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

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.

Preliminary evaluation of a novel nine-biomarker profile for the prediction of autism spectrum disorder

“…These early observations were confirmed by our research group [20]. We previously recorded abnormal levels of the mitochondrial plasma markers pyruvate, lactate dehydrogenase, creatine kinase, glutathione-S-transferase (GST), caspase 7 and respiratory complex I (RCI) in children with ASD compared to those of age-and gender-matched control subjects.…”

“…We previously recorded abnormal levels of the mitochondrial plasma markers pyruvate, lactate dehydrogenase, creatine kinase, glutathione-S-transferase (GST), caspase 7 and respiratory complex I (RCI) in children with ASD compared to those of age-and gender-matched control subjects. Moreover, our study demonstrated that most severely affected children had both RC I and GST abnormalities and that caspase 7, a marker of mitochondrial dysfunction, was the most discriminating biomarker between patients with ASDand controls [20].…”

Assessment of Biometal Profile in Children with Autism Spectrum Disorder, with Attention Deficit Hyperactivity Disorder, or with Other Psychiatric Diagnoses: A Comparative Outpatient Study

“…The pathophysiological etiologies which precipitate autism symptoms remain elusive and controversial in many cases, but both genetic and environmental factors (and their interactions) have been implicated [25].…”

Differential Metabolites in Chinese Autistic Children: A Multi-Centre Study Based on Urinary 1H-NMR Metabolomics Analysis

“…Some metabonomic studies have indicated the presence of elevated biomarkers in blood and urine samples from ASD patients, and these biomarkers include pyruvate, lactate, and mitochondrial-related enzymes [12][13][14]. Major analytical techniques for metabolomics are nuclear magnetic resonance spectroscopy (NMR) and chromatography, including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS).…”