Cerebral Folate Deficiency in PANDAS/PANS and Autism Spectrum Disorder

Pathophysiological Connections

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is characterized by sudden-onset obsessive-compulsive symptoms precipitated by streptococcal infection, while PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) represents a broader disorder with similar symptoms triggered by various infections and insults 2, 3, 4
CFD is recognized as a metabolic condition associated with ASD and represents an important treatable cause of ASD symptoms, particularly in children with neurological deficits 1

CFD should be suspected in children with ASD who present with developmental regression outside of typical ASD speech loss, seizures, or hypotonia/dystonia - symptoms that may also be present in some PANS/PANS cases 1
Both PANDAS/PANS and ASD with CFD can present with obsessive-compulsive behaviors, although the onset pattern differs (sudden in PANDAS/PANS versus more gradual in typical ASD) 2, 4

For children presenting with symptoms of ASD, PANDAS, or PANS, consider testing for FRAAs, particularly if there are neurological symptoms, developmental regression, or movement disorders 1
The American College of Medical Genetics considers CFD a "low incidence yet high impact" metabolic disorder in ASD and emphasizes maintaining a high index of suspicion, although they do not recommend routine metabolic testing in all ASD cases 1