Editorial comment: Folic acid therapy in the fragile X syndrome

The nature extent of the special roles of folates in the nervous system remains controversial (Erbe, 1979). In the classic studies of Herbert (1962), amnesia and insomnia developed during the fourth month of a folate-deficient diet and progressive irritability appeared in the fifth month. These were reversed two days after giving folates. No evidence has been presented to suggest that the patients with fragile X syndrome are folate deficient although few data have been published. There is evidence that the pathways of folic acid metabolism are intact (Wang and Erbe, 1983; Branda et al, 1983; Popovich et al, 1980). Objective measures of the effects of giving folate supplementation to nondeficient individuals are essentially limited to increased quantities of folates in urine (Boss et al, 1980). No assays for beneficial effects of folic acid doses over and above the dose needed to prevent deficiency have been identified, this being an almost uncharted area for the water-soluble vitamins in general. Correspondingly it is not completely established that giving high doses of folic acid is safe at least for patients with seizures and other neurologic abnormalities (Ch'ien et al, 1975).