MTHFR Gene Mutation Symptoms and Treatment

Methylenetetrahydrofolate reductase is a gene that makes a protein (enzyme). The function of the enzyme activity is associated with the processing of amino acids (such as plasma homocysteine) that are the building blocks of proteins. So, let’s get into that a bit more.

Methylenetetrahydrofolate reductase (MTHFR) is one of the many enzymes that our body produces. Enzymes are molecules that are catalysis or reaction starters. Very broadly speaking, the molecules that interact with enzymes are called substrates and, depending on what the enzyme does to the substrate, the final outcome is called a product. What does this mean for MTHFR enzyme? Specifically, it is involved in a chemical reaction that encompasses the conversion of the vitamin folate (you may have heard of it as being called B9). Even more specifically, it converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate (5-MTHF) (this is a longish chemical reaction that results in a conversion that we will spare you). The latter molecule is more commonly known as folic acid or simply folate. This 5-MTHF, or folic acid, subsequently reacts with vitamin B12 to convert the amino acid homocysteine to methionine. (Note that this process involves a donation of a CH3 or a methyl group in the process of homocysteine converting into methionine, a procedure that is one of the most common and vital in many body processes.) Ultimately, the body takes the methionine and uses it for several other crucial processes in the body.

To summarize, the MTHFR gene provides the code for a set of instructions to make the MTHFR enzyme that ensures the body has enough of the amino acid methionine. And why, you may wonder, is this so important?

Well, as it turns out, methionine is a big deal. It is one of the nine essential amino acids (that we get from nutrition) that the body needs for proper functioning. In fact, it is vital for growth and tissue repair. For example, it is involved in enhancing the pliability of skin and hair and strengthens nails. Furthermore, the sulfur that the methionine provides is very useful for protecting cells from external damaging factors such as pollutants. It also slows the aging process of cells as well as helps with the uptake of selenium and zinc. It also ensures no excess fat builds up in the liver.

However, as beneficial as methionine is for the body, too much of a good thing isn’t good, either. Excess amounts of the amino acid have been found in association with an increased risk for heart disease. It has also been found to worsen psychopathological effects in schizophrenic individuals. Ultimately, it has also been speculated that an excess of the amino acid can be lethal.


So, too little methionine is not good, but too much of it is also bad. This just means that it a regulatory mechanism that ensures the maintenance of an ideal concentration of methionine is important. Hopefully, you can see how mutations in the gene can cause dysfunctional MTHFR proteins (enzymes) that are eventually unable to be effective key players in the aforementioned conversion reaction that ultimately results in appropriate methionine concentrations that are needed for proper functioning.

In fact, individuals with MTHFR mutations have been diagnosed with an array of conditions. These include homocystinuria (body’s lack of ability to process the homocysteine and methionine properly with associated symptoms such as abnormal blood clotting, cognitive impairment as well as skeletal abnormalities), age-related hearing loss, alopecia areata (spot baldness), anencephaly (defects that take place during brain and spinal cord development), spina bifida (another kind of spinal cord development issue), and a number of other disorders. The list of symptoms is really long, and it includes anxiety, bipolar disorder, depression, certain types of cancer, chronic pain, fatigue, and recurrent miscarriages in women of childbearing age to name but a few.

While there are several gene variations that have been found to be somehow related to MTHFR-related issues, there are two specific mutations that have been used for genetic testing. These are C677T and A1298C. The letters here refer to the nucleic acids that are affected. In other words, at location 677 of the DNA sequence, instead of a cysteine, there is a threonine. The same for location 1298—there is an adenine instead of a cysteine.

Overall, there are several symptoms and conditions that are specific to MTHFR genetic mutation, which is why physicians must take great care to make sure a proper diagnosis is given. A very sure indication of a MTHFR mutation-related condition is high levels of homocysteine. Treatments to ameliorate the condition include supplementation of the vitamin deficiencies (folate, choline, vitamins B12, B6, or riboflavin). These, of course, would be in addition to the other specific health conditions that have been observed.

By now, the role of methionine is probably becoming even more apparent. You are probably also thinking you should be making sure that you have enough folic acid. And this is true. If in any doubt, make sure you get your genes checked out and, just to be extra sure, make sure you get enough folic acid to keep those methionine levels from getting out of control.

Laura Day