Biomarkers of Susceptibility and Toxicity in Children with ASD

This program will discuss research conducted by Dr. Kern and colleagues that examines the role of susceptibility and toxicity in the pathology/etiology of ASD. The main topic will be transsulfuration metabolites (a biomarker of susceptibility) and urinary porphyrins (a biomarker of environmental toxicity). The program will also include the results of a follow-up study that examines exposure. A study was undertaken to examine biomarkers in children with autism spectrum disorder (ASDs). The biomarkers included the transsulfuration metabolites (a biomarker of susceptibility) and urinary porphyrins (a biomarker of environmental toxicity). The transsulfuration metabolites included plasma-reduced glutathione (GSH), plasma-oxidized glutathione (GSSG), plasma cysteine, plasma taurine, serum/plasma sulfate, and serum/plasma-free sulfate.

The findings from the study were:

1. Participants diagnosed with ASDs had significantly (p<0.001) decreased plasma-reduced GSH, plasma cysteine, plasma taurine, serum/plasma sulfate, and serum/plasma-free sulfate relative to controls.

2. Participants diagnosed with ASDs had significantly (p<0.001) increased plasma GSSG relative to controls.

3. Participants with severe ASDs had significantly increased urinary porphyrins associated with mercury intoxication (pentacarboxyporphyrin, precoproporphyrin and coproporphyrin) in comparison to participants with mild ASDs, whereas other urinary porphyrins were similar in both groups.

4. Mercury-associated urinary porphyrins were significantly correlated with increasing CARS scores and GSSG levels, whereas other urinary porphyrins did not show these relationships.

5. Participants with ASDs had significantly increased levels of three urinary porphyrins known to be associated with Hg intoxication, pentacarboxyporphyrin, precoproporphyrins and coproporphyrins, in comparison to the levels for these in the typically developing children. No significant differences were found in non-Hg- associated urinary porphyrins (uroporphyrins, and 6- and 7-carboxyporphyrins).

6. Participants’ overall ATEC scores and their scores on each of the ATEC subscales (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) were linearly related to urinary porphyrins associated with mercury toxicity.

7. Typically developing children with less mercury exposure (i.e., less exposure to mercury in vaccines and mercury from coal-burning) show a significantly decreased body-burden of mercury in comparison to the body-burden of mercury in typically developing children with greater exposure.