Rudi Hayden

Urologist

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Blood-tests Explained


Disclaimer:

This website is intended to assist with patient education and should not be used as a diagnostic, treatment or prescription service, forum or platform. Always consult your own healthcare practitioner for a more personalised and detailed opinion

Homocysteine


At a Glance

Why Get Tested?

To help determine if you are folate-deficient or vitamin B12-deficient; to determine if you are at increased risk of heart attack or stroke; to help diagnose a rare inherited disorder called homocystinuria

When to Get Tested?

When your healthcare provider suspects that you have a vitamin B12 or folate deficiency; when you have had a heart attack or stroke and do not have traditional risk factors, such as unhealthy lipid levels; as part of routine newborn screening or when a health practitioner suspects that an infant or young person may have homocystinuria

Sample Required?

A blood sample taken by needle from a vein in the arm; sometimes a urine sample in addition to the blood sample

Test Preparation Needed?

You may be instructed to fast for 10 to 12 hours prior to this test.

The Test Sample

What is being tested?

Homocysteine is an amino acid that is typically present in very small amounts in all cells of the body. That is because the body normally converts homocysteine into other products quickly. Since vitamins B6, B12, and folate are necessary to metabolize homocysteine, increased levels of the amino acid may be a sign of deficiency in those vitamins. This test determines the level of homocysteine in the blood and/or urine.

Elevated homocysteine may also be related to a higher risk for coronary heart disease, stroke, peripheral vascular disease (fatty deposits in peripheral arteries), and hardening of the arteries (atherosclerosis). Several mechanisms have been proposed for how homocysteine leads to cardiovascular disease (CVD) risk, including damaging blood vessel walls and supporting the formation of inappropriate blood clots, but direct links haven not been confirmed. There are also several studies that indicate no benefit or lowering of CVD risk with folic acid and B vitamin supplements. So far, the American Heart Association does not consider it a major risk factor for heart disease.

A rare inherited condition called homocystinuria (also called cystathionine beta synthase deficiency) can also greatly increase homocysteine in the blood and urine. In homocystinuria, one of several different genes is altered, leading to a dysfunctional enzyme that does not allow the normal breakdown of the precursor to homocysteine, called methionine. Methionine is one of the eleven essential amino acids that must come from the diet because the body cannot produce it.

Without the proper enzyme to break them down, homocysteine and methionine begin to build up in thebody. Babies with this condition will appear normal at birth but within a few years begin to develop signs such as a dislocated lens in the eye, a long slender build, long thin fingers, skeletal abnormalities, osteoporosis, and a greatly increased risk of thromboembolism and of atherosclerosis that can lead to premature CVD.

The buildup in the arteries may also cause intellectual disability, mental illness, slightly low IQ, behavioral disorders, and seizures. Some of those may be alleviated if the condition is detected early, which is why all states screen newborns for homocystinuria.

How is the sample collected for testing?

A blood sample is taken by needle from a vein in the arm. Sometimes a urine sample is also collected.

Is any test preparation needed to ensure the quality of the sample?

Fasting for 10 to 12 hours may be required prior to blood testing.

The Test

How is it used?

The homocysteine test may be used a few different ways:

  • A health practitioner may order a homocysteine test to determine if a person has a vitamin B12 or folate deficiency. The homocysteine concentration may be elevated before B12 and folate tests are abnormal. Some health practitioners may recommend homocysteine testing in malnourished individuals, the elderly, who often absorb less vitamin B12 from their diet, and individuals with poor nutrition, such as drug or alcohol addicts.
  • Homocysteine may be ordered as part of a screen for people at high risk for heart attack or stroke. It may be useful in someone who has a family history of coronary artery disease but no other known risk factors, such as smoking, high blood pressure, or obesity. However, the exact role that homocysteine plays in the progression of cardiovascular disease has not been established, so the utility of the screening test continues to be questioned. Routine screening, such as that done for total cholesterol, has not been recommended.
  • Tests for both a urine and blood homocysteine may be used to help diagnose homocystinuria if a health practitioner suspects that an infant or child may have this inherited disorder. In the U.S., all babies are routinely tested for excess methionine, a sign of homocystinuria, as part of their newborn screening. If a baby's test is positive, then urine and blood homocysteine tests are often performed to confirm the findings.

When is it ordered?

This test may be ordered when a health practitioner suspects that a person may have a vitamin B12 and/or folate deficiency. Signs and symptoms are initially subtle and nonspecific. People with an early deficiency may be diagnosed before they experience any overt symptoms. Other affected people may experience a variety of mild to severe symptoms that can include:

  • Diarrhea
  • Dizziness
  • Fatigue, weakness
  • Loss of appetite
  • Paleness
  • Rapid heart rate
  • Shortness of breath
  • Sore tongue and mouth
  • Tingling, numbness, and/or burning in the feet, hands, arms, and legs (with B12 deficiency)

Homocysteine testing may be ordered as part of assessing a person's risk of cardiovascular disease, depending on the individual's age and other risk factors. It may also be ordered following a heart attack or stroke to help guide treatment.

This test is may be ordered when newborn screening detects an elevated level of methionine or if an infant or child has signs and symptoms of homocystinuria. Babies with this condition will appear normal at birth, but if not treated, they will, within a few years, begin to develop signs such as a dislocated lens in the eye, a long slender build, long thin fingers, and skeletal abnormalities.

What does the test result mean?

In cases of suspected malnutrition or vitamin B12 or folate deficiency, homocysteine levels may be elevated. If an individual does not get enough B vitamins and/or folate through diet or supplements, then the body may not be able to convert homocysteine to forms that can be used by the body. In this case, the level of homocysteine in the blood can increase.

Studies from the mid- to late-1990s suggested that people who have elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels. Investigating the link between high homocysteine levels and heart disease remains an active area of research. At present, however, the use of homocysteine levels for risk assessment of cardiovascular disease (CVD), peripheral vascular disease, and stroke is uncertain given that several trials investigating folic acid and B vitamin supplementation indicate no benefit or lowering of CVD risk.

Additionally, a 2012 study of multiple datasets, including 50,000 people with coronary heart disease, called the potential for a cause-and-effect relationship between homocysteine levels and heart disease into question. The American Heart Association (AHA) does acknowledge the relationship between homocysteine levels and heart attack/stroke survival rates but doesn't consider elevated homocysteine a major risk factor for CVD.

While the AHA does not recommend widespread use of folic acid and B vitamins to reduce risk of heart attack and stroke, it does promote a balanced, healthy diet and advise health practitioners to consider overall risk factors and diet in managing cardiovascular disease.

In newborn testing, greatly increased concentrations of homocysteine in the urine and blood mean that it is likely that an infant has homocystinuria and indicates the need for further testing to confirm the cause of the increase.

Is there anything else I should know?

When test results suggest homocystinuria, liver or skin biopsy samples are sometimes tested to determine whether the enzyme cystathionine beta synthase (CBS) is present.The absence of this enzyme is the most common cause of homocystinuria.Genetic tests may be ordered to test for one or more of the most common gene mutations.If someone has a strong family history of early atherosclerosis or a family member has been diagnosed with homocystinuria, then that person should be tested for the gene mutation that was found in the family member.

Homocysteine levels can increase with age, when a person smokes, and with the use of drugs such as carbamazepine, methotrexate, and phenytoin. Homocysteine levels are lower in women than in men. Women's concentrations increase after menopause, possibly due to decreased estrogen production.