November 8, 2010

Urinary Porphyrin Excretion in Neurotypical and Autistic Children

Environ Health Perspect. 2010 Oct;118(10):1450-7. Epub 2010 Jun 24.
Urinary porphyrin excretion in neurotypical and autistic children.

Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL, Granpeesheh D, Mumper E, Bradstreet JJ, Echeverria D, Heyer NJ, Rooney JP.

Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98105, USA.

BACKGROUND: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).

OBJECTIVES: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.

METHODS: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.

RESULTS: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.

CONCLUSIONS: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.

Urinary Porphyrin Excretion in Neurotypical and Autistic Children
Comparison of Urinary Porphyrins in NT and AU Children

Our findings suggest that mean concentrations of uro- and precoproporphyrins are comparable between NT and AU children of the same age ranges. In contrast, the concentrations of all remaining porphyrins, particularly hexacarboxyl-, pentacarboxyl-, and coproporphyrins, were significantly higher in AU children than NT children, especially in older age groups. Several possibilities might account for these differences. Of initial concern, Hg exposure appears unlikely to play a role in this effect, because no significant differences were observed between NT and AU subjects for indices of past exposure to Hg from dental or medical sources, as reported by parents/caregivers. Additionally, urinary Hg concentrations, measures of recent Hg exposure, were very low among all subjects in this study (Table 2), and no significant differences between diagnostic groups were observed. As noted recently (Woods et al. 2009a), incipient although statistically nonsignificant changes in urinary porphyrin concentrations were seen among children with urinary Hg concentrations derived from prolonged dental amalgam Hg exposure on the order of 3.2 µg/g creatinine. This is nearly 10 times the mean urinary Hg concentration observed among children in this study. Similar findings describing very low blood Hg levels and insignificant differences between NT and AU children have recently been reported (Hertz-Picciotto et al. 2010). These observations do not preclude a possible role of Hg exposure from sources not measured or validated in the present study, especially during the perinatal period, in the etiology of autism or related neurodevelopmental disorders in some children, particularly in relation to genetic variation that may predispose to increased risk of the neurotoxic effects of Hg as Hg0 as reported in adults (Echeverria et al. 2005, 2006, 2010; Heyer et al. 2009). Our findings indicate instead that porphyrin metabolism, particularly in preadolescent children, may be too disordered or differently regulated to permit detection of the Hg-mediated changes in urinary porphyrin excretion apparent in adult subjects. Further studies using a substantially larger population, such as the National Children's Study now in progress (National Children's Study 2010), are required to resolve this question.

1 comment:

drking33 said...

This article's understanding of reality is based on a flawed premise -- namely that comparable exposure to mercury translates into an expectation of comparable bioaccumulation of mercury.
Based on the recent Polish paper, Maria Dorota Majewska1, Ewa Urbanowicz, Paulina Rok-Bujko, Irena Namysłowska, Paweł Mierzejewski. Age-dependent lower or higher levels of hair mercury in autistic children than in healthy controls.
Acta Neurobiol Exp 2010, 70: 196–208, it is clear that the preceding premise is flawed because, even in studies where the exposures are the same and the children with a diagnosis in the autism spectrum are carefully matched to comparable controls, the mercury excretion patterns between the two groups, cases group and the matched case-controls group, differ significantly and the differences are age-dependent differences that reflect a significantly lower excretion by those with an ASD diagnosis at the early age where the doses of thimerosal-preserved vaccines have recently been administered and a higher excretion by those with an ASD diagnosis than the matched controls at a later age, indicating that the case group of children are still excreting mercury from their prior (Thimerosal-preserved vaccine bolus-dose) exposures while the children in the matched control-group have obviously excreted much of their vaccine-related mercury and are now excreting relatively low levels of mercury in their hair.
Hopefully, the preceding remarks will help some to understand that this article does point to differences between those with a diagnosis in the autism spectrum and "neurotypicals".
However, its authors seem to be driven to obscure this reality.
For more concerning the clear differeinces between the urinary porphyrin profiles of children with an ASD diagnosis and NT children, see the pertinent articles posted on the CoMeD web site: