Cerebral folate deficiency and leukoencephalopathy caused by a mitochondrial DNA deletion

Ann Neurol. 2006 Feb;59(2):394-8. doi: 10.1002/ana.20746.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Chemistry / genetics
  • Child
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / genetics*
  • Folic Acid / blood
  • Folic Acid / cerebrospinal fluid
  • Folic Acid Deficiency / complications
  • Folic Acid Deficiency / genetics*
  • Folic Acid Deficiency / pathology
  • Gene Deletion*
  • Humans
  • Kearns-Sayre Syndrome / cerebrospinal fluid
  • Kearns-Sayre Syndrome / etiology
  • Kearns-Sayre Syndrome / genetics*
  • Kearns-Sayre Syndrome / pathology
  • Magnetic Resonance Imaging / methods
  • Male
  • Muscles / metabolism

Substances

  • DNA, Mitochondrial
  • Folic Acid