AUTISM: A GENETIC PERSPECTIVE
There has been a steady climb on the rate of Autism with much discussion on the possible causes for this increase. Food allergies such as gluten and dairy, vaccines are in the discussion as well as vitamin D deficiencies and prenatal nutritional deficits will affect vitamin B cofactors and ultimately affecting the epigenetic profile of the individual.
This paper is going to focus on methylation and epigenetics and the ability to turn on and turn off the DNA signals. Essentially how we need to address Autism from a genetic perspective, which can affect the ability to not only detoxify and remove toxins but also its impact on the formation and removal of neurotransmitters.
In particular we are going to focus on the MTHFR gene. This gene has gained a lot of attention in recent years thanks to the efforts of Dr. Ben Lynch and Amy Yasko.
The role of MTHFR is to help convert an inactive form of folate into a more active form, which can then be cycled through to produce methyl donors. These methyl donors assist in the detoxification process, neurotransmitter production and choline production.
However it is very common to have single polymorphisms (SNPS) in two genes in particular the C677T and the A1298C. These SNPS affect how the genes function and will affect the body’s ability to push the folate through the cycle. There are also several very important cofactors that allow the cycle to function properly, B2, B6 and B12
The MTHFR genes SNPS at the C677T and A1298c will affect the individuals ability to detoxify as it will affect the methionine cycle as well as the transsulfuration cycle. We are also concerned with the Biopetrin cycle and the need to make neurotransmitters.
Another gene which is also very important in evaluating Neurotransmitters is the
COMT gene. This gene helps to break down neurotransmitters in particular the catecholamines, norepinephrine, epinephrine and dopamine
When consulting with a patient it is important to understand the production of the neurotransmitters as well as the removal. If there is a breakdown of any of these functions it will affect the patient symptomatically. Are the excitable, attention deficit issues, OCD perhaps it is not clearing out as well. Or are they more dull easily fatigue and difficulty connecting in life. This could me more of a dopamine production issue.
Therefore when we support someone with the MTHFR defect we are not only benefitting detoxification but also neurotransmitter production.
A large part of the Autism population is going to have more of a MTHFR deficiency where they are not going generate as much dopamine as necessary.
With regards to COMT , it is the neurotransmitter metabolizer, it helps to inactivate certain neurotransmitters so they are no longer influencing the body. This process can be greatly affected by toxins.
SUPPORT OF MTHFR AND COMT
For support of individuals with both the MTHFR and COMT gene mutations we need to be extremely cautious. I like to proceed slowly so as not to overburden the body.
Balancing the recommendations of methyl folate and B12 can at times be tricky. For example, giving more methylfolate and the body begins to produce more neurotransmitters the body will have a difficulty clearing them with a COMT gene mutation. Since the COMT is greatly affected by toxins and the environment if there is a further burden on this system we can then see a buildup and have the adverse effects from methylfolate.
If this situation occurs it is important to begin to dose with Niacin .
Dosing is extremely important after analyzing whether they are heterozygous or homozygous for the A1298C or C677T or a compound heterozygous. We also must address the COMT Val158met gene to help us determine where we should start and at what dose.
Generally, I do not like to give two methylated products. I like adenosyl and or hydroxycobalamin along with Methyl folate or 5-MTHF. I will address the transsulfuration pathway and look at B6 , B2 and perhaps NAC. I like PC to support choline production especially with a BHMT SNP.
To support the COMT pathway we look at 5- HTP , theanine, B6 and magnesium. If they have the VAL/VAL representation they will be able to clear neurotransmitters at a higher rate. We want to make sure the body can produce enough neurotransmitters so we can provide B complex, methyl folate, vitamin C, and D.
Individuals with the COMT Met/Met representation they will have a lower activity therefore we can support them with magnesium and be cautious with the methyl folate. 5-HTP and SAMe can be beneficial. Generally supplements like phenylalanine, L-dopa and L-tyrosine are not going to work for them. Theanine is a great choice here.
In summary, when evaluating a patient with multiple genetic snps it is important to take into account age, size, detoxification or gastrointestinal issues and begin the dosing slowly and titrate on up to minimize or prevent any adverse reactions.