Folate metabolism in humans

Several lines of evidence have linked folate metabolism to the expression of the fragile site at Xq27. Sutherland (1979) observed that expression of this marker depends on the composition of the culture medium and that deficiency of the folic acid and thymidine promotes expression of the fragile site in lymphocytes, as does the addition of methotrexate. Several investigators (Glover, 1981; Tommerup et al, 1981) independently showed that expression of the fragile site can be elicited by adding 5-fluorodeoxyuridine, an inhibitor of thymidylate synthase to culture medium containing folic acid but not thymidine. Indeed, Lejeune (1981) has claimed successful treatment of males with fragile X syndrome, the administration of folic acid and folinic acid (5-formyltetrahydrofolate) leading to decreased expression of the Xq27 fragile site and greatly reduced aggressiveness. These and other studies have stimulated persons of diverse backgrounds to confront complicated aspects of folate metabolism. The information that follows is intended to facilitate discussion and investigation in the context of the fragile X syndrome.