WASHINGTON- Scientists from the National Institutes of Health have announced the discovery of a basic metabolic defect which could explain the development of spina bifida and other neural tube defects.

A study of 81 Irish mothers of children with neural tube defects revealed significantly higher blood levels of homocysteine during pregnancy than seen in 323 mothers of normal children. The excess of homocysteine appears to result from inefficient conversion of methionine.

Previous studies have demonstrated conclusively that women who take folic acid near the time of conception greatly reduce their chances of bearing children with neural tube defects. Related studies have also shown that women with lower than normal blood levels of folate and B12 are more likely to bear children with neural tube defects.

However, many mothers of children with neural tube defects have normal B12 and folate levels during pregnancy. This suggests the presence of a metabolic abnormality rather than a simple vitamin deficiency might be involved in the development of such birth defects, the researchers note.

Homocysteine is a sulfur-containing amino acid produced by demethylation of methionine, an amino acid essential for dietary metabolism. The researchers tested homocysteine levels because conversion of this protein to methionine via methionine synthase is the only reaction in the human body that requires both folate and B12. The researchers also measured methylmalonic acid levels to rule out any generalized B12 abnormalities.

The researchers believe a defect in the enzyme methionine synthase may produce the increase in homocysteine levels and the subsequent neural tube defects. Methionine synthase is a key enzyme in the production of the myelin sheath which surrounds the neural tube.

The observation of lower than normal B12 levels seen in correlation with high homocysteine levels in mothers of babies with neural tube defects appears to support this hypothesis, suggesting they had more difficulty metabolizing homocysteine than did the mothers of normal infants.

The study results suggest that women who are in the early stages of pregnancy or who are planning to conceive in the near future may require dietary supplementation with vitamin B12 as well as folic acid in order to reduce the risk of neural tube defects. World health authorities which are now considering guidelines for fortification of food products with folic acid may now have to factor B12 into the discussion. The current study suggests that adding B12 to food could decrease the dose of folic acid required.

This study appeared in The Lancet, v. 345, 1/21/95, 149-151 (Mills et al.)

Science Updates Index

What's News Index

Feedback