Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial.

OBJECTIVES: To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down's syndrome. DESIGN: Randomised controlled trial with two by two factorial design. SETTING: Children living in the Midlands, Greater London, and the south west of England. PARTICIPANTS: 156 infants aged under 7 months with trisomy 21. INTERVENTION: Daily oral supplementation with antioxidants (selenium 10 mug, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo. MAIN OUTCOME MEASURES: Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months. RESULTS: Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval -2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, -1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results. CONCLUSIONS: This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down's syndrome. TRIAL REGISTRATION: Clinical trials NCT00378456.

Developmental patterns and neuropsychological assessment in patients with carbohydrate-deficient glycoconjugate syndrome type IA (phosphomannomutase deficiency).

Carbohydrate-deficient glycoconjugate (CDG) syndrome type I due to phosphomannomutase deficiency (CDGIA) is the most common among a group of metabolic disorders characterized by a defective glycosylation of glycoconjugates. Clinically it is a multisystem disease with an important involvement of the central nervous system including pontocerebellar atrophy. Here the developmental patterns and results of neuropsychological assessment of four young adults with CDGIA syndrome are reported. The patients, aged 14-26 years, had classical clinical findings of CDGIA syndrome and olivopontocerebellar atrophy of severe degree. They had a marked delay in all areas of psychomotor development and gained to walk with aid, perform manipulative abilities and develop a communicative language after the 7th year. Later on, the acquired abilities remained stable, while self-help skills gradually improved, allowing the patients to join the family life. On neuropsychological assessment, there was mental retardation of variable degree with a special impairment of visuoperceptual skills, visuospatial organization, eye-hand coordination, verbal memory and language. Such findings, may be partially explained by the supratentorial atrophy in our patients and add more evidences to the role of the cerebellum and brainstem in the acquisition of non-motor cognitive functions. This study expands our understanding on the clinical spectrum of CDGIA syndrome and may be helpful for planning rehabilitation and education.