Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers

Metab Brain Dis. 2017 Dec;32(6):1983-1997. doi: 10.1007/s11011-017-0085-2. Epub 2017 Aug 22.


Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is behaviorally defined by social and communication impairments and restricted interests and repetitive behaviors. There is currently no biomarkers that can help in the diagnosis. Several studies suggest that mitochondrial dysfunction is commonly involved in ASD pathophysiology, but standard mitochondrial biomarkers are thought to be very variable. In the present study we examine a wide variety of plasma biomarkers of mitochondrial metabolism and the related abnormalities of oxidative stress and apoptosis in 41 ASD patients assessed for ASD severity using the Childhood Autism Rating Scales and 41 non-related age and sex matched healthy controls. Our findings confirm previous studies indicating abnormal mitochondrial and related biomarkers in children with ASD including pyruvate, creatine kinase, Complex 1, Glutathione S-Transferase, glutathione and Caspase 7. As a novel finding, we report that lactate dehydrogenase is abnormal in children with ASD. We also identified that only the most severe children demonstrated abnormalities in Complex 1 activity and Glutathione S-Transferase. Additionally, we find that several biomarkers could be candidates for differentiating children with ASD and typically developing children, including Caspase 7, gluthatione and Glutathione S-Transferase by themselves and lactate dehydrogenase and Complex I when added to other biomarkers in combination. Caspase 7 was the most discriminating biomarker between ASD patients and healthy controls suggesting its potential use as diagnostic marker for the early recognition of ASD pathophysiology. This study confirms that several mitochondrial biomarkers are abnormal in children with ASD and suggest that certain mitochondrial biomarkers can differentiate between ASD and typically developing children, making them possibly useful as a tool to diagnosis ASD and identify ASD subgroups.

Keywords: Autism; Caspase 7; Complex I; Energy metabolism; Lactate dehydrogenase; Mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autism Spectrum Disorder / blood
  • Autism Spectrum Disorder / diagnosis*
  • Biomarkers / blood*
  • Caspase 7 / blood*
  • Child
  • Child, Preschool
  • Glutathione Transferase / blood*
  • Humans
  • L-Lactate Dehydrogenase / blood*
  • Male
  • Mitochondria / metabolism
  • Oxidative Stress
  • Severity of Illness Index


  • Biomarkers
  • L-Lactate Dehydrogenase
  • Glutathione Transferase
  • Caspase 7