Urinary porphyrin excretion in neurotypical and autistic children.

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.

The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels.

This study investigated the relationship of children's autism symptoms with their toxic metal body burden and red blood cell (RBC) glutathione levels. In children ages 3-8 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal body burden was assessed by measuring urinary excretion of toxic metals, both before and after oral dimercaptosuccinic acid (DMSA). Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic metals. Variations in the severity of autism measurements could be explained, in part, by regression analyses of urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione (adjusted R(2) of 0.22-0.45, P < .005 in all cases). This study demonstrates a significant positive association between the severity of autism and the relative body burden of toxic metals.

Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.

Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism.

The potential of a store and forward tele-behavioral platform for effective treatment and research of autism.

This paper describes the justification and the design principles of a behavioral medicine store & forward telemedicine platform to facilitate the capturing and communication of spontaneous patient behaviors for the improved evaluation, diagnosis and ongoing treatment of people with autism. This Tele-Behavioral Health platform will allow families and other caregivers to readily capture spontaneous patient behaviors for subsequent evaluation by appropriate medical specialists. A unique feature of the system is its capability to archive and index the data for access as well as comparison over time by clinicians and other researchers. Such a system may serve as a precursor to further advances in other health information technology applications leading to more effective treatment and a better understanding of this disability.

pH mediated inhibition of the cell to cell spread of herpes simplex virus infection.

The relationships between the environmental pH and the replication and spread of herps simplex virus (HSV) infection in rabbit skin (RS) cell cultures was studies. Relative to the plaque formation at pH7.0, incubation of RS cells with medium adjusted to pH 6.6 resulted in a 50 to 70 per cent decrement in plaque number. The addition of overlay media adjusted to pH 6.0 or 6.3 precluded HSV plaque formation. Select HSV-1 (type 1) and HSV (type 2) strains readily survived a 3 day incubation with medium adjusted to pH 6.3 as demonstrated by plaque production following a medium shift to pH 7.0. Rs cells incubated with medium at pH 6.3 did not replicate. The survival of RS cells incubated for 3 days with medium adjusted to pH 6.3 was demonstrated by renewed cell proliferation following a medium change from pH 6.3 to 7.0. The progeny virus yields of two HSV strains replicating in RS cells incubated with medium adjusted to pH 6.3 or 7.0 were equivalent at 24 or 48 hours post infection and were indicative of a productive infection. The inhibition of HSV plaque formation at pH 6.3 was not due to an alteration of cell receptors but was the result of an inhibition in the cell to cell spread of the virus. These results are discussed with regard to the possibility that the decline in pH associated with the inflammatory response may serve as a host defense against HSV infections.