Alpha-1 Antitrypsin

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Also known as: Alpha1-antitrypsin; A1AT; AAT
Formal name: Alpha1 antitrypsin
Related tests: Protein electrophoresis; Total protein; Blood gases; Liver panel

At a Glance

Why Get Tested?

To help diagnose the cause of early onset emphysema and/or liver dysfunction; to establish the risk of developing alpha-1 antitrypsin deficiency-related emphysema and/or liver disease and determine the likelihood that children might inherit the risk

When to Get Tested?

When you show signs of liver disease as an infant or young child, when you develop emphysema before age 40, or when you have a close relative with alpha-1 antitrypsin deficiency

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

The Test Sample

What is being tested?

Alpha-1 antitrypsin (AAT) is a protein that is produced in the liver and released into the bloodstream. AAT helps to inactivate several enzymes but primarily works to protect the lungs from elastase. Elastase is an enzyme produced by neutrophils and it is part of the body’s normal response to injury and inflammation. Elastase breaks down proteins so that they can be removed and recycled by the body but, if its action is not regulated by AAT, elastase will also begin to break down and damage lung tissue.

AAT is produced at the direction of two copies of a protease inhibitor (SERPINA1) gene. This gene is co-dominant, which means that each SERPINA1 gene copy is responsible for producing half of the body’s AAT. If there is a change or mutation in one or both of the gene copies, then less AAT and/or dysfunctional AAT is produced. If the resulting AAT production drops down to 30% of normal or less, then the affected person will experience a disorder called alpha-1 antitrypsin deficiency. Patients with this disorder are at a considerable risk of developing emphysema, a progressive lung disease, in early adulthood. If they smoke, or are exposed to occupational dust or fumes, the lung damage tends to occur sooner and be more severe.

If the AAT produced is dysfunctional, it tends to accumulate in the liver cells that produce it. As it builds up in these cells, the AAT forms abnormal protein chains and begins to destroy the cells and damage the liver. About 10% of those affected with AAT deficiency will be jaundiced as a newborn. Many improve on their own but, in severe cases, these infants may require a liver transplant to survive. AAT deficiency is currently the most common genetic cause of liver disease in the pediatric population.

The amount and function of the AAT created depends on the mutation inherited. While there are more than 75 different alleles in the SERPINA1 gene, only a few are common. Most people in the U.S., about 90%, have two copies of the normal M gene (MM). The most common of the abnormal forms are S and Z. Those people with:

  • One copy of M and one of S or Z (MS or MZ) will produce reduced amounts of AAT but should have enough to protect themselves. They will be carriers of the condition, however, and can pass it on to their children.
  • Two copies of S (SS) may be asymptomatic or moderately affected (they produce about 60% of the required AAT).
  • One copy of S and one of Z (SZ) are at an increased risk of developing emphysema (they produce about 40% of normal AAT).
  • Two copies of Z (ZZ) are the most severely affected (they only produce about 10% of the required AAT) along with those who have one or two copies of rare forms of the SERPINA1 gene which are “null” (they do not produce any AAT).

Types of AAT Tests
Different AAT tests can be used to measure the amount of AAT, determine which types and concentrations of AAT protein are present, and determine which SERPINA1 gene alleles a patient has.

  • Alpha-1 Antitrypsin, this test measures the level of AAT present.
  • Alpha-1 Antitrypsin Phenotype, separates out the different variants of alpha-1 protein being produced and compares them to known patterns. It also allows an estimation of the amount of each type present. Since AAT is an alpha1 globulin type of protein, a regular protein electrophoresis test can be used to screen for a severe AAT deficiency.
  • Alpha-1 Antitrypsin DNA testing, genetic testing can be done to identify which protease inhibitor gene mutations (SERPINA1 gene alleles) are present. Only the most common mutations are usually evaluated (M, S, Z). This test can be used to help evaluate affected patients and their family members.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

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

No test preparation is needed.

The Test

How is it used?

