Quantification of coenzymeQ10 in South African pediatric patients with electron transport chain deficiencies

Abstract

CoenzymeQ10 (CoQ10) is an important component of the mitochondrial electron transport chain (ETC). Co010 deficiency mainly affects children, and patients present with heterogeneous clinical phenotypes. Patients frequently respond to treatment with CoQ10 supplementation, but with disparate responses. This study was aimed at quantifying muscle CoQ10 concentrations in patients with ETC deficiencies. The samples of the experimental group of this study were received from muscle biopsies performed to determine underlying mitochondrial disorders. These biopsies were performed on patients with a Mitochondrial Disease Criteria ≥ 6 or when they had two or more unrelated organ systems involved, or any of the classical phenotypes associated with muscle mitochondrial disorders. After homogenization of the samples, 600 x g supernatants were used for analyses of the ETC enzyme activities. These same homogenate supernatants were used for CoQ10 quantification. A liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was standardized for the quantification of CoQ10 in muscle samples, using a stable isotope dilution approach. The experimental group that was investigated in this study consisted of one hundred and fifty five patients of which seventy nine were clinically referred controls and seventy six had confirmed mitochondrial disorders. Statistical inference of the clinically referred controls showed that not race, age, or gender had any influence on the measured CoQ10 concentrations. A central 95% reference interval was established for CoQ10 concentrations in 600 x g supernatants using the clinically referred controls. After comparing all the ETC deficient patients to the newly established reference interval, it was found that eight patients, all with combined (CoQ10 dependent) complex 11+111 (Cll+lll) deficiencies, had deficient CoQ10 concentrations (below the 2.5th % of the reference interval). These eight patients are very likely to benefit from Co010 supplementation, and this association of CoQ10 deficiency and Cll+lll deficiency can serve as future selection criteria for patients who may benefit from CoQ10 supplementation