Treatable Neurodegenerative Disorder: Cerebral Folate Transport Deficiency--Two Children from Southern India

Area of Science:

• Neurology
• Genetics
• Biochemistry

Background:

• Cerebral folate transport deficiency impairs folate transport across the blood-brain barrier, leading to low levels of 5-methyltetrahydrofolate (5MTHF) in cerebrospinal fluid (CSF).
• This condition can cause significant neurological impairments in children.

Observation:

• Two children presented with delayed milestones, regression, seizures, tremors, ataxia, and neuroimaging findings of cerebral and cerebellar atrophy.
• Genetic testing identified pathogenic variants in the FOLR1 gene in both patients, confirming cerebral folate deficiency.

Findings:

• Both children showed significant improvements in development, behavior, ataxia, and seizure frequency after initiating folinic acid treatment.
• The study highlights two cases of cerebral folate transport deficiency caused by FOLR1 gene variants.

Implications:

• Cerebral folate transport deficiency should be suspected in children with global developmental delay, epilepsy, and ataxia, especially with characteristic neuroimaging findings.
• Prompt diagnosis and treatment with folinic acid are essential for improving neurological outcomes, though late diagnosis may lead to partial response.