{"orpha":26791,"name":"Multiple acyl-CoA dehydrogenase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Glutaric acidemia type 2","Glutaric aciduria type 2","MAD deficiency","MADD"],"definition":"Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid and amino acid oxidation and is a clinically heterogeneous disorder ranging from a severe neonatal presentation with metabolic acidosis, cardiomyopathy and liver disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-26791/","orphanet_url":"https://www.orpha.net/en/disease/detail/26791","names":{"fr":{"name":"Déficit multiple en acyl-CoA déshydrogénases","synonyms":["Acidurie glutarique type 2","Acidémie glutarique type 2","Déficit en MAD","MADD"],"definition":"Le déficit multiple en acyl-CoA déshydrogénases (DMAD) est un trouble de l'oxydation des acides gras et des acides aminés. Il s'agit d'une maladie cliniquement hétérogène, variant d'une présentation sévère néonatale avec une acidose métabolique, une cardiomyopathie et une hépatopathie à une forme modérée infantile/adulte avec des crises de décompensation métabolique, une faiblesse musculaire et une insuffisance respiratoire."},"de":{"name":"Acyl-CoA-Dehydrogenase-Mangel, multipler","synonyms":["Glutarazidurie Typ 2","Glutarazidämie Typ 2","MAD-Mangel","MADD"],"definition":"Der Multiple Acyl-CoA-Dehydrogenase (MAD)-Mangel (MADM) ist eine Störung der Fettsäure- und Aminosäureoxidation. Die Krankheit ist klinisch heterogen und reicht von schweren Symptomen im Neugeborenenalter (metabolische Azidose, Kardiomyopathie, Leberfunktionsstörung) bis zu leichten Symptomen bei Kindern/Erwachsenen (episodische Stoffwechselentgleisung, Muskelschwäche, Atemnot)."},"es":{"name":"Deficiencia múltiple de acil-CoA deshidrogenasa","synonyms":["Acidemia glutárica tipo 2","Aciduria glutárica tipo 2","Deficiencia de MAD","MADD"],"definition":"La deficiencia múltiple de acil CoA-deshidrogenasa (MADD) es una alteración de la oxidación de los ácidos grasos y los aminoácidos y un trastorno clínicamente heterogéneo que va desde la presentación neonatal grave con acidosis metabólica, miocardiopatía y hepatopatía, hasta una enfermedad leve de la infancia o la edad adulta con descompensación metabólica episódica, debilidad muscular e insuficiencia respiratoria."},"it":{"name":"Deficit multiplo di acil-CoA deidrogenasi","synonyms":["Acidemia glutarica, tipo 2","Aciduria glutarica, tipo 2","Deficit di MAD","Deficit di flavoproteina trasportatrice di elettroni","Deficit di flavoproteina trasportatrice di elettroni ubichinone ossidoreduttasi","MADD"],"definition":"Il deficit multiplo di acil-CoA deidrogenasi (MADD) è un difetto dell'ossidazione degli acidi grassi e degli aminoacidi ed è una malattia clinicamente eterogena che varia da una forma neonatale grave associata ad acidosi metabolica, cardiomiopatia e malattia epatica, a una forma lieve del bambino/adulto con episodi di scompenso metabolico, debolezza muscolare e insufficienza respiratoria."},"nl":{"name":"Meervoudige acyl-CoA-dehydrogenasedeficiëntie","synonyms":["Glutaaracidemie type 2","Glutaaracidurie type 2","MAD-deficiëntie","MADD","Meervoudige acyl-CoA-dehydrogenasedeficiëntie"],"definition":"Multipele acyl-CoA-dehydrogenasedeficiëntie (MADD) is een aandoening van de vetzuur- en aminozuuroxidatie en is een klinisch heterogene aandoening die varieert van een ernstige neonatale presentatie met metabole acidose, cardiomyopathie en leverziekte, tot een milde ziekte van de kindertijd/volwassenenheid met episodische metabole decompensatie, spierzwakte en ademhalingsstoornissen."},"pt":{"name":"Deficiência de desidrogenação de acil-CoA múltipla","synonyms":["Acidúria glutárica tipo 2","Deficiência de flavoproteína de transferência de eletrões","Deficiência de flavoproteína de transferência de eletrões ubiquinona oxidorredutase"]},"pl":{"name":"Mnogi niedobór dehydrogenazy acetylo-CoA","synonyms":["MADD","Niedobór MAD","Kwasica glutarowa typu 2","Acyduria glutarowa typu 2"]},"cs":{"name":"Mnohonásobný deficit acyl-CoA dehydrogenázy","synonyms":["Glutarová acidemie, typ 2","Glutarová acidurie, typ 2","Deficit MAD","MADD","Deficit flavoproteinů přenášejících elektrony","Deficit flavoproteinů přenášejících elektrony v ubikvinonové oxidoreduktáze"]},"uk":{"name":"Множинний дефіцит ацил-КоА-дегідрогенази","synonyms":["Глутарова ацидемія 2 типу","Глутарова ацидурія 2 типу","Дефіцит MAD","MADD"],"definition":"Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid and amino acid oxidation and is a clinically heterogeneous disorder ranging from a severe neonatal presentation with metabolic acidosis, cardiomyopathy and liver disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure."},"zh":{"name":"多种酰基辅酶A脱氢酶缺乏症","synonyms":["戊二酸尿症2型"]},"tr":{"name":"Çoklu açil-CoA dehidrojenaz eksikliği","synonyms":["MADD","MAD eksikliği","Glutarik asidemi tip 2","Glutarik asidüri tip 2"]}},"xrefs":[{"source":"OMIM","code":"231680","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C52.01","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"977130875"},{"source":"MONDO","code":"0009282","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D054069","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268596","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6523","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10090590","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":309120,"name":"Acyl-CoA dehydrogenase deficiency","classifications":[150,156]},{"orpha":217591,"name":"Fatty acid oxidation and ketogenesis disorder with hypertrophic cardiomyopathy","classifications":[146,156,233]},{"orpha":206953,"name":"Muscular lipidosis","classifications":[156,181]}],"children":[{"orpha":394532,"name":"Multiple acyl-CoA dehydrogenase deficiency, mild type","type":"Clinical subtype"},{"orpha":394529,"name":"Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"FLAD1","name":"flavin adenine dinucleotide synthetase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"27259049[PMID]","hgnc":"24671","ensembl":"ENSG00000160688","omim":"610595","loci":["1q21.3"],"via":{"orpha":394529,"name":"Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type"}},{"symbol":"FLAD1","name":"flavin adenine dinucleotide