Signs and symptoms of MTHFR banner

Signs and symptoms of MTHFR

What are the signs and symptoms of MTHFR in adults and children?

The MTHFR gene mutation can cause a range of symptoms, depending on the type and severity of the mutation.


Those who are heterogeneous (one copy of the C677T or A1298C mutation) are less likely to have severe symptoms because their MTHFR enzyme still functions at around 65%. Those who are homozygous for the C677T mutation have only 30% of normal enzyme function, which means they are more likely to experience symptoms.1


Knowing how to recognize the symptoms can help you to understand whether you are affected, and what kind of treatment to seek.

List of MTHFR signs and symptoms in adults

Neurological symptoms

Toxicity symptoms

Miscellaneous symptoms

  • Hearing loss
    The MTHFR C677T mutation appears to increase the risk of hearing impairment in middle-aged and elderly people

When should you contact a doctor?

If you are experiencing symptoms that affect your quality of life, consult your doctor or health professional.


If you or members of your family are affected by cardiovascular issues, mental health disorders, or recurrent miscarriages, it may be helpful to find out if you have a MTHFR genetic mutation. MTHFR testing can be requested from your doctor or you can purchase an at-home test kit online. 

Depression, anxiety, and other mood disorders (bipolar disorder, schizophrenia) Several studies have linked the C677T mutation to an increased risk for anxiety and depression.2
Behavioral disorders (ADHD, autism)
Genetic research shows that MTHFR C677T is linked to the development of ADHD.3
A recent meta-analysis has also linked autism spectrum disorders to MTHFR.4
Insomnia
Chronic fatigue and chronic pain syndromes
MTHFR mutations can be associated with chronic pain syndromes due to folate metabolism pathways affecting nerve function over time.5
Heavy metal toxicity
MTHFR C677T has been associated with increased levels of cobalt and arsenic, while MTHFR A1298C is associated with increased levels of potassium and lead. Heavy metals and SNPs in the genes are capable of inducing toxicity even at low levels and can cause a variety of health issues.9
Poor liver function
SAMe is mainly needed for methylation of a large variety of substrates (DNA, proteins, lipids and many other small molecules) and polyamine synthesis, so if SAMe levels are low (as in the case of MTHFR) the normal function of the liver will be also affected.10 Patients with chronic liver disease often have reduced SAMe biosynthesis.

Frequently Asked Questions about MTHFR Symptoms

What are the signs and symptoms of MTHFR?

Signs of MTHFR may include high homocysteine levels, mental health disorders such as depression, and some behavioral disorders such as autism and ADHD. Each of these conditions has its own set of symptoms.

What does MTHFR feel like?

MTHFR is different for every individual, depending on the type and severity of the mutation. People with a double mutation may be more likely to experience more significant symptoms associated with high homocysteine, such as cardiovascular disorders and depression. People with a single mutation may not experience many symptoms in their lifetime at all.

Are stork bites a sign of MTHFR?

There is no evidence that stork bites are a sign of MTHFR mutations. Stork bites (also known as a salmon patch) are a common birthmark that appear on a baby’s skin and usually disappear within 1 to 2 years.15
The homozygous MTHFR C677T is a risk factor for having children with nonsyndromic cleft lip with or without cleft palate. MTHFR A1298C polymorphism is not a risk factor.16
Pre-conceptional folic acid supplementation is hypothesized to increase the risk of tongue-tie (ankyloglossia) in infants, but more research is pending.17

Is a sacral dimple a sign of MTHFR?

Sacral dimples are not a sign of MTHFR and are rarely associated with spina bifida.18

Cardiovascular symptoms

High homocysteine levels (hyperhomocysteinemia) Both C677T and A1298C have been implicated in causing elevated homocysteine levels, which is a risk factor for cardiovascular diseases and stroke.

Homocystinuria: Is an accumulation of homocysteine and its byproducts in the blood and urine due to impaired methionine metabolism.

Thrombosis and vascular lesions (blood clots)

High blood pressure

Migraine and headaches

Fertility symptoms

Male infertility
MTHFR is associated with an increased risk of male infertility.6

Failure to conceive and/or recurrent pregnancy loss/miscarriages
Some research shows that a homozygous MTHFR gene mutation may triple the risk of miscarriage.7

Neural tube defects and congenital anomalies in children
Impaired homocysteine metabolism is a possible risk factor for NTDs and unexplained recurrent embryo losses in early pregnancy.8

List of MTHFR symptoms in children

Neurodevelopmental disorders
The MTHFR C677T polymorphism can increase the risk of a child developing autism spectrum disorder.11

Neural tube defects and congenital anomalies
MTHFR A1298C combined with MTHFR C677T has been shown to increase the risk of spina bifida in children.12

Behavioral disorders
Some research has indicated a possible relationship between ADHD and MTHFR in children.13

Asthma
MTHFR C677T is associated with higher susceptibility to asthma in children.14

MTHFR Symptoms | Key takeaways

MTHFR gene mutations may cause certain symptoms depending on the type of mutation you have
MTHFR symptoms are usually related to health conditions that develop due to low folate levels
Recognizing symptoms can help you to understand whether you are affected by low folate and/or MTHFR

Product Recommendations

MTHFR Supplements: L-Methylfolate, Vitamin B12 Supplement, Multivitamin & Magnesium

MTHFR Supplements: L-Methylfolate, Vitamin B12 Supplement, Multivitamin & Magnesium
(2)

$125.00

NUTRIENTS DESIGNED FOR THOSE STARTING WITH MTHFR TREATMENT
Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - Bachelor of Science in Nursing

Medical Reviewer:

Kari Asadorian - Bachelor of Science in Nursing
Jamie Hope - Founder of Methyl-Life

Edited By:

