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.


CONCLUSIONS
Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations.
Komaki
Hirofumi
H
Department of Pediatric Neurology, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Nishigaki
Yutaka
Y
Fuku
Noriyuki
N
Hosoya
Hiroko
H
Murayama
Kei
K
Ohtake
Akira
A
Goto
Yu-Ichi
Y
Wakamoto
Hiroyuki
H
Koga
Yasutoshi
Y
Tanaka
Masashi
M
D000328:Adult; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009154:Mutation; D009759:Nystagmus, Pathologic / Q000235:genetics / Q000473:pathology; D011773:Pyruvates / Q000627:therapeutic use*
D004272:DNA, Mitochondrial; D011773:Pyruvates; D004247:DNA; D003576:Electron Transport Complex IV