Mitochondrial enzymes were studied in 5 unrelated children with neuropathologically proven subacute necrotizing encephalomyelopathy (Leigh syndrome) at the College of Physicians and Surgeons, New York. Four patients showed psychomotor regression, opthalmoparesis, nystagmus, optic atrophy, hypotonia, areflexia, ataxia, and abnormal breathing beginning in the second year and died after 3 to 4 years of an intermittently progresssive course. The fifth child was floppy at birth, regressed at 5 mos, and died of congestive heart failure at 7½ mos. All had lactic acidosis and autopsies showed typical symmetrical necrotic and cystic lesions in the brain stem and cerebellum. Muscle biopsy was normal by light microscopy but showed mitrochondrial changes on ultrastructural examination. A decrease in cytochrome c oxidase (COX) activity was found in brain, muscle, kidney, heart, liver and in cultured fibroblasts. The authors conclude that COX deficiency is an important cause of Leigh syndrome. 
COMMENT. The family history was negative in these patients but previous reports of autosomal recessive inheritance and occurrence in siblings are common. In one family from Quebec, 7 members in two generations had a mitochondrial encephalopathy and COX deficiency. Diverse clinical and pathological expressions of Leigh’s disease in this family was explained by maternal transmission of varying proportions of mutant mitochondrial DNA . Leigh syndrome, previously termed Leigh’s disease and first described in 1951, appears to be nonspecific biochemically as well as clinically. In addition to the COX deficiency described above, defects of the pyruvate dehydrogenase multienzyme complex and pyruvate carboxylase have been reported. An inhibitor of the brain enzyme that catalyzes the formation of thiamine triphosphate has been found in the urine but the test is not diagnostic. Consistent early clinical features in the infantile cases are a quiet immobility with lack of crying and hypotonia.