People with autism may have changed folate or methionine metabolism, suggesting that the folate–methionine cycle may play an important role in the etiology of autism. The SNPs or single nucleotide polymorphisms such as SLC19A1, DHFR, RFC and MTHFR are involved in the folate metabolism pathway impairing methylation.
Polymorphisms in folate-related pathway genes and disruptions in folate-related metabolism may be related to glutathione abnormalities associated with autism. Supplementation with folate during the prenatal and conception periods has been shown to lower the risk of ASD in offspring.
Treatment with folinic acid, a reduced form of folate, normalized cerebral spinal fluid folate concentrations and significantly improved neurological symptoms.
Interestingly, individuals with Rett syndrome, a disorder closely related to ASD, have also been found to have cerebral folate deficiency
Folate receptor α (FRα) autoantibodies (FRAAs) occur in higher number in autism spectrum disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. Those with FRAA-positive antibodies have better improvement in verbal communication than control with no FRAA-positive antibodies.
Clinically, folinic acid improves language, social and motor skills in children with autism and other developmental delays.
Frye R. E. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Molecular Psychiatry 65-66 October 2016
Frye R. E. Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor α autoimmune disorder. Received: 14 November 2015 | Revised: 7 February 2017 | Accepted: 9 February 2017 DOI: 10.1111/jne.12461
Mahmuda Naila Al. A Study of Single Nucleotide Polymorphisms of the SLC19A1/RFC1 Gene in Subjects with Autism Spectrum Disorder. International Journal of Molecular Sciences 17(5):772: 67-68 May 2016