Autism Etiology and General Recommendations based on Genetic Tests

With the advent of the genomics movement, patients around the world are performing genetic tests in hopes of understanding the underlying dynamics, etiology, causes, symptoms and behaviors associated to their conditions.

Given the complexity of the Autism Spectrum Disorder (ASD), many parents are performing genetic tests on their children in order to (hopefully) uncover key aspects of the genetic makeup of the disorder that may help them take specific actions to treat their children. Some of those parents voluntarily provided their children’s genetic reports to the Author of this article in order to create a unified story with the observations and recommendations that happened to be the most common across the reports.

Objectives

  • To create an easy-to-read unified report to elicit the underlying etiology of the Autism disorder based on genetic reports
  • To create a series of common recommendations that may serve as reference to other parents with children in the Autism spectrum
  • To summarize the recommendations of reports that may serve to other parents to evaluate the relative benefits of performing genetic tests on their ASD children
  • To provide a frame of reference so parents know what to expect when performing genetic tests in light of the financial investment they represent

Method

Seven parents located in Spain and Belgium voluntarily submitted their reports to the Author for analysis. The reports were all performed and analyzed by the company Genomic Genetics International based in Barcelona, Spain. The reports contained a series of findings and recommendations based on the tests performed on 7 children ranging between 3 and 14 years of age at the time of the test and that were performed between December 2015 and January 2019. The Author read the reports and created a unified story based on the common elements and their recommendations.

Limitations

Even though there is an increasing number of parents currently submitting their reports to be included in order to have a more representative sample (which will be updated as new information comes in), it is important to note that the goal of this research was not to perform a quantitative research on the variants and expressions to elicit the genetic code for Autism but to create a common list of observations and recommendations from some of the labs that are performing these tests so parents may contrast their current treatment protocols with the list of recommendations provided by labs across multiple children. By analyzing reports qualitatively, we may get a glimpse on the etiology of the disorder from the genetic perspective, which is generally explained as a chain reaction of events where the Autistic behaviors may be the ultimate manifestation of a series of genetic, metabolic, hormonal and chemical imbalances that elucidate the underlying pathology and may serve as a reference for parents seeking to confirm or modify the treatment strategies for their ASD children.

Disclosure

The Author has no financial interest in the company Genomic Genetics International or in any other lab performing genetic tests, and worked pro bono in the collection of the data, analysis, and writing of this article.

Etiology

According to the genetic reports, Autistic behaviors may be understood as the ultimate manifestation of a series of genetic “combinations of risk” that may trigger (or inhibit) key enzymatic pathways for the production and metabolism of certain neurotransmitters that are fundamental for brain activity and that may also enhance pro-inflammatory or inhibit anti-inflammatory agents in the body.

An example of this is the combination of risk associated with the production of catecholamine.

Catecholamine is a neurotransmitter that is a precursor of ACTH (adrenocorticotropic), a hormone that can produce lethargy and that can also inhibit the development of oxytocin, necessary for the development of language, sociability and that at low levels may cause lack of empathy.

Catecholamine is also a precursor to other neurotransmitters essential for brain activity, such as dopamine, adrenaline, noradrenaline and epinephrine.

  • Dopamine: In high levels produces a tendency to anxiety, excitability and nervousness, with increased risk of changes in mood and sleep disorders. Excess dopamine can also induce tics, repetitive acts, spasms, and involuntary movements
  • Adrenaline: In high levels may cause atypical alertness, nervousness, irritability,
    and greater difficulty of the body to relax
  • Histamine: May produce allergies and atypical sensitivities to food
  • Seratonin: A neurotransmitter responsible for regulating emotional behavior, sleep, sensitivity to pain, and the release of hormones. At high levels it increases beta-endorphins that could lead to behavioral disorders such as self-injury, and it plays a crucial role in the formation of synapses and overall neurodevelopment

Another example of common genetic combinations of risk are those that affect the activity of the MTHFR enzyme, the ADRB2 gene, the ACE gene, the COMT enzyme, the MET gene, the GSTM1/GSTT1 enzymes, the interleukin gene (IL6 / IL1B / IL10), the vitamin D receptor gene (VDR), and the enzymes CYP2C9, CYP2D6 and NAT2 ,

  • MTHFR: Participates in important methylation processes, i.e. elimination of toxins and heavy metals in the body
  • ADRB2: Related to tolerance to psychological stress, which might lead to manifestations such as tachycardia, sweating, increased tics and stuttering
  • ACE: Related to mineral balance in the body, i.e. decreased sodium excretion and increased urinary potassium excretion
  • COMT: Associated with the metabolism of dopamine, and associated to structural and functional changes in the cerebral cortex and hippocampus during the early stages of development
  • MET: Related to learning disabilities, gastrointestinal and immune system complications
  • GSTM1/GSTT1: Associated to glutathione production that participates in important methylation processes leading to the elimination of toxins and heavy metals in the body
  • IL6 / IL1B / IL10 and VDR: Associated to general processes of inflammation in the organism
  • CYP2C9, CYP2D6, NAT2: Drug-metabolizing enzymes associated with the risk of toxicity due to a genetic inability to metabolize certain drugs at their standard doses

From these combinations of risk, the company Genomic Genetics International provides parents with a series of “prevention strategies” that aim at regulating the production and metabolism of neurotransmitters in order to reduce Autistic behaviors.

