Recently, I had the pleasure of attending MAPS conference with the theme ‘Autism and Genetics’. I often leave conferences with a bunch of reference material, great nuggets to use in practise and feeling full. This one I felt like I drank water from a fire hose and drowned in all of this fascinating information…So I’ve sat with it a bit, sifted through my notes, and have come out the other side SO excited that I had the chance to dig deeper into my favorite area of practise right now – Autism.
We know autism is a multifaceted condition influenced by an interplay of genetic, environmental, neurological, and biochemical factors. While no two children with autism are the same, emerging research is helping us better understand some of the underlying contributors. Three critical areas to consider are mitochondrial function, detoxification capacity, and the gut microbiome—systems that are especially vulnerable during early development.
Mitochondria, the energy-producing organelles in our cells, are essential for proper brain development and function. Children with autism often show signs of mitochondrial dysfunction, leading to fatigue, immune imbalance, and impaired cellular repair. Additionally, a sluggish detoxification system may make it harder for a child to clear environmental toxins, such as heavy metals and pesticides, which can interfere with neurodevelopment. Lastly, the gut-brain axis—modulated by the diversity and balance of microbes in the intestines—has a profound effect on mood, behavior, and cognitive function. Disruptions in the gut microbiome, often due to diet, antibiotic exposure, or infection, can fuel inflammation and neurological imbalance.
Yet, how do genetics come into play? Let’s talk about how specific genetic polymorphisms—or SNPs (single nucleotide polymorphisms)—may contribute to autism risk by affecting neurotransmitter balance, detoxification, folate metabolism, and immune regulation.
Often times with genetics and specifically SNPs we hear about MTHFR. So let’s talk about the obvious first, yet more importantly, get into some of the juicier SNPs quickly after
MTHFR (Methylenetetrahydrofolate Reductase): MTHFR mutations affect the body’s ability to convert folic acid into methylfolate and subsequently into methyltetrahydrofolate (this is the active form that the body uses). This is a necessary step in the methylation cycle (methylation runs over FOUR HUNDRED (!!) different enzymes in our body). A dysfunctional MTHFR gene can result in low SAMe (S-adenosylmethionine) and high homocysteine, both of which are red flags for oxidative stress, poor detoxification, and epigenetic dysregulation. These disruptions can impair neural development, immune regulation, and cellular repair, increasing the risk of autism.
That’s not all though!
MAO (Monoamine Oxidase): MAO genes (particularly MAO-A) regulate the breakdown of key neurotransmitters such as serotonin, dopamine, and norepinephrine. Certain MAO polymorphisms can lead to either excessive or insufficient enzymatic activity. When MAO function is compromised, it may contribute to mood instability, aggression, or emotional dysregulation—traits sometimes seen in children on the spectrum. Because neurotransmitter balance is vital for attention, sleep, and social interaction, impaired MAO activity can play a significant role in behavioral symptoms.
COMT (Catechol-O-Methyltransferase): The COMT gene is responsible for breaking down catecholamines—dopamine, epinephrine, and norepinephrine. A slow COMT variant can lead to heightened stress sensitivity, anxiety, and trouble modulating sensory input, while a fast variant may deplete dopamine too quickly, affecting focus and motivation. COMT also plays a role in estrogen metabolism and methylation, both crucial for detoxification and brain function. This is helpful to work with/support when patients are going through puberty.
MTR & MTRR (Methionine Synthase and Methionine Synthase Reductase): The MTR and MTRR genes support the recycling of vitamin B12 and folate within the methylation cycle. When polymorphisms occur in these genes, the body may struggle to maintain adequate methylation status (remember how this runs over 400 different enzymes in our body??), further reducing SAMe levels and increasing homocysteine. This creates a biochemical environment more susceptible to neuroinflammation and oxidative stress, which may impair brain development and immune tolerance in early life.
GABRB3 (Gamma-Aminobutyric Acid Type A Receptor Beta3 Subunit): The GABRB3 gene influences the function of GABA, the brain’s primary inhibitory neurotransmitter. Impairment here can result in altered levels of BDNF (brain-derived neurotrophic factor), which is essential for neuron growth, synaptic plasticity, and learning. GABRB3 mutations are associated with increased autism risk, seizures, and difficulty with sensory integration, often manifesting as hyperactivity or severe anxiety.
FOLR1 (Folate Receptor Alpha): The FOLR1 gene codes for folate receptors that transport folate into the brain. When FOLR1 is compromised, folate transport across the blood-brain barrier is reduced, potentially leading to cerebral folate deficiency. This impairs DNA methylation, neurotransmitter synthesis, and myelination—all crucial for early brain development. Children with FOLR1 autoantibodies or SNPs may benefit from folinic acid therapy under a clinician’s guidance. Enter leucovorin – a hot topic right now in the news. FOLR1 autoantibodies are the culprit here, and leucovrin has the cape on to save the day.
GAD1 (Glutamate Decarboxylase 1): GAD1 encodes the enzyme that converts glutamate into GABA. When this conversion is hindered, the result can be excess glutamate—an excitatory neurotransmitter linked to anxiety, sensory sensitivity, and neuroinflammation. Inadequate GABA levels from GAD1 mutations can make social interaction, emotional regulation, and sleep more difficult, all common challenges in autism.
MBL2 (Mannose-Binding Lectin 2): MBL2 is a gene involved in innate immune function. Variants in MBL2 can reduce the body’s ability to fight off fungal and bacterial infections, especially in the gut. This can predispose children to chronic candida overgrowth, gut inflammation, and immune dysregulation—all of which have been associated with autism-like behaviors.
While it may be tempting to view these SNPs as definitive causes of autism, it’s vital to remember that genetic variations only set the stage—they do not write the script. A child may carry one or several of these polymorphisms without ever developing autism or related challenges. It is the combination of genetic susceptibility and environmental influences—such as diet, toxin exposure, infection, and stress—that ultimately determines how these genes are expressed. I have spoken to parents so much this past week of exactly this concept – that autism is multi factorial. As naturopathic doctors, our role is to look at the whole child. By identifying genetic vulnerabilities early, we can make informed decisions about nutritional support, detoxification, lifestyle, and gut health, all while honoring the uniqueness of each individual child. Supporting a child with autism is not about “fixing” them—it’s about optimizing their environment so they can thrive in their own way. With compassion, science, and a holistic lens, we can empower families with the tools to support their child’s development from the inside out.
