Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that breaks down the amino acid homocysteine. The MTHFR gene that codes for this enzyme has the potential to mutate, which can either interfere with the enzyme’s ability to function normally or completely inactivate it.
People have two MTHFR genes, inheriting one from each of their parents. Mutations can affect one (heterozygous) or both (homozygous) of these genes.
There are two common types, or variants, of MTHFR mutations: C677T and A1298C.
These gene mutations are relatively common. In fact, in the United States, around 25% of people of Hispanic descent and 10–15% of people of Caucasian descent have two copies of C677T.
The mutations can lead to high levels of homocysteine in the blood, which may contribute to several health conditions, including:
This article looks at MTHFR mutations in more detail, including related health conditions, diagnosis, and treatment options. It also discusses how MTHFR mutations can affect pregnancy.
Mutations in the MTHFR gene can affect the body’s ability to process amino acids — namely, homocysteine — which can lead to some adverse health outcomes.
Conditions that researchers have associated with MTHFR gene mutations include:
- homocysteinemia, which is the term for abnormally high levels of homocysteine in the blood or urine
- ataxia, which is a neurological condition that affects coordination
- peripheral neuropathy, which is a neurological condition that damages the nerves
- microcephaly, which is a condition present at birth in which the head is smaller than usual
- scoliosis, which refers to an abnormal curvature of the spine
- anemia, which means that there is a lack of healthy red blood cells in the body
- cardiovascular diseases, such as blood clots, stroke, and heart attack
- mental health conditions, such as depression
- behavior disorders, such as attention deficit hyperactivity disorder
Symptoms vary among individuals and depend on the type of mutation they have. People usually do not know that they have an MTHFR mutation unless they experience severe symptoms or undergo genetic testing.
Having one or two MTHFR mutations can slightly increase the levels of homocysteine present in the blood. This condition is called homocysteinemia.
Homocysteine is an amino acid that the body produces by breaking down dietary proteins. Having high levels of homocysteine can damage blood vessels and lead to blood clots. People who have high homocysteine levels tend to have low levels of vitamin B12.
Complications associated with having homocysteinemia due to MTHFR mutations include:
- abnormal blood clotting
- developmental delays
- blood clots
- poor coordination
- numbness or tingling in the hands and feet
A doctor can determine whether or not a person has an MTHFR variant by reviewing their medical history, considering their current symptoms, and performing a physical examination. The doctor may recommend running a blood test to check the person’s homocysteine levels.
Although it is possible to identify an MTHFR gene mutation through genetic testing, organizations such as the American Heart Association (AHA) recommend against screening for common MTHFR gene variants in regards to cardiovascular risk.
This is because the common gene mutations alone, without other symptoms, are not considered major risk factors for heart disease, and the results of testing have little impact on medical management.
MTHFR mutations will not change a person’s treatment plan for any other condition they happen to have. If a person with an MTHFR mutation has a blood clot, for example, they will usually receive the same treatment for the blood clot as someone who does not have this type of mutation.
Researchers have conducted multiple studies to determine the relationship between this type of mutation and pregnancy complications, but the data have been insufficient in their conclusions.
Existing research has not shown that attempting to intervene in an MTHFR mutation would change the outcome of a pregnancy. For this reason, current guidelines from multiple sources state not to routinely screen for this mutation.
People inherit one copy of the MTHFR gene from each of their parents, which means that everyone has two MTHFR genes. Mutations can occur in one or both of these genes.
Having a parent or close relative with an MTHFR gene mutation can increase a person’s risk of inheriting the same variant themselves.
People who have two parents with a mutation have an increased risk of having a homozygous MTHFR mutation.
A person should contact a doctor if they experience any symptoms of a folate or vitamin B12 deficiency, which may include:
- shortness of breath
- a loss of appetite or unintentional weight loss
- muscle weakness
- numbness, tingling, or pain in the hands or feet
- dizziness or a loss of balance
- mouth sores
- mood changes
A person should also contact a doctor if they experience any symptoms of anemia, which may include:
- shortness of breath
- an irregular heartbeat
MTHFR mutations do not affect everyone in the same way. People who have one or more MTHFR variants may have higher-than-normal levels of homocysteine in their blood or urine.
Although existing research has identified associations between MTHFR variants and numerous health conditions, more research is necessary to determine the exact effects of these gene mutations on health.
People can speak with a doctor about the benefits and risks of genetic testing. However, most health organizations do not recommend genetic testing unless a person experiences significant health effects.