Alpha-1 antitrypsin, or AAT, is a protein made in the liver that circulates in the bloodstream. AAT protects healthy tissues from damage by the body’s disease-fighting immune system cells. An AAT deficiency can cause lung disease, liver disease or both. Low levels of AAT can allow lung damage, while abnormally shaped AAT can build up and damage the liver.

Causes of Alpha-1 Antitrypsin Deficiency

AAT deficiency is a rare disease inherited from parents. It is caused by mutations in a gene that provides instructions for making AAT. Depending on the mutation involved AAT may cause lung disease, liver disease or both.

Types of Alpha-1 Antitrypsin Deficiency

Genetic mutations can alter the production or structure of AAT. One mutation causes too little AAT to be produced. Another distorts the protein’s normal shape, making it harder for it to circulate as it should.

Normally, AAT helps limit the action of an enzyme that plays an important role in lung function. When there is not enough AAT to control this enzyme, it causes lung tissue damage, especially when the lungs have already been damaged by tobacco smoke. This tissue damage leads to chronic obstructive pulmonary disease, or COPD, a group of diseases that include emphysema.

When AAT is abnormally shaped, the protein gets stuck and accumulates in the liver. The buildup of abnormal AAT leads to inflammation, cell damage in the form of hepatitis, scarring (also known as cirrhosis) and, potentially, liver cancer. In addition, when AAT cannot leave the liver, there is too little circulating in the blood, contributing to lung disease as well as liver disease.

In some rare cases, either type of AAT deficiency can cause panniculitis, an inflammation in the tissue just below your skin’s outer layers.

Signs and Symptoms of Alpha-1 Antitrypsin Deficiency

AAT deficiency does not always cause symptoms. When they do occur, they depend on which tissues are affected and the extent of damage.

General symptoms may include:

• fatigue
• frequent infections
• rapid heartbeat
• vision problems
• unintended weight loss

Lung disease symptoms may include:

• chest pain that is worse when inhaling
• excessive coughing with phlegm
• shortness of breath, especially with physical activity
• wheezing

Liver disease symptoms may include:

• easy bruising
• jaundice, which is the yellowing of skin and eyes
• swollen abdomen

How is Alpha-1 Antitrypsin Deficiency Diagnosed?

AAT deficiency is diagnosed through a combination of tests including:

• blood tests to measure levels of alpha-1 antitrypsin
• imaging tests to look for signs of damage in the lungs and liver and determine the severity
• genetic tests to identify AAT-associated abnormal genes
• lung and liver function tests

Treatments for Alpha-1 Antitrypsin Deficiency

Currently, there is no cure for AAT deficiency, and there is no specific therapy for AAT-related liver disease. Treatments focus on improving symptoms, slowing lung tissue damage and managing complications. Options may include:

• augmentation therapy, which uses plasma from healthy donors to increase levels of normal AAT in the blood and help delay lung damage
• medications to treat specific symptoms, such as antibiotics for infections
• drugs such as bronchodilators and inhaled steroids to help with breathing problems
• oxygen therapy to improve blood oxygen levels
• pulmonary rehabilitation (exercise and lifestyle changes) to improve lung function

In advanced cases, lung transplant or liver transplant may be considered.