Role of folate receptor autoantibodies in infantile autism

Abstract

During pregnancy, maternal folate receptor alpha (FRα) autoantibodies could block folate transfer to the fetus and increase the risk of neural tube defects.1 The prevalence of blocking FRα antibodies in healthy adult women was estimated at 4–7% in Spain,2 9–13% in Ireland3 and 10–15% in the US population.1 A low titer of this antibody in a fraction of the adult population appears to be non-pathologic. Postnatally acquired FR autoantibodies blocking folate transport to the brain have been associated with the infantile-onset cerebral folate deficiency syndrome,4 which in a number of patients manifests as low-functioning autism with neurological deficits.5 In a US population with autism spectrum disorder (ASD), either the blocking- or the binding-type autoantibody was detected in 75% of the children and high-dose folinic-acid supplementation improved the core symptoms of autism in these children.6 We studied a population of infantile autism, non-autistic controls with developmental deficits and their parents in Belgium (research project supported by FNRS Belgium No: 3.4.540.09.F). Serum was tested for FRα-blocking autoantibodies as described previously.4 Plasma homocysteine and serum folate were also measured. The samples were coded and blinded to all analysis.