Neurologists and geneticists at the University of Barcelona, Spain and other centers analyzed cerebral folate levels in 584 children with neurologic disorders that required diagnostic lumbar puncture. Deficiency of 5-methyltetrahydrofolate (5-MTHF) was detected in the CSF of 71 (12%) patients. Mild to moderate deficiency (n=63; 19-63 nmol/L) was associated with perinatal asphyxia, CNS infection, and diseases of probable genetic origin (inborn errors of metabolism, white matter disorders, Rett syndrome, or epileptic encephalopathies). Severe 5-MTHF depletion (n=8; range, 0.6-13 n/mol/L) was detected in specific mitochondrial disorders, metabolic defects, or cerebral degenerations (severe MTHF reductase deficiency, Kearns-Sayre syndrome, biotin-responsive striatal necrosis, acute necrotizing encephalitis, and FOLRI transporter gene defect). CSF folate levels correlated with plasma levels in cerebral folate deficiency. Thirty-five of 71 patients (49%) with decreased 5-MTHF had other abnormalities of biogenic amines, homovanillic acid, 5-hydroxyindoleacetic acid, and pterins in CSF. [1]

COMMENT. Partial cerebral folate deficiency may occur as a secondary abnormality in acquired CNS disorders and in genetic and congenital encephalopathies. Severe deficiencies are caused by inborn errors of folate metabolism or cerebral transport defects across the blood-CSF barrier (FOLR1 mutation). In the above study, children younger than 1 year had epilepsy (infantile spasms and neonatal seizures), perinatal asphxia or CNS infection. Older children were diagnosed with inherited disease, mitochondrial disorders or cerebellar atrophy syndrome. The mechanism of acquired cerebral folate deficiency in neurologic disorders is not definitely determined. Children with seizure disorders are at risk of low serum folate, and antiepileptic drugs may be a contributing factor in some cases. The value of folinic acid supplement in cerebral folate deficiency is under investigation.