Heavy metals and specific porphyrine levels in children with autism

  • Marta Macedoni-Lukšič Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana Inštitut za avtizem in sorodne motnje, Goričane 84, 1215 Medvode
  • David Gosar Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana
  • Jasna Oražem Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana
  • Jana Kodrič Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana
  • Petra Lešnik-Musek Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana
  • Mirjana Zupančič Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana
  • Alenka France-Štiglic Univerzitetni inštitut za klinično kemijo in biokemijo, Univerzitetni Klinični center Ljubljana, Zaloška 2, 1000 Ljubljana
  • Alenka Sešek-Briški Univerzitetni inštitut za klinično kemijo in biokemijo, Univerzitetni Klinični center Ljubljana, Zaloška 2, 1000 Ljubljana
  • David Neubauer Univerzitetna Pediatrična bolnica, Bohoričeva 20, 1000 Ljubljana
  • Joško Osredkar Univerzitetni inštitut za klinično kemijo in biokemijo, Univerzitetni Klinični center Ljubljana, Zaloška 2, 1000 Ljubljana
Keywords: autism, children, heavy metals, vaccination, thymerosal

Abstract

Background: The aim of our study was to determine the levels of heavy metals in blood (zinc, copper, aluminium, lead, mercury), as well as the specific porphyrin levels in the urine of patients with ASD compared with patients with other neurological disorders.

Methods: The study was performed in a group of children with ASD (N = 52, average age = 6.2y) and control group of children with other neurological disorders (N = 22, average age = 6.6y), matched in terms of intellectual abilities (Mann-Whitney U = 565.0, p = .595). Measurement of heavy metals in blood was performed by atomic absorption spectrometry, while the HPLC method by means of a fluorescence detector was used to test urinary porphyrin levels. Results were compared across groups using a multivariate analysis of covariance (MANCOVA). In addition, a generalized linear model was used to establish the impact of group membership on the blood Cu/Zn ratio.

Results: In terms of heavy metal blood levels, no significant difference between the groups was found. However, compared to the control group, ASD group had significantly elevated blood Cu/Zn ratio (Wald χ2 = 6.6, df = 1, p = .010). Additionaly, no significant difference between the groups was found in terms of Uroporphyrin I, Heptacarboxyporphyrin I, Hexacarboxyporphyrin and Pentacarboxyporphyrin I. However, the levels of Coproporphyrin I and Coproporphyrin III were lower in the ASD group compared to the controls.

Conclusions: Due to the observed higher Cu/Zn ratio we’d suggest that blood levels of zinc and cupper should be tested in all children with ASD and a Zn supplement should be given as needed.

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References

Prevalence of Autism Spectrum Disorders–Autism and Developmental Disabilities Monitoring Network, United States, 2006. Erratum in: MMWR Surveill Summ. 2009; 58(SS10): 1–20.

King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol 2009; 38: 1224–34.

Sinzig J, Walter D, Doepfner M. Attention deficit/hyperactivity disorder in children and adolescents with autism spectrum disorder: symptom or syndrome? J Atten Disord 2009; 13: 117–26.

Anholt GE, Cath DC, van Oppen P et al. Autism and ADHD symptoms in patients with OCD: are they associated with specific OC symptom dimensions or OV symptom severity? J Autism Dev Disord 2010; 40: 580–9.

Fombonne E. Commentary: on King and Bearman. Int J Epidemiol 2010; 38: 1241–2.

Macedoni-Lukšič M. Stopenjska obravnava otrok s spektroavtističnimi motnjami. In: Kržišnik C, Battelino T, eds. Izbrana poglavja iz pediatrije. Ljubljana: Medicinska fakulteta, Katedra za pediatrijo; 2011. p. 311–17.

Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011; 68: 1095–102.

Rutter M. Aetiology of autism: findings and questions. J Intell Dis Res 2005; 49: 231–8.

Casey JP, Magalhaes T, Conroy JM, Regan R, Shah N, Anney R et al. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum Genet 2012; 131: 565–79.

Devlin B, Scherer SW. Genetic architecture in autism spectrum disorder. Curr Opin Genet Dev 2012; 22: 229–37.

Macedoni-Lukšič M, Krgović D, Zagorac A, Zagradišnik B, Kokalj-Vokač N. Array-comparative genomic hybridization as a powerful tool for detection of small genetic abnormalities in children with autism spectrum disorders. Med Razgl 2012; 51: S5.

Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect 2006; 114: 1119–25.

Schendel DE, Diguisseppi C, Croen LA, Fallin MD, Schieve LA, Wiggins LD. The study to explore early development (SEED): a multisite epidemiologic study of autism by the centers for autism and developmental disabilities research and epidemiology (CADDRE) network. J Autism Dev Disord 2012; 42: 2121–40.

Stoltenberg C, Schjolberg S, Bresnahan M et al. The autism birth cohort (ABC): a paradigm for gene-environment-timin research. Mol Psychiatry 2010; 15: 676–80.

King MD, Fountain C, Dakhlallah D, Bearman PS. Estimated autism risk and older reproductive age. Am J Public Health 2009; 99: 1673–9.

Shelton JF, Tancredi DJ, Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res 2010; 3: 30–9.

Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012; 129: 1121–8.

Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ Helath perspect 2011; 119: 873–7.

Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic-related air pollution, particulare matter, and autism. JAMA Psychiatry 2013; 70: 71–7.

Zerbo O, Iosif AM, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmetal delay? Results from the CHARGE study. J Autism Dev Disord 2013; 43: 25–33.

Shelton JF, Hertz-Picciotto I, Pessah IN. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environ Health Perspect 2012; 120: 944–51.

Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hertiala J, Allayee H et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE case-control study. Am J Clin Nutr 2012; 96: 80–9.

Braunschweig D, Duncanson P, Boyce R, Hansen R, Aschwood P, pessah IN et al. Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord 2012; 42: 1435–45.

Aschwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, van de Walter J. Association of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 2011; 232: 196–9.

Aschwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, van de Walter J. Altered T cell responses in children with autism. Brain Behav Immun 2011; 25: 840–9.

Costa LG, Aschner M, Vitalone A, et al. Developmental neuropathology of environmental agents. Annu Rev Pharmacol Toxicol 2004; 44: 87–110.

Geier DA, Audhya T, Kern JK, Geier MR: Blood mercury levels in autism spectrum disorders: Is there a treshold level? Acta Neurobiol Exp 2010; 70: 177–86.

James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 2004; 80: 1611–7.

Kobal AB. Možni vpliv živega srebra na patogenezo avtizma. Zdrav Vestn 2009; 78: 37–44.

Geier DA, Geier MR. A prospective assessement of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotox Res 2006; 10: 57–64.

Brester MA. Biomarkers of xenobiotic exposures. Ann Clin Lab Sci 1988; 18: 306–17.

Nataf R, Skorupka C, Amet L, Lam A, Springbett A, Lathe R. Porphyrinuria in childhood autistic disorder: implicationsfor enviromental toxicity. Toxicol Appl Pharmacol 2006; 214: 99–108.

Wang L, Angley MT, Gerber JP, Sorich MJ. A review of candidate urinary biomarkers for autism spectrum disorder. Biomarkers 2011; 16: 537–552.

Sarkany RP. Porphyria. From Sir Walter Raleigh to molecular biology. Adv Exp Med Biol 1999; 455: 235–41.

Gross U. Erythropoetic and hepatic porphyrias. J Inherit Metab Dis 2000; 23: 641–661.

Woods JS. The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercury exposure in humans. Toxicol Appl Pharmacil 2005; 206: 113–20.

Cohen DJ, Johnson WT, Caparulo BK. Pica and elevated blood lead level in autistic and atypical children. Am J Dis Child 1976; 130: 47–8.

Osredkar J, Sustar N. Copper and zinc, Biological role and significance of cupper/zinc imbalance. J Clinic Toxicol 2011; doi/10.4172/2161–0494.S3–001

DiGirolamo AM, Ramirez-Zea M. Role of zinc in maternal and child mental health. Am J Clin Nutr 2009; 89: 940S-5S.

Plum LM, Rink L, Haase H. The essential toxin: Impact of zinc on human health. Int. J. Environ. Res. Public Health 2010; 7: 1342–65.

Kang YJ. Metallothionein redox cycle and function. Exp Biol Med 2006; 231: 1459–67.

Russo AJ, DeVito R. Analysis of copper and zinc plasma concentration and the efficacy of zinc therapy in individuals with Asperger’s syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS) and autism. Biomarker Insights 2011; 6: 127–33.

Yasuda H, Yashida K, Yasuda Y, Tsutsui T. Infantile zinc deficiency: Association with autism spectrum disorders. Sci Rep 2011; 1, 129; DOI: 10.1038/srep00129.

