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Traditionally known as "The Curse of the Celts," Neural Tube Defects (NTDs) are at least twice as common in people of Celtic ancestry. So it is fitting that this "curse" should now be lifted by the Irish scientists at Trinity College Dublin and the Health Research Board, in co-operation with the National Institute of Child Health and Human Development in Washington DC, which has granted the Irish scientists $600,000 in the past three years.

They found the first piece of the jigsaw when they learned that the risk to the foetus of developing a NTD varied eightfold, depending on how rich its mothers diet is in folate. A woman with a folic acid level of 400ug per litre has a risk of 0.8 per 1,000 of having a baby with an NTD. But reduce her status to 150ug - still within the normal range - and her risk will magnify to 6.0 per 1,000.

Diet was clearly significant, but folate levels alone did not explain the whole story. There had to be a genetic link, especially considering that NTDs are more common in some gene pools than others, regardless of folic acid levels.

The next piece of the jigsaw was the discovery that Irish women who subsequently gave birth to children with NTDs had abnormally high levels of homocysteine, a metabolite. This implicated any one of three possible enzymes, one of which was 5, 10-methylenetetra-hydrofolate reductase. When Prof. Steve Whitehead did a genetic analysis for reductase in people with spina bifida and compared them with a control group , he found that abnormal reductase accounts for 13 percent of spina bifida.

The link is so convincing that mutations concerning this enzyme or one of the other two identified are almost certain to be responsible for another 60 percent of cases, in all accounting for three-quarters of NTDs, says Prof. Scott from the Trinity team.

The significance to the developing embryo of the discovery of the role of reductase is this: the enzyme needs folic acid to make DNA, and if the embryo cannot make DNA rapidly enough at the proper rate, it cannot divide cells fast enough. The genetic mutation in the enzyme prevents the embryo metabolising folic acid normally, giving them a higher-than-normal requirement of folic acid in order to maintain adequate levels of cell division.

If the foetus which inherits this defect gets a massive injection of folic acid from its mothers bloodstream, it will probably be normal, but if it does not, it is likely to have a neural tube defect.

The astonishing rapidity with which this cell division happens is crucial to the story. It takes the neural tube only four days to close, and without sufficient folate the cells cannot divide rapidly enough and the neural tube remains open. The extent of the opening can vary from slight and insignificant to profound and fatal. Some people with NTDs are not diagnosed until they receive spinal X-rays in adulthood, while others are so badly affected that they die soon after birth.

This information is critical for any woman who is thinking about becoming pregnant, because NTDs occur during a critical window of development between the 24th and 28th day of gestation - before many women even know that they have conceived.

Six percent of people inherit the genetic mutation which prevents them from metabolising folic acid properly and therefore puts them at risk of NTDs. So why are most of these not born with NTDs? A foetus which has this problem metabolising folic acid will be able to close its spinal column during the crucial four-day opportunity to do so - if it gets huge boosts of the micronutrient from its mother's bloodstream.

This is where supplementation comes in. While screening for the genetic defect is a possibility, it may be more practical simply to fortify all women's diets with folic acid, not just those at risk.

Prof. Scott predicts the government, including our own, will decide to fortify flour and bread with folic acid in an effort to prevent NTDs. Breakfast cereals are already fortified and some milks are as well.

The best advice is for any woman who could become pregnant - whether she is planning to or not - is to take 400 mcg of folic acid per day throughout her child-bearing years, either as a supplement or in fortified foods.

Another significant finding of the research is that fathers are almost as important as mothers in NTDs. In order to inherit a strong risk of spina bifida, the foetus must have two parents with the genetic defect.

In everybody's genes there are two copies of a piece of genetic information. Those two bits are read off and give a message to make a protein, which is an enzyme - in this case reductase.

If you are normal, you have two normal copies. If you are heterozygote, you have one abnormal and one normal copy, and if you are homozygote you have two abnormal copies of the enzyme.

In order to inherit the defect the foetus needs to be homozygote - in other words it needs two copies of the faulty message, one from the mother and one from the father.

The Trinity team's breakthrough will eventually result in the identification of the other genes involved in the so-called folate responsive NTDs, says Prof. Scott. Since these account for 75 percent of all cases, most NTDs will soon be avoided.