Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects?

Vitamin levels were measured in twenty women under 35 years of age with a history of two or more neural tube defect pregnancies. Each index case was compared with a female control matched for age, obstetric history and social class. The mean concentration of red cell folate in the subjects was 178 ng/ml, significantly lower than the mean of 268 ng/ml for the control group (P = 0.005). Red cell folate levels showed a linear relationship with the number of neural tube defect pregnancies, the levels being lowest in women who had had three or four affected offspring. There was no significant difference in serum folate; plasma or white cell vitamin C; plasma vitamin A; thiamine, riboflavine or pyridoxine status; serum vitamin B12; plasma vitamin E; total protein, albumin, transferrin, magnesium, copper or zinc. Diet was assessed by a questionnaire. The dietary intakes of total folate and other vitamins except vitamin A were lower in the subjects than the controls but none of the differences were statistically significant. Regression analysis showed a difference between subjects and controls in the relationship of red cell folate to dietary folate. This study demonstrates an association between susceptibility to offspring with neural tube defects and depressed red cell folate levels which cannot be entirely attributed to a lower dietary intake of folate. It is postulated that one factor predisposing to the occurrence of neural tube defects may be an inherited disorder of folate metabolism.