By Marcia Zimmerman, CN, October 2010
“Diagnostic criteria for autism spectrum and attention deficit disorders have traditionally relied solely on behavioral criteria without consideration for potential biomedical underpinnings. The use of biomarkers is of great importance in young children with ADHD or individuals at any age with ASD.” James Jeffrey Bradstreet, M.D., et al.
Key Words: biomarker, metabolic abnormalities, glutathione, metallothionein, oxidative stress, methylation
Autism has been difficult to diagnose, particularly in its very early stages and this is when it can most easily be treated. Consequently scientific focus has shifted toward identifying metabolic abnormalities through biomarker testing. These tests characterize ASD and can also be used to distinguish it from ADHD. One of the earliest ways to identify children at risk for ASD may be testing umbilical cord blood for mercury when they are born.1 And while this may help in early treatment, what can you do with a child who is already on the spectrum?
Biomarkers are chemicals that can be objectively measured and give evidence of normal or disturbed metabolic processes and/or toxin burden. Such abnormalities are associated with deficits in development, cognition, focus, and attention. Biomarkers can also be a useful guide for biomedical intervention.2
In previous Zimmerman Files we discussed the effects of toxin exposure on metabolism (August) and the genetic and epigenetic basis for ASD (September). Let’s now take a look at how these factors affect the health of ASD and ADHD children.
Multiple Biological Problems
Children with ASD and/or ADHD have multiple metabolic abnormalities. Many of these overlap, but distinct patterns can be seen between the two disorders through biomarker testing.3 Both ASD and ADHD children bio-accumulate toxic metals because their protective detoxification systems aren’t working properly. Mercury is the toxin most connected with ASD while lead is the principle toxin associated with ADHD.4 Reduced capacity of glutathione and metallothionein, two proteins that detoxify heavy metals, has been discovered in both conditions.5,6,7 Oxidative stress levels rise because the body cannot remove harmful free radicals generated by toxins. ASD and ADHD children have higher levels of oxidative stress than normal children.8
Biomarkers for Oxidative Stress
Glutathione status can be determined by measuring red blood cell levels of the amino acids cysteine, taurine, reduced glutathione, oxidized glutathione, and free and total sulfate.9 Several studies have also found that ASD children have significantly lower blood levels of total and reduced glutathione as compared to non-ASD children.10 Interestingly, some parents of ASD children were found to have impaired glutathione and methylation capacity, as well. They may not have been on the spectrum but had other neurological impairments, such as depression, anxiety or even ADD.11 This evidence supports the genetic underpinnings of ASD. Methylation is described in detail in the September Zimmerman File as it applies to faulty genetic switching from epigenetic effects. These switches determine genetic expression and they are can be disordered by toxic burden.12
Biomarkers for Toxic Metals
Toxic metals such as mercury, lead, cadmium, and arsenic can be measured in blood and hair. Hair can be an excellent indicator of long term exposure while blood is a better indicator of recent exposure.13,14 The inability of an ASD or ADHD child to clear toxic metals from their body can be determined by a biomarker test for a specific group of urinary porphyrins.15
Gastrointestinal Disorders in Autism
Gastrointestinal disorders and associated symptoms are commonly reported in children with ASD.16 Verbal communication is difficult for many of these children and they may not be able to clearly describe their symptoms.17 These may include abdominal pain, constipation, chronic diarrhea, and gastroesophageal reflux disease (GERD).18 Inflammation of the intestinal wall, possible caused by toxic metal burden and the resulting oxidative stress, can lead to immune problems, malabsorption, disordered intestinal flora and sensitivity to certain dietary proteins such as wheat and casein.19,20,21,22 Biomarker testing for food sensitivities, intestinal inflammation, gut microflora, parasites, amino acids, and short chain fatty acids, can be done with a stool sample.
1 Grandjean, P; Budtz-Jergensen; “Umbilical Cord Mercury Concentration as Biomarker of Prenatal Exposure to Methylmercury” Environ Health Perspect 2005;113:905-908.
2 Bradstreet, JJ; Smith, S. et al.; “Biomarker-Guided Interventions of Clinically Relevant Conditions Associated with Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder” Altern Med Review 2010;15:15-32.
4 Nicolescu, R; Petcu, C; “Environmental Exposure to Lead, but not Other Neurotoxic Metals, Relates to Core Elements of ADHD in Romanian Children: Performance and Questionnaire Data” Environ Res 2010;110:476-483.
5 Geier DA; Kern, JK; et. Al.; “Biomarkers of Environmental Toxicity and Susceptibility in Autism” J Neurological Sci 2009;280:101-108.
6 Adams, JB.; Barel, M.; et al.; “The Severity of Autism is Associated with Toxic Metal Body Burden and Red Blood Cell Glutathione Levels” J Toxicol 2009;doi:10.1155/2009/532640.
7 McFadden; “PphenotypicVariation inh Xenobiotic Metabolism and Adverse Environmental Response: Focus on Sulfur-Dependent Detoxification Pathways” Toxicology 1996;111:43-65.
8 McGinnis, WR; “Oxidative Stress in Autism” Altern Therapies 2004;10:22-37.
9 Grier, DA; Kern, JK; et al.; “A Prospective Study of Transsulfuration Biomarkers in Autistic Disorders” J Neurological Sci J 2009;280:101-108.
10 James, SJ; Rose, S’ et al.; “Cellular and Mitochondrial Glutathione Redox Imbalance in Lymphoblastoid Cells Derived From Children with Autism” FASEB J 2009;23:2374-2383.
11 James, S.J.; Meinyk, S.; “Abnormal Transmethylation/transsulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism” J Autism Dev Disord 2008;38:1966-1975
12 James, SJ; Cutler, P; et al; “Metabolic Biomarkers of Increased Oxidative Stress and Impaired Methylation Capacity in Children with Autism” Am J Clin Nutr 2004;80:1611-7.
13 Majewska, MD; Urbanowicz, E.; et al.; “Age-Dependent Lower of Higher Levels of Hair Mercury in Autistic Children Than in Healthy Children” Acta Neurobiol Exp. 2010;70:196-208.
14 Irva Hertz-Picciotto; Green, PG; et al.; “Environ Health Perspec 2010;118:161-166.
15 Woods, JS; Armel, SE.; “Urinary :Porphyrin Excretion in Neurotypical and Autistic Children” Environ Health Perspec. 2010.
16 White, JF; “Intestinal Pathophysiology in Autism” Exp Biol Med. 2003;228:639-649.
17 Horvath, K.; Perman, JA.; “Autism and Gastrointestinal Symtptoms” Curr Gastroenterology Rep. 2002;4:251-258.
18 Buie, T.; Campbell, DB.; et al.; “Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals with ASDs: A Consensus Report” Pediatrics 2010;125:S1-S18.
19 Jyonouchi, H.; Geng, L.; et al.;”Impact of Innate Immunity in a Subset of Children with Autism Spectrum Disorders: a Case Control Study” J Neuroinflam. 2008;5:52 doi:10.1186/1742-2094-5-52.
20 Jyonouchi, H.; Geng, L.; “Evaluation of an Association Between Gastrointestinal Symptoms and Cytokine Production Against Common Dietary Proteins in Children with Autism Spectrum Disorders” J Pediatr 2005;146:605-10.
21 Parracho, HM.; Bingham, MO.; et al.; “Differences Between the Gut Microflora of Children with Autistic Spectrum Disorders and That of Healthy Children” J Med Microbiology 2005;54:987-991.
22 Evans, C.; Dunjstan, RH.; et al.; “Altered Amino Acid Excretion in Children with Autism” Nutritional Neuroscience 2008;11:9-17.