Alpha-1 Antitrypsin (AAT) Deficiency
Alpha-1 antitrypsin deficiency (AAT deficiency) is an inherited condition that raises your risk for lung and liver disease. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. The liver makes it. If the AAT proteins aren’t the right shape, they get stuck in the liver cells and can’t reach the lungs.
Variants (also known as mutations) in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene provides instructions for making a protein called alpha-1 antitrypsin, which protects the body from a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (especially the lungs) if not tightly controlled by alpha-1 antitrypsin.
Variants in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin or an abnormal form of the protein that cannot control neutrophil elastase. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. Abnormal alpha-1 antitrypsin can also accumulate in the liver and damage this organ.
Environmental factors, such as exposure to tobacco smoke, chemicals, and dust, likely impact the severity of alpha-1 antitrypsin deficiency.
Some people with Alpha-1 do not develop related diseases and have no symptoms. You might never know you have the disorder. People who have symptoms usually notice them between ages 20 and 50.
People with lung diseases caused by Alpha-1 have symptoms like those caused by chronic obstructive pulmonary disease (COPD). Shortness of breath especially with exertion, is most common. COPD is a group of lung conditions with symptoms that can include:
- Allergies that last all year.
- Extreme tiredness.
- Frequent chest colds.
- Shortness of breath.
- Unexplained weight loss.
Some adults with Alpha-1, and about 10% of infants with Alpha-1, develop liver disease. Signs and symptoms of liver diseases caused by Alpha-1 may include:
- Easy bruising.
- Jaundice (yellowing of the skin and eyes).
- Swelling in the belly or legs from fluid.
- Vomiting blood.
How is alpha-1 antitrypsin deficiency (Alpha-1) diagnosed?
Doctors often first diagnose people with Alpha-1 as having asthma, because the disorders share many symptoms, especially shortness of breath. If you don’t respond to asthma treatment, your doctor may order several tests to diagnose Alpha-1. Alternatively, you might ask your doctor whether Alpha-1 could be causing you symptoms and request being tested. These can include:
- Blood test: A doctor takes a sample of your blood to measure your levels of AAT and your Alpha-1 type (i.e., which, if any, abnormal genes for Alpha-1 you have) as well as other substances.
- Imaging tests: Tests such as X-rays and CT scans help doctors confirm identifying signs of Alpha-1 in the lungs. These tests can show the location of any damage and how severe it is.
- Genetic tests: Your doctor may study a blood sample to identify abnormal genes associated with Alpha-1.
MANAGEMENT AND TREATMENT
What are the treatments for alpha-1 antitrypsin deficiency (Alpha-1)?
Treatment for Alpha-1 depends on the type of disease it causes. Your treatment options might include:
- Augmentation therapy: Doctors increase your AAT levels with donated AAT. If you have emphysema due to Alpha-1, augmentation therapy may be considered and you may be recommended to receive weekly or monthly infusions (injections into a vein). This treatment may continue for the rest of your life.
- Lung transplant: A new, healthy lung from a lung transplant can relieve respiratory problems.
- Medication: Steroids and other drugs called bronchodilators can help make it easier for you to breathe by opening airways in the lungs.
- Oxygen therapy: Receiving extra oxygen through a mask or tube in the nostrils can help you breathe more comfortably.
- Pulmonary rehabilitation: Exercises and behavioral changes can relieve breathing problems to improve your daily functioning. Such therapy allows you to do more with the lung function that you have.
What are the complications associated with alpha-1 antitrypsin deficiency (Alpha-1)?
Complications of Alpha-1 depend on the disease it causes:
- Lungs: If you develop lung disease, complications may include emphysema or bronchiectasis(damage to the walls of the airways in your lungs).
- Liver: If Alpha-1 causes liver disease, you may experience swelling of your abdomen and legs, have a higher risk of infections, or develop liver scarring or cancer.
- Skin: In rare cases, some people with Alpha-1 develop a skin disease called panniculitis. This condition can cause painful red lumps in the skin. The lumps may break open and discharge liquid or pus.
How can you prevent alpha-1 antitrypsin deficiency (Alpha-1)?
Because it is inherited (you’re born with it), you can’t prevent Alpha-1. But having the disorder does not mean you’ll develop any of the diseases related to it.
You can reduce your risk of developing emphysema caused by Alpha-1 by not smoking and not using e-cigarettes. You can lower your risk by avoiding being exposed to tobacco smoke and other lung irritants, such as the chemicals produced by vaping. Use safety equipment (like face masks) if you need them for your job. Avoiding breathing in irritating dusts is important, especially for people with dusty jobs, like coal mining, steel mill work, etc.
If you have a family member with Alpha-1 and want to have children, you may want to speak with a genetic counselor. The counselor can help you learn about the risks of passing the disorder to your biological child.
Who is at risk of developing alpha-1 antitrypsin deficiency (Alpha-1)?
People are at higher risk for Alpha-1 if they have a family member with the disorder.
What resources are available for people with alpha-1 antitrypsin deficiency (Alpha-1)?
You may find helpful information from one or more of the following organizations: