Late diagnosis of cerebral folate deficiency: Fewer seizures with folinic acid in adult siblings

Neurol Genet. 2015 Dec 22;2(1):e38. doi: 10.1212/NXG.0000000000000038. eCollection 2016 Feb.


Cerebral folate deficiency is a genetically heterogeneous condition.(1) Mutations in FOLR1 are responsible for a rare but treatable form of cerebral folate deficiency (OMIM #613068).(1) The gene codes for folate receptor alpha (FRα), a specific CNS folate transporter. Individuals with FOLR1-related folate deficiency present with ataxia, dyskinesia, spasticity, seizures, and regression in cognitive abilities and motor skills during early childhood.(2) Seizures commonly observed include generalized tonic-clonic, atonic, and myoclonic.(3) To date, there have been 18 individuals with FOLR1-related cerebral folate deficiency diagnosed in childhood and reported in the literature.(3-5) Early diagnosis is crucial, as high-dose folinic acid (2-5 mg/kg/day) has been reported to be an effective treatment that can ameliorate or even prevent further neurodegeneration, although no long-term treatment studies have been performed.(1,3,5,6) We present the late diagnosis of adult siblings with cerebral folate deficiency due to FOLR1 mutations and their subsequent treatment.