Alpha-1 antitrypsin (AAT) testing is used to help diagnose alpha-1 antitrypsin deficiency as 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.
Testing 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 be done in people of any age.
Three types of AAT tests are available. One or more of these may be used to evaluate an individual:
Alpha-1 antitrypsin measures the level of the protein AAT in blood.
Alpha-1 antitrypsin phenotype testing evaluates the amount and type of AAT being produced and compares it to normal patterns.
Alpha-1 antitrypsin genotype testing (DNA testing) can be used to establish which SERPINA1 gene alleles are present, including the normal wild type M allele or variant alleles. This test does not identify every variant, but it will detect the most common ones (S and Z) as well as variants that may be common in a particular geographical area or family. Once the affected person's SERPINA1 gene alleles have been identified, other family members may be tested to establish their own risk of developing emphysema and/or liver involvement as well as the likelihood that their children might inherit the disease.
An infant has jaundice that lasts for more than a week or two, an enlarged spleen, fluid accumulation in the abdomen (ascites), persistent itching (pruritus), and other signs of liver injury.
A person younger than 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 person 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.
Someone has a close relative with alpha-1 antitrypsin deficiency.
An individual has an affected family member and wants to know the likelihood of having an affected child.
The American Thoracic Society recommends AAT testing when individuals are diagnosed with certain conditions such as:
Emphysema at a young age (younger than 45 years old) and/or no obvious risk factors for the disease, such as smoking
Bronchiectasis, a condition in which the airways are stretched and/or widened
A low level of AAT in blood indicates that the person tested may have alpha-1 antitrypsin deficiency. The lower the level of AAT, the greater the risk of developing emphysema.
In people with an abnormal form of AAT, the risk of developing disease depends on how much is produced and which variant is present. A variant with very low activity may lead to both emphysema (because it does not protect the lungs) and liver disease (because of the buildup of abnormal AAT inside liver cells).
Most people in the U.S. have two copies of the normal wild type (MM) gene and produce sufficient AAT.
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. The degree of AAT deficiency and the degree of lung and/or liver damage can vary greatly. Two people with the same abnormal genes may have very different disease courses. As with any genetic testing, a genetic counselor can explain the likelihood that the disease may be passed on to the affected person's children.
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.
Individuals with two copies of S (SS) may be asymptomatic or moderately affected (they produce about 60% of normal AAT).
People with one copy of S and one of Z (SZ) are at an increased risk of developing emphysema (they produce about 40% of normal AAT).
Individuals who have 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 that are "null"(they do not produce any AAT).
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 oral contraceptive use, pregnancy, and stress. These temporary or chronic AAT increases may cause levels to appear normal in people with mild to moderate AAT deficiency.
AAT levels may be decreased in neonatal respiratory distress syndrome and in conditions that cause a decrease in serum proteins, such as kidney disease, malnutrition, and some cancers.
Protein electrophoresis is a test that evaluates many different proteins in the blood. Sometimes the test will detect a deficiency in AAT unexpectedly, when it is done for a different purpose. In those cases, follow-up testing for AAT may confirm a deficiency of the protein, even if there are no signs or symptoms of disease.
This article was last reviewed on June 10, 2013. | This article was last modified on June 10, 2013.
The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.
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