Jamie Hope - Founder of Methyl-Life

References

  1. Stephan Moll, Elizabeth A. Varga; "Homocysteine and MTHFR Mutations"; Circulation; 2015 Jul

    https://www.ahajournals.org/doi/10.1161/circulationaha.114.013311

  2. Yu-Xin Zhang, Lu-Ping Yang, Cong Gai, Cui-Cui Cheng, Zhen-yu Guo, Hong-Mei Sun, Die Hu; "Association between variants of MTHFR genes and psychiatric disorders: A meta-analysis"; Frontiers in psychiatry; 2022 Aug

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433753/

  3. Xinyao Meng, Ji-Long Zheng, Mao-Ling Sun, Hai-Yun Lai, Bao-Jie Wang, Jun Yao, Hongbo Wang; "Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis"; PLoS One; 2022 Jul

    https://pubmed.ncbi.nlm.nih.gov/35834596/

  4. Yan Li, Shuang Qiu, Jikang Shi, Yanbo Guo, Zhijun Li, Yi Cheng, Yawen Liu; "Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis"; BMC pediatrics; 2020 Sep

    https://pubmed.ncbi.nlm.nih.gov/32972375/

  5. Joseph Visingardi, Jan A. Paredes Mogica, Padma Sundaram, Talia Denis, Courtney Bellomo, Artem Loktev, Charles Argoff, Elise J.B. De; "MTHFR mutation: Another unifying etiology of chronic overlapping pain conditions"; Continence; 2023 Dec

    https://www.sciencedirect.com/science/article/pii/S2772973723009104

  6. Mancheng Gong, Wenjing Dong, Tingyu He, Zhirong Shi, Guiying Huang, Rui Ren, Sichong Huang, Shaopeng Qiu, Runqiang Yuan; "MTHFR 677C>T Polymorphism Increases the Male Infertility Risk: A Meta-Analysis Involving 26 Studies"; PLoS One; 2015 Mar

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368707/

  7. W L Nelen, E A Steegers, T K Eskes, H J Blom; "Genetic risk factor for unexplained recurrent early pregnancy loss"; Lancet; 1997 Sep

    https://pubmed.ncbi.nlm.nih.gov/9310606/

  8. Yang Yu, Fang Wang, Yihua Bao, Xiaolin Lu, Li Quan, Ping Lu; "Association between MTHFR gene polymorphism and NTDs in Chinese Han population"; International journal of clinical and experimental medicine; 2014 Sep

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211806/

  9. Amandeep Kaur, Mohan Jairath, Anupam Kaur; "Heavy metals and genetic variations in folate metabolism pathway: A gene-environment interaction"; Indian journal of public health; 2023 Jul-Sep

    https://pubmed.ncbi.nlm.nih.gov/37929396/

  10. José M Mato, M Luz Martínez-Chantar, Shelly C Lu; "S-adenosylmethionine metabolism and liver disease"; Annals of hepatology.; 2014 May

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4027041/

  11. Yan Li, Shuang Qiu, Jikang Shi, Yanbo Guo, Zhijun Li, Yi Cheng, Yawen Liu; "Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis"; BMC pediatrics; 2020 Sep

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517654/

  12. N Akar, E Akar, G Deda, S Arsan; "Spina bifida and common mutations at the homocysteine metabolism pathway"; Clinical genetics; 2000 Mar

    https://pubmed.ncbi.nlm.nih.gov/10782931/

  13. Cem Gokcen, Nadir Kocak, Ahmet Pekgor; "Methylenetetrahydrofolate reductase gene polymorphisms in children with attention deficit hyperactivity disorder"; International journal of medical sciences; 2011

    https://pubmed.ncbi.nlm.nih.gov/21897766/

  14. Min Li, Yu Tang, Er-Yao Zhao, Chao-Hui Chen, Li-Li Dong; "Relationship between MTHFR gene polymorphism and susceptibility to bronchial asthma and glucocorticoid efficacy in children"; Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.; 2021 Aug

    https://pubmed.ncbi.nlm.nih.gov/34511169/

  15. Leelawadee Techasatian, Vilounna Sanaphay, Pongsatorn Paopongsawan, Lawrence A Schachner; "Neonatal Birthmarks: A Prospective Survey in 1000 Neonates"; Global pediatric health; 2019 Mar

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442070/

  16. Xinjuan Pan, Ping Wang, Xinjuan Yin, Xiaozhuan Liu, Di Li, Xing Li, Yongchao Wang, Hongle Li, Zengli Yu; "Association between Maternal MTHFR Polymorphisms and Nonsyndromic Cleft Lip with or without Cleft Palate in Offspring, A Meta-Analysis Based on 15 Case-Control Studies"; International journal of fertility & sterility.; 2015 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4355933/

  17. Yona Amitai, Helen Shental, Luba Atkins-Manelis, Gideon Koren, Chen Stein Zamir; "Pre-conceptional folic acid supplementation: A possible cause for the increasing rates of ankyloglossia"; Medical Hypotheses; 2020 Jan

    https://www.sciencedirect.com/science/article/abs/pii/S0306987719311259?via%3Dihub

  18. Peyton Wilson, Erin Hayes, Andrew Barber, Jacob Lohr; "Screening for Spinal Dysraphisms in Newborns With Sacral Dimples"; Clinical pediatrics; 2016 Oct

    https://pubmed.ncbi.nlm.nih.gov/27554766/

Table of Contents

Product Recommendations

MTHFR Supplements: L-Methylfolate, Vitamin B12 Supplement, Multivitamin & Magnesium

MTHFR Supplements: L-Methylfolate, Vitamin B12 Supplement, Multivitamin & Magnesium
(2)

$125.00

NUTRIENTS DESIGNED FOR THOSE STARTING WITH MTHFR TREATMENT