Diagnosis of MADD is aided by urinary organic acid analysis and blood acylcarnitine profile.Ĭlassical MADD has been known to occur secondary to deficiency in electron transfer flavoprotein (ETF) or ETF:ubiquinone oxidoreductase (ETF:QO). The clinical heterogeneity of adult-onset forms pose a challenge for diagnosis with the vast majority displaying mild or atypical biochemical abnormalities. MADD is associated with a highly diverse clinical phenotype, ranging from the lethal neonatal onset type with congenital anomalies, to the adult onset type with milder and variable clinical presentation. Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disorder characterized by mitochondrial electron transfer system defects and impaired fatty acids metabolism. Lipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders characterized by impaired fatty acids oxidation. Our 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. The diagnosis of MADD was established and the patient was treated with riboflavin which resulted in rapid clinical and biochemical improvement. This missense variant was predicted to be deleterious but its association with lipid storage in muscle is unclear. In addition, a previously unreported variant c.1042C > T (p.Arg348Trp) in ACOT11 gene was found. 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. Diagnostic testing demonstrated lipid accumulation in muscle fibres and elevated plasma acyl carnitine levels. We report a patient presented with severe muscle weakness and exercise intolerance, suggestive of LSM. Whole exome sequencing (WES) with clinical correlations can be useful in identifying genomic alterations for targeted therapy. Classical multiple acyl-CoA dehydrogenase deficiency (MADD) is known to occur secondary to mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene. Lipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders with great variations in the clinical phenotype and age of onset.