Defect in succinate oxidation by isolated muscle mitochondria in a patient with symmetrical lesions in the basal ganglia.

A 3-year-old boy was referred for evaluation of psychomotor retardation. He had a waddling gait with proximal hypotonia and paresis. Computed tomography (CT scan) and magnetic resonance imaging (MRI) of the brain demonstrated symmetrical lesions in the basal ganglia suggesting bilateral necrosis. Lactate and pyruvate levels in blood and cerebrospinal fluid were persistently elevated. A biopsy of the quadriceps muscle showed normal light microscopic findings except for a slightly raised number of lipid droplets. Electron microscopy confirmed this and also showed a rather large number of subsarcolemmal mitochondria without crystalline inclusions. Biochemical studies showed a normal carnitine level and normal mitochondrial enzyme activities in muscle homogenate, including succinate-cytochrome c reductase. However, intact isolated mitochondria failed to oxidize succinate. An explanation for this paradoxical finding is a deficiency in that part of the coenzyme Q (CoQ) that is reduced by the succinate dehydrogenase complex. The differential diagnosis between Leigh's syndrome and infantile bilateral striatal necrosis (IBSN) is discussed. The role of neuroradiology in prompting complementary investigations is stressed.