MTHFR Gene Mutation and Autism

The methylenetetrahydrofolate reductase gene, also known as MTHFR, plays a role in amino acid processing by converting homocysteine to methionine and activating folate (B9). When this gene mutates, these processes will not work as they should, which can lead to excess homocysteine in the blood. Excess homocysteine is inflammatory, increases the risk for cardiovascular diseases, and can lead to birth defects.

In this article, you will learn about the mutation of the MTHFR gene and how it is related to Autism Spectrum Disorder.

What Is Mthfr Gene Mutation?

People inherit two MTHFR genes – one gene from each biological parent. The mutation can occur in one or both genes. Mutations can happen when a cell is dividing, and the copy does not match the original.

One of the main consequences of MTHFR gene mutations is that folate cannot be activated in the body.

Active folate is critical during early pregnancy, helping the baby’s neurodevelopment. Being deficient in folate can lead to the baby having neural tube defects such as spina bifida, low or very low birth weight, and language deficits.

What Is Autism Spectrum Disorder?

The American Psychiatric Association defines Autism Spectrum Disorder (ASD) as a complex developmental condition involving persistent challenges with social communication, restricted interests, and repetitive behavior. The Diagnostic and Statistical Manual 5 includes specific criteria that must be met for someone to receive a diagnosis of Autism Spectrum Disorder.

Signs and Symptoms of Autism Spectrum Disorders

Some signs of Autism Spectrum Disorders may become apparent before the child reaches one year of age, and signs of needing additional support become more apparent by the time the child reaches two to three years of age. If the infant misses developmental milestones, further evaluations should be completed.

Some of the signs and symptoms of Autism Spectrum Disorders include:

Social communication deficits in children diagnosed with ASD such as:

• Delayed language development
• Challenges understanding and using nonverbal cues
• Aversion to maintaining eye contact
• Stilted or scripted speech
• Difficulty making and keeping friends

Restricted interests and repetitive behaviors like:

• Extreme difficulty coping with change
• Sensory hypersensitivity, such as an aversion to loud noises
• Arranging things in a particular manner.

The severity and combination of signs and symptoms vary widely among children with Autism Spectrum Disorders. Early identification and intervention are critical to provide appropriate support and therapies for each child’s unique needs.

Why Is Folate Important?

Folate, also known as Vitamin B9, is responsible for many critical functions, including:

• Cell division
• DNA synthesis
• Produce proteins
• Red blood cell production
• Assist with tissue growth and repair

Active folate metabolization is critical in methylation, a chemical process that adds a methyl group to other molecules. The body’s methylation process is negatively affected when one or both MTHFR genes are mutated.

Folic acid is the synthetic form of Folate. The current research is unclear about whether folic acid should be avoided in those with an MTHFR mutation.

How Are MTHFR and Autism Spectrum Disorder Linked?

While there is a strong link between MTHFR gene mutations and Autism Spectrum Disorder, it is still being researched.

Some studies have suggested a potential association between specific variants of the MTHFR gene and an increased risk of Autism Spectrum Disorder. The MTHFR gene variants involved, notably the C677T and A1298C variants, may impact how efficiently the MTHFR enzyme works, affecting folate metabolism and methylation processes.

It is the disturbance in the methylation process that has been proposed as a potential contributor to neurodevelopmental disorders like ASD since methylation is critical for brain development and functioning.

Dietary and Supplement Strategies for MTHFR-Related Neurodevelopmental Disorders

Given the proposed link between MTHFR and Autism Spectrum Disorder, addressing nutritional modifications becomes crucial. A comprehensive approach involves dietary changes and targeted supplementation to support optimal methylation and neurotransmitter balance in those with Autism Spectrum Disorder.

Below are some common nutrients we supplement for our patients. It is strongly recommended that a medical professional, such as a registered dietitian specializing in working with those with MTHFR mutations, be consulted before beginning any supplementation.

Methylfolate Supplementation

Methylfolate, the active form of folate, can help those with MTHFR gene mutations. Taking the active form gives the body an adequate supply of methyl groups to complete those crucial biochemical processes discussed previously.

Vitamin B12 Supplementation

Vitamin B12, also called cobalamin, and folate work together in the methylation cycle. Ensuring sufficient levels of both vitamins is critical for proper methylation. Methylcobalamin is the active form of vitamin B12 and is the recommended B12 supplement for those with MTHFR mutations.

Betaine (Trimethylglycine) Supplementation

Betaine can serve as a methyl donor, providing methyl groups that support the methylation process. It is found in foods like beets, spinach, and whole grains. Supplementation with betaine may be beneficial for individuals with MTHFR gene mutations.

Choline-Rich Foods

Choline, like betaine, is a methyl donor. Including Choline-rich foods in the diet can support methylation processes. Foods like eggs (including the yolk), liver, and broccoli are rich in Choline.

One study showed Choline supplementation in mice with MTHFR gene mutations improved repetitive and social behaviors and anxiety.

Avoidance of Folate Antagonists

Some medications and substances can interfere with folate metabolism. Individuals with MTHFR gene mutations may need to be cautious about these factors. These factors include certain anticonvulsant drugs and excessive alcohol consumption.

Balanced Diet

A well-rounded, nutrient-dense diet that includes a variety of fruits, vegetables, lean proteins, and whole grains provides essential vitamins and minerals necessary for overall health, including neurodevelopment.

Genetic Testing and Personalized Approaches

Genetic testing can provide valuable information about an individual’s MTHFR status. Working with healthcare professionals, including genetic counselors and clinical nutritionists, can help tailor interventions based on testing results to specific genetic profiles.

If an MTHFR gene mutation is suspected in those with Autism Spectrum Disorders, requesting a blood test for the gene mutation is appropriate. Knowing if MTHFR mutations are playing a role in the person’s ASD can assist with planning appropriate interventions.

Conclusion

A meta-analysis shows that those with Autism Spectrum Disorder have a higher frequency of the MTHFR C677T mutations. An appropriate nutrition plan and supplementation may help relieve some signs and symptoms for those with ASD. It is critical to work with a registered dietitian specializing in MTHFR mutations and ASD to ensure an appropriate plan is developed.