MTHFR and isolated spina bifida: Although the functional consequences of the 5,10-MTHFR A1298C variant are not well known, it is a risk factor for neural tube defects,26,27 and compound heterozygosity (5,10-MTHFR 677CT/1298AC) has been reported to have a biochemical profile similar to that of 677TT homozygosity.1,28