Porphyrin changes in autism

Porphyrins and physiology

This is a group of normal compounds that are produced in the body, derived originally from 5-aminolevulinic acid, to make bile compounds and heme,   This is well described: see web site from Metametrix.  They show how the modification of body heavy metals would be expected to produce changes in the ratios of porphyrins being excreted in the urine. 

Urinary porphyrins

The reason why these are measured easily is because the method required is relatively simple, partly because many porphyrins are fluorescent or coloured.

Interpretation

It is difficult in these samples to assume that mercury poisoning is involved when generally mercury levels are not measured in the patients at the same time.   Detoxification of heavy metals followed by further porphyrin tests are not carried out and so currently research is difficult to interpret at this point.  One group did detoxify the autism group but did not find any change in heavy metal presence.  This does not explain the higher levels of the specific porphyrins.   Further research is required with much higher numbers of cases.

 

 

 

Porphyrins are made in this format, with 4 cyclic molecules in a ring. The different types, including heme are different from each other through chemical modifications of the outer sections and the carriage of metal ions in the middle of the ring

 

 

Porphyrin physiology

 

Urinary Porphyrin Profiling extract from Laboratory Evaluations in Functional and Integrative Medicine (Richard Lord and James Bralley Eds) see: www.metametrix.com/PDFs/Documents/Porphyrins_white_paper.pdf

 

Clinical case

Awareness is the name of the game: clinical and biochemical evaluation of a case of a girl diagnosed with acute intermittent porphyria associated with autism. Luder AS, Mamet R, Farbstein I, Schoenfeld N. Cell Mol Biol (Noisy-le-grand). 2009 Feb 16;55(1):19-22   diagnosed heterozygous Acute Intermittent Porphyria (AIP) in a 15 yr old girl, who first presented with autism at the age of 4 years. This phenotypic association has not been previously reported. In addition to the unrecognized phenotype, her normal urinary aminolevulinic acid and porphobilinogen, findings which are not compatible with symptomatic porphyria according to well established criteria, could also have led to a missed diagnosis of neuroporphyria. However, the diagnosis of AIP was established on the basis of a 64% reduction in erythrocyte hydroxymethylbilane synthase (HMBS) activity and the finding of a known causative AIP mutation (p.D178N). We therefore recommend that porphyria should be considered in autistic children

 

 

Changes in the urine in autism

Raised urine porphyrin levels have now been reported from all the sources but cannot be used as a diagnostic test as there is clearly a number of cases of ASD in which the level is within the normal.  The argument currently is that it is due to mercury toxicity and no other causes have been put forward. 

 

a)      Geier DA, Geier MR. A prospective study of mercury toxicity biomarkers in autistic spectrum disorders. J Toxicol Environ Health A. 2007 Oct;70(20):1723-30.   (significantly raised in autistic children in USA and in urinary samples in France: the different porphyrins found explained.)

b)      Geier DA, Geier MR. A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotox Res. 2006 Aug;10(1):57-64.  (A significant increase (1.7-fold) in median coproporphyrin levels was observed among non-chelated ASD patients versus chelated ASD patients. Porphyrins should be routinely clinically measured in ASDs, and potential ASD treatments should consider monitoring porphyrin levels. Additional research should be conducted to evaluate the potential role for mercury exposure in some ASDs)

c)      Nataf R, Skorupka C, Amet L, Lam A, Springbett A, Lathe R. Porphyrinuria in childhood autistic disorder: implications for environmental toxicity. Toxicol Appl Pharmacol. 2006 Jul 15;214(2):99-108. (French group also finding high porphyrins and discusses the possible association with heavy metal exposure)

d)      Porphyrinuria in childhood autistic disorder is not associated with urinary creatinine deficiency. Nataf R, Skorupka C, Lam A, Springbett A, Lathe R. Pediatr Int. 2008 Aug;50(4):528-32.  No significant difference in creatinine (CRT) was observed between any of the categories analyzed, also when corrected for age and gender. In contrast, urinary coproporphyrin levels were significantly higher in autistic disorder versus reference groups, either when expressed as absolute values (independent of CRT levels) or when normalized to CRT.

e)      An investigation of porphyrinuria in Australian children with autism. Austin DW, Shandley K. J Toxicol Environ Health A. 2008;71(20):1349-51. A consistent trend in abnormal porphyrin levels was evidenced when data was compared with those previously reported in the literature. The results are suggestive of environmental toxic exposure impairing heme synthesis. Three independent studies from three continents have now demonstrated that porphyrinuria is concomitant with ASD, and that Hg may be a likely xenobiotic to produce porphyrin profiles

 

Involvement with heavy metal toxicity

 

Woods JS. Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity. Can J Physiol Pharmacol. 1996 Feb;74(2):210-5. (Mercury selectively alters porphyrin metabolism in kidney proximal tubule cells, leading to an altered urinary porphyrin excretion pattern.  Changes in the urinary porphyrin profile are highly correlated with the dose and duration of mercury exposure and persist for up to 20 wk following cessation of mercury treatment. In the present studies, the utility of urinary porphyrin profile changes as a biomarker of mercury exposure in human subjects was evaluated. Urinary porphyrin concentrations were measured in dentists participating in the Health Screening Programs conducted during the 1991 and 1992 annual meetings of the American Dental Association and compared with urinary mercury levels measured in the same subjects. Among dentists with no detectable urinary mercury, mean concentrations of urinary porphyrins were within the established normal ranges for male human subjects. In contrast, among dentists with urinary mercury in excess of 20 micrograms/L, mean urinary concentrations of four- and five-carboxyl porphyrins as well as of precoproporphyrin were elevated three to four times those of unexposed subjects.  These findings suggest that urinary porphyrin profiles may serve as a useful biomarker of mercury exposure in clinical or epidemiologic studies of mercury-related human health risks.)

 

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