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Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A
Vincent Th Ramaekers1, Jeffrey M Sequeira2, Marco DiDuca1
1Center of Autism, University Hospital Liège (CHU), Belgium.
Insights
Serum autoantibodies to folate receptor alpha (FRα) are common in children with autism. Treatment with folinic acid and nutrient correction improved autism symptoms and outcomes in a clinical trial.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Serum autoantibodies to folate receptor alpha (FRα) are a common biomarker in children with infantile autism and their parents.
- These autoantibodies impair folate transfer to the brain and fetus, unlike rare monogenetic abnormalities.
- Poor outcomes with behavioral interventions necessitate exploring treatments for FRα autoimmunity and nutritional deficiencies.
Purpose of the Study:
- To investigate the efficacy of treating folate receptor alpha (FRα) autoimmunity combined with nutritional correction in children with autism.
- To assess the impact of high-dose folinic acid and nutrient repletion on autism symptom severity and recovery.
- To evaluate the prevalence of FRα autoantibodies in autistic children and their parents.
Main Methods:
- A self-controlled therapeutic trial was conducted on 82 children with nonsyndromic infantile autism.
- Participants underwent comprehensive nutritional assessments; FRα autoantibodies were measured in patients and their families.
- Treatment involved correcting nutritional deficiencies and administering high-dose folinic acid for positive FRα antibody tests, with outcomes assessed using the Childhood Autism Rating Scale (CARS) over 2 years.
Main Results:
- FRα autoantibodies were detected in 75.6% of children with autism, 34.1% of mothers, and 29.4% of fathers, compared to 3.3% in controls.
- Two years of treatment significantly reduced CARS scores from severe to moderate/mild autism (p<0.0001), with 20.7% achieving complete recovery.
- Higher FRα antibody titers, positive maternal antibodies, or antibodies in both parents correlated with a less favorable prognosis.
Conclusions:
- Combining nutritional deficiency correction with high-dose folinic acid improves outcomes for children with autism.
- Maternal FRα antibodies or antibodies in both parents may indicate a need for early intervention before and during pregnancy.
- Targeting FRα autoimmunity and associated nutritional deficits offers a promising therapeutic strategy for autism.
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.
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