MTHFR deficiency is a mild condition associated with a slightly higher risk of neural tube defects and pregnancy loss. Roughly 40% of Americans are carriers of MTHFR deficiency, while 10% have the condition. For the vast majority, it causes no problems with their health or the health of their children. The mild MTHFR deficiency for which Counsyl tests should not be confused with severe MTHFR deficiency.
The MTHFR enzyme is involved in the conversion of the amino acid homocysteine to another amino acid, methionine. People with mild MTHFR deficiency have a decreased ability to perform this conversion, and as a result they have higher levels of homocysteine in their body and lower levels of the vitamin folate.
There are two common mutations found in the MTHFR gene, A222V and E429A (also known as C677T and A1298C respectively). Having one copy of either mutation (being a carrier) is not thought to have any impact on one’s health or that of one’s children.
The following gene combinations may be significant. Note that they are only significant if they raise the level of homocysteine in the blood, and this does not happen in everyone:
For women, two copies of the A222V mutation has been associated with a 2 to 3-fold higher risk of having a child with severe neural tube defects such as spina bifida. This type of birth defect normally affects 1 in 1,000 births, so women with two A222V mutations would face a 2 to 3 in 1,000 risk, which is still low.
Taking folate supplements has been shown to reduce neural tube defects by 75% and may be doing so by normalizing levels of homocysteine in the body.
Some studies have shown that mild MTHFR deficiency may be beneficial in lowering the risks for colorectal cancer or boosting immunity to certain pathogens. These findings are tentative, however.
This mutation pairing is thought to share the same risks as described above for the A222V/A222V mutation pairing.
This mutation pairing is NOT associated with any elevated risks for health problems.
Mild MTHFR deficiency is very common. The table below shows the results of numerous studies conducted worldwide looking at the A222V mutation. The first number represents the percentage of the population who is a carrier and the second number represents the percentage of the population thought to be affected.
|Ethnic Group||Carrier Rate||Affected Rate|
The E429A mutation is less well-studied, but is also thought to be quite common. In three studies, the A222V/E429A mutation pairing was found in 17% of Americans, 15% of Canadians, and 20% of Dutch people.
Most people with mild MTHFR deficiency require no treatment. Because food in the United States is often fortified with vitamins, most people eat sufficient amounts of folate to compensate for higher levels of homocysteine.
Pregnant women with the condition—and all pregnant women—are advised to take folate supplements (folic acid) before and during pregnancy to reduce the risk of birth defects by as much as 75 to 85%. These vitamins are particularly important for women with MTHFR deficiency.
Based on current scientific knowledge, most people with MTHFR deficiency will be totally unaffected by it. Women face a slightly elevated risk of having a child with neural tube defects, however the risk is still low.
Explanations of an extensive number of genetic diseases written for everyday people by the U.S. government's National Institutes of Health.
The nation's leading non-profit dedicated to improving the health of babies by reducing birth defects, premature birth, and infant mortality.
1275 Mamaroneck Avenue
White Plains, NY 10605
Phone: (914) 997-4488 (national office)