de ALDH6A1","Retraso del desarrollo por deficiencia de MMSDH"],"definition":"El retraso del desarrollo por deficiencia de metilmalonato semialdehído deshidrogenasa es un error innato del metabolismo de los aminoácidos de cadena ramificada, genético y poco frecuente, con un fenotipo clínico y bioquímico altamente variable. Por lo general, se caracteriza por retraso global del desarrollo de leve a grave, incremento de ácido metilmalónico y, ocasionalmente, de los niveles plasmáticos de ácido láctico y aciduria metilmalónica crónica, que puede ir acompañada de una elevación de aminoácidos o ácidos orgánicos adicionales en orina (p. ej., beta-alanina, metionina, ácido 3-hidroxipropiónico, 3-aminoisobutírico y/o 3-hidroxiisobutírico). También se han descrito casos de microcefalia, dismorfia craneofacial leve, hipotonía axial, insuficiencia hepática y anomalías del sistema nervioso central visibles por resonancia magnética."},"it":{"name":"Ritardo dello sviluppo da deficit di metilmalonato semialdeide deidrogenasi","synonyms":["Ritardo dello sviluppo da deficit di ALDH6A1","Ritardo dello sviluppo da deficit di MMSDH"],"definition":"Il ritardo dello sviluppo da deficit di metilmalonato semiladeide deidrogenasi è un errore genetico raro, congenito del metabolismo degli aminoacidi a catena ramificata. Il quadro clinico e il fenotipo biochimico sono molto variabili, per lo più caratterizzati da ritardo dello sviluppo globale da lieve a grave, aumento dei livelli di acido metilmalonico nel plasma e, occasionalmente, di acido lattico, e da aciduria metilmalonica cronica, che possono associarsi ad un aumento degli altri acidi organici o degli aminoacidi nelle urine (ad esempio beta-alanina, metionina, acido 3-idrossipropionico, acido 3-aminoisobutirrico e/o acido idrossiisobutirrico). Può associarsi a microcefalia, lievi dismorfismi craniofacciali, ipotonia assiale, insufficienza renale ed anomalie del sistema nervoso centrale evidenti alla RMN."},"nl":{"name":"Ontwikkelingsachterstand door methylmalonaat-semialdehydedehydrogenasedeficiëntie","synonyms":["Ontwikkelingsachterstand door ALDH6A1-deficiëntie","Ontwikkelingsachterstand door MMSDH-deficiëntie"],"definition":"Ontwikkelingsachterstand door methylmalonaat-semialdehydedehydrogenasedeficiëntie is een zeldzaam, genetisch, aangeboren defect van het metabolisme van vertakte aminozuren, en vertoont een zeer variabel klinisch en biochemisch fenotype dat doorgaans gekarakteriseerd wordt door milde tot ernstige algehele ontwikkelingsachterstand, verhoogde gehaltes van methylmalonzuur, en occasioneel, melkzuur, in het plasma, en chronische methylmalonacidurie, mogelijk gepaard met een stijging van bijkomende organische zuren of aminozuren in de urine (e.g. bèta-alanine, methionine, 3-hydroxypropaanzuur, 3-amino-isobutaanzuur en/of 3-hydroxy-isobutaanzuur). Microcefalie, milde craniofaciale dysmorfie, axiale hypotonie, leverfalen, en afwijkingen van het centrale zenuwstelsel bij MRI werden ook reeds gerapporteerd."