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Role of folate receptor autoantibodies in infantile autism

Molecular Psychiatry volume 18, pages 270–271 (2013)Cite this article

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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.

Table 1 summarizes the results for 75 children with infantile autism and their parents compared with 30 non-autistic controls with developmental delay. A total of 74 mothers of children with autism and 50 fathers were available for testing. Although there was an expected preponderance of males in the autistic group, age and serum folate for both groups were similar, while homocysteine was in the normal range (5–15 μmol l−1).

Table 1 Results and distribution of serum FR autoantibodies among 75 children with infantile autism, developmentally retarded non-autistic controls and their parents
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Authors and Affiliations

  1. Centre de Reference d’Autisme Liege, Centre Hospitalier Universitaire Liège, Liège, Belgium

    V T Ramaekers

  2. Departments of Medicine and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA

    E V Quadros & J M Sequeira

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  1. V T Ramaekers
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  2. E V Quadros
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Correspondence to V T Ramaekers.

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Competing interests

Two authors (EVQ and JMS) are co-inventors in a patent for the detection of folate-receptor antibodies in serum, issued to the Research Foundation of the State University of New York.

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Ramaekers, V., Quadros, E. & Sequeira, J. Role of folate receptor autoantibodies in infantile autism. Mol Psychiatry 18, 270–271 (2013). https://doi.org/10.1038/mp.2012.22

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