Neural tube defects and a disturbed folate dependent homocysteine metabolism

Folate administration; substantially reduces the risk on neural tube defect s (NTD). The interest for a disturbed homocysteine (Hcy) metabolism in rela tion to NTD was raised by the observation of elevated blood Hey levels in m others of a NTD child. This observation resulted in the examination of enzy mes involved in the folate dependent Hey metabolism. This leads to the iden tification of the first and likely a second genetic risk factor for NTD. Th e C677T and A1298C mutations in the methylenetetrahydrofolate reductase (MT HFR) gene are associated with an increased risk of NTD and cause elevated H ey concentrations. These levels can be normalized by an additional folate i ntake. Thus, a dysfunctional MTHFR partly explains the observed elevated He y levels in women with NTD pregnancies, and also in part the protective eff ect of folate on NTD. Although, the MTHFR polymorphisms are only moderate r isk factors, population wide they may account for an important part of the observed NTD prevalence. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.