A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2018 | Number 1, Volume 32

Folate receptor autoantibodies more common in ASD families

A new study adds to evidence that folate receptor autoantibodies are more common in children with autism spectrum disorders (ASD) and their families than in neurotypical controls. 

Folate is a nutrient essential for normal development before birth and during infancy. Autoantibodies to folate receptor alpha (FRα) can block folate transport from the mother to an unborn child during pregnancy, as well as blocking folate transport to the brain in infants. 

Edward Quadros and colleagues evaluated 82 children with autism, 53 of their unaffected siblings, 65 of their fathers, and 70 of their mothers for the presence of FRα autoantibodies (Ab), comparing them to 52 unrelated controls. They report, “Overall, 76 percent of the affected children, 75 percent of the unaffected siblings, 69 percent of fathers, and 59 percent of mothers were positive for either blocking or binding Ab, whereas the prevalence of this Ab in the normal controls was 29 percent.” 

The researchers’ findings extend earlier research showing a significant association of FRα antibodies with ASD. Quadros and his colleagues say that these autoantibodies appear to have a familial origin, and that while they do not directly cause ASD—since the unaffected siblings also had a high prevalence of the autoantibodies—they may contribute to developmental problems when combined with other factors. The researchers note that while folic acid and folate are actively transported by FRα, folinic acid—a different form of folate—is transported via a different mechanism. A separate team of researchers headed by Richard Frye earlier reported that folinic acid treatment results in improvements in language and communication in children with ASD and FRα autoantibodies. 

“Although, at present, the clinical trials using folinic acid have some limitations, the consistent positive findings of this safe and well-tolerated treatment raise the potential of a treatment that addresses core symptoms of ASD while also targeting pathophysiological abnormalities,” Quadros and colleagues conclude. 

In addition, the researchers say that the high prevalence of folate receptor autoantibodies in parents “raises the possibility of supplementing the parents positive for [the autoantibodies] before pregnancy occurs and the mother throughout the pregnancy with folinic acid to prevent folate deficiency in the fetus.” 


“Folate receptor autoantibodies are prevalent in children diagnosed with autism spectrum disorder, their normal siblings and parents,” Edward V. Quadros, Jeffrey M. Sequeira, W. Ted Brown, Clifford Mevs, Elaine Marchi, Michael Flory, Edmund C. Jenkins, Milen T. Velinov, and Ira L. Cohen, Autism Research, February 2, 2018 (epub prior to print publication). Address: Edward V. Quadros, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, [email protected].