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

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

John Shoffner  1 , Barbara Trommer  1 , Audrey Thurm  1 , Cristan Farmer  1 , William A Langley 3rd  1 , Laura Soskey  1 , Aldeboran N Rodriguez  1 , Precilla D'Souza  1 , Sarah J Spence  1 , Keith Hyland  1 , Susan E Swedo  2
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CSF concentrations of 5-methyltetrahydrofolate in a cohort of young children with autism

John Shoffner et al. Neurology. .

Abstract

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.

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Figures

Figure.
Figure.. Distribution of CSF 5-methyltetrahydrofolate (5-MTHF) values at time 1 and time 2
Mean age at visit 1 was 42.7 ± 11.3 months. Mean time to follow-up was 29.7 ± 8.3 months (range 14–43 months). Medical Neurogenetics provided CSF 5-MTHF reference ranges: 40–150 nmol/L for 2–5 years, 40–128 nmol/L for 5–10 years. In the current study, values <40 nmol/L were considered low. (A) Individual CSF 5-MTHF values; (B) mean values at each time point. Accounting for age, mean CSF 5-MTHF did not change significantly between time 1 and time 2 (F = 0.16, p = 0.69).
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