Autism, urinary porphyrins and mercury

I appreciate that the title of this post is probably going to result in an immediate 'click away' for some folk but for those who've endured it I'd like to talk briefly about the findings reported by Eman Khaled and colleagues [1]. Namely the observation that: "ASD [autism spectrum disorder] children in the present study had increased blood Hg [mercury] and Pb [lead] levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype."

OK, language and terminology first. I don't like the use of the term 'healthy control children' set in the context of autism research it has to be said. Whilst the label of autism does indeed place someone at a significantly greater risk of various health-related complaints (see here), the connotation that someone with autism is 'unhealthy' solely as a function of their autism label is not universally borne out by the research data. Why not therefore just call controls 'control children' eh?

Next up, porphyrins in the context of autism have been covered before on this blog (see here). Although linked to processes such as heme synthesis, there have been suggestions that analysis of urinary porphyrins might also provide some important information on "renal mercury content" [2]. Mercury (Hg) has been a hot potato in the context of autism for quite a few years (see here) and discussions on this topic have sometimes turned pretty nasty (see here). The sweeping idea that all autism is 'caused' by mercury poisoning (and there are various types of the stuff) has not been supported by the peer-reviewed literature on this topic (see here) but there have been some important outliers detected (see here) potentially indicative of some role for at least some on the autism spectrum. As for lead (Pb), well let's just say that few people have anything good to say about lead exposure, particularly when it comes to childhood lead exposure (see here) and with autism in mind, the label seemingly does not guarantee lead safety (see here).

So, Khaled et al went about looking at levels of various urinary porphyrins as a function of both diagnostic status (autism, controls, siblings of autism participants) and also Hg and Pb load. They found that: "children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children." Again, sorry for the 'healthy' bit (these are the authors' words and not mine). They also observed that: "Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation."

This work is by no means flawless. I could go on about the preferred method of analysis - "high-performance liquid chromatography (HPLC)" - used to separate/detect urinary porphyrins (with fluorescence detection as per other research by authors on this paper [3]) as not exactly being the gold-standard for example. I might also quibble about the idea that 'dental amalgam restoration' rates are no replacement for actually measuring circulating levels of maternal mercury either (bearing in mind this would need to be done in archived samples too). There are holes in this work, of that there is no doubt.

But... it is a rather uncomfortable observation that time and time again, some children diagnosed with autism seem to be in possession of a somewhat higher than expected body burden of mercury, or at least testing positive for such a burden. Science has yet to fully understand the hows and whys of such findings for at least a group of people diagnosed with autism and what might be done to reduce any biological load and its various impacts on biological systems. Whether as Khaled and colleagues observe "a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity" stands up to further independent scientific scrutiny is another question but I'm minded not to just glaze over these and other findings in the peer-reviewed literature as if they did not exist. They do exist and for those children/adults potentially registering with high levels of mercury (or other heavy metals) the onus is on treating such toxicities rather than just further adding to some growing health inequalities simply as the result of a label called 'autism'...

Oh, and adding to the 'hot potato' theme, I'll be coming to the paper by Kerns and colleagues [4] on this topic quite soon.

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[1] Khaled EM. et al. Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder. Metab Brain Dis. 2016 Jul 13.

[2] Pingree SD. et al. Quantitative evaluation of urinary porphyrins as a measure of kidney mercury content and mercury body burden during prolonged methylmercury exposure in rats. Toxicol Sci. 2001 Jun;61(2):234-40.

[3] Macedoni-Lukšič M. et al. Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders. Biol Trace Elem Res. 2015 Feb;163(1-2):2-10.

[4] Kern JK. et al. The relationship between mercury and autism: A comprehensive review and discussion. J Trace Elem Med Biol. 2016 Sep;37:8-24.

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Khaled EM, Meguid NA, Bjørklund G, Gouda A, Bahary MH, Hashish A, Sallam NM, Chirumbolo S, & El-Bana MA (2016). Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder. Metabolic brain disease PMID: 27406246