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

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Abstract

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.

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Acknowledgements

The authors would like to thank Shaik AL-Amodi Autism Research Chair and the parents of autistic children, without whom this work was not possible.

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MAK, performed all the biochemical assays as part of her PhD thesis, ABB, Supervised the practical work and co-drafted the manuscript, LA provided samples and participated in the diagnosis of the autistic samples, AE designed the study and drafted the manuscript, REF, interpretation of data and critically revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Richard E. Frye.

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The data will not be shared because autistic patients from Autism Research and Treatment Centre, College of Medicine, King Saud University, did not give consent to the public release of their data but only to participate in the present study.

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This work was funded by King Abdul Aziz City for Science and Technology (KACST).

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The authors declare that they have no competing interests.

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This study was certified by the local Ethical Committee of Faculty of medicine, King Saud University, Riyadh, Saudi Arabia.

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Khemakhem, A.M., Frye, R.E., El-Ansary, A. et al. Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers. Metab Brain Dis 32, 1983–1997 (2017). https://doi.org/10.1007/s11011-017-0085-2

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