Pyruvate oxidation in neuromuscular diseases. Evidence of a genetic defect in two families with the clinical syndrome of Friedreich's ataxia

To seek clues of metabolic derangements in neurornuscular diseases, the oxidations of pyruvate and succinate were studied in biopsied muscle. Pyruvate oxidation in 7 of 19 spinocerebellar degenerations (0.327± 0.040 prnoles × gm-1 noncollagenous protein content × hr-l) and 8 of 19 motor neuropathies (0.367± 0.029) was less than in controls with myopathic disease (1.096±0.91) or normal muscle (1.707± 0.181) (means± S.E.M.). The rates were independent of several physiologic variables, of the ratios of Type I::Type ll fibers in the specimens, and of the degree of neuropathy. Succinate was oxidized normally. Serially cultured fibroblasts from three patients from families with Friedreich9s ataxia also oxidized pyruvate more slowly than did controls (0.11± 0.03 vs. 0.30± 0.02 cpm × mcg-19 protein × hr-1. These two families with ataxia appear to have a genetic defect that affects pyruvate oxidation in some unknown way.