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
A blood sample drawn from a vein in your arm
Test Preparation Needed?
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.
Ask a Laboratory Scientist
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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
Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 45-46.
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp 198-199.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 138-143.
Fairman P, and Malhotra R. (2008 October 29, Updated). Alpha1-Antitrypsin Deficiency. eMedicine [On-line information]. Available online at http://www.emedicine.com/med/TOPIC108.HTM through http://www.emedicine.com. Accessed March 2009.
Ohar, J. (2008 January 15). New Data on Chronic Obstructive Pulmonary Disease CME/CE. Medscape from CHEST 2007: Pulmonary Disease [On-line information]. Available online at http://www.medscape.com/viewarticle/568542 through http://www.medscape.com. Accessed March 2009.
(2007 November). What Is Alpha-1 Antitrypsin Deficiency? National Heart, Lung, and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/aat/aat_whatis.html through http://www.nhlbi.nih.gov. Accessed March 2009.
(2007 September 28, Updated). Alpha-1 Antitrypsin Deficiency. American Liver Foundation [On-line information]. Available online at http://www.liverfoundation.org/education/info/alphaone/ through http://www.liverfoundation.org. Accessed March 2009.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Barclay, L. and Lie, D. (2003 October 10). New Guidelines for Alpha-1 Antitrypsin Deficiency. Medscape Medical News [On-line News and CME]. Available online at http://www.medscape.com/viewarticle/462776 through http://www.medscape.com.
Huskey, R., Maintained (1998 November 10, Updated). Alpha-1 Antitrypsin Deficiency. From Principles of Medical Genetics by Gelehrter and Collins, 1990 (Williams & Wilkins). Available online at http://www.people.virginia.edu/~rjh9u/antitryp.html through http://www.people.virginia.edu.
Maxton, D. (2000 August 21). Alpha-1 antitrypsin deficiency. Netdoctor.co.uk [On-line information]. Available online at http://www.netdoctor.co.uk/diseases/facts/alpha1def.htm through http://www.netdoctor.co.uk.
Shaffer, E. Alpha1-Antitrypsin Deficiency. The Merck Manual – Second Home Edition [On-line information]. Available online at http://www.merck.com/pubs/mmanual_home2/sec10/ch136/ch136f.htm through http://www.merck.com.
Alpha-1 Related Emphysema. American Lung Association [On-line information]. Available online at http://www.lungusa.org/diseases/luna1ad.html through http://www.lungusa.org.
University of Utah (2003). Alpha-1-antitrypsin. Genetic Testing of Newborn Infants, Genetic Science Learning Center [On-line information]. Available online at http://gslc.genetics.utah.edu/units/newborn/infosheets/alpha.cfm through http://gslc.genetics.utah.edu.
Alpha-1 Antitrypsin Deficiency. Children’s Liver Disease Foundation [On-line information]. Available online at http://www.childliverdisease.org/aatd.html through http://www.childliverdisease.org.
Alpha-1 Antitrypsin Deficiency (A-1ATD). MedicineNet.com [On-line information]. Available online at http://www.medicinenet.com/Alpha_1_Antitrypsin_Deficiency/article.htm through http://www.medicinenet.com.
Alpha-1-Antitrypsin and Alpha-1-Antitrypsin Phenotype. ARUP’s Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_al38.jsp#1141235 through http://www.aruplab.com.
Kaufman, D. (2003 May 7). Alpha-1 Antitrypsin Deficiency. MEDLINEplus Health Information, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000120.htm.
Martell, B. (2003 May 12). Alpha-1 antitrypsin. MEDLINEplus Health Information, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003715.htm.