Short-chain acyl-CoA dehydrogenase deficiency - A cause of ophthalmoplegiaand multicore myopathy

Objective: To determine an underlying genetic defect within the differentia l diagnosis of congenital multicore myopathy. Background: A 13.5-year-old g irl presented with congenital-onset facial and neck weakness, slowly progre ssive severe limb girdle and axial myopathy, respiratory weakness, cardiomy opathy, progressive joint contractures, lumbar lordosis, progressive extern al ophthalmoplegia with ptosis, and cataracts. Muscle biopsy at; 3 years re vealed type I fiber predominance and hypotrophy, multicores with a focal de crease in mitochondria and oxidative enzymes, and internal nuclei. Methods and Results: Serum carnitine was decreased (total, 18.2 mu mol/L; free, 11. 7 mu mol/L). Urine organic acids intermittently revealed very large amounts of ethylmalonic and methylsuccinic acids intermittently, with elevated but yrylglycine, 2-methylbutyrylglycine, and tiglylglycine. Fibroblast acylcarn itine profiles revealed marked butyrylcarnitine elevation. Electron-transfe rring flavoprotein-linked reduction enzymatic assay of fibroblasts with but yryl-coenzyme A (CoA) as substrate, after immunoinactivation of medium-chai n acyl-CoA dehydrogenase activity, revealed a complete absence of short-cha in acyl-CoA dehydrogenase (SCAD) activity. No SCAD protein was detectable w ith Western blot analysis. Conclusions: This patient expands the clinical p henotype of SCAD deficiency and emphasizes the need for its consideration i n the differential diagnosis of progressive external ophthalmoplegia and co ngenital multicore myopathy.