Histologic and biochemical analyses of muscle biopsies from 33 patients with Leigh encephalopathy were performed at the National Institute of Neuroscience, Tokyo and Tokushima University School of Medicine, Japan. Cytochrome c oxidase activity was decreased or absent in 7 patients (21%), 10 patients (30%) had biochemical defects including 2 with pyruvate dehydrogenase complex, 4 with cytochrome c oxidase, 1 with NADH-cytochrome c reductase and 3 with multiple complex deficiencies. None had DNA deletions in the muscle mitochondria. 
COMMENT. A mitochondrial DNA mutation in the ATPase 6 gene was reported in 7 of 40 patients with neuropathologically or MRI defined Leigh syndrome but no known biochemical defect . A high abundance of the “NARP” mutation (neuropathy, ataxia, and retinitis pigmentosa) can cause Leigh syndrome and should be looked for in patients without biochemical defects. In another report, a 7 year old girl presented with a partial pyruvate carboxylase deficiency and basal ganglia lesions compatible with Leigh’s disease . The biochemical defects in Leigh encephalopathy are probably heterogeneous.