Common Genetic Mutations

Common genetic mutations may be one of the reasons why some children survive an overload of environmental toxicity, whereas others suffer from an array of chronic illnesses ranging from autism to asthma to juvenile diabetes. There are many contributing factors involved in this “perfect storm” of events, but more than likely, one of these factors may be the presence of one or more genetic differences.

MTHFR Mutation

MTHFR stands for methylenetetrahydrofolate reductase, which is the enzyme required for converting folic acid into its bioavailable form (5 methyltetrahydrofolate). 5MTHF then reacts with homocysteine to form methionine. This conversion is important, because if an individual is unable to complete this step of the process, he or she will not be able to get around the methylation cycle efficiently, and therefore will not produce methyl groups at a healthy rate.

Moreover, 5MTHF is a type of folate that crosses the blood brain barrier; folic acid does not. The methylation process requires the presence of 5MTHF in the brain. Not surprisingly, children on the autism spectrum have been found to have Cerebral Folate Deficiency (CFD), which means an insufficiency of folate in the brain. CFD is more than likely due in part to the MTHFR mutation, one of the common genetic mutations in children with autism.

There are two forms of the MTHFR mutation:

  • The C677T mutation is responsible for the conversion of homocysteine to methionine. Individuals with this mutation have high levels of homocysteine, which is associated with both heart disease, and with Alzheimer’s.
  • The A1298C mutation is associated with SAMe and does not result in overproduction of homocysteine. Rather, this form of the MTHFR mutation is potentially associated with the inability to convert BH2 to BH4. BH4 is required for serotonin synthesis, dopamine synthesis, and ammonia detoxification.

MTR Mutation

MTR stands for methionine synthase, which is the enzyme that converts homocysteine back to methoinine. The MTR A2756G mutation causes an up-regulation in this gene, which results in an increase in activity, rather than a decrease in activity. In this instance, the conversion of homocystiene back to methoinine requires B12. An increase in the activity of this enzyme could thus result in the depletion of B12 in susceptible individuals.

MTRR Mutation

MTRR stands for methionine synthase reductase, which is an enzyme that works in conjunction with the MTR enzyme to help with the conversion of homocysteine to methoinine by regenerating B12. The MTRR A66G mutation reduces the activity of this enzyme, resulting in even further depletion of B12 in susceptible individuals.

CBS Mutation

CBS stands for cystathionine-B synthase, which is the enzyme that converts homocysteine to cysteine. Both the C699T and the C1080T mutations cause up-regulations in the enzyme’s activity. Individuals with this mutation will therefore generate high levels of cysteine. High levels of cysteine in the body favor the conversion of cysteine to taurine and to sulfate, rather than to glutathione. Individuals with this mutation thus produce increased levels of sulfur groups, increased ammonia, and decreased glutathione.

SUOX Mutation

SUOX stands for sulfite oxidase, which works in concert with CBS to convert sulfite groups to sulfate groups, a process called sulphation. Individuals with the SUOX mutation cannot properly process sulfur-containing foods and turn the sulfites into less-toxic sulfates. Since sulphation is an important factor not only in the detoxification pathways, but also for food and environmental allergies, many people with allergy sensitivities will also carry the SUOX gene.

The SUOX pathway requires molybdenum to function properly. Individuals with CBS up regulations need to support the SUOX pathway by supplementing with molybdenum.

COMT Mutation

COMT stands for catechol O methyl transferase, which is an enzyme that uses methyl groups in order to inactivate dopamine. Individuals with COMT mutations (COMT + or COMT ++) have decreased activity at this site. These people will therefore use fewer methyl groups and inactivate dopamine less efficiently.

COMT status is extremely important when determining whether or not an individual can tolerate methyl groups. Individuals who are COMT ++ are less likely to tolerate supplementation with methyl groups (i.e., SAMe, methyl B12, etc). Individuals who are COMT –, however, most often do very well with the supplementation of methyl groups.

COMT ++ individuals will have higher dopamine levels, as they do not break down dopamine efficiently. COMT– individuals will have lower dopamine levels.

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Sources & References

Arnold, P.A., et al. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006 Jul;63(7):769-76.

Bidwell, L.C., et al. Genetic influences on ADHD symptom dimensions: Examination of a priori candidates, gene-based tests, genome-wide variation, and SNP heritability. Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):458-466.

Bowers, K., et al. Glutathione pathway gene variation and risk of autism spectrum disorders. J Neurodev Disord. 2011 Jun;3(2):132-43.

Esmaiel, N.N., et al. The potential impact of COMT gene variants on dopamine regulation and phenotypic traits of ASD patients. Behav Brain Res. 2020 Jan 27;378:112272.

Hausman-Cohen, S., et al. Utilizing Genomically Targeted Molecular Data to Improve Patient-Specific Outcomes in Autism Spectrum Disorder. Int J Mol Sci. 2022 Feb 16;23(4):2167.

Hausman-Cohen, S.R., et al. Genomics of Detoxification: How Genomics can be Used for Targeting Potential Intervention and Prevention Strategies Including Nutrition for Environmentally Acquired Illness. J Am Coll Nutr. 2020 Feb;39(2):94-102.

Hwang, I.W., et al. Association of Monoamine Oxidase A (MAOA) Gene uVNTR and rs6323 Polymorphisms with Attention Deficit and Hyperactivity Disorder in Korean Children. Medicina (Kaunas). 2018 May 18;54(3):32.

Li, Y., et al. Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis. BMC Pediatrics. 2020(20)449.

Meng, X., et al. Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis. PLoS One. 2022 Jul 14;17(7):e0271170.

Rahbar, M.H., et al. Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder. Genes (Basel). 2022 May 29;13(6):975.

Sadeghiyeh. T., et al. Association of MTHFR 677C > T and 1298A > C polymorphisms with susceptibility to attention deficit and hyperactivity disorder. Fetal Pediatr Pathol. 2020 Oct;39(5):422-429.

Way, H., et al. Genomics as a Clinical Decision Support Tool: Successful Proof of Concept for Improved ASD Outcomes. J Pers Med. 2021 Jun 24;11(7):596.