synthetase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28433476[PMID]","hgnc":"24671","ensembl":"ENSG00000160688","omim":"610595","loci":["1q21.3"],"via":{"orpha":394532,"name":"Multiple acyl-CoA dehydrogenase deficiency, mild type"}},{"symbol":"ETFA","name":"electron transfer flavoprotein subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3481","ensembl":"ENSG00000140374","omim":"608053","loci":["15q24.2-q24.3"],"via":{"orpha":394529,"name":"Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type"}},{"symbol":"ETFA","name":"electron transfer flavoprotein subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3481","ensembl":"ENSG00000140374","omim":"608053","loci":["15q24.2-q24.3"],"via":{"orpha":394532,"name":"Multiple acyl-CoA dehydrogenase deficiency, mild type"}},{"symbol":"ETFB","name":"electron transfer flavoprotein subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3482","ensembl":"ENSG00000105379","omim":"130410","loci":["19q13.41"],"via":{"orpha":394529,"name":"Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type"}},{"symbol":"ETFB","name":"electron transfer flavoprotein subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3482","ensembl":"ENSG00000105379","omim":"130410","loci":["19q13.41"],"via":{"orpha":394532,"name":"Multiple acyl-CoA dehydrogenase deficiency, mild type"}},{"symbol":"ETFDH","name":"electron transfer flavoprotein dehydrogenase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3483","ensembl":"ENSG00000171503","omim":"231675","loci":["4q32.1"],"via":{"orpha":394529,"name":"Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type"}},{"symbol":"ETFDH","name":"electron transfer flavoprotein dehydrogenase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3483","ensembl":"ENSG00000171503","omim":"231675","loci":["4q32.1"],"via":{"orpha":394532,"name":"Multiple acyl-CoA dehydrogenase deficiency, mild type"}},{"symbol":"SLC25A32","name":"solute carrier family 25 member 32","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28443623[PMID]_26933868[PMID]","hgnc":"29683","ensembl":"ENSG00000164933","omim":"138480","loci":["8q22.3"],"via":{"orpha":394532,"name":"Multiple acyl-CoA dehydrogenase deficiency, mild type"}}],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.47,"area":"United States","status":"Not yet validated","source":"ORPHANET_24190796[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"Europe","status":"Not yet validated","source":"ORPHANET"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.5,"area":"Israel","status":"Validated","source":"33239050[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.0,"area":"Specific population","status":"Validated","source":"33239050[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-09-24","source":"2658591[PMID]_19249206[PMID]_20370797[PMID]_26403312[PMID]_18289905[PMID]","terms":[{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009020","label":"Exercise-induced muscle fatigue","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003326","label":"Myalgia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003701","label":"Proximal muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003344","label":"3-Methylglutaric aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000377","label":"Abnormal pinna morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000924","label":"Abnormality of the skeletal system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001284","label":"Areflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003234","label":"Decreased circulating carnitine concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001410","label":"Decreased liver function","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003551","label":"Difficulty climbing stairs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002094","label":"Dyspnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0045045","label":"Elevated plasma acylcarnitine levels","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003219","label":"Ethylmalonic aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003546","label":"Exercise intolerance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030199","label":"Fatigable weakness of neck muscles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003150","label":"Glutaric aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002614","label":"Hepatic periportal necrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000348","label":"High forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003307","label":"Hyperlordosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025435","label":"Increased circulating lactate dehydrogenase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012240","label":"Increased intramyocellular lipid droplets","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003648","label":"Lacticaciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001942","label":"Metabolic acidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000118","label":"Phenotypic abnormality","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:0003202","label":"Skeletal muscle atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000506","label":"Telecanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000260","label":"Wide anterior fontanel","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000078","label":"Abnormality of the genital system","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001735","label":"Acute pancreatitis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001638","label":"Cardiomyopathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006543","label":"Cardiorespiratory arrest","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002171","label":"Gliosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002282","label":"Gray matter heterotopia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000113","label":"Polycystic kidney dysplasia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002091","label":"Restrictive ventilatory defect","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006582","label":"Reye syndrome-like episodes","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003201","label":"Rhabdomyolysis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003691","label":"Scapular winging","frequency":"Very rare (<4-1%)","criteria":null}]}}