Folate, homocysteine and neural tube defects: An overview

Folate administration substantially reduces the risk on neural tube defects (NTD), The interest for studying a disturbed homocysteine (Hcy) metabolism in relation to NTD was raised by the observation of elevated blood Hey lev els in mothers of a NTD child. This observation resulted in the examination of enzymes involved in the folate-dependent Hey metabolism Thus far, this has led to the identification of the first and likely a second genetic risk factor for NTD. The C677T and A1298C mutations in the methylenetetrahydrof olate reductase (MTHFR) gene are associated with an increased risk of NTD a nd cause elevated Hey concentrations. These levels can be normalized by add itional folate intake. Thus, a dysfunctional MTHFR partly explains the obse rved elevated Hey levels in women with NTD pregnancies and also! in part, t he protective effect of folate on NTD, Although the MTHFR polymorphisms are only moderate risk factors, population-wide they may account for an import ant part of the observed NTD prevalence.