Mitochondrial diseases associated with cerebral folate deficiency.

WITH CEREBRAL FOLATE DEFICIENCY Cerebral folate deficiency (CFD) has been defined as any neuropsychiatric condition associated with isolated lowering of 5-methyltetrahydrofolate (5MTHF) levels in CSF and normal systemic folate metabolism.1 CFD has been detected in the infantile-onset CFD syndrome (mediated by serum folate receptor [FR] autoantibodies of the blocking type1) and Aicardi-Goutières and Rett syndromes. In Kearns-Sayre syndrome (KSS), systemic folate deficiency or low CSF 5-MTHF have long been recognized.2,3 Because active transport of 5-MTHF across the choroid plexus epithelial cells is mediated by ATP-dependent processes, we conducted a study to determine CSF 5-MTHF in a series of patients with mitochondrial disorders.