Coenzyme Q10 (ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21.

Endogenous coenzyme Q10 is an essential cofactor in the mitochondrial respiratory chain, a potent antioxidant, and a potential biomarker for systemic oxidative status. Evidence of oxidative stress was reported in individuals with trisomy 21. In this study, 14 children with trisomy 21 had significantly increased (P < 0.0001) plasma ubiquinone-10 (the oxidized component of coenzyme Q10) compared with 12 age- and sex-matched healthy children (historical controls). Also, the mean ratio of ubiquinol-10 (the biochemically reduced component):total coenzyme Q10 was significantly decreased (P < 0.0001). After 3 months of ubiquinol-10 supplementation (10 mg/kg/day) to 10 patients with trisomy 21, the mean ubiquinol-10:total coenzyme Q10 ratio increased significantly (P < 0.0001) above baseline values, and 80% of individual ratios were within normal range. No significant or unexpected adverse effects were reported by participants. To our knowledge, this is the first study to indicate that the pro-oxidant state in plasma of children with trisomy 21, as assessed by ubiquinol-10:total coenzyme Q10 ratio, may be normalized with ubiquinol-10 supplementation. Further studies are needed to determine whether correction of this oxidant imbalance improves clinical outcomes of children with trisomy 21.

Coenzyme Q10 absorption and tolerance in children with Down syndrome: a dose-ranging trial.

Controlled studies of coenzyme Q(10) dosing and tolerance have been reported in adults, but not in pediatric patients. This study compares low- and high-dose coenzyme Q(10) (LiQ-NOL syrup) absorption and tolerance in children with Down syndrome. After a 1-month low-dose (1.0 mg/kg/day) run-in period, all participants received high-dose coenzyme Q(10) (10.0 mg/kg/day) for two additional months (in randomized sequence as one daily dose or split into two daily doses). Chemistry profiles and complete blood counts were determined just before and at the study completion. Plasma coenzyme Q(10) concentrations were determined initially and at each study visit. Parents reported adverse events and study drug evaluations using standardized forms. Most of the 16 children who completed this study tolerated high-dose coenzyme Q(10) well. Uncooperative behavior resulted in premature withdrawal of two participants, and may have been treatment-related. Pre- and posttreatment laboratory test changes were considered to be clinically nonsignificant. Study results indicate that high-dose coenzyme Q(10) (10 mg/kg/day) is well-absorbed and well-tolerated by most children with Down syndrome, and appears to provide plasma concentrations which are comparable to previous adult studies administering much higher coenzyme Q(10) dosages.

Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome.

Blood gene expression profiling has been applied to a variety of hematological malignancies, autoimmune disorders, and infectious diseases. This study applies this approach to genetic diseases without obvious blood phenotypes. Three genetic diseases including tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome were compared with a group of healthy controls. RNA from whole blood was surveyed using Affymetrix U133A arrays. Each disease was associated with a unique gene expression pattern in blood that can be accurately distinguished by a classifier. Genes on chromosome 21 were overexpressed in Down's syndrome, and genes controlling cell cycle and proliferation were associated with tuberous sclerosis complex type 2 or neurofibromatosis type 1. A subset of genes involved in cardiac development or remodeling were overexpressed in patients with Down's syndrome and congenital heart defects. These findings suggest that blood gene expression profiling on a broader basis might be useful for genetic disease screening/diagnosis and might help elucidate mechanisms and pathways that lead to genotype-phenotype differences.