The respiratory-chain deficiencies are a broad group of largely untreatable diseases. Among them, coenzyme Q₁₀ (ubiquinone) deficiency constitutes a subclass that deserves early and accurate diagnosis.

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 Q₁₀ content. Clinical follow-up and detailed biochemical investigations of respiratory chain activity were carried out over the 3 years of oral quinone administration.

Deficiency of coenzyme Q₁₀-dependent respiratory-chain activities was identified in muscle biopsy, circulating lymphocytes, and cultured skin fibroblasts. Undetectable coenzyme Q₁₀ and results of radiolabelling experiments in cultured fibroblasts supported the diagnosis of widespread coenzyme Q₁₀ 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.

Particular attention should be paid to multiple quinone-responsive respiratory-chain enzyme deficiency because this rare disorder can be successfully treated by oral ubidecarenone.