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. Ann Neurol 2006