Original Article A Study of the Treatment of Rett Syndrome With Folate and Betaine

We tested the hypothesis that increasing methyl-group pools might promote transcriptional repression by other methyl-binding proteins or by mutant methyl-CpG-binding protein 2 with altered affinity, ameliorating the clinical features of Rett syndrome. A 12-month, double-blind, placebo-controlled folate–betaine trial enrolled 73 methyl-CpG-binding protein 2 mutation positive female participants meeting consensus criteria for Rett syndrome. Participants were randomized as young (< age 5 years) or old ( age 5 years). Structured clinical assessments occurred at baseline, 3, 6, and 12 months. Primary outcome measures included quantitative evaluation of breathing and hand movements during wakefulness, growth, anthropometry, motor/behavioral function, and qualitative evaluations from electroencephalo-grams and parent questionnaires. In all, 68 participants completed the study. Objective evidence of improvement was not found. Subjective improvement from parent question-naires was noted for the <5 years group. This study should inform future treatment trials regarding balancing participants with specific mutations and comparable severity to minimize selection bias