Journal of Autism and Developmental Disorders

, Volume 42, Issue 3, pp 367–377 | Cite as

Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

  • Stepan Melnyk
  • George J. Fuchs
  • Eldon Schulz
  • Maya Lopez
  • Stephen G. Kahler
  • Jill J. Fussell
  • Jayne Bellando
  • Oleksandra Pavliv
  • Shannon Rose
  • Lisa Seidel
  • David W. Gaylor
  • S. Jill James
Original Paper

Abstract

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism.

Keywords

Autism Oxidative stress Metabolic Epigenetics Glutathione DNA methylation 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Stepan Melnyk
    • 1
    • 3
  • George J. Fuchs
    • 1
    • 3
  • Eldon Schulz
    • 1
    • 3
  • Maya Lopez
    • 1
    • 3
  • Stephen G. Kahler
    • 1
    • 3
  • Jill J. Fussell
    • 1
    • 3
  • Jayne Bellando
    • 1
    • 3
  • Oleksandra Pavliv
    • 1
    • 3
  • Shannon Rose
    • 1
    • 3
  • Lisa Seidel
    • 1
    • 3
  • David W. Gaylor
    • 2
  • S. Jill James
    • 1
    • 3
  1. 1.Department of PediatricsUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Department of BiostatisticsUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Department of PediatricsArkansas Children’s Hospital Research InstituteLittle RockUSA

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