An alpha-1 antitrypsin level is ordered to help diagnose the cause of early onset emphysema, especially when a person does not have obvious risk factors such as smoking or exposure to lung irritants such as dust and fumes.

Alpha-1 antitrypsin is also ordered to help diagnose the cause of persistent jaundice and other signs of liver dysfunction. This is done primarily in infants and young children but may also be done in patients of any age.

Alpha-1 antitrypsin phenotype testing may be ordered if the alpha-1 antitrypsin concentration is lower than normal. It looks at the amount and type of AAT being produced and compares it to normal patterns.

DNA testing may be done as a follow-up to an alpha-1 antitrypsin level and phenotype. Once it has been established that an abnormality exists, then the DNA genetic testing can be ordered to establish which SERPINA1 gene alleles are present. This test does not test for every variant, just the most common ones - M, S, and Z, as well as any that may be common in a particular geographical area or family. Once the affected person’s SERPINA1 gene alleles have been determined, other family members may be tested to establish their own possible risk of developing emphysema and/or liver involvement as well as the likelihood that their children might inherit it.

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When is it ordered?

Alpha-1 antitrypsin testing may be ordered when a newborn or infant has jaundice that lasts for more than a week or two, an enlarged spleen, ascites, pruritus, and other signs of liver injury. It may be ordered when a person under 40 years of age develops wheezing, a chronic cough or bronchitis, is short of breath after exertion and/or shows other signs of emphysema. This is especially true when the patient is not a smoker, has not been exposed to known lung irritants, and when the lung damage appears to be located low in the lungs. AAT testing may also be done when you have a close relative with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin phenotype testing is ordered when a patient has a decreased level of AAT. DNA testing is performed when the AAT test indicates that the patient has lower than normal level of AAT and when the alpha-1 antitrypsin phenotype test indicates that some or all of the AAT protein being produced appears to be a variant. It may also be ordered in the rare case when no AAT is being produced. AAT DNA testing may be done on close relatives when there is an affected family member and when a patient wants to determine their risk of having an affected child.

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What does the test result mean?

AAT concentrations are primarily important when they are lower than normal and/or indicate that the AAT being produced is abnormal. The lower the level of normal AAT, the greater the risk of developing emphysema.

With abnormal AAT, it depends on how much is produced and how abnormal it is. Low concentrations of abnormal AAT in the blood may lead to both emphysema (because of the lack of lung protection) and to liver disease because of the buildup of dysfunctional AAT inside the liver cells producing it.

When DNA testing indicates the presence of one or two abnormal copies of the SERPINA1 gene, less AAT and/or abnormal AAT will be produced and the variant copies can be passed on to the patient’s children. The degree of AAT deficiency and the degree of lung and/or liver damage experienced is very variable. Two people with the same gene copies may have very different disease courses.

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Is there anything else I should know?

AAT is an acute phase reactant. This means that it will be elevated in acute and chronic inflammatory conditions, infections, and with some cancers. Increased levels of AAT may also be seen with infections, oral contraceptives, pregnancy, stress, and thyroid infections. Although an increased amount of AAT may be present, this test is not usually measured or used as a monitoring tool in these situations. This may cause levels to be "normal" in persons with mild to moderate AAT deficiency when they also have another condition that increases AAT.

AAT concentrations may be decreased with neonatal respiratory distress syndrome and with conditions that decrease serum proteins such as kidney disease (nephrotic syndrome), malnutrition, and some cancers.

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Common Questions

1.  What can I do to take care of myself if I have alpha-1 antitrypsin deficiency?

Don’t smoke. Taking care of your lungs can increase your lifespan and delay the onset of emphysema. Avoid lung irritants such as dust and fumes, get regular pneumonia shots and an annual influenza shot, get prompt medical attention for lung infections, and get regular exercise to help maintain lung function.

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2.  How common is alpha-1 antitrypsin deficiency?

It is thought to be one of the most frequent genetic deficiencies in Caucasians. The American Lung Association estimates that there are as many as 100,000 people in the U.S. who were born with AAT deficiency and that as many as 25 million Americans are carriers of the condition.

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

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