Cerebral folate deficiency

Dev Med Child Neurol. 2009 Mar;51(3):180-2. doi: 10.1111/j.1469-8749.2008.03185.x.


Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration of head growth, hypotonia, and ataxia, followed in one-third of children by dyskinesias (choreo-athetosis, hemiballismus), spasticity, speech difficulties, and epilepsy. The low level of 5-methyltetrahydrofolate in the CSF can result from decreased transport across the blood-brain barrier, which is most probably because of the blocking of folate transport into the CSF by the binding of folate receptor antibodies to the folate receptors in the choroid plexus. Treatment of the condition with folinic acid for prolonged periods can result in significant improvement of clinical symptoms and a return of 5-methyltetrahydrofolate levels in the CSF to normal. In view of this response to treatment in CFD and allied conditions, a case can be made for screening the CSF of patients with neurological disorders of unknown origin.

Publication types

  • Review

MeSH terms

  • Blood-Brain Barrier / physiopathology
  • Brain Diseases / cerebrospinal fluid
  • Brain Diseases / complications*
  • Brain Diseases / drug therapy
  • Cerebral Cortex / pathology*
  • Cerebral Cortex / physiopathology
  • Child
  • Folic Acid Deficiency / cerebrospinal fluid
  • Folic Acid Deficiency / complications*
  • Folic Acid Deficiency / drug therapy
  • Humans
  • Infant
  • Tetrahydrofolates / cerebrospinal fluid


  • Tetrahydrofolates
  • 5-methyltetrahydrofolate