Porphyrins and autism

Excluding pretty boy vampire consumers, it is well known that human blood is a fantastic source of nutrients for lots of different pathogens. A recent article by Pishchany and Skarr* (full-text) said as much, with particular focus on the iron and amino acid content of hemoglobin - the oxygen-carrying protein which makes blood red - as a target for some invading critters. I don't want to dwell too much on blood-borne pathogens and their dietary habits (burp, excuse me) but this paper does provide quite a nice introduction into something which has cropped up over the years in relation to autism spectrum conditions, the porphyrins.

I'll readily admit that porphyrins are not generally part of my 'knows what he is talking about' repertoire, a very limited repertoire by all accounts, and so once again the caveat is not to take my word as gospel. Porphyrins are an interesting class of compounds notably involved with hemoglobin by way of heme, a co-factor of hemoglobin. Porphyrins and porphyria - a group of genetic disorders involving various 'faulty' enzymes needed to make heme - have been banded around autism research circles for quite a few years now. That, alongside some recent interest in porphyrins on social media brought me to this post and a review of some of the evidence suggesting involvement with autism.

One of the earliest papers that I've been able to find on porphyria in general medicine is this one** (full-text) by Dobriner and colleagues (1938). It makes for an interesting read because not only does it introduce some of the porphyrins looked at in later publications but it also talks about the effects of daily injections of liver extract on both symptoms and the presentation of porphyrins. Of course I am not advocating liver extract injections for anything (please file under 'words that I thought I would never utter in a sentence') but it provides a good historical record.

The paper by James Woods and colleagues*** (full-text) is as good as any to start with when looking at porphyrins and autism spectrum conditions. I am reliably informed that Dr Woods is a bit of an expert when it comes to all things porphyrin as per some of his other publications (here and here). Indeed this paper**** (full-text) has quite a nice graphical aid as to the different type of porphyrins and their biosynthesis which are subsequently discussed in this post.

Back to the 2010 paper, aside from finding little difference in levels of confounding compounds like mercury across their groups (see recent post here), they did report "... the mean concentrations of hexacarboxyl- (p < 0.01), pentacarboxyl- (p < 0.001), and copro- (p < 0.009) porphyrins were significantly higher among AU [autism] compared with NT [neurotypical] groups". What this translates as is the suggestion that whilst young children seem to have naturally high levels of porphyrins excreted in urine, the levels detected at a group level in autism were elevated beyond those normally expected.

Woods and colleagues go on to speculate that either genetic or mitochondrial (or both) issues might be areas worth pursuing to account for their findings; both areas which also have more than a passing relationship to at least some cases of autism. Indeed a sort of add-on paper from the Woods group***** (full-text) even more recently published by this group talks about issues with porphyrin metabolism as being "... strong predictors of both AUT and PDD-NOS". There are also some interesting urinary creatinine findings in this paper also (see here for previous discussions).

Other authors have also reported similar findings to Woods and colleagues. I say similar but Kern and colleagues****** suggested that alongside elevated levels of urinary pentacarboxy- and copro-porphyrins, elevated levels of precoproporphyrins were also found. The caveat being that this studied relied on a much smaller participant group. There are other studies noting similar findings quite consistently and across different countries including Korea (Youn et al, 2010) and Australia (Austin & Shandley, 2008).

All in all, I would be tempted to say that irrespective of a link between heavy metals or not, elevated levels of porphyrins quite consistently appearing in cases of autism should be the topic of a lot more research. At the moment, no-one really knows how issues with porphyrins fits into autism and its presentation. There are some discussions linking such issues to the role of heme in neuronal glutaminergic chemistry and tryptophan-serotonin chemistry, both of which have been connected to autism.

 I'd better add porphyrins to the autism research wish list.

* Pishchany G. & Skaar EP. Taste for blood: hemoglobin as a nutrient source for pathogens. PLoS Pathogens. March 2012
DOI: 10.1371/journal.ppat.1002535

** Dobriner K. et al. The excretion of porphyrins in congenital porphyria. Journal of Clinical Investigation. 1938; 17: 761-764.

*** Woods JS. et al. Urinary porphyrin excretion in neurotypical and autistic children. Environmental Health Perspectives. 2010; 118: 1450-1457
DOI: 10.1289/ehp.0901713

**** Daniell WE. et al. Environmental chemical exposures and disturbances of heme synthesis. Environmental Health Perspectives. 1997; 105: 37-53

***** Heyer NJ. et al. Disordered porphyrin metabolism: a potential biological marker for autism risk assessment. Autism Research. February 2012.
DOI: 10.1002/aur.236

****** Kern JK. et al. Toxicity biomarkers in autism spectrum disorder: a blinded study of urinary porphyrins. Pediatrics International. 2011; 53: 147-153
DOI: 10.1111/j.1442-200X.2010.03196.x