Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency

Background The respiratory-chain deficiencies are a broad group of largely untreatable diseases, Among them, coenzyme Q(10) (ubiquinone) deficiency constitutes a subclass that deserves early and accurate diagnosis. Methods We assessed respiratory-chain function in two siblings with severe encephalomyopathy and renal failure. We used high-performance liquid chromatography analyses, combined with radiolabelling experiments, to quantify cellular coenzyme Q(10) content. Clinical follow-up and detailed biochemical investigations of respiratory chain activity were carried out over the 3 years of oral quinone administration, Findings Deficiency of coenzyme Q(10)-dependent respiratory-chain activities was identified in muscle biopsy, circulating lymphocytes, and cultured skin fibroblasts, Undetectable coenzyme Q(10) and results of radiolabelling experiments in cultured fibroblasts supported the diagnosis of widespread coenzyme Q(10) deficiency. Stimulation of respiration and fibroblast enzyme activities by exogenous quinones in vitro prompted us to treat the patients with oral ubidecarenone (5 mg/kg daily), which resulted in a substantial improvement of their condition over 3 years of therapy. Interpretation Particular attention should be paid to multiple quinone-responsive respiratory-chain enzyme deficiency because this rare disorder can be successfully treated by oral ubidecarenone.