Alpha-1 antitrypsin deficiency

What causes alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency (AATD) is caused by changes (pathogenic variants, also known as mutations) in the SERPINA1 gene. This gene gives the body instructions to make a protein called alpha-1 antitrypsin (AAT). One of the jobs of AAT is to protect the body from another protein called neutrophil elastase. Neutrophil elastase is an enzyme that helps the body fight infections, but it can also attack healthy tissues (especially the lungs), if not controlled by AAT.

Genetic changes that cause AAT may mean that the body's liver cells make too little or no AAT, or make a form (variant) of AAT that does not work well (abnormal AAT). This allows neutrophil elastase to destroy lung tissue, causing lung disease.

In addition, abnormal AAT can build up in the liver and cause damage to the liver, especially in people who have two copies of the specific genetic variant called allele Z (sometimes written as PI*ZZ). Liver problems do not occur in people who do not make any detectable AAT, for example when a person has two null alleles of the SERPINA1 gene.

The severity of AATD may also be worsened by environmental factors such as exposure to tobacco smoke, dust, and chemicals.

Last updated on 05-01-20

How is alpha-1 antitrypsin deficiency diagnosed?

Alpha-1 antitrypsin deficiency (AATD) may first be suspected in people who have symptoms of liver disease at any age, or who have symptoms of lung disease (such as emphysema), especially when there is no obvious cause or it is diagnosed at a younger age.

Confirming the diagnosis involves a blood test showing a low level the alpha-1 antitrypsin protein (AAT) in the blood, and either:

  • Detecting an AAT protein variant that does not work properly (functionally deficient) using a special test called isoelectric focusing.


  • Finding a disease causing change (pathogenic variant, also called mutation) in both copies of the SERPINA1 gene by genetic testing. (This confirms the diagnosis when the above-mentioned tests are not performed or their results are not in agreement.)

Specialists involved in the diagnosis may include primary care doctors, lung specialists (pulmonologists), and/or liver specialists (hepatologists ).

Last updated on 05-01-20

How might alpha-1 antitrypsin deficiency be treated?

In general, the treatment of medical problems associated with alpha-1 antitrypsin deficiency (AATD) includes the standard medical therapies and supportive care for the specific medical problem. However, there is one special therapy available to some people with AATD who have lung problems called augmentation therapy (sometimes called replacement therapy).

Augmentation therapy aims to increase the blood level of alpha-1 antitrypsin protein (AAT) by adding purified, human AAT directly into the person's blood through intravenous (IV) infusion. The goal is to prevent the progression of lung disease. Skin problems usually get better as well. Augmentation therapy does not affect liver disease associated with AATD.

Augmentation therapy is indicated only when people with AATD:

  • Are older than 18 years of age.
  • Have levels of alpha-1 antitrypsin in blood that are less than 11 micromoles/liter.
  • Have pulmonary function tests (spirometer ) that show airway obstruction.
  • Do not smoke or have stopped smoking for at least the last 6 months.
  • Are willing to be get the infusions weekly at the hospital.
  • Do not have immunoglobulin A deficiency, because the therapy with alpha-1 may contain traces of immunoglobulin type A (IgA), and patients with IgA deficiency may have antibodies against IgA.
  • In some cases it is also done in people who have normal airflow, but who have a CT scan that shows emphysema in the lung.

Other treatments depend on symptoms but may include:

  • Antibiotics to treat infections.
  • Bronchodilators and inhaled steroids can help open the airways and make breathing easier.
  • Exercise program.
  • Oxygen.
  • Lung volume reduction surgery.
  • Lung transplantation for patients with advanced emphysema due to severe AAT deficiency.
  • Liver transplantation for patients with severe liver disease. After a liver transplant the AAT deficiency is corrected, because normal donor liver produces and secretes normal AAT.

Routine recommendations to avoid medical complications include:

  • Vaccination against hepatitis A and B.
  • Preventive vaccines against influenza and pneumococcal vaccines.
  • Avoid using tobacco.
  • Avoid or minimize drinking alcohol (for those at risk for liver disease).
  • Avoid other environmental risk factors such as chemical exposures.
  • Liver function tests periodically for people with two copies of the Z allele (PI*ZZ).
  • Lung function test every six to 12 months people with severe AATD.
  • Liver ultrasound, in cases of liver disease, every 6 to 12 months to monitor for fibrotic changes (cirrhosis) and liver cancer (hepatocellular carcinoma).

Last updated on 05-01-20

Healthcare Resources

Alpha-1 Foundation Genetic Counseling Center

Alpha-1 Foundation Genetic Counseling Center. The Call Center offers information and resources to individuals, family members and medical professionals on the genetics of Alpha-1 and provides information on testing options. Contact 800-785-3177 to ask a genetic counselor questions about alpha 1 antitrypsin deficiency.

Last updated on 04-27-20

Selected Full-Text Journal Articles

Alpha-1 antitrypsin deficiency - articles

Sandhaus RA, Turino G, Brantly ML, et al. The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult. Chronic Obstr Pulm Dis (Miami). 2016; 3(3):668-682.

Last updated on 04-27-20

Name: Alpha-1 Antitrypsin Deficiency Canada Inc. Alpha-1 Canada 13300 Tecumseh Road East, Suite #241
Tecumseh, ON, N8N 4R8, Canada
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Phone: +1-305-567-9888 Toll Free: +1-800-245-6809 (Patient Info) Fax : +1-305-567-1317 Email: Url:
Name: American Liver Foundation 39 Broadway, Suite 2700
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Phone: +1-212-668-1000 Toll Free: +1-800-465-4837 (Helpline) Email: Url:
Name: Alpha-1 Awareness UK PO Box 8294
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