Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue.

A patient is described with subacute necrotizing encephalomyelopathy proven by autopsy. A slight increase of blood pyruvate and lactate levels with an increased lactate/pyruvate ratio and frequently increased beta-hydroxybutyrate/acetoacetate ratio suggested a disorder of mitochondrial oxidation. A cytochrome c oxidase deficiency was shown in peripheral muscle tissue with some residual cytochrome c oxidase activity in heart muscle. Normal cytochrome c oxidase activity was present in liver tissue. Because of the markedly higher levels of pyruvate and lactate in CSF compared with blood and an increased lactate/pyruvate ratio in CSF, there may also have been defective activity of cytochrome c oxidase in brain tissue. After a period of apparently normal development, the child's clinical condition gradually deteriorated and she died at age 6 years due to respiratory insufficiency. This study illustrates the fact that Leigh's disease is not linked to a single inherited molecular defect.