Alpha-1 Antitrypsin Testing

About the Test

Purpose of the test

The purpose of alpha-1 antitrypsin testing is to look for indications of an AAT deficiency. AAT tests can be used for diagnosis, screening, and treatment planning.

Diagnosis is the process of identifying the cause after a person has already shown symptoms of a health problem. Diagnostic testing may be performed to detect AAT deficiency in people who have symptoms that could be related to this disorder.

Screening is checking for a health problem before it has caused any symptoms. Because AAT deficiency is inherited, some family members of people with AAT deficiency may be tested even if they have not experienced any signs of the condition.

Treatment planning is the way a doctor determines the optimal treatment for a patient. In some cases, therapy for lung problems may be influenced by testing for AAT deficiency.

What is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency is an inherited condition that is associated with a heightened risk of lung and liver disease. AAT deficiency is relatively rare, but research indicates that it often goes undiagnosed.

The AAT protein helps protect tissues in certain parts of the body from damage. People who don’t have enough AAT are more likely to develop potentially serious health conditions including:

• Chronic obstructive pulmonary disorder (COPD): COPD is a lung disorder marked by impaired breathing. Emphysema is a type of COPD triggered by damage to the lungs. COPD is the most common complication of AAT deficiency, and AAT deficiency is estimated to cause up to 3% of cases of emphysema in the United States. People with AAT are more likely to have emphysema if they also smoke or are exposed to chemicals or dusts that irritate the lungs.
• Liver diseases: Some people with an AAT deficiency experience damage to the liver. Examples of liver diseases that can be related to AAT deficiency include hepatitis, which is inflammation of the liver, and cirrhosis, which is scarring of the liver. AAT deficiency can also heighten the risk of primary liver cancer.
• Panniculitis: While much less common, an AAT deficiency can cause panniculitis, which is a condition involving red nodules on the skin that feel painful and hot. These nodules most often occur around the buttocks, thigh, or abdomen.

Some research indicates that an AAT deficiency may be related to other kinds of health problems, but links to other conditions have not been clearly proven.

What does the test measure?

Alpha-1 antitrypsin is a type of protein. Specifically, it is a protease inhibitor, which means that it helps block the effects of certain substances that can inflict damage on cells of the lungs and liver.

There are several kinds of AAT tests. Tests can measure blood levels of the AAT protein and look for evidence of AAT proteins that are abnormal or not functioning correctly. In addition, testing can look for the inherited genetic variations that cause AAT deficiency.

There are four main categories of AAT deficiency testing. Each type of testing measures something different about AAT:

• AAT blood level test: This test measures the amount of AAT protein found in a sample of blood to see if AAT levels are abnormal.
• AAT phenotype test: This test checks for the presence of abnormal forms of the AAT protein in the blood. A technical name for this type of testing is isoelectric focusing.
• AAT genotyping: This test looks for specific genetic changes in your DNA that are linked to an AAT deficiency. AAT genotyping can be done with a blood sample or by taking a swab from the inside of your cheek.
• DNA sequencing: This type of testing creates a more complete picture of the section of your DNA that provides the code for the AAT protein. It enables the identification of uncommon genetic variants that may not be found on an AAT genotyping test.

Depending on the circumstances, a doctor may prescribe one or more of these tests to determine whether a person has an inherited condition affecting the alpha-1 antitrypsin protein. Multiple tests may be prescribed at the same time, or they can be done in a sequence of initial testing with follow-up tests to confirm the first result.

When should I get an alpha-1 antitrypsin test?

Alpha-1 antitrypsin testing may be performed under several different circumstances.

For diagnosis, testing is only done when you have signs or symptoms that could be explained by an underlying AAT deficiency. For example, AAT testing is frequently performed in people who have tests that show reductions in their ability to exhale air out of the lungs, which is common in people with emphysema and COPD.

Other signs and symptoms that may warrant diagnostic AAT testing to be recommended include:

• Emphysema that begins at age 45 or earlier, occurs in nonsmokers, or has certain anatomic features related to how it affects the lungs
• A family history of emphysema or liver disease
• Asthma that starts during adulthood, especially if it doesn’t get better with treatment
• Bronchiectasis, which is enlargement of the tubes that carry air to the lungs
• Panniculitis, which involves painful nodules on the skin
• Liver disease without a known cause

In infants, AAT testing may be advised if there are signs or symptoms of abnormal liver function.

AAT testing may be considered if you have a first-degree family member who has been diagnosed with AAT deficiency. In most cases, you will be offered genetic counseling beforehand to discuss the benefits and downsides of AAT tests in your case.

AAT deficiency is more common in some geographic areas and populations groups. Prevalence of the condition is highest in people of European descent. The decision about whether to conduct AAT testing may be affected by the extent of AAT deficiency in your specific area or ancestry group.

It is important to talk with a doctor who can most concretely address whether you have any potential signs of AAT deficiency and whether AAT testing is appropriate in your situation.