John Shoffner1, Barbara Trommer1, Audrey Thurm1, Cristan Farmer1, William A Langley1, Laura Soskey1, Aldeboran N Rodriguez1, Precilla D'Souza1, Sarah J Spence1, Keith Hyland1, Susan E Swedo2. 1. From Medical Neurogenetics (J.S., W.A.L., K.H.); Georgia State University (J.S.), Atlanta; Pediatrics & Developmental Neuroscience Branch (B.T., A.T., C.F., L.S., A.N.R., P.D., S.J.S., S.E.S.), National Institute of Mental Health, National Institutes of Health, Bethesda, MD; State University of New York Downstate Medical Center (B.T.), Brooklyn; and Department of Neurology (S.J.S.), Boston Children's Hospital, MA. 2. From Medical Neurogenetics (J.S., W.A.L., K.H.); Georgia State University (J.S.), Atlanta; Pediatrics & Developmental Neuroscience Branch (B.T., A.T., C.F., L.S., A.N.R., P.D., S.J.S., S.E.S.), National Institute of Mental Health, National Institutes of Health, Bethesda, MD; State University of New York Downstate Medical Center (B.T.), Brooklyn; and Department of Neurology (S.J.S.), Boston Children's Hospital, MA. swedos@mail.nih.gov.
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.
OBJECTIVE: To examine the association between cerebral folate deficiency and autism, this study examined CSF5-methyltetrahydrofolate (5-MTHF) concentrations in a group of young children with autism, investigated the natural variation in CSF5-MTHF over time, and assessed the relationship between CSF5-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 CSF5-MTHF measurements (Pearson r[p] = 0.38 [0.04]; 95% CI 0.02-0.64). Neither the CSF5-MTHF levels nor changes over time correlated with the clinical features of autism. CONCLUSIONS:CSF5-MTHF levels vary significantly over time in an unpredictable fashion and do not show a significant relationship to typical clinical features of autism. Reduced CSF5-MTHF levels are a nonspecific finding in autism. Our data do not support the use of lumbar puncture for assessment of CSF5-MTHF in autism.
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