Methylenetetrahydrofolate reductase, or 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 mutation: C677T and A1298C.
These mutations in rare occasions lead to high levels of homocysteine in the blood, which may contribute to numerous health conditions, such as:
In this article, we look at MTHFR mutations in more detail, including related health conditions, diagnosis, and treatment options. We also discuss 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 adverse health outcomes.
Conditions that researchers have associated with MTHFR gene mutations include:
- homocystinemia, which is the term for abnormally high levels of homocysteine in the blood or urine
- ataxia, a neurological condition that affects coordination
- peripheral neuropathy, a neurological condition that damages the nerves
- microcephaly, a condition present at birth in which the head is smaller than usual
- scoliosis, an abnormal curvature of the spine
- anemia, which means that a person has a lack of healthy red blood cells
- cardiovascular diseases, such as blood clots, strokes, and heart attacks
- mental health and behavior disorders, such as depression and attention deficit hyperactivity disorder (ADHD)
Symptoms vary both among individuals and depending on the type of mutation. 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 homocystinemia.
Homocysteine is an amino acid that the body produces by breaking down dietary proteins. 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 B-12.
Symptoms of homocystinemia 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 a person has an MTHFR variant by reviewing their medical history, considering their current symptoms, and performing a physical examination. A doctor may recommend running a blood test to check a person’s homocysteine levels.
Although it is possible to identify an MTHFR gene mutation through genetic testing, organizations such as the American Heart Association 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 factor for heart disease, and results of testing have little impact on medical management.
Medical treatment is not always necessary for MTHFR variants. Dietary and lifestyle changes can often help offset any resulting nutritional deficiencies.
However, people may require medical treatment if they have high homocysteine levels. A doctor may suggest that people with elevated homocysteine levels take the following supplements:
- folic acid
- vitamins B-6 and B-12
- 5-methyltetrahydrofolate (5-MTHF)
It is important to speak with a doctor before starting any of these supplements. There are different causes of elevated homocysteine and the treatment may differ for each cause.
Women who test positive for an MTHFR mutation may have an increased risk of preeclampsia, blood clots, recurrent miscarriages, or giving birth to a baby with congenital disabilities. Multiple studies have been done to determine relationship between the mutation and pregnancy complications, but the data is insufficient in their conclusions.
Current research has not shown that attempting to intervene on the MTHFR mutation would change the outcome of the pregnancy. Thus, current guidelines from multiple sources state to not routinely screen for the 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 genes.
Having a parent or close relative with an MTHFR gene mutation can increase a person’s risk of inheriting the same variant.
People who have two parents with mutations have an increased risk of having a homozygous MTHFR mutation.
A person should see a doctor if they experience symptoms of a folate or vitamin B-12 deficiency, which may include:
- shortness of breath
- loss of appetite or unintentional weight loss
- muscle weakness
- numbness, tingling, or pain in the hands or feet
- dizziness or loss of balance
- mouth sores
- mood changes
A person should also see a doctor if they experience symptoms of anemia, which may include:
- shortness of breath
- irregular heartbeat
Having an MTHFR mutation does 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 current 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 their 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.