Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status.

BACKGROUND: Seven genes involved in folate metabolism are located on chromosome 21. Previous studies have shown that folate deficiency may contribute to mental retardation in Down's syndrome (DS). METHODOLOGY: We investigated the effect of oral folate supplementation (daily dose of 1.0+/-0.3 mg/kg) on cognitive functions in DS children, aged from 3 to 30 months. They received 1 mg/kg leucovorin or placebo daily, for 12 months, in a single-centre, randomised, double-blind study. Folinic acid (leucovorin, LV) was preferred to folic acid as its bioavailability is higher. The developmental age (DA) of the patients was assessed on the Brunet-Lezine scale, from baseline to the end of treatment. RESULTS: The intent-to-treat analysis (113 patients) did not show a positive effect of leucovorin treatment. However, it identified important factors influencing treatment effect, such as age, sex, and concomitant treatments, including thyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period. This analysis of 87 patients (43 LV-treated vs. 44 patients on placebo) revealed a positive effect of leucovorin on developmental age (DA). DA was 53.1% the normal value with leucovorin and only 44.1% with placebo (p<0.05). This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment (59.5% vs. 41.8%, p<0.05). No adverse event related to leucovorin was observed. CONCLUSION: These results suggest that leucovorin improves the psychomotor development of children with Down's syndrome, at least in some subgroups of the DS population, particularly those on thyroxin treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00294593.

Laterality in persons with intellectual disability. I--do patients with trisomy 21 and Williams-Beuren syndrome differ from typically developing persons?

Persons with trisomy 21 (T21) and Williams-Beuren syndrome (WBS) have different brain abnormalities which may affect manual laterality. We assessed 45 persons with T21 and 34 with WBS (mean age 13) and 81 typically developing children (TD). Manual laterality was assessed with a fifteen-item task administered two times, and Bishop's card-reaching task. We found more left-handers in the T21 group compared to the other two groups. Inconsistent laterality was higher in the two groups with genetic diseases than in the TD group. For Bishop's test, both T21 and WBS participants were less right-oriented than the TD group. They displayed different response patterns in midline crossing when reaching for the cards, but did not display more midline crossing inhibition than the TD group. Is atypical handedness linked to specific genetic syndromes and, more specifically for persons with T21, to the trisomy of some of the genes?