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Homocystinuria due to MTHFR deficiency


Other Names for this Disease
  • 5,10 alpha methylenetetrahydro-folate reductase deficiency
  • 5,10-alpha-methylenetetrahydro-folate reductase deficiency
  • Homocysteinemia due to methylenetetrahydro-folate reductase deficiency
  • Homocysteinuria due to methylenetetrahydro-folate reductase deficiency
  • Homocystinuria due to methylene tetrahydrofolate reductase deficiency
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I have MTHFR deficiency. Can you tell me more about this in lay language?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is homocysteinemia due to MTHFR deficiency?

Homocystinuria due to MTHFR deficiency refers to a metabolic condition caused by rare MTHFR gene mutations that result in severe homocystinuria, abnormal clotting, developmental delay, seizures, intellectual disability, and microcephaly.[1] It is inherited in an autosomal recessive fashion.

For more information on common MTHFR gene mutations (such as C677T) visit our page: MTHFR gene mutation
Last updated: 7/20/2011

What are the signs and symptoms of homocysteinemia due to MTHFR deficiency?

People with MTHFR gene mutations develop elevated levels of homocysteine in their blood (homocysteinemia) or urine (homocystinuria). Risks for health effects vary depending on the severity of homocysteinemia or homocysteinuria.[1]

A few cases of severe homocysteinemia have been due to rare MTHFR gene mutations (sometimes in combination with a second common MTHFR gene mutation). Symptoms in these patients varied greatly but often involved pronounced neurological symptoms and blood vessel disease. The age of the patients when they first experienced symptoms varied from infancy to adulthood.[2]

Common MTHFR gene mutations cause less severe, although still significantly raised levels of homocysteine. The most well studied MTHFR mutation, is C677T. An estimated 11% of Americans carry two copies of this mutation. People with two copies of C677T have higher homocysteine levels than those without the mutation (people with one copy of C677T have mildly raised homocysteine levels).[3] 

Many studies have investigated the health effects of high homocysteine levels and/or having two C677T MTHFR gene mutations. Studies suggest that an elevated level of homocysteine in the blood is associated with an increased risk for heart disease, including coronary heart disease and stroke.[4]

Weaker associations have been suggested between high homocysteine levels and narrowing of the carotid arteries (the arteries on each side of your neck), blood clots in deep veins (often in the lower leg and thigh), a sudden blockage in a lung artery, and pregnancy complications (such as preeclampsia, placental abruption, fetal growth restriction, stillbirth, and neural tube defects).[1][5][4][6]

Studies involving MTHFR and homocysteine and the following conditions have been completed, but with conflicting and varied results:[6]

Hypertension
Hyperlipidemia
Psoriasis
Infertility
Recurrent pregnancy loss
Down’s syndrome
Spina bifida
Parkinson disease
Alzheimer disease
Migraine
Cerebral venous thrombosis
Psychiatric disorders
Schizophrenia
Breast cancer
Cervical cancer
Ovarian cancer
Esophageal cancer
Oral cancer
Liver cancer
Pancreatic cancer
Prostate cancer
Bladder cancer
Lung cancer
Stomach cancer
Colorectal cancer
Acute lymphoblastic leukemia

Last updated: 7/20/2011

What causes homocysteinemia due to MTHFR deficiency?

Homocysteinemia due to MTHFR deficiency is caused by mutations in the MTHFR gene, which provides the instructions for making an enzyme called MTHFR. MTHFR is important for a chemical reaction in the body involving forms of the vitamin called folate.  A change or mutation in the MTHFR gene may result in an enzyme that doesn't work like it should. Once the MTHFR enzyme has finished its work on the folate, the folate is ready to be used in the body. One of its jobs it to process a chemical called homocysteine, changing it to methionine which is used for making proteins and other important compounds.[5] 

There are many different gene mutations that can occur in the MTHFR gene that can result in a MTHFR enzyme that is not working as it should. The most common MTHFR gene mutation is the C677T mutation.[5]
Last updated: 7/20/2011

How is homocysteinemia due to MTHFR deficiency inherited?

This condition is inherited in an autosomal recessive fashion, which means that both copies of the gene in each cell have mutations in the MTHFR gene. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.[1]
Last updated: 7/20/2011

Is genetic testing available for homocysteinemia due to MTHFR deficiency?

Genetic testing for homocysteinemia due to MTHFR deficiency is available. It should be noted that health problems tend not to be related to whether someone has a MTHFR gene mutation or even a MTHFR enzyme deficiency, but whether the deficiency is leading to elevated levels of homocysteine in the blood (homocysteinemia) or urine. GeneTests lists the names of laboratories that are performing clinical genetic testing for MTHFR deficiency. To view the contact information for the clinical laboratories conducting testing click here.

Please note: Most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.
Last updated: 1/11/2011

How might homocysteinemia due to MTHFR deficiency be treated?

The optimal treatment for people with homocysteinemia due to MTHFR deficiency is unknown.  Studies of treatment with folic acid, vitamin B6, and vitamin B12 supplementation have been reported; however the benefit of this treatment is unclear. While vitamin therapy can reduce the levels of homocysteine, the evidence that these lower levles are associated with a reduction in the risk of complications due to homocysteinemia is lacking. Much of the literature on this topic is conflicting, with some studies reporting benefit, some no improvement, and some an increased risk for complications.[3][7]
Last updated: 7/20/2011

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:

Last updated: 11/27/2014

References
  • Homocystinuria. Genetics Home Reference (GHR). 2008; http://www.ghr.nlm.nih.gov/condition=homocystinuria. Accessed 3/16/2011.
  • Homocystinuria due to deficiency of N(5,10)-Methylenetetrahydrofoloate reductase activity. Online Mendelian Inheritance in Man. 2007; http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=236250. Accessed 5/13/2009.
  • Homocysteine. American Academy of Family Physicians. 2006; http://familydoctor.org/online/famdocen/home/articles/249.html. Accessed 5/13/2009.
  • Rosenson RS, Kang DS. Overview of homocysteine. In: Fletcher RH, Freeman MW. UpToDate. Waltham, MA: UpToDate; 2015; Accessed 3/27/2015.
  • MTHFR. Genetics Home Reference (GHR). Februrary 2011; http://ghr.nlm.nih.gov/gene/MTHFR. Accessed 7/14/2011.
  • Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015 Jan; 58(1):1-10. Accessed 3/27/2015.
  • Goodnight SH and Griffin JH. Hereditary Thrombophilia. In: Ernest Beutler, Marshall A. Lichtman, Barry S. Coller, Thomas J. Kipps, and Uri Seligsohn. Williams Hematology, 6th ed. Philadelphia, PA: McGraw-Hill ; 2001;
  • Homocystinuria due to deficiency of N(5,10)-Metylenetetrahydrofolate Reductase Activity. Online Medelian Inheritance of Man (OMIM). June 2007; http://www.omim.org/entry/236250. Accessed 7/11/2011.
Other Names for this Disease
  • 5,10 alpha methylenetetrahydro-folate reductase deficiency
  • 5,10-alpha-methylenetetrahydro-folate reductase deficiency
  • Homocysteinemia due to methylenetetrahydro-folate reductase deficiency
  • Homocysteinuria due to methylenetetrahydro-folate reductase deficiency
  • Homocystinuria due to methylene tetrahydrofolate reductase deficiency
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.