Bayley N, Zupančič M, Kavčič T. Lestvice zgodnjega razvoja Nancy Bayley. (2. izd.). Ljubljana: Center za psihodiagnostična sredstva, 2004.

Wechsler D., Boben D, Bucik T. Priročnih za Wechslerjevo lestvico inteligentnosti za otroke. (3. izd.). Ljubljana: Center za psihodiagnostična sredstva, 2001.

Boben D. Slovenska standardizacija Ravenovih progresivnih matric: norme za CPM, SPM in APM. Ljubljana: Center za psihodiagnostična sredstva, 2003.

Strauss E, Shernan EM, Spreen O. A Compendium of Neuropsychological Tests. (3. izd.). New York: Oxford University Press, 2006.

Faber S, Zinn GM, Kern II JC, Kingston HMS. The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers, 2009; 14: 171–80.

Bjørklund G. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp, 2013; 73: 225–36.

Crăciun EC, Ursu M, Predescu E, Bjørklund G, Dronca M. The status of whole blood zinc and copper levels in autistic children. Romanian Review of Laboratory Medicine, 2009; 15: 132.

Kiddie JY, Weiss MD, Kitts DD, Levy-Milne R, Wasdell MB. Nutritional status of children with attention deficit hyperactivity disorder: A pilot study. Int J Pediatrics 2010; doi: 10.1155/767318.

Dufault R, Schnoll R, Lukiw WJ, et al. Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Behav and Brain Functions 2009; 5: 44–59.

Woody RM. Oxidative stress in autism. Alternative Therapies 2004; 10: 22–36.

Osredkar J. Oksidativni stres. Zdrav Vestn 2012; 81: 393–406.

Russo AJ, deVito R. Analysis of copper and zinc plasma concentration and the efficacy of zinc therapy in individuals with Asperger’s syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS) and autism. Biomarker Insights 2011; 6: 127–33.

Hertz-Picciotto I, Green PG; Delwiche L, Hansen R, Walker C, Pessah IN. Environ Health perspect 2009; 118: 161–6.

Mutter J. is dental amalgam sahe for humans? The opinion of the scientific committee of the European Commission. J Occupat Med Toxicol 2011; 6: 2.

Stehr-Green P, Tull P, Stellfeld M, Mortenson PB; Simpson D. Autism and thimerosal-containing vaccines: lack of consistent evidence for an association. Am J Prevent Med 2003; 25: 101–6.

Nelson KB, Bauman ML. Thimerosal and autism? Pediatrics 2003; 111: 674–8.

Parker SK, Schwartz B, Todd J, Pickering LK. Thimerosal-containing vaccines and autistic spectrum disorder: A critical review of published original data. Pediatrics 2004; 114: 793–803.

Madsen KM, Lauritse MB, Pedersen CB, et al. Thimerosal and the occurence of autism: negative ecological evidence from danish population-based data. Pediatrics 2003; 112: 604–6.

Hornig M, Chian D, Lipkin WI. Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry 2004; 9: 833–845.

Stamova B, Green PG, Tian Y, Hertz-Picciotto I, Pessah IN, Hansen R et al. Correlations between gene expression and mercury levels in blood of boys with and without autism. Neurotox Res 2011; 19: 31–48.

Gerecht M, Austin DW. The plausibility of a role for mercury in the etiology of autism: a cellular perspective. Toxicol Environ Chem 2011; 93: 1251–73.

Thompson MR, Boekelheide K. Multiple environmental chemical exposures to lead, mercury and polychlorinated biphenyls among childbearing-aged women (NHANES 1999–2004): Body burden and risk factors. Environ Res 2013; 121: 23–30.

Sarigiannis DA, Hansen U. Considering the cumulative risk of mixtures of chemicals – A challenge for policy makers. Environ Health 2012; 11(1 Suppl): S18–30.

How to Cite
1.
Macedoni-Lukšič M, Gosar D, Oražem J, Kodrič J, Lešnik-Musek P, Zupančič M, France-Štiglic A, Sešek-Briški A, Neubauer D, Osredkar J. Heavy metals and specific porphyrine levels in children with autism. TEST ZdravVestn [Internet]. 1 [cited 7May2024];83(5). Available from: http://vestnik-dev.szd.si/index.php/ZdravVest/article/view/1214
Issue
Vol 83 No 5 (2014): May
Section
Original article


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