General Recommendations

What follows is the summary of the most common recommendations that consist of a list of medications to avoid, dietary guidelines, supplements and exercise aiming at regulating the enzymatic activity responsible for the production and metabolism of the neurotransmitters of interest, as well as serving as catalysts in methylation processes, and regulate the excretion of minerals.

Medications to avoid

  • Acetaminophen (or paracetamol)
  • Beta-agonists, e.g. bronchodilators ventolin, fenoterol, etc.

Diet

  • Free of gluten, dairy, sugar, white flour, pesticides, artificial ingredients, sausages, processed foods, hydrogenated fats, fruits rich in sugars (e.g. banana or mango), corn, vegetable oils, monosodic glutamate (e.g. soy sauce, tomato, cured cheeses), red meats (especially ox, bull, deer, horse or foal), smoked foods, grilled or very made, and foods rich in tyrosine and phenylalanine
  • Rich in healthy fats, protein, fiber, antioxidants, blue fish (e.g. anchovies and sardines), lean meats (turkey / chicken without skin) from organic farms, foods rich in magnesium (almonds, peas, chickpeas, brown rice, oats, spinach, lettuce, borage, asparagus, watercress, cucumber, radish, plum, melon, celery, endives, apricots, raspberries, pears, pineapple, orange, dates, papaya and peach) and rich in zinc (lentils, sardines, celery, asparagus, fig, eggplant, potato, peach)
  • Reduce table salt

Supplements

  • Omega 3 (DHA)
  • B-complex (B2, B3, B6, B9, B12)
  • Vitamins A, C, D, E
  • GABA
  • Calcium
  • Magnesium
  • Zinc
  • Selenium
  • Phosphorus
  • Olive leaf extract
  • Glutathione precursors (e.g. N-acetylcysteine, whey protein, folinic acid, and –if not allergic to sulfates– sulforaphane)

Exercise

Avoid prolonged periods of immobilization and exercise to promote detoxification

Observations

  • It is important to note that none of the reports analyzed mentioned strategies to “correct” any of the genetic combinations of risk as such. There is no mention of how to activate or deactivate the mutations or genetic expressions that cause the disorders but are limited to making recommendations regarding diet, supplements, exercise, and medications to avoid
  • None of the reports mentions the use of cannabis oil or other derivatives of the cannabis plant known to promote desinflammation and production of neuroreceptors to regulate brain activity
  • There is also no mention of alternative treatments (e.g. stem cells, HBOT, et al.) that participate in anti-inflammatory and tissue regeneration/repair processes
  • Among the clearest benefits of performing genetic testing is the possibility of reducing or preventing the risk of drug toxicity due to the pharmacogenetic identification of drug-metabolizing enzymes associated with the inability of the organism to digest certain drugs at their standard doses
  • The majority of the conclusions of the reports are “mono-genetic” which means that they draw conclusions from observing specific genetic variants in isolation. An example of this are the APOE3 and APOE4 variants related to the capacity of neuroplasticity of the patient. Based on these variants, the reports make assertions related to the relative capacity of the patient to develop language and other learning and cognitive abilities. However, when following patients prospectively, it has been shown that many of these assertions have proven wrong. Patients with reported APOE variants that predicted an inability to develop language do so (at least to some extent) and patients with comorbidities generally limiting neuroplasticity (e.g. cerebral palsy) were reported a “favorable cognitive and neurodevelopmental” prognosis. This disconnect may be due to the lack of poly-genetic evaluations to (effectively) understand the “combinations” of risk in a more precise way, or due to the inherent error that genetic tests are subject to
  • Given the above, if parents so choose to perform these tests, it would be advisable to contrast the recommendations of these reports with blood, urine, etc. analytics whenever possible in order to validate the observations and not to take the conclusions as definitive but as possible areas of opportunity to investigate and obtain additional information on the underlying processes that permit to correct the Autistic symptoms and behaviors

Acknowledgements

A very big “Thank you!” to all the parents that provided their children genetic reports to unify the comments and recommendations. Special thanks to Natalia Marmol that reviewed the manuscript and provided valuable comments

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