Biochemical studies and therapy in subacute necrotizing encephalomyelopathy (Leigh's syndrome)

The clinical course, biochemical abnormalities, and the effects of vitamin therapy in subacute necrotizing encephalomyelopathy are described in a patient who was serially evaluated from birth. Important features include increased cerebrospinal protein, elevated blood lactic acid values, and abnormal macular morphology detected when the patient was asymptomatic. Renal tubular acidosis and alaninemia were noted shortly after the onset of symptoms. No clinical improvement was noted with pharmacologic doses of biotin, thiamine (hydrochloride or propyldisulfide), or lipoic acid. Hepatic pyruvate carboxylase was within the range of control values early in the disease but was negligible in postmortem material. The clinical and biochemical course suggests that low levels of hepatic pyruvate carboxylase in postmortem material were secondary effects of an otherwise as yet unknown biochemical process. Decreased cerebral pyruvate carboxylase activity at autopsy was documented for the first time.