Alpha-1 Antitrypsin

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 (variations) 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.

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

No test preparation is needed.