ubiquinone and Prader-Willi-Syndrome

To assess body composition of infants with Prader-Willi syndrome (PWS) by using deuterium dilution and investigating the efficacy of early institution of growth hormone (GH) therapy in increasing lean mass (LM) and preventing massive obesity.. One group of 11 children with PWS <2 years before and during 30-month GH therapy (GH group) was compared with 6 infants administered only coenzyme Q(10) for 1 year (Q10 group). LM adjusted for height (LM(Ht)) and relative fat mass (%FM(Age)) standard deviation scores (SDS) were calculated from data of 95 healthy children.. Initially, LM(Ht) of all patients was below the normal average. LM(Ht) decreased by -0.46 +/- 0.3 SD (P=.03) per year in the Q10 group but rose by 0.25 +/- 0.3 SD (P=.02) per year during GH therapy, normalizing after 30 months (-0.70 +/- 1.0 SD). Despite low to normal weight for height (WfH), %FM(Age) was above the normal average (GH group, 31.0% +/- 4.5%, Q10 group, 32.4% +/- 9.5%). In the Q10 infants, %FM(Age) increased by 0.71 +/- 0.7 SD per year, whereas in the GH group, %FM(Age) remained more stable up to 30 months.. Diminished LM(Ht) found in infants with PWS further declines during the early years. Early institution of GH therapy lifts LM(Ht) into the normal range and delays fat tissue accumulation.

Topics: Body Composition; Female; Human Growth Hormone; Humans; Infant; Male; Obesity; Prader-Willi Syndrome; Recombinant Proteins; Statistics, Nonparametric; Ubiquinone

Carnitine deficiency or coenzyme Q10 (CoQ10) deficiency may present with hypotonia, poor growth, easy fatigability, and apnea. This constellation of findings can also be seen in individuals with Prader-Willi syndrome (PWS). Animal studies indicate that increased fat mass due to obesity negatively correlates with both carnitine and CoQ10 levels in skeletal muscle. Increased body fat and obesity are characteristic of individuals with PWS. Currently, there is no documentation of serum carnitine levels, and only one study investigating plasma CoQ10 levels, in individuals with PWS. Fasting serum carnitine and plasma CoQ10 levels were measured in 40 individuals with molecularly confirmed PWS (ages 1-27 years; 19 F/21 M), 11 individuals with early-onset morbid obesity of unknown etiology (ages 3-13 years; 5 F/6 M), and 35 control siblings from both groups (ages 1-24 years; 19 F/16 M). There were no significant differences among the three groups in either total carnitine, free carnitine, or CoQ10 levels. However, individuals with PWS had higher serum levels of carnitine esters (P = 0.013) and higher ester-to-free carnitine ratios (P = 0.0096) than controls suggesting a possible underlying impairment of peripheral carnitine utilization and mitochondrial energy metabolism in some individuals with PWS. Serum sampling identified no significant differences in total and free carnitine or CoQ10 levels between individuals with PWS, obese individuals, and sibling control groups. Muscle biopsy or measurement in leukocytes or cultured skin fibroblasts could be a better method to identify abnormalities in carnitine and CoQ10 metabolism in individuals with PWS than peripheral blood sampling.

Topics: Carnitine; Case-Control Studies; Child; Female; Humans; Male; Prader-Willi Syndrome; Siblings; Ubiquinone

Muscle hypotonia and failure to thrive are key symptoms of Prader-Willi syndrome (PWS) allowing diagnosis during infancy already. Improved general care as well as Coenzyme Q(10) (CoQ(10)) and growth hormone (GH) are administered to improve PWS children's outcome. This study aims to investigate psychomotor development of young PWS children in relation to body weight and body composition at baseline as well as to the effects of GH or CoQ(10) therapy. Twenty-six young children (age 1.0 +/- 0.1 years, mean +/- SEM) with PWS genetically proven at age 0.1 +/- 0.1 years (17 deletions, 8 maternal disomy) were divided into three groups: Group 1 on GH therapy (started in 1994-1996, 6 mg/kg/week) tolerating low body weight (<50th centile), group 2 on GH (1997-2000) and group 3 on CoQ(10) (2001-2002, 2.5 mg/kg/day orally), both combined with active early weight management to achieve weight >50th centile. Anthropometry, body composition and Griffith's developmental scores (DQs) were assessed before therapy and after 12 months. DQs were not related to infants' weight, lean mass or genetic background. DQs improved significantly with chronological age and were best in the most recently diagnosed group. Improved psychomotor development, mainly due to progress in locomotor development, did not differ between GH and CoQ(10) treated groups. In conclusion, while only GH has significant effects on growth and body composition, GH and CoQ(10) therapy act equally on psychomotor development of PWS infants. However, improving psychomotor development may merely reflect an age-related phenomenon additionally depending on early diagnosis and introduction of appropriate care.

Topics: Developmental Disabilities; Genotype; Growth Hormone; Humans; Infant; Longitudinal Studies; Phenotype; Prader-Willi Syndrome; Retrospective Studies; Sex Factors; Ubiquinone

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial respiratory chain and an important scavenger of reactive oxygen species. Low levels are found in individuals with reduced energy expenditure, cardiac and skeletal muscle dysfunction, and mitochondrial disorders, many of these manifestations are seen in individuals with Prader-Willi syndrome (PWS). In addition, CoQ10 supplementation frequently is given to individuals with this syndrome. To determine if CoQ10 levels are decreased in PWS, we studied plasma CoQ10 levels in 16 subjects with PWS, 13 with obesity of unknown cause, and 15 subjects without obesity but of similar age and compared with body composition. Plasma CoQ10 levels were significantly decreased (P < 0.05), using several statistical approaches in subjects with PWS (0.45 +/- 0.16 microg/ml), compared to subjects without obesity (0.93 +/- 0.56 microg/ml), but not different from subjects with obesity (0.73 +/- 0.53 microg/ml). When plasma CoQ10 was normalized relative to cholesterol, triglyceride, and creatinine levels and fat and lean mass [determined by dual energy X-ray absorptiometry (DEXA)] in the subjects with either PWS or obesity, no significant differences were observed. However, a lower muscle mass was found in the PWS subjects.

Topics: Adolescent; Adult; Body Constitution; Coenzymes; Female; Humans; Male; Obesity; Prader-Willi Syndrome; Ubiquinone