CSF concentrations of 5-methyltetrahydrofolate in a cohort of young children with autism

Neurology. 2016 Jun 14;86(24):2258-63. doi: 10.1212/WNL.0000000000002766. Epub 2016 May 13.


Objective: To examine the association between cerebral folate deficiency and autism, this study examined CSF 5-methyltetrahydrofolate (5-MTHF) concentrations in a group of young children with autism, investigated the natural variation in CSF 5-MTHF over time, and assessed the relationship between CSF 5-MTHF and symptoms.

Methods: CSF was collected from 67 children with a diagnosis of DSM-IV-TR autistic disorder (age, mean ± SD 43 ± 11 months), with a second CSF sample obtained 1-3 years later on 31 of these subjects (time to follow-up, 30 ± 8 months).

Results: At time 1, 7% (5/67) of participants had 5-MTHF <40 nmol/L. At follow-up, 23% (7/31) of participants had 5-MTHF <40 nmol/L (only one of whom had been low at time 1). A moderate correlation with a very wide confidence interval (CI) was observed between time 1 and time 2 CSF 5-MTHF measurements (Pearson r[p] = 0.38 [0.04]; 95% CI 0.02-0.64). Neither the CSF 5-MTHF levels nor changes over time correlated with the clinical features of autism.

Conclusions: CSF 5-MTHF levels vary significantly over time in an unpredictable fashion and do not show a significant relationship to typical clinical features of autism. Reduced CSF 5-MTHF levels are a nonspecific finding in autism. Our data do not support the use of lumbar puncture for assessment of CSF 5-MTHF in autism.

Trial registration: ClinicalTrials.gov NCT00298246.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autistic Disorder / blood
  • Autistic Disorder / cerebrospinal fluid*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Child
  • Child, Preschool
  • Folic Acid / blood
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Neuropsychological Tests
  • Severity of Illness Index
  • Tetrahydrofolates / cerebrospinal fluid*


  • Biomarkers
  • Tetrahydrofolates
  • Folic Acid
  • 5-methyltetrahydrofolate

Associated data

  • ClinicalTrials.gov/NCT00298246