Autoantibodies to folate receptors in the cerebral folate deficiency syndrome

N Engl J Med. 2005 May 12;352(19):1985-91. doi: 10.1056/NEJMoa043160.

Abstract

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28 children with cerebral folate deficiency, 5 of their mothers, 28 age-matched control subjects, and 41 patients with an unrelated neurologic disorder. Serum from 25 of the 28 patients and 0 of 28 control subjects contained high-affinity blocking autoantibodies against membrane-bound folate receptors that are present on the choroid plexus. Oral folinic acid normalized 5MTHF levels in the cerebrospinal fluid and led to clinical improvement. Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood*
  • Autoimmune Diseases / diagnosis*
  • Biological Transport
  • Blood-Brain Barrier
  • Carrier Proteins / immunology*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Choroid Plexus
  • Female
  • Folate Receptors, GPI-Anchored
  • Folic Acid / blood
  • Folic Acid / metabolism*
  • Folic Acid Deficiency / blood
  • Folic Acid Deficiency / cerebrospinal fluid
  • Folic Acid Deficiency / immunology*
  • Humans
  • Male
  • Receptors, Cell Surface / immunology*
  • Tetrahydrofolates / cerebrospinal fluid*

Substances

  • Autoantibodies
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Receptors, Cell Surface
  • Tetrahydrofolates
  • Folic Acid
  • 5-methyltetrahydrofolate