ABSTRACT
Porphyrins are formed as intermediates in the biosynthesis of heme, a process that proceeds in essentially all eukaryotic tissues. In humans and other mammals, porphyrins with 8,7,6,5, and 4 carboxyl groups are commonly formed in excess of that required for heme biosynthesis and are excreted in the urine in a well-established pattern (Bowers et al. 1992; Woods et al. 1993). In previous studies we described specific changes in the urinary porphyrin excretion pattern (porphyrin profile) associated with prolonged exposure to mercury (Hg) in either organic or elemental forms (Pingree et al. 2001a; Woods et al. 1991, 1993). These changes are characterized by dose-and time-related increases in urinary concentrations of
pentacarboxyl (5-carboxyl) and copro-(4-carboxyl) porphyrins and also by the appearance of precoproporphyrin, an atypical porphyrin [molecular weight (mw) = 668] that elutes on high-performance liquid chromatography (HPLC) prior to coproporphyrin (mw = 655) (Woods et al. 1991). The potential utility of these porphyrin changes as a biomarker of Hg exposure and body burden in adults with occupational exposure to elemental mercury (Hg0) has been described (Bowers et al. 1992; Gonzalez-Ramirez et al. 1995; Woods 1995; Woods et al. 1993)
Autism (AU), or autistic spectrum disorder (ASD), represents a serious neurodevelopmental disorder that affl icts as many as 1 in 110 children in the United States (Rice 2009). Although genetic factors likely play a principal role in the etiology of autism, a number of studies suggest that environmental exposures, occurring especially at critical periods of neurological development, may trigger events etiologic in AU/ASD among some children. In this respect, several reports (Kern et al. 2007; Mutter et al. 2005; Windham et al. 2006) have implicated prenatal and/or postnatal Hg exposure as associated with autism, in terms of frequency of exposure as well as total body burden. Notably, important mechanistic and toxicokinetic distinctions between different forms of Hg (Burbacher et al. 2005) or in child-specifi c factors (Faustman et al. 2000) that might affect susceptibility to Hg in autism remain to be fully considered in studies of this association. Nonetheless, some of the neuropsychiatric disturbances associated particularly with Hg0 exposure, such as cognition and communication defi cits, sensory dysfunction, and impaired motor coordination, are notably similar to those observed in autism and ASD (Echeverria et al. 1998; Kolevzon et al. 2007).
