What actually distinguishes the three potential diagnoses? To have autism a child struggles with social delays, language delays, and repetitive or obsessive behaviors. To have Asperger Syndrome a child has social delays, later delays in communication and language usage (without early language delay), average or above intelligence, and obsessive behaviors. To have PDD-NOS means a child has social and communication issues, but does not fully meet the criteria for either of the other two diagnoses. If that all seems relatively arbitrary and confusing, that's because it is (Bertin, M., 2012).
Side Note: condensing the spectrum diagnosis also will show a drop in autism according to a new study.
ASD is an umbrella diagnosis for a clutch of symptomology that is not well understood by many. Those of us in the autism community struggle with the label because we find it a dishonest description of our child's disability. We also feel that the decades of unproductive genetic research has wasted precious time that could have been spent addressing the specific diagnostic biomarkers of this disorder. But, that is all changing now. In the past 5 years the biological symptoms of autism are now coming to surface thanks to a few researchers that have understood the need of science in this area.
Key Points To Understanding The Diagnosis
Many recent studies suggest that cases of autism have been increasing (1, 6, 10-22). Charman (48) suggested three possible explanations for the increases: (1) recent studies include artifacts that produce a false increase, (2) the current rate is correct but does not indicate a true increase, (3) and
the current increase is correct and indicates a real increase... The incidence of autistic individuals appears to be continuing to increase, and the societal and economic costs associated with this increase are substantial. Although artifacts associated with observed increases in various studies
cannot be ruled out, from a precautionary standpoint, it seems prudent to assume that at least some portion of this increase in incidence is real and results from environmental factors interacting with susceptible populations. As such exposure is potentially preventable, identification of relevant
candidate environmental factors should be a research priority. (McDonald, M., Paul, J., 2010).
Future studies should examine for novel or increasing exposures to environmental factors from gestation to at least age 3 for our calculated 1988-1989 birth cohorts... Any candidate environmental factor also should be examined for differences in the level of exposure among the different study areas used in our analyses... The possibility of exposure to several environmental factors acting
synergistically on susceptible populations also cannot be ruled out... Toxicological examination of any candidate environmental factor also would need to be conducted. Candidate factors would need to be disruptive to early human neural development, routes of exposure would need to be consistent with bioavailability to fetuses and infants, and the timing of increases in the production, use, or disposal of a factor resulting in human exposure would have to be consistent with our calculated changepoints and exposure gradients (McDonald, M., Paul, J., 2010).
More science on the epidemic of autism "72% (professional psychologists) reported wither the true rate may have, or definitely has, increased" (DeSoto et al., 2013). Further, Dave et al published a peer reviewed article, which also documented a statistically significant increase in autism when thinking about the prevalence or displacing other mental disorders (Dave et al., 2014).
Specific Diagnostic Biomarkers Of Autism
1. Immune System Dysfunction (low levels of immunoglobulin G etc).
"One of our first findings was that immunoglobulin G was much lower in children with autism," Van de Water says. IgG, as it is more commonly called, is an antibody sub-type responsible for the majority of the immune response to invading pathogens.
"This tells us there is likely something wrong in a very basic cell-signaling pathway."
Van de Water and her collaborators also have found that antibody responses to vaccines against bacteria are lower than expected in people with autism, while antiviral responses are fairly normal. This, she explains, was their first clue that the problem lies in the innate immune response – the short-term, non-specific host response to pathogens. Her goal now is to study whether children with autism have autoantibodies to brain proteins and if mothers of children with autism show exaggerated immune responses to proteins in fetal brains.
"We want to know the function of these antibodies during gestation" (UCDavis Medicine, 2007).
Microglia are specifically adapted to sense various types of danger and differentially react with a classical or alternative reparative response. Our understanding of macrophage function has shifted away from focusing on cell lineage to a more systems-based biology of gene networks accomplishing the detoxification and immune functions. With our greater appreciation of microglial involvement in the innate immune response, we have entered a new era in which the modulation of microglia can be proposed as a means of modulating neurological disease (Kofler, J., Wiley, C., 2011).
