Folinic Acid Treatment of Parents Positive for Folate Receptor Autoantibodies Could Reduce the Risk of Autism in Their Offspring

Folate receptor-alpha (FRα) transports folate to germline cells and across the placental and blood-brain barrier to the brain. FRα autoantibodies (FRαAb) occur in ~70% of autistic children devoid of genetic defects, and ~1/3 of their asymptomatic parents. Folinic acid circumvents blocked folate transport. In children positive for FRαAb whose parents tested negative for FRαAb, high dose folinic acid treatment before 3 ½ years, results in improved outcome (88%). High autism prevalence with poor outcome (29%) is observed when mothers or both parents are positive for FRαAb. We postulated that folinic acid treatment of parents before and during pregnancy may reduce the risk of autism in further offspring. In a prospective open label pilot study, parents with positive FRαAb wishing to have further children, took daily levo-folinic acid (3.75 mg) or an equivalent dose of dl-folinic acid (7.5 mg) three months before conception and throughout pregnancy. Among five families where all mothers and three fathers tested positive for FRαAb, folinic acid prevented autism in all 7 children born. This contrasts significantly (Fisher’s exact test p=0.011) with the high autism prevalence of 54 % in offspring from 28 untreated families where either only mothers (n=15) or both parents (n=13) had FRαAb. Therefore, folinic acid intervention before and throughout pregnancy, in parents positive for FRαAb, may reduce the risk of autism in their offspring.