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

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.