I have attempted to write this explanation – about the MTHFR gene – for more than a year now, often surrendering because it just gets so complicated (see diagram on right – and that is a simplified version)!

However, almost daily now, I need to explain the testing and interventions that revolve around the MuthrF#$Ker gene, which produces an enzyme that can assist in the brain’s ability to process (among many other important body reactions) in patients with ASD.

So, here is my simplified version, which covers the important steps for our understanding about testing and treatment for autism:

1. Folate (natural), folic acid (synthetic), Folinic acid (active) and 5-methyl folate (active) are not exactly the same a form of Vitamin B9.

2. There are several reasons why the levels of the B9 might be reduced:
• Reduced intake. Picky eaters and kids don’t usually savor green leafy vegetables or lentils.
• Problems with internal state of health will affect availability. Synthetic folic acid must go through the liver, natural folate is metabolized through the intestines.
• Antibodies that bind to, or block the active compound. This is why doctors check the Folate Receptor Antibody Test (FRAT). The presence of such inappropriate barriers implicates reduced activity, so administration of additional vitamin should help alleviate difficulties.
• Any ‘weakness’ in the body’s inability to convert the vitamin – that includes the MTHFR gene that regulates the enzyme called methylene tetrahydrofolate reductase.

3. The most studied and concerning genetic variations are often designated as C677>T, A1298>C. Hieroglyphics aside, we  inherit a ‘C‘ and an ‘A’ from each parent, and each deviation yields a less potent enzyme, so the implication is that giving the active forms of the vitamin can be beneficial. (Dr. Google, and many labs will report variations as pertains to the risk of hyperhomocysteinemia, a medical condition observed in approximately 5% of the general population, associated with an increased risk for many disorders.) For ASD, improved communication is the goal of treatment.

4. The supplements include L-methyl folate, available as a prescription under Deplin®. A web search of this product will often result in a call from parents, “My child doesn’t have schizophrenia or depression!” Marketing. Improved outlook is just one of the treatment outcomes. As noted previously, in ASD the aim is more efficient neural processing.

5. Another intervention is available as folinic acid (<1 mg dosages) and as the prescription, Leucovorin. An Internet inquiry may stimulate a call, such as, “My child doesn’t have cancer or get chemotherapy.” Different market. At a recent MedMaps.org conference, I asked two top researchers whether they prefer one or the other active form. Each doctor replied with the opposite answer. Availability and cost help determine choice, and sometimes we try both.

Conclusion
The various forms of folate appear to be safe, effective interventions that can address weaknesses in the area of oral-motor functioning in individuals with ASD. In practice, agitation is the principle side effect, and too much ‘stimming’ or aggression is reason for discontinuance.

The gene controlling MTHFR production is important, but not the only one affecting multiple enzymatic pathways that lead to successful data processing. We are already discovering other critical genetic steps (SOD, COMT, etc.) and there are thousands of other genetic crossroads that will improve our understanding and lead to successful interventions.

For our more advanced readers – please feel free to submit any corrections, etc. that you feel might be necessary.