Diagnosis Of Multiple acyl-CoA Dehydrogenase Deficiency Research Articles

Multiple acyl-Coa dehydrogenase deficiency (MADD) – adult and neonatal presentation

Multiple acyl-CoA dehydrogenase deficiency (MADD), or glutaric acidemia type II, is an autosomal recessive disorder of oxidative metabolism. MADD has a wide clinical spectrum with clinical presentation in the neonatal period with or without congenital malformations, through to later onset. Episodes of clinical decompensation may be triggered by catabolic stressors such as intercurrent illnesses and prolonged fasting. The diagnosis of MADD is made according to the profiles of urine organic acids and plasma or dried blood spot (DBS) acylcarnitines.

Late-onset multiple acyl-CoA dehydrogenase deficiency mimicking myositis in an elderly patient: a case report

BackgroundLate-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare and treatable inherited lipid storage myopathy. Here, we report an elderly patient with MADD mimicking myositis.Case presentationAn 80-year-old woman had progressive weakness in her limbs, exercise intolerance, and no muscle pain for 3 months. The patient’s serum creatine kinase level was slightly elevated. The initial diagnosis was myositis. However, muscle biopsy showed many cytoplasmic vacuoles stained with oil red O, indicating the presence of lipid storage myopathy. The plasma acylcarnitine profile showed increased medium-chain and long-chain acylcarnitine species, consistent with the diagnosis of MADD. Riboflavin treatment dramatically improved muscle weakness.ConclusionsMADD should be considered when evaluating elderly patients with subacute muscle weakness.

Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report

BackgroundLipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders with great variations in the clinical phenotype and age of onset. Classical multiple acyl-CoA dehydrogenase deficiency (MADD) is known to occur secondary to mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene. Whole exome sequencing (WES) with clinical correlations can be useful in identifying genomic alterations for targeted therapy.Case presentationWe report a patient presented with severe muscle weakness and exercise intolerance, suggestive of LSM. Diagnostic testing demonstrated lipid accumulation in muscle fibres and elevated plasma acyl carnitine levels. Exome sequencing of the proband and two of his unaffected siblings revealed compound heterozygous mutations, c.250G > A (p.Ala84Thr) and c.770A > G (p.Tyr257Cys) in the ETFDH gene as the probable causative mutations. In addition, a previously unreported variant c.1042C > T (p.Arg348Trp) in ACOT11 gene was found. This missense variant was predicted to be deleterious but its association with lipid storage in muscle is unclear. The diagnosis of MADD was established and the patient was treated with riboflavin which resulted in rapid clinical and biochemical improvement.ConclusionsOur findings support the role of WES as an effective tool in the diagnosis of highly heterogeneous disease and this has important implications in the therapeutic strategy of LSM treatment.