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Folate Receptor Antibody Test (FRAT®)

Folic acid delivery to the brain is vital for optimal development and function of the brain. Folate Receptor A is responsible for transporting folic acid and its active component 5-MTHF into the brain, placenta, and ovaries. Antibodies have been observed in various diseases to be present and either block the folate receptor or bind the folic acid resulting in decreased absorption of folic acid in the brain. 

In one example of a rare disorder, these antibodies can block the entry of folate to the brain resulting in cerebral folate deficiency (CFD). Other studies have shown a substantial number of children with Autism Spectrum Disorder (ASD) to also have antibodies to the folate receptor. Current evidence suggests that these antibodies may be responsible for reducing the transport of folate and its active metabolites (most notably 5-MTHF) across the blood brain barrier in ASD. Because of the concern for diminished folic acid transport into the brain through the folate receptor, Folinic acid (leucovorin) was known to cross the blood brain barrier without the need of the Folate Receptor A, resulting in an increase in active metabolites of folic acid. In studies with ASD, children were found to have clinical improvement in eye contact and speech following dosing of Leucovorin. We recommend every child with Autism be evaluated for Folate Receptor Antibodies.

The FRAT® is able to measure the presence of the Folate Receptor antibodies. In addition to CFD and Autism, the FRAT®is also able to observe antibodies in sub-fertility in women and pregnant women carrying fetuses with neural tube defects (NTD). It has been proposed that the administration of metabolites of folate, such as 5-MTHF and Folinic acid, has resulted in clinical improvements, because these metabolites can enter the brain through carriers other than FRA, most notably the Reduced Folate Carrier.


“The association of FRA Autoantibodies with pregnancy-related complications,

CFD syndrome, and autism spectrum disorders and response to folate therapy is

highly suggestive of the involvement of these Autoantibodies in the disruption of

brain development and function via folate pathways.

Because these Autoantibodies are associated with various pathologies during

fetal and neonatal development, early detection and intervention could prevent

or reverse the consequences of exposure to these Autoantibodies.”

– Jeffrey M. Sequeira