We evaluated the coenzyme Q10 (CoQ) levels in patients who were diagnosed with mitochondrial oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders (n=72). Data from the 72 cases in this study revealed that 44.4% of patients showed low CoQ concentrations in either their skeletal muscle or skin fibroblasts. Our findings suggest that secondary CoQ deficiency is a common finding in OXPHOS and non-OXPHOS disorders. We hypothesize that cases of CoQ deficiency associated with OXPHOS defects could be an adaptive mechanism to maintain a balanced OXPHOS, although the mechanisms explaining these deficiencies and the pathophysiological role of secondary CoQ deficiency deserves further investigation.
Mitochondrial Diseases/pathology , Oxidative Phosphorylation , Ubiquinone/analogs & derivatives , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Muscles/pathology , Prevalence , Skin/pathology , Ubiquinone/deficiency , Young Adult
BACKGROUND: It has been demonstrated that glucose transporter (GLUT1) deficiency in a mouse model causes a diminished cerebral lipid synthesis. This deficient lipid biosynthesis could contribute to secondary CoQ deficiency. We report here, for the first time an association between GLUT1 and coenzyme Q10 deficiency in a pediatric patient. CASE PRESENTATION: We report a 15 year-old girl with truncal ataxia, nystagmus, dysarthria and myoclonic epilepsy as the main clinical features. Blood lactate and alanine values were increased, and coenzyme Q10 was deficient both in muscle and fibroblasts. Coenzyme Q10 supplementation was initiated, improving ataxia and nystagmus. Since dysarthria and myoclonic epilepsy persisted, a lumbar puncture was performed at 12 years of age disclosing diminished cerebrospinal glucose concentrations. Diagnosis of GLUT1 deficiency was confirmed by the presence of a de novo heterozygous variant (c.18+2T>G) in the SLC2A1 gene. No mutations were found in coenzyme Q10 biosynthesis related genes. A ketogenic diet was initiated with an excellent clinical outcome. Functional studies in fibroblasts supported the potential pathogenicity of coenzyme Q10 deficiency in GLUT1 mutant cells when compared with controls. CONCLUSION: Our results suggest that coenzyme Q10 deficiency might be a new factor in the pathogenesis of G1D, although this deficiency needs to be confirmed in a larger group of G1D patients as well as in animal models. Although ketogenic diet seems to correct the clinical consequences of CoQ deficiency, adjuvant treatment with CoQ could be trialled in this condition if our findings are confirmed in further G1D patients.
Ataxia/etiology , Glucose Transporter Type 1/deficiency , Mitochondrial Diseases/etiology , Muscle Weakness/etiology , Ubiquinone/deficiency , Adolescent , Ataxia/diagnosis , Ataxia/diet therapy , Cation Transport Proteins , Diet, Ketogenic , Dietary Supplements , Female , Glucose Transporter Type 1/genetics , Humans , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/diet therapy , Muscle Weakness/diagnosis , Muscle Weakness/diet therapy , Mutation , Sodium-Hydrogen Exchanger 1 , Sodium-Hydrogen Exchangers , Ubiquinone/analogs & derivatives , Ubiquinone/therapeutic use , Vitamins/therapeutic use
