Coenzyme Q(10) defects may be associated with a deficiency of Q(10)-independent mitochondrial respiratory chain complexes

BACKGROUND: Coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ(10) biosynthesis pathway, or to mutations in genes unrelated to CoQ(10) biosynthesis. CoQ(10) defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ(10) supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ(10) levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ(10) deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ(10) defect may be associated with a deficiency of CoQ(10)-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ(10) defect could be associated with MRC deficiency, we quantified CoQ(10) by LC-MSMS in a cohort of 18 patients presenting CoQ(10)-dependent deficiency associated with MRC defect. We found decreased levels of CoQ(10) in eight patients out of 18 (45 %), thus confirming CoQ(10) disease. CONCLUSIONS: Our study shows that CoQ(10) defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ(10) supplementation.