Cerebral folate deficiency and leukoencephalopathy caused by a mitochondrial DNA deletion

Objective: Our aim was to describe a child with an incomplete form of Kearns-Sayre syndrome who presented profound cerebrospinal fluid (CSF) folate deficiency and his response to folinic acid supplementation Methods: CSF 5-methyltetrahydrofolate was analyzed by HPLC with fluorescence detection and mitochondrial DNA deletions by southern blot hybridization. Results: Cranial magnetic resonance imaging showed a leukoencephalopathy. Profound CSF 5-methyltetrahydrofolate deficiency was observed with normal blood folate values and decreased CSF/serum folate ratio, suggesting a transport defect across the blood-brain barrier. Folinic acid treatment was established, and after 1 year clinical response to folinic supplementation was remarkable, with almost normal white matter image. Interpretation: The clinical response after folinic therapy highlights the need for the study of cerebral folate deficiency in patients with mitochondrial disorders and white matter lesions.