Folate-Responsive Neurologic Diseases

Folate is a water-soluble vitamin of the B complex group, and is required for optimal health, growth, and development. In humans, it cannot be synthesized de novo. As a cofactor or coenzyme, folate plays key biological roles in a variety of physiologic processes: maintenance and repair of the genome, regulation of gene expression, amino-acid metabolism, neurotransmitter synthesis, and the formation of myelin. Dietary folates must undergo multiple, tightly regulated absorption and metabolic processes before their cellular utilization occurs. Clinical conditions associated with abnormal body folate status are very diverse. They range from genetic syndromes defined prior to conception, to malformations that develop during embryogenesis (neural tube defects), to disorders that are postnatally acquired and progressive (e.g., cerebral folate deficiency, or folinic acid-responsive seizures). Central nervous system folate deficiency or impaired availability can occur in the settings of normal or decreased systemic folate levels. Because the majority of patients respond to treatment with folinic acid, pediatric neurologists should remain vigilant to the possibility of deficiencies of folate in patients with unexplained neurologic disorders. The deleterious outcomes of untreated patients underscore the importance of making an early diagnosis.