Compound Heterozygote MTHFR

What Is MTHFR?
MTHFR (5,10-methylenetetrahydrofolate reductase – what a mouthful…) is a specific gene found on a specific chromosome within every cell in every person The MTHFR gene produces an enzyme responsible for a multi-step process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.

What is a MTHFR Mutation?
An abnormal change in gene structure, called a mutation, of the MTHFR gene can cause a disruption of the MTHFR enzyme’s normal function of breaking down homocysteine.
The two common MTHFR gene mutations occur at specific locations called “positions” along the gene. The one we generally test for is located at position 677. At this location, one amino acid base pair is different, in that Cytosine is replaced by Thymine. This mutation is thus called C677T. Another mutation we test for occurs at position 1298. At this location, Adenine is replaced by Cytosine and is therefore called A1298C.

MTHFR mutations are common. The mutations can be “heterozygous” meaning they occur only on one strand or “allele” of the chromosome, or they can be “homozygous”, occurring on both alleles. The frequency of a heterozygous C677T mutation is common, occurring in about 35% of the population. The homozygous C677T mutation is about 5-10% of the population. A mutation in A1298T is more common but is generally less problematic. The homozygous variety of A1298T occurs in 9% of the population. Another mutation involves both the C677T and the A1298T alleles. This is a “compound heterozygous” condition that occurs in approximately 17% of the population.

How Does MTHFR affect Pregnancy?
If the MTHFR gene is malfunctioning, homocysteine can build up and cause problems, both in the cardiovascular system, but also with pregnancy. At this time, we’ll confine this discussion to the impact on pregnancy.

Some MTHFR mutations are more serious than others as far as their ability to cause problems during pregnancy. Specifically, women who have multiple pregnancy losses are more likely to have a MTHFR gene mutation.

The association of MTHFR and recurrent pregnancy loss is under great debate. Some clinicians and researchers feel that the mutations can cause blood clots between the developing placenta and uterine wall, thus preventing transport of vital nutrition to the developing fetus. This usually occurs early in pregnancy when the embryo or fetus is most vulnerable.

It is unlikely that the exact mechanism of how MTHFR affects pregnancy loss will be worked out in the near future. As a result, women and clinicians need to understand that there is no set “standard of care” protocol for dealing with recurrent miscarriage in the presence of a MTHFR mutation.