A review of: Austin, D., Shandley, K. (2008). An Investigation of Porphyrinuria in Australian Children with Autism. Journal of Toxicology and Environmental Health, Part A, 71(20), 1349-1351. DOI: 10.1080/15287390802271723

The journal of Toxicology and Environmental Health just published a study conducted in Australia examining the possible link between mercury and autism. The study examined urinary porphyrins as a measure of mercury exposure in children with autism. Porphyrinuria, or the excess urinary excretion of porphyrin, is purported to reflect heavy metal exposure and in particularly mercury. Two previous studies (Nataf et al., 2006, and Geier & Geier, 2007) used this urinary measure and reported increased levels of porphyrins in children with autism when compared to typically developing children. In the current study the authors examined urinary samples of 41 patients with ASD (detailed diagnostic procedure information was not provided). The age of the sample ranged from 1 to 16 (average 6). There were 30 boys and 11 girls. The authors did not include a control group. That is, no local comparison group of typically developing children was used. Instead, the authors compared the levels of porphyrins of the Australian sample with the control samples (typically developing kids) used by the two previous studies as well as to ‘normative’ laboratory ranges obtained from a French laboratory and the normative ranges published in a 1996 European study (Minder and Schneider-Yin, 1996).

The authors reported that the ratio of uroporphyrin to coproporphyrin (CP to UP) was statistically significantly higher in the Australian ASD group when compared to all control samples of the previous studies. The comparison effect sizes were very large, namely: 1.60 when compared to the Geier & Geier sample, 1.54 when compared to the Nataf et al sample, and 1.46 when compared to the 1996 normative sample. Effect size is a measure of the differences between the means of two groups that is not as sensitive (not affected by) the very large differences in sample sizes between these studies. Effect sizes in this range (1.46 to 1.60) indicate that the differences between the groups were very substantial.

A final thought. I can not discuss the merits of this particular urinary measure as reflective of mercury exposure or mercury toxicity, since this is beyond my understanding of heavy metal metabolism, thus I would simple make one final comment regarding the methodology of this study. I am very surprised that the authors did not include a local comparison sample, especially since their intention was to replicate the previous findings within a local Australian group. This is a strong limitation of the study. The results indicate that the Australian ASD group is statistically significantly different than the typically developing group used in the two previous samples (one from the USA and another from France) in regards to CP to UP ratio, but the results provide no information as how this ASD group compares to typically developing children in the sample geographical regions.

However, the data is compelling in showing a strong difference in the CP to UP ratio between the Australian sample and typically developing children in the USA and France. Does this mean that mercury causes autism? Not at all. Readers should be careful not to make conclusions about causal mechanisms from these type of association studies. There are multiple possible interpretations of the data, including the possibility that heavy metal exposure may play a role in the development of ASD. However, it is also possible that CP/UP ratio differences between these groups are the result, rather than the cause, of physiological differences in Autism. The results of this study do not support one interpretation more than the other. The results simply indicate that the groups are different in CP to UP ratio. The data do not tell us why these groups are different, or whether mercury causes autism.

ResearchBlogging.org

Geier, D. A., and Geier, M. R. 2007. A prospective study of mercury toxicity
biomarkers in autistic spectrum disorders. J. Toxicol. Environ. Health,
A 70:1723–1730.

Minder, E. I., and Schneider-Yin, X. 1996. Age-dependent reference values
of urinary porphyrins in children. Eur. J. Clin. Chem. Clin. Biochem.
34:439–443.

Nataf, R., Skorupka, C., Amet, L., Lam, A., Springbett, A., and Lathe, R. 2006.
Porphyrinuria in childhood autistic disorder: Implications for environmental
toxicity. Toxicol. Appl. Pharmacol. 214:99–108.

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4 Responses to Autism and Porphyrinuria: Mercury Exposure in an Australian Sample

  1. Anonymous says:

    Since I can’t get the full text of this paper, I have a couple of questions that I hope you can help with:
    1. Did the authors offer a discussion/explanation of why they didn’t test a local non-ASD comparison group?
    2. Do they give a range of results on an individual basis or is the data only reported as grouped means? If so, what is the standard deviation on the results? Is the differential similar for all study participants?

    Thanks.
    Regan

  2. Hello Regan. Answers to your questions:

    1. No. The authors did not provide any information as to why a local comparison sample was not used.

    2. No individual differences were reported. The group means (SD) for the CP to UP ratio were as follow:

    ASD group:
    16.31 (9.37)

    Control from Geier & Geier:
    5.56 (1.48)

    Control from Nataf:
    5.35 (3.56)

    Minder & Chneider-Yim norms:
    5.12(5.50)

  3. Anonymous says:

    Thank you. Much appreciated.
    Regan

  4. A couple of clarifications from questions emailed to me:

    —-
    1) what are the ages of the children (re:
    opportunities to be exposed to mercury in any form)

    The mean age for the autism group was 6 (range 1-16). No additional description of the age distribution was provided.

    2) vaccination
    history, if any (I wouldn’t assume that Australians do things the way
    Americans do) since this is the burning issue for so many people.

    The authors did not provide information about previous vaccination history. The only exclusion criteria stated was a history of chelation therapy or genetic disorder (Fragil x, Prader-Willi, or Rett)

    Thank you. N.

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