coenzyme-q10 and Developmental-Disabilities

Coenzyme Q(10) (CoQ(10)) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ(10) is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ(10) supplementation. CoQ(10) deficiency has been associated with five major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy, and (5) nephrotic syndrome. In a few patients, pathogenic mutations have been identified in genes involved in the biosynthesis of CoQ(10) (primary CoQ(10) deficiencies) or in genes not directly related to CoQ(10) biosynthesis (secondary CoQ(10) deficiencies). Respiratory chain defects, ROS production, and apoptosis contribute to the pathogenesis of primary CoQ(10) deficiencies. In vitro and in vivo studies are necessary to further understand the pathogenesis of the disease and to develop more effective therapies.

Topics: Atrophy; Cerebellum; Child; Chromosome Aberrations; Developmental Disabilities; Disease Progression; DNA Mutational Analysis; Genes, Recessive; Humans; Infant, Newborn; Kidney Diseases; Kidney Glomerulus; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Spinocerebellar Degenerations; 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

The authors measured coenzyme Q10 (CoQ10) concentration in muscle biopsies from 135 patients with genetically undefined cerebellar ataxia. Thirteen patients with childhood-onset ataxia and cerebellar atrophy had markedly decreased levels of CoQ10. Associated symptoms included seizures, developmental delay, mental retardation, and pyramidal signs. These findings confirm the existence of an ataxic presentation of CoQ10 deficiency, which may be responsive to CoQ10 supplementation.

Topics: Adolescent; Adult; Cerebellar Ataxia; Cerebellum; Child; Coenzymes; Developmental Disabilities; Dietary Supplements; Disease Progression; Electromyography; Electron Transport; Female; Humans; Magnetic Resonance Imaging; Male; Mitochondria; Muscle Hypotonia; Muscle, Skeletal; Seizures; Ubiquinone