Extra Chromosome & Absent Enzyme; A look at Down Syndrome and MTHFR

Down Syndrome is a genetic mutation identified by an extra 21st chromosome. MTHFR is a genetic mutation identified by the absence of a vital enzyme essential for folate metabolism. There is an intimate connection between these 2 conditions, and by identifying MTHFR in children with Down Syndrome risks for many co-morbid conditions can be reduced or eliminated.
Contributing Factors
Environmental and Maternal Disposition. There has been recent research showing there is a higher incidence of children with Down syndrome born to mothers that are positive for MTHFR. Multiple polymorphisms were identified in this study which simply correlates the association. Practically speaking MTHFR mutations are seen in elevated levels in autism, spina bifida, fetal cardiac defects and Down syndrome. However, to solely implicate genetics in any medical condition is bad medicine. The environment plays such a large role in influencing our genes. Because of the role that MTHFR plays in folate metabolism and Homocysteine metabolism this association bears regard and acknowledgement.
It has been well researched that Children with Down Syndrome have higher incidences of:
Midline Development Issues
Heart defects. Almost one-half of babies with Down syndrome have congenital heart disease, the most common type of birth defect. MTHFR mutations are associated with a higher incidence of Heart Defects. MTHFR effects “midline development” the heart is an organ that develops form the midline in utero.
Hypothyroidism. Occurs more often in children with Down syndrome than in children without Down syndrome. Close evaluation of thyroid health, diet, supplements and possibly medication can assist in balancing this condition. Again, the thyroid is developed from the “midline” embryonic tissue. The same layer that is effected by the presence of MTHFR mutations. Research shows us children with Down syndrome are born to mothers with MTHFR mutations themselves. Genetics, and an extra chromosome leads to a much higher incidence of hypothyroidism.
Dental problems. Children with Down syndrome generally have a higher palate. This changes the landscape of the mouth and jaw and can cause teeth and speech development that differs from what is expected. Gum disease, is also very common. Gum Disease is well studied as a problem with digestion, bacteria imbalance and nutrient deficiency. MTHFR mutations are closely correlated with dental problems. Again, the gums and teeth develop from the “midline” during pregnancy. MTHFR mutations cause an “inefficiency” of folate metabolism. When this system is impaired the body uses additional vitamins and minerals (stored in the teeth and bones) to properly run its cycles. If nutrient levels are lower that the body’s demand the teeth and gums will suffer.
Sense Organs Issues
Vision problems. More than 60% of children with Down syndrome have vision problems. MTHFR defects can affect the eye. The vessels of the eye are so small that any kind of inflammation or excessive toxicity can “get stuck” in the small vessels of the eye and effect vision.
Hearing loss. About 75% of children with Down syndrome have some hearing loss, sometimes because of problems with ear structures. Children with Down syndrome also tend to get a lot of ear infections, due to narrow canals and anatomic variation which should be watched closely. MTHFR is more highly associated with sensory issues associated with hearing impairments.

Immunity and Blood Issue</strong>s
Infections. Kids with Down syndrome are 12 times more likely to die from untreated and unmonitored infections compared to kids without Down syndrome. The Immune system develops differently in kids with Down Syndrome, which can cause problem with immunity. This poses challenges with children and the current immunization schedule. In children with impaired immunity, vaccines can cause unanticipated reactions, which can lead to further health concerns. MTHFR and its ability to metabolize folate plays an intimate role in the immune system. These mutations can cause reduced immune function, bone marrow suppression and the inability to produce proper components of the immune system.
Blood disorders. Are common in children with Down syndrome. There is a 10 to 15 higher incidence of developing leukemia. Kids with Down Syndrome are at higher risk for a diagnosis of anemias of all kinds (low iron, low B12, high red blood cells, etc.). MTHFR is the enzyme that controls folate (B9) metabolism, however proper signaling of methylation, the pathway signaled by the MTHFR enzyme also requires proper interface with B!2 and B6, without these other B vitamins the pathway operates ineffectively and can further problems with anemias of all kinds.
Structural Issues
Hypotonia (poor muscle tone). Poor muscle tone and low strength is a common contributor to “delayed” milestones in Children with Down Syndrome. Low Tone can also effect nursing, swallowing, speech development, constipation and coordination.

