Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders

Abstract

Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children's present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder.

High Serum Levels of Serum 100 Beta Protein, Neuron-specific Enolase, Tau, Active Caspase-3, M30 and M65 in Children with Autism Spectrum Disorders

“…A decreased serum glutathione (GSH)/oxidized glutathione (GSSG) redox ratio has also been shown in patients with ASD [42]. Increased peripheral oxidative stress and malondialdehyde (lipid peroxidation marker) levels [43,44] have also been reported in children with ASD. The fact that at high concentrations S100B increases reactive oxygen species [19], and the high serum S100B values consistent with our own study [22,23], suggest that S100B may be associated with the pathogenesis of ASD.…”

Transcriptional control of amino acid homeostasis is disrupted in Huntington’s disease

“…Depletion of branched chain amino acids has been implicated in muscle shrinkage observed in HD (5). Similarly, a pathogenic role for cysteine deficiency in HD is supported by the beneficial effects of N-acetylcysteine (8,27) and couples with evidence for cysteine disturbances in other conditions of oxidative stress including aging, neurodegeneration, AIDS, and insulin resistance syndrome (28)(29)(30)(31)(32). Disturbances of cysteine disposition in multiple diseases may reflect a form of "cysteine stress" with widespread impact.…”

Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go?

“…Laboratory changes, including lower plasma methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione, were also noted in children with ASD ( 26 , 29 ). Abnormal transsulfuration metabolism and reduced antioxidant capacity were also noted in ASD ( 30 ). Therefore, vitamin B12 has been used for elevating methylation capacity and improving the “redox status” of children with ASD.…”