Pyruvate therapy for Leigh syndrome due to cytochrome c oxidase deficiency

Background: Recently we proposed the therapeutic potential of pyruvate therapy for mitochondrial diseases. Leigh syndrome is a progressive neurodegenerative disorder ascribed to either mitochondrial or nuclear DNA mutations. Methods: In an attempt to circumvent the mitochondrial dysfunction, we orally applied sodium pyruvate and analyzed its effect on an 11-year-old female with Leigh syndrome due to cytochrome c oxidase deficiency accompanied by cardiomyopathy. The patient was administered sodium pyruvate at a maintenance dose of 0.5 g/kg/day and followed up for 1 year. Results: The exercise intolerance was remarkably improved so that she became capable of running. Echocardiography indicated improvements both in the left ventricle ejection fraction and in the fractional shortening. Electrocardiography demonstrated amelioration of the inverted T waves. When the pyruvate administration was interrupted because of a gastrointestinal infection, the serum lactate level became elevated and the serum pyruvate level, decreased, suggesting that the pyruvate administration was effective in decreasing the lactate-to-pyruvate ratio. Conclusions: These data indicate that pyruvate therapy was effective in improving exercise intolerance at least in a patient with cytochrome c oxidase deficiency. General significance: Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations. (C) 2009 Elsevier B.V. All rights reserved.