MTHFR and Its Role in Homocysteine

C. Matheson, RHIA, CCS HIM Leave a Comment

MTHFR and Its Role in Homocysteine

MTHFR. Sounds almost rude, doesn’t it? However, it is NOT something for which your mother would threaten to wash your mouth out with soap, I promise. MTHFR stands for methylenetetrahydrofolate reductase – so obviously, using the abbreviation is easier than saying that mouthful every time.

What, exactly, IS MTHFR? It’s a genetic mutation affecting approximately 30% of the world’s population. The mutation affects how the body turns vitamins B-12 and B-9 into more usable forms. These usable forms of B-12 and B-9 make glutathione, which is a major antioxidant; without it, manifestations of abnormal DNA occur more often, meaning you wouldn’t have an effective way to use the antioxidant your body. You’d be more likely to develop diseases like heart disease, cancer, and diabetes along with other diseases that plagued your ancestors. See Chart A.

B-12 and B-9 considered part of “B-complex vitamins which help the body in a number of ways, including:

• Converting carbs into fuel (glucose), which in turn, produces energy;
• Proper use of fats and protein;
• Contributing to healthy liver, skin, hair, and eyes; and
• Aiding the nervous system’s proper functioning.

While words like “genetic mutation” usually conjure up bad thoughts, there are some “good” genetic mutations, like those that protect a person from heart disease. While MTHFR, it’s not a “good” mutation, it’s not as bad as others. This  mutation can lead to high levels of homocysteine in the blood (homocystinemia) and/or urine (homocystinuria), and can affect your B-12 and folate levels.

Homocysteine is an amino acid that interacts with B vitamins to create amino acids and antioxidants that synthesize proteins and reduce inflammation. It can also increase liver health among other things.

Gene mutations are inherited from your parents at the time of conception. Your risk of having a homozygous mutation is higher if both parents have mutations of the MTHFR gene. There are two specific variants associated with the MTHFR gene. You can have either one, both, or neither of these variants. Having one genetic variant is termed heterozygous, and in the case of MTHFR, it is less likely to contribute to health problems. Having two variants is termed homozygous, and it is believed this causes more serious health issues.

The specific MTHFR gene variants are:

C677T – About 30 – 40% of the American population may have this mutation. Approximately 25% of people of Hispanic descent and 10 -15% of Caucasians have this variant.

A1298C – Though research of this variant is limited; existing studies are, more often than not, geographical or ethnic-based.

• It is possible to have both MTHFR variants.

Having an MTHFR variant does not automatically mean you will develop
homocystinemia or homocystinuria. If you do exhibit high homocysteine levels, all you may need is a vitamin B supplement. However, you will likely need treatment if you have very high homocysteine levels. Your physician will work with you to determine if you need further examination/testing and treatment. Chart B shows potential causes of high homocysteine levels.

Research concerning homocysteine and it’s relationship to the MTHFR gene is still evolving. Physicians are recognizing it’s importance and ICD-10-CM has codes related to these conditions. CPT also has codes for testing needed to identify homocysteine levels as well as homocystinemia/homocystinuria. See the Coding Reference Chart for specific code numbers that can be assigned when appropriate.

To learn more about ICD-10-CM codes that one lab uses to identify medical necessity for homocysteine testing, see the link under the “Of Interest” section below.

There is also a link for a sample clinical policy for homocysteine testing used by a managed care company.

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Example: ICD-10 Codes That Meet Medical Necessity for Homocysteine Testing


Methylenetetrahydrofolate reductase (MTHFR) is a genetic mutation that can lead to abnormal homocysteine levels which can be caused by a variety of reasons, including deficiencies of some of the vitamins included under the category of B-complex vitamins. This blogs delves into MTHFR mutations as well as causes of high homocysteine levels and associated conditions. It also looks at both ICD-10-CM and CPT codes that can be used when coding the conditions.

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