Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy.

TLDR

A familial syndrome of lactacidemia, mitochondrial myopathy, and encephalopathy was studied by examining the electron transport system in affected muscle, noting progressive muscle weakness, fatigability, and central nervous system dysfunction. Muscle mitochondria from affected siblings showed markedly reduced CoQ10 content (3.7 % of controls) and low activity of CoQ10‑dependent complexes I‑III and II‑III, while other complexes and serum/fibroblast CoQ10 were normal, confirming a tissue‑specific CoQ10 biosynthesis defect as the cause of the familial mitochondrial cytopathy.

Abstract

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.