What Does the MTHFR Gene Mutation Cause?

There are two common MTHFR mutations, known as C677T and A1298C.

The term MTHFR stands for methylenetetrahydrofolate reductase. MTHFR is an enzyme that breaks down the amino acids' homocysteine and folate. Homocysteine is an amino acid that works to maintain the body’s cells. Folate is one of the B-vitamins needed to make red and white blood cells in the bone marrow. Folate also converts carbohydrates into energy and produces DNA and RNA. Each plays an important role in the body’s daily functions and both are important.

There are two common MTHFR mutations, known as C677T and A1298C. Having one copy of C677T or one copy of A1298C is not associated with health risks. Likewise, having two copies of A1298C is not associated with significant health risks. However, people with two copies of the C677T mutation, as well as people who have one copy of both the mutations, have increased health risks. 

Once genetically mutated, MTHFR may not be able to function normally. In turn, homocysteine levels and folate levels may be elevated or unbalanced, disturbing the body functions.

Conditions of the MTHFR gene mutation vary from person to person and from variant to variant. Conditions associated with MTHFR include

• Increased susceptibility to cardiovascular and thromboembolic diseases (blood clots, stroke, embolism, and heart attacks)
• Depression
• Anxiety
• Bipolar disorder
• Schizophrenia
• Colon cancer
• Leukemia (blood cancer)
• Severe pain and tiredness
• Nerve pain
• Migraines
• Pregnancy issues and increased miscarriages

Deficiency in MTHFR causes homocystinuria. Homocystinuria is a genetic condition that results from poor metabolism of folate (also called vitamin B9). Homocystinuria usually does not show symptoms in a newborn baby. 

If untreated, children show signs and symptoms of severe homocystinuria in infancy. Newborn screening in most states includes a screening test for homocystinuria so that newborn infants can be treated early. However, symptoms of homocystinuria due to MTHFR variants can below but may present later in childhood or in adulthood. 

Symptoms of homocystinuria due to MTHFR deficiency include

• Abnormal clotting 
• Developmental delay
• Seizures
• Intellectual disability
• Global developmental delays
• Low muscle tone 
• Seizures
• Failure to thrive (failure to grow)
• Small head size 
• Mental health problems 
• Behavior problems (e.g., attention deficit disorder and hyperactivity)
• Life expectancy will vary, depending on the severity of the deficiency. 

Treatment is typically required when a patient has very high homocysteine levels. Treatment of MTHFR gene mutation includes

• Lifestyle modifications (healthy diet, no smoking, and keeping the body physically fit)
• Vitamin B supplements (such as folic acid) are most commonly prescribed by doctors to treat MTHFR mutation 
• Multivitamins
• The doctor may suggest supplementation to address deficiencies, along with medications or treatments to address the specific health condition. Treatments for any disease caused by the MTFR mutation (e.g., for depression antidepressants) may be prescribed.

Understanding both the MTHFR mutation and genetic conditions at large is rather complicated. The MTHFR mutation does not affect everyone in the same way. Yet those with the mutation may have higher-than-normal levels of homocysteine in their blood or urine, and symptoms due to such issues may arise. 

Unless these symptoms are present, genetic testing is often discouraged. Healthcare professionals often recommend monitoring enzyme activity alongside other preventative measures. Treatment options are available for the MTHFR gene mutation. Patients with or without symptoms are advised to eat well and lead a healthy lifestyle filled with exercise, proper sleep, and other lifestyle habits that support wellbeing.