Altered Heavy Metals and Transketolase Found in Autistic Spectrum Disorder

Abstract

Autism and autism spectrum disorder (ASD) are developmental brain disorders with complex, obscure, and multifactorial etiology. Our recent clinical survey of patient records from ASD children under the age of 6 years and their age-matched controls revealed evidence of abnormal markers of thiol metabolism, as well as a significant alteration in deposition of several heavy metal species, particularly arsenic, mercury, copper, and iron in hair samples between the groups. Altered thiol metabolism from heavy metal toxicity may be responsible for the biochemical alterations in transketolase, and are mechanisms for oxidative stress production, dysautonomia, and abnormal thiamine homeostasis. It is unknown why the particular metals accumulate, but we suspect that children with ASD may have particular trouble excreting thiol-toxic heavy metal species, many of which exist as divalent cations. Accumulation or altered mercury clearance, as well as concomitant oxidative stress, arising from redox-active metal and arsenic toxicity, offers an intriguing component or possible mechanism for oxidative stress-mediated neurodegeneration in ASD patients. Taken together, these factors may be more important to the etiology of this symptomatically diverse disease spectrum and may offer insights into new treatment approaches and avenues of exploration for this devastating and growing disease.

Assessment of metal content and oxidative stress in autistic Egyptian patients

“…It was hypothesized that children with autism have a decreased detoxification capacity for Hg because of genetic polymorphism(Mutter et al, 2005).Pb level was significantly higher in our patients with autism compared with the control participants. This finding is in agreement with the findings of El-Ansary et al(2011), but was not in agreement with that ofTian et al (2011), who concluded that there were no significant differences in blood Pb levels among children with autism and controls Obrenovich et al (2011). emphasized the importance of chelating agents as preventive measures for autism.…”

Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic

“…Arsenic, a metalloid that can exist in both organic and inorganic forms, has been found to have harmful effects on the human nervous system (ATSDR 2007;USEPA 2002). Similar to results seen in studies of lead and mercury, results from these studies have been inconsistent, with several reporting no association (Adams et al 2006;Fido & Al-Saad 2005;Adams et al 2013;Rahbar et al 2012;Adams et al 2013), others reporting higher levels of arsenic in children with ASD (Obrenovich et al 2011), and another study reporting lower concentrations in children with ASD compared to controls (Kern et al 2007). …”

Environmental factors associated with autism spectrum disorder: a scoping review for the years 2003–2013

“…Biomarkers included altered levels of oxidative stress defence systems, including metallothioneins and antioxidant enzymes. 215 Other markers of oxidative stress, associated heavy metal toxicity and/or low detoxification capacity included abnormal markers of thiol metabolism, 216 transsulfuration abnormalities, 30 urinary organic acids, 29 and increased lead and potassium ions, ATPase activity and lipid peroxidation products. 217 …”