So what does all that mean?
Let's look at low glutathione levels in ASD children first. What is glutathione AKA gamma-Glutamylcysteineglycine (GHS): This protein that is made up of three amino acids (cysteine, glutamic acid, and glyceine) is prolific in nearly all the cells in the body, powerful antioxidant, potent anti-viral, anti-cancer agent, detoxifies toxins, promotes the protections of proteins, promotes DNA repair, maintains cellular homeostasis, most notably is maintains normal brain function.
Now that we know what glutathione dose let's look at what suppresses it in the body; acetaminophen (Tylenol) and other pharmaceuticals, acetone, solvents, paint removers, fuels, fuel by-products, heavy metals (mercury (dental amalgams), lead, cadmium, copper, etc.), pesticides, herbicides, nitrates and other food preservatives of chemical origin (in salami, hot dogs, hams, bologna, smoked foods, etc.), artificial sweetener aspartame, benzopyrenes (tobacco smoke, barbequed foods, fuel exhaust, etc.), alcohol, household chemicals (synthetically scented and colored detergents and fabric softeners, air fresheners, mothballs, mildew removers, cleaners and bleach, lawn and plant fertilizers, etc.), housewares chemicals (non-stick coating of pans and skillets, plastic containers and linings of tin cans and other food packaging), formaldehyde and styrene (photocopiers and toner printers), chlorine in treated water, medical X-rays, UV radiation, industrial pollutants (Immune Health Science, 2013). I have highlighted some of the more common elements that we in the autism community associate with vaccine injury, but as you can see our population is inundated with glutathione reducers.
The glutathione redox status is also connected with mitochondrial function (discussed later). And is it not interesting that children who have ASD have a high incidence of mitochondrial dysfunction without the gene mutation, called "acquired mitochondrial dysfunction" (Frye et al., 2013).
Collectively, these studies suggest a critical role for microglia in the innate immune response to CNS pathogens, leading to the activation of adaptive immune functions, most importantly Ag presentation capacity. Microglia have been suggested to play a role in MS, a human T cell-mediated autoimmune demyelinating disease (5). MS has been suggested to be initiated and/or exacerbated by infections, particularly in the CNS (4). Thus, the innate immune response to pathogens infecting the CNS may play an important role in the development and/or exacerbation of the underlying autoimmune response, in which triggering of proinflammatory cytokine production by the microglial innate immune response may play an important role" (Olson, J., Miller, S., 2004).
Sub-group 1: Elevated Lactate - mito dysfunction with no underlying gene mutation
Sub-group 2: Elevated AST - oxidative stress rather than impaired mitochondrial function
Sub-group 3: Elevated Alanine/Lysine ratio - mito dysfunction associated with Complex 1 deficiency
Sub-group 4: Elevated Multiple Acylcarnitines - no mito, associated w/ clostridia bacteria
Dr. Frye researched deeper into the abnormal lab findings of each group and found further lab abnormalities that were unique to each sub-group.
Sub-group 1: Elevated urine 2-methyl-3-hydroxybutyric acid, and ammonia
Sub-group 2: Lower urine 5-oxoproline (AKA pyroglutamate, a metabolite involved in glutathione utilization and recovery). May signal glutathione depletion.
Sub-group 3: Elevated alanine and urine pyruvate. Sub-group had a higher rate of epilepsy.
Sub-Group 4: Elevated C5OH, C12, C14, C14:OH and C16 acylcarnitines; not consistent with any known fatty oxidation disorder. Elevated urine 3-OH-3methylglutaric acid; citric acid cycle dysfunction. Sub-group had a higher rate of autistic regression.
Now I can go into demyelination and methylation, which is all tied into these systems and how that impacts neurological disease (autism etc) but I will save that for another day.
To review further: Current science in brain/biological disorders, autoimmunity, and mitochondrial disease in autism.
Evaluating the weight of peer-review, ASD is presenting as a systemic abnormality creating immune dysregulation/inflammation, impaired detoxification, redox regulation/oxidative stress, and mitochondrial dysfunction. Caused by toxicant exposures with genetic interplay.