By Jamie Eske

Reviewed by Shilpa Amin MD, CAQ, FAAFP

Methylenetetrahydrofolate reductase, or MTHFR, is an enzyme that breaks down the amino acids homocysteine and folate. 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.

Mutations in MTHFR genes occur in approximately 25% of people of Hispanic descent and 10–15%of people of European descent.

These mutations often lead to high levels of homocysteine in the blood, which can contribute to numerous health conditions, such as:

• birth abnormalities
• cardiovascular disease
• glaucoma
• mental health disorders
• certain types of cancer

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.

Conditions linked with MTHFR mutation

Mutations in the MTHFR gene can affect the body’s ability to process amino acids — namely homocysteine and folate — which can lead to adverse health outcomes.

Conditions that researchers have associated with MTHFR gene mutations include:

• homocystinuria, 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)

Possible signs and symptoms

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 or urine. This condition is called homocystinuria.

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 homocystinuria due to MTHFR mutations include:

• abnormal blood clotting
• developmental delays
• seizures
• microcephaly
• blood clots
• poor coordination
• numbness or tingling in the hands and feet

Learn more about homocystinuria here.

Diagnosis

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 and the American Congress of Obstetricians and Gynecologists recommend against screening for common MTHFR gene variants.

Treatment options for related health issues

Folic acid may help people with elevated homocysteine levels.

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
• methionine
• 5-methyltetrahydrofolate (5-MTHF)