FOLR1 and epilepsy: This autosomal recessive disorder manifests in late infancy with severe developmental regression, movements disturbances, epilepsy, and leukodystrophy with low CSF 5-MTHF (the active folate metabolite) in the presence of normal folate metabolism outside the CNS.3 Folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function.3 Mutations in the FOLR1 gene coding for folate receptor alpha (FRα) predominantly affecting cerebral folate transport leads to low CSF 5-MTHF levels.