Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid

Neuropediatrics. 2005 Dec;36(6):380-5. doi: 10.1055/s-2005-873078.


Background: Previous studies in Rett syndrome (RS) patients suggested various abnormalities in biogenic amines, pterins, and folate values in cerebrospinal fluid (CSF). Our aim was to analyse these metabolites in CSF of 16 RS patients (age range: 2 - 23 years). Biogenic amines, pterins, and 5-methyltetrahydrofolate were measured by HPLC with electrochemical and fluorescence detection.

Results: CSF values of 5-methyltetrahydrofolate were decreased in 8 out of 16 RS patients (average: 53.6 nmol/L; range: 19 - 92) when compared with our reference values (average: 74.6 nmol/L; range: 45 - 127). These eight patients had epilepsy, while 4 out of 16 RS patients who did not have epilepsy showed normal CSF 5-methyltetrahydrofolate concentrations. Values of biogenic amines or pterins were decreased in four of the patients with low values of 5-methyltetrahydrofolate. No correlation was observed between CSF values of 5-methyltetrahydrofolate and pterins, biogenic amines, or age. Supplementation with folinic acid was applied in six out of the eight patients with CSF 5-methyltetrahydrofolate deficiency. An improvement was noticed in all cases.

Conclusions: An important percentage of RS patients showed 5-methyltetrahydrofolate concentrations under the reference values. Therefore, analysis of CSF 5-methyltetrahydrofolate seems advisable in RS, especially in patients with epilepsy and those resistant to antiepileptic drugs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biogenic Amines / blood
  • Biogenic Amines / cerebrospinal fluid*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • Dose-Response Relationship, Drug
  • Female
  • Folic Acid / analogs & derivatives
  • Folic Acid / blood
  • Folic Acid / cerebrospinal fluid
  • Humans
  • Leucovorin / therapeutic use*
  • Methyl-CpG-Binding Protein 2 / genetics
  • Pteroylpolyglutamic Acids / blood
  • Pteroylpolyglutamic Acids / cerebrospinal fluid*
  • Rett Syndrome / cerebrospinal fluid*
  • Rett Syndrome / drug therapy*
  • Rett Syndrome / genetics
  • Statistics, Nonparametric
  • Vitamin B Complex / therapeutic use*


  • Biogenic Amines
  • Methyl-CpG-Binding Protein 2
  • Pteroylpolyglutamic Acids
  • Vitamin B Complex
  • 5,11-methenyltetrahydrohomofolate
  • Folic Acid
  • Leucovorin