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Autism and Phthalate Metabolite Glucuronidation

Friday, 3 May 2013: 14:00-18:00
Banquet Hall (Kursaal Centre)
X. Ming1, T. P. Stein2, M. D. Schluter3 and R. A. Steer3, (1)Neurosciences and Neurology, UMDNJ-New Jersey Medical School, Newark, NJ, (2)Surgery, UMDNJ-School of Osteopathic Medicine, Strateford, NJ, (3)UMDNJ-School of Osteopathic Medicine, Strateford, NJ
Background: Exposure to environmental chemicals (ECs) may precipitate Autism Spectrum Disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. 

Objectives: To determine whether the efficiency of this pathway is compromised in children with ASD. 

Methods: We measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, Diethylhexyl phthalate (DEHP).  DEHP is first hydrolyzed to mono-2-ethylhexyl phthalate (MEHP) and then further metabolized by a series of oxidation reactions to mono-(2-ethyl-5-oxohexyl) phthalate (5-oxo MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5-OH MEHP) and mono-(2-ethyl-5-carboxypentyl phthalate (5-cx MEPP) which are then glucuronidated. We compared the efficiency of glucuronidation for conjugation in 50 children with ASD and against 53 controls.  Spot urines were collected and analyzed for the fraction of each metabolite conjugated by isotope dilution-liquid chromatography mass spectrometry–mass spectrometry. 

Results: Conjugation capacity was consistently lower with the ASD group based on both the median and adjusted mean values of OH-MEHP and 5-oxo MEHP in each group.   There was a statistically significant correlation between the fractions 5-OH MEHP conjugated with 5-oxo-MEHP (r = .51, P < .001) suggesting a common pathway. 

Conclusions: The glucuronidation pathway is compromised in some children with ASD. Because the glucuronidation pathway is responsible for the detoxification of many compounds, which one(s) are compromised in ASD cannot be said at this time.

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