Could Folate Receptor Autoantibodies Be the Missing Link in PANS/PANDAS?
Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and its related condition PANDAS are complex, often overwhelming diagnoses. Families face sudden and dramatic changes in a child’s behavior—obsessive-compulsive symptoms, severe anxiety, tics, regression, and more—frequently linked to infections like strep. Standard treatment often involves antibiotics, psychiatric medications, and immune support. But what happens when those child therapy treatments don’t work?
A recent study published in the Journal of Personalized Medicine offers a promising new lead: folate receptor alpha autoantibodies (FRAAs) may be part of the picture—and they could open the door to more targeted, safer treatments for affected children.
Understanding the Link: FRAAs, Folate, and the Brain
Folate (vitamin B9) plays a critical role in brain development and function. The brain relies on a special transporter—folate receptor alpha (FRα)—to bring folate across the blood-brain barrier. When the immune system mistakenly produces autoantibodies against this receptor (FRAAs), folate can't reach the brain efficiently. This condition is known as cerebral folate deficiency (CFD) and has previously been linked to autism spectrum disorder (ASD), movement disorders, and even psychiatric symptoms like depression and psychosis.
This study is the first to investigate whether FRAAs might also be found in children with PANS/PANDAS—and the results were striking.
Study Findings: FRAAs Are Common in PANS/PANDAS
The researchers analyzed blood samples from 47 children diagnosed with PANS or PANDAS.
Here’s what they found:
63.8% of patients tested positive for FRAAs.
Of those, 83.3% had binding FRAAs, which interfere with the folate receptor’s function.
A smaller percentage had blocking FRAAs, which directly prevent folate from binding.
Children with severe tics had significantly higher binding titers, while those with ASD showed lower titers.
These findings suggest that a disruption in folate transport may underlie some of the symptoms of PANS/PANDAS. Most importantly, this could explain why some children don’t fully respond to antibiotics or immunotherapy.
Leucovorin: A Safe, Targeted Treatment Option
One of the most compelling parts of the study involved treatment. The researchers highlighted a case in which a child with FRAA-positive PANS improved significantly after being treated with leucovorin—a prescription form of folate that bypasses the blocked receptor.
Leucovorin (also known as folinic acid) has been shown in previous studies to improve:
Communication
Repetitive behaviors
It is also well-tolerated and widely considered safe, making it a compelling option for children with suspected folate receptor dysfunction.
What This Means for Parents and Providers
If your child has been diagnosed with PANS or PANDAS and has not responded to conventional treatment, it may be worth exploring FRAA testing. This simple blood test could identify children who are candidates for leucovorin therapy, potentially unlocking a safer, more effective path to symptom relief.
This research also reinforces the idea that PANS/PANDAS is not a one-size-fits-all condition—and that personalized approaches, like those we offer at Philadelphia Integrative Psychiatry, can make a profound difference.
Want to learn more or schedule an appointment?
Text or call our office at 610-999-6414 to speak with our intake team.
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Disclaimer: This guide is for informational purposes only and not a substitute for medical advice. Any treatment—whether a supplement, medication, procedure, injection, therapy, or device—carries potential risks, especially when used in excess or by individuals with certain medical conditions or genetic predispositions. Always consult a qualified healthcare provider before starting any treatment.