Many of these problems can be addressed with skilled providers educated in the specificity of Down Syndrome Concerns. MTHFR pathways assist to eliminate toxins in the body. The benefit of an efficient elimination system means the body reduces its exposure to toxins and therefore reduces its potential for disease. Keeping MTHFR in good working order helps the body better balance muscle and strength development as well as reduce the problems associated with low tone.
Atlantoaxial Instability. Is present in 20% of children with Down syndrome. This is associated with an increased incidence of spinal cord injury and should be evaluated by a skilled provider for the best course of treatment. MTHFR is not associated with Atlantoaxial instability, however it is well reported that individuals with MTHFR have a higher incidence of damage to ligaments and tendons when ingesting “floxin” antibiotics. This should be thoroughly researched by any provider prescribing antibiotics to children with Down syndrome.
Digestion Absorption and Elimination
Digestive problems. Digestive problems in kids with Down syndrome, range from structural defects in the digestive system, food sensitivity or food allergy, and food aversions or addictions. Due to the metabolic and genetic components with Down syndrome very specific diets can be recommended and useful for a lifetime of healthy digestion, assimilation and weight balance. The research shows that approximately 80% of individuals with MTHFR have food allergy or food sensitivity. Remember that individuals with MTHFR have a harder time with detoxification where as individuals with Down syndrome have an impaired immune system.
Celiac disease. Is very common with Down syndrome. Celiac is an immune and gastrointestinal inability to digest the protein found in wheat and other grains containing gluten. Gluten should be completely avoided throughout a lifetime, this can be of benefit for a host of conditions that are associated and co-diagnosed along with Down syndrome. Individuals diagnoses with MTHFR have a 60% incidence of having Celiac disease as well. This is an important screening for all kids with any sort of immune dysregulation. Kids with Down syndrome can be susceptible earlier and with more severe symptoms.
Mental & Emotional
Mental health and emotional problems. There is a very high incidence of anxiety, depression, perseveration, and Attention Deficit Hyperactivity Disorder associated with Down syndrome. Individuals with MTHFR have higher incidence of anxiety, and depression. In some cases, the proper balance of specific B vitamins can improve symptoms in a very short timeframe avoiding medication and its problematic side effects.
Sleep disorders. Many children with Down syndrome have disordered sleep. This can be due in part to obstructive sleep apnea, narrow structures in the head and neck, food sensitivities or side effects of medication. MTHFR mutations can certainly cause issues with sleep. When folate metabolism is impaired a dysregulation in the body occurs. Also, effecting sleep can be B12 levels which can cause bedwetting, anxiety and restlessness

In conclusion Down syndrome and MTHFR are closely related and treating and supporting proper functioning of the MTHFR enzyme can dramatically improve outcomes or assist to avoid complications kids with Down syndrome may occur in their lifetime.
1. Bull, M. J., & the Committee on Genetics. (2011). Health supervision for children with Down syndrome. Pediatrics, 128, 393–406. [top]
2. So, S. A., Urbano, R. C., & Hodapp, R. M. (2007) Hospitalizations of infants and young children with Down syndrome: Evidence from inpatient person-records from a statewide administrative database. Journal of Intelle
3. Hardy, O., Worley, G., Lee, M. M., Chaing, S., Mackey, J., Crissman, B., et al. (2004). Hypothyroidism in Down syndrome: screening guidelines and testing methodology. American Journal of Medical Gen
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078648/pdf/nihms-259545.pdf
5. http://www.sciencedirect.com/science/article/pii/S1110863015000889
6. https://www.ncbi.nlm.nih.gov/pubmed/11807890
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168164/
8. http://ajcn.nutrition.org/content/70/4/429.long


Warrior or Worrier? The truth about COMT


Catechol-O-methyltransferase (COMT) is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. COMT is mostly found in the peripheral nervous system, and less significantly found in the Central Nervous System, and found in the highest concentration in the liver.


There are 2 types of COMT expression, the warrior and the worrier.



Generally have a higher IQ

do better on tests

better toxin elimination

higher estrogen elimination

higher incidence of ADHD

Higher pain tolerance

Normal magnesium levels

Normalized B12 and folate levels

Even tempered


Slower estrogen elimination and estrogen dominance
Lower pain tolerance

Increased probability of addiction and anorexia

PMS worse in females

Enhanced response to stimulants

Red face after exercise & Decreased Sweating

Lower Mg levels

Lower Intracellular b12 and folate

Prone to mood swings and mania








COMT is the enzyme that allows you to spare the “feel good hormones” dopamine and nor-epinephrine. If this enzyme is completely blocked mood swings and addiction can occur. Keeping the gut healthy with probiotics and a good diet assures proper conversion of the amino acids needed to manufacture quality neurotransmitters. Lots of antibiotics and processed food can impair digestion and create impairments in conversion and manufacturing.

One of the most important jobs that COMT has, is to degrade dopamine, in the brain, where it is broken down by MAO (monoamine oxidase). MAO is Another important snp/gene that encodes an enzyme partially responsible for the metabolism of several neurotransmitters such as dopamine and serotonin. The monoamine oxidase family of enzymes, metabolize monoamines (neurotransmitters and neuromodulators consisting of a single amine).

COMT is the enzyme that introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids, are substrates of COMT. This is why individuals with a COMT mutation are considered estrogen sensitive and estrogen dominant.

By discussing and understanding the biochemistry and intricacies of the COMT enzyme we can begin to see the problems with it when individuals have missing or reduced functioning.

COMT mutations cause great difficulty with detoxing. COMT pathways toss out good and bad minerals indiscriminately leaving low level magnesium (among others), an essential mineral to uptake b12 properly.  B12 levels can be supplemented with success using lithium orotate, please check with a provider about dosing. Supplementing with lithium to enhance transport may in fact cause a b12 deficiency if its not done properly.

Individuals with a COMT mutation are generally volatile susceptible to depression, mood disorders and issues with toxicity.  This means be mindful of your stress and moods and put some supports in place during times of physical and emotional stress. Addiction is common with individuals carrying this SNP too, I highly recommend early and often discussions around drugs, alcohol and other addictive substances or behaviors.


COMT mutations can make people sensitive to phenols. Phenols are found in purple and red foods, such as strawberries and red grapes, these slow the function of the enzyme further. When the COMT enzyme slows there can be mood swings, insomnia or anxiety. Symptoms of people with phenol sensitivities are heat intolerant suffer from headaches and insomnia.


In a nutshell, individuals with COMT mutations require individualized, targeted treatment and should be addressed on all facets of wellness!