Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial

Abstract EN

Background.

In contrast to multiple rare monogenetic abnormalities, a common biomarker among children with infantile autism and their parents is the discovery of serum autoantibodies directed to the folate receptor alpha (FRα) localized at blood-brain and placental barriers, impairing physiologic folate transfer to the brain and fetus.

Since outcome after behavioral intervention remains poor, a trial was designed to treat folate receptor alpha (FRα) autoimmunity combined with correction of deficient nutrients due to abnormal feeding habits.

Methods.

All participants with nonsyndromic infantile autism underwent a routine protocol measuring CBC, iron, vitamins, coenzyme Q10, metals, and trace elements.

Serum FRα autoantibodies were assessed in patients, their parents, and healthy controls.

A self-controlled therapeutic trial treated nutritional derangements with addition of high-dose folinic acid if FRα autoantibodies tested positive.

The Childhood Autism Rating Scale (CARS) monitored at baseline and following 2 years of treatment was compared to the CARS of untreated autistic children serving as a reference.

Results.

In this self-controlled trial (82 children; mean age ± SD: 4.4 ± 2.3 years; male:female ratio: 4.8:1), FRα autoantibodies were found in 75.6 % of the children, 34.1 % of mothers, and 29.4 % of fathers versus 3.3 % in healthy controls.

Compared to untreated patients with autism (n=84) whose CARS score remained unchanged, a 2-year treatment decreased the initial CARS score from severe (mean ± SD: 41.34 ± 6.47) to moderate or mild autism (mean ± SD: 34.35 ± 6.25; paired t-test p<0.0001), achieving complete recovery in 17/82 children (20.7 %).

Prognosis became less favorable with the finding of higher FRα autoantibody titers, positive maternal FRα autoantibodies, or FRα antibodies in both parents.

Conclusions.

Correction of nutritional deficiencies combined with high-dose folinic acid improved outcome for autism, although the trend of a poor prognosis due to maternal FRα antibodies or FRα antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy.