Mitochondrial enzymes in hereditary ataxias

As a test of the hypothesis that mitochondrial abnormalities are common in patients with hereditary ataxias, the activities of two mitochondrial enzymes were studied in platelets from an unselected series of patients. For the group of ataxies, the activity of the pyruvate dehydrogenase complex (PDHC) was 68% of the control (P < 0.01) and that of glutamate dehydrogenase (GDH) was 81% of the control (P < 0.05). Of the ataxies studied, 30% had activities of either or both mitochondrial enzymes more than 2 SD below the control mean. Immunoblots of PDHC revealed antibody cross-reacting material in platelets and fibroblasts very similar to those in human brain and appeared normal in platelets from patients with ataxias. Immunoblots of GDH showed a single antibody cross-reacting material in brain but at least two species in normal fibroblasts and platelets. The pathophysiology of hereditary ataxias may often involve mitochondrial damage associated with secondary decreases in the activities of mitohcondrial enzymes.