To report two cases of adult-onset myopathy due to Multiple acyl-CoA Dehydrogenase Deficiency (MADD).

MADD is a rare, autosomal-recessive disorder of fatty acid oxidation. Although late-onset MADD is described, it remains a diagnostic challenge.  Diagnosis is complex requiring concordant findings from muscle biopsy, acylcarnitine profiling, urine organic acids and identification of pathogenic variants in ETFA, ETFB, or ETFDH genes.

Case Report.

Case 1: 46-year-old female with one year of muscle aches and exercise intolerance. Initial examination showed normal muscle strength. CK was mildly elevated, and EMG showed non-irritable myopathy. Muscle biopsy showed increased lipid droplets in type 1 muscle fibers without necrosis or inflammation. Quantitative serum acylcarnitine profiling showed several elevated acylcarnitines with low serum carnitine levels. Genetic testing showed heterozygosity with a pathogenic variant in ETFDH, c.1601C>T (p.Pro534Leu). She was treated with riboflavin and L-carnitine with some improvement in symptoms.

Case 2: 37-year-old female with two years of proximal muscle aches and exercise intolerance. She had elevated CK levels. Reportedly she had a normal EMG and muscle biopsy. A repeat EMG showed non-irritable myopathy. Repeat muscle biopsy showed increased lipid droplets in type 1 muscle fibers without necrosis or inflammation. A quantitative serum acylcarnitine profiling showed several elevated acylcarnitines. Quantitative urine acylglycine profile was abnormal. Genetic testing showed she was heterozygous for pathogenic variants in CPT2, c.388C>T (p.Ser113Leu) and ETFDH, c.413T>G (p.Leu138Arg), and heterozygous for a VUS in ETFA, c.295A>G (p.Thr99Ala). Biochemical profile is more consistent with MADD than CPTII.

These are two cases of MADD presenting as adult-onset myopathy. Our patients are heterogeneous for pathogenic variants, yet manifest symptoms in adulthood with histologic and biochemical profiles consistent with MADD. It is possible that a second variant was missed by genetic testing but demonstrates the need for multiple concordant findings for diagnosis.