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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.

Symptoms

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What are the signs and symptoms of Homocystinuria 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

The Human Phenotype Ontology provides the following list of signs and symptoms for Homocystinuria due to MTHFR deficiency. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can use the MedlinePlus Medical Dictionary to look up the definitions for these medical terms.

Signs and Symptoms Approximate number of patients (when available)
Autosomal recessive inheritance -
Behavioral abnormality -
Gait disturbance -
Homocystinuria -
Hyperhomocystinemia -
Incoordination -
Muscle weakness -
Paresthesia -
Seizures -
Stroke -

Last updated: 3/1/2015

The Human Phenotype Ontology (HPO) has collected information on how often a sign or symptom occurs in a condition. Much of this information comes from Orphanet, a European rare disease database. The frequency of a sign or symptom is usually listed as a rough estimate of the percentage of patients who have that feature.

The frequency may also be listed as a fraction. The first number of the fraction is how many people had the symptom, and the second number is the total number of people who were examined in one study. For example, a frequency of 25/25 means that in a study of 25 people all patients were found to have that symptom. Because these frequencies are based on a specific study, the fractions may be different if another group of patients are examined.

Sometimes, no information on frequency is available. In these cases, the sign or symptom may be rare or common.


References
  1. Homocystinuria. Genetics Home Reference (GHR). 2008; http://www.ghr.nlm.nih.gov/condition=homocystinuria. Accessed 3/16/2011.
  2. 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.
  3. Homocysteine. American Academy of Family Physicians. 2006; http://familydoctor.org/online/famdocen/home/articles/249.html. Accessed 5/13/2009.
  4. Rosenson RS, Kang DS. Overview of homocysteine. In: Fletcher RH, Freeman MW. UpToDate. Waltham, MA: UpToDate; 2015; Accessed 3/27/2015.
  5. MTHFR. Genetics Home Reference (GHR). Februrary 2011; http://ghr.nlm.nih.gov/gene/MTHFR. Accessed 7/14/2011.
  6. 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.


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.