},"pt":{"name":"Perturbação do desenvolvimento por deficiência de metilmalonato semialdeído desidrogenase","synonyms":["Perturbação do desenvolvimento por deficiência de ALDH6A1","Perturbação do desenvolvimento por deficiência de MMSDH"]},"pl":{"name":"Opóźnienie rozwoju z powodu niedoboru dehydrogenazy semialdehydu metylomalonowego","synonyms":["Opóźnienie rozwoju z powodu niedoboru ALDH6A1","Opóźnienie rozwoju z powodu niedoboru MMSDH"],"definition":"*Opóźnienie rozwoju z powodu niedoboru dehydrogenazy semialdehydu metylomalonowego jest rzadkim, genetycznie uwarunkowanym, wrodzonym błędem metabolizmu aminokwasów rozgałęzionych, z bardzo zmiennym fenotypem klinicznym i biochemicznym, który zwykle charakteryzuje się łagodnym lub ciężkim całościowym opóźnieniem rozwoju, podwyższonym poziomem kwasu metylomalonowego oraz niekiedy również stężenia kwasu mlekowego w osoczu i przewlekłą kwasicą metylomalonową, której może towarzyszyć podwyższone stężenie innych kwasów organicznych lub aminokwasów w moczu (np. beta-alaniny, metioniny, kwasu 3-hydroksypropionowego, 3-aminoizomasłowego i/lub 3-hydroksyizomasłowego). Opisywano również małogłowie, łagodną dysmorfię twarzoczaszki, hipotonię osiowej, oraz niewydolność wątroby i nieprawidłowości ośrodkowego układu nerwowego w badaniu MRI.inf brsup"},"cs":{"name":"Vývojové opoždění způsobené deficitem methylmalonátsemialdehyddehydrogenázy","synonyms":["Vývojové opoždění způsobené deficitem ALDH6A1","Vývojové opoždění způsobené deficitem MMSDH"]},"uk":{"name":"Затримка розвитку через дефіцит метилмалонатдегідрогенази напівдегідрогенази","synonyms":["Затримка розвитку через дефіцит ALDH6A1","Затримка розвитку через дефіцит MMSDH"],"definition":"A rare, genetic, inborn error of branched-chain amino acid metabolism disorder, with a highly variable clinical and biochemical phenotype, typically characterized by mild to severe global developmental delay, elevated methylmalonic acid and, occasionally, lactic acid plasma levels, and chronic methylmalonic aciduria, which may be accompanied by elevation of additional organic or amino acids in urine (e.g. beta-alanine, methionine, 3-hydroxypropionic, 3-aminoisobutyric and/or 3-hydroxyisobutyric acid). Microcephaly, mild craniofacial dysmorphism, axial hypotonia, liver failure, and central nervous system abnormalities on MRI have also been reported."},"zh":{"name":"甲基丙二酸半醛脱氢酶缺乏所致发育迟缓","synonyms":["甲基丙二酸半醛脱氢酶缺乏所致发育迟缓"],"definition":"甲基丙二酸半醛脱氢酶缺乏所致发育迟缓是一种罕见的先天性支链氨基酸代谢紊乱的遗传性疾病，临床和生化表型多样，其典型特征是轻度到重度全面发育迟缓，甲基丙二酸升高，偶有血乳酸水平升高和慢性甲基丙二酸尿症，可伴尿中其他有机酸或氨基酸（例如β-丙氨酸、蛋氨酸、3-羟基丙酸、3-氨基异丁酸和/或3-羟基异丁酸）升高。小头畸形、轻度颅面畸形、轴向张力减退、肝功能衰竭和MRI显示中枢神经系统异常也有报道。"},"tr":{"name":"Metilmalonat semialdehit dehidrogenaz eksikliğine bağlı gelişme geriliği","synonyms":["MMSDH eksikliğine bağlı gelişme geriliği","ALDH6A1 eksikliğine bağlı gelişme geriliği"]}},"xrefs":[{"source":"OMIM","code":"614105","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":"index","validated":true,"icd11_uri":"1700759193"},{"source":"MONDO","code":"0013579","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5190633","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79197,"name":"Disorder of branched-chain amino acid metabolism","classifications":[150,156]}],"children":[],"genes":[{"symbol":"ALDH6A1","name":"aldehyde dehydrogenase 6 family member A1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21863277[PMID]_10971205[PMID]","hgnc":"7179","ensembl":"ENSG00000119711","omim":"603178","loci":["14q24.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Europe","status":"Not yet validated","source":"ORPHANET"}],"phenotypes":null}