New Evidence Favors the Folate Hypothesis for Autism
Brian Hoyle


May 31, 2011 (Denver, Colorado) — A new study has documented the presence of a polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) — essential for the metabolism of vitamin B9 (folate) — which almost doubles the chance of autism spectrum disorder (ASD). The data provide further genetic evidence for a link between folate and autism.

... Dietary supplementation with folate has been anecdotally liked to the improvement of symptoms of ASD, "despite a lack of medical evidence and endorsement," Dr. Schulteis told Medscape Medical News.

... Genetic evidence for a folate connection with autism was first reported in a study of 168 autistic children that chronicled the doubled prevalence of MTHFR polymorphisms in those with autism, compared with those in the control group (J Am Phys Surg. 2004;9[4]:106-108).

Dr. Schulteis and his colleagues established the MTHFR registry in 2002, and used the accumulated data to examine the reported genetic link in detail. The database contains information on patients who have been screened for the 677A→T and 1298A→C MTHFR polymorphisms in connection with other clinical concerns.

[My understanding from SNPedia ::rs1801131 is a SNP in the MTHFR gene, representing an A>C mutation at mRNA position 1298, thus this SNP is also known as A1298C. the risk allele is G or C.
rs1801133 is also a SNP in the MTHFR gene. Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, and rs1801133(C;T) heterozygotes have ~65% activity, compared to the most common genotype, rs1801133(C;C). : non risk : GG or CC (A or T is the risk allele )].
http://www.snpedia.com/index.php/Rs1801133]

Scrutiny of the records of 487 patients younger than 26 years of age revealed that 246 (51%) had 1 of the 2 mutations. The 677A→T mutation was predominate, affecting 67% of the patients. Fourteen of these individuals had ASD, which is appreciably greater than the accepted Centers for Disease Control and Prevention predicted prevalence of 4.43 (or 1 in 110) in young people. The prevalence rate of ADS in the control subjects conformed to the 1 in 110 rate.


"Our results add credence to the folate hypothesis, at least in this select number of ASD cases. These data should not be taken as a recommendation for change regarding folate supplementation...
"Other genes that impair folate transport and metabolism may also contribute to the risk of abnormal neurodevelopment, but MTHFR C677T is also a known risk for placental abruption (miscarriage) under 'normal' folate nutritional status, which is minimized under conditions that enhance maternal folate status during pregnancy."

"Therefore, it is highly likely that the folic acid food fortification/supplementation era has increased the birthrate of individuals with this polymorphism. They require more folic acid for neurodevelopment after birth, and are more susceptible to functional folate deficiency and neurodevelopment disorders, such as autism...

"http://www.medscape.com/viewarticle/743620