Mitochondrial disorders in degenerative ataxias

Current theory implicates mitochondrial defects in the mechanism of neuronal degeneration in several movement disorders. We performed analyses of mitochondrial function in 61 patients with different forms of degenerative ataxias. Mitochondrial enzyme defects were proven in five of 16 (31%) patients with Friedreich's ataxia, in 14 of 30 (47%) patients with autosomal dominant late onset cerebellar ataxia, and in three of six (50%) patients with sporadic cerebellar atrophy. No abnormalities were found in secondary forms of cerebellar degenerations (due to paraneoplastic disorder, alcohol or sprue) or in spastic paraplegia. Mitochondrial defects affected most frequently the respiratory chain (19 patients) and especially its complex I(11 patients). Carnitine deficiency was found in three patients and severe loss of myoadenylate deaminase in one patient. Genetic abnormalities could be proved neither in mitochondrial DNA nor in recently defined ataxia genes. Our results indicate that mitochondrial dysfunction occurs frequently in cerebellar atrophies. Therefore, disturbance of oxidative energy metabolism may be involved in the pathogenesis of degenerative ataxias, but it remains to be elucidated whether mitochondrial defects are primary or secondary effects.