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. firstname.lastname@example.org
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.