Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy

The electron transport system of muscle mitochondria was examined in a familial syndrome of lactacidemia, mitochondrial myopathy, and encephalopathy. The propositus, a 14-year-old female, and her 12-year-old sister had suffered from progressive muscle weakness, abnormal fatigability, and central nervous system dysfunction since early childhood. In the propositus, the state 3 respiratory rate of muscle mitochondria with NADH-linked substrates and with succinate was markedly reduced. The levels of cytochromes a + a₃, b and c + c₁ were normal. The activities of complexes I, II, III, and IV of the electron transport chain were normal or increased. By contrast, the activities of complex I-III and of complex II-III, both of which need coenzyme Q₁₀ (CoQ₁₀), were abnormally low. On direct measurement, the mitochondrial CoQ₁₀ content was 3.7% of the mean value observed in 10 controls. Serum and cultured fibroblasts of the propositus had normal CoQ₁₀ contents. In the younger sister, the respiratory activities and CoQ₁₀ level of muscle mitochondria were similar to those observed in the propositus. The findings establish CoQ₁₀ deficiency as a cause of a familial mitochondrial cytopathy and suggest that the disease results from a tissue-specific defect of CoQ₁₀ biosynthesis.