Alpha-1 antitrypsin (AAT) deficiency happens when you do not make enough AAT protein. The AAT protein is made in your liver. This protein enters your blood and protects your organs, including the lungs, from damage. For example, your immune system is your body’s defense against bacteria and viruses but if it is overactive, it can damage your body while fighting diseases. The AAT protein prevents you from having too much inflammation in your lungs. Without enough AAT protein, your immune system may damage your lungs and lead to lung disease.
AAT deficiency is an inherited disease. “Inherited” means it is passed from parents to children through gene. Every person inherits two AAT genes, one gene from each parent. If you inherit a mutated gene from each parent, you will have AAT deficiency.
If you inherit a mutated AAT gene from one parent and a normal AAT gene from the other parent, you are a carrier for the condition. You might have lower levels of AAT protein in your blood, but you most likely will not have AAT deficiency. However, you might develop some complications of AAT deficiency if you smoke or regularly breathe in dust and fumes. You might also pass the mutated gene to your children.
The AAT gene can have different mutations. The most common mutations that cause AAT deficiency are called PiZ and PiS. The image below shows how mutated AAT genes are passed to children.
Even if you inherit two mutated AAT genes, you may not have any complications. You may never even realize that you have AAT deficiency. Scientists are conducting research to find out why some people who have AAT deficiency develop complications while others do not.
AAT deficiency can affect people of any race or ethnicity. However, the condition occurs most often in white people of European backgrounds.
If you have first-degree relatives (siblings, parents, or children) with AAT deficiency, you are at a higher risk for the condition. Even so, it does not mean that you will develop one of the diseases related to the condition.
Some risk factors make it more likely that you will develop lung disease if you have AAT deficiency. Cigarette smoking is the leading risk factor for serious lung disease if you have AAT deficiency. Your risk for lung disease also may go up if you breathe in dust, fumes, or other toxic substances.
You may want to talk to your doctor about testing for AAT deficiency if you have a parent, sibling, or child with the condition, even if you do not have symptoms. Learn more about testing for AAT deficiency.
There is no way to prevent AAT deficiency because the condition is inherited. You may want to talk to a genetic counselor if you are planning to have children and think they are at risk of having AAT deficiency. A genetic counselor can answer questions about the risk and explain the choices that are available.
If you have AAT deficiency, you can take steps to prevent or delay lung diseases related to AAT deficiency. One important step is to quit smoking. If you do not smoke, do not start.
Talk with your doctor about programs and products that can help you quit smoking. If you have trouble quitting smoking on your own, consider joining a support group. Many hospitals, workplaces, and community groups offer classes to help people quit smoking.
For more information about how to quit smoking, visit Smoking and Your Heart and the National Heart, Lung, and Blood Institute's Your Guide to a Healthy Heart. For free help and support to quit smoking, you may call the National Cancer Institute’s Smoking Quitline at 1-877-44U-QUIT (1-877-448-7848).
Also, try to avoid secondhand smoke and places with dust, fumes, or other toxic substances that you may inhale. Check your living and working spaces for things that may irritate your lungs. Examples include flower and tree pollen, ash, allergens, air pollution, wood-burning stoves, paint fumes, and fumes from cleaning products and other household items.
The first lung-related symptoms of AAT deficiency may include shortness of breath, less ability to be physically active, and wheezing. Some people may not have any symptoms or complications. AAT deficiency can lead to lung and liver diseases.
Symptoms of AAT deficiency include:
These symptoms usually appear in people between 20 and 50 years old. At first, many people who have AAT deficiency are diagnosed with asthma. This is because wheezing also is a symptom of asthma. Also, people who have AAT deficiency respond well to asthma medicines.
Some people who have AAT deficiency may have liver damage. Signs of liver damage include jaundice and swelling in your legs. Rarely, AAT deficiency can cause skin problems, such as painful lumps or patches.
AAT deficiency can lead to:
Early diagnosis can help you prevent serious complications by avoiding risk factors such as smoking.
AAT deficiency usually is diagnosed after you develop a lung or liver disease that is related to the condition. But knowing the symptoms and getting an early diagnosis is important to help prevent serious disease, especially with treatment and lifestyle changes.
You may see different specialists, or your doctor may order several diagnostic tests to diagnose AAT deficiency.
Your doctor will ask about your risk factors. This includes your lifestyle habits and environment, such as smoking or regularly breathing in dust. Your doctor will ask if you have relatives who have AAT deficiency or a lung or liver disease and whether you have any signs or symptoms of lung disease. Your doctor will also do a physical exam including listening to your lungs.
Your doctor may recommend tests to confirm a diagnosis of AAT deficiency. He or she also may recommend tests to check for lung- or liver-related conditions.
Lung function tests measure how much air you can breathe in and out, how fast you can breathe air out, and how well your lungs deliver oxygen to your blood. CT scans use X-rays to create detailed pictures of parts of the body.
These tests show how well your lungs are working and whether you have COPD or other lung diseases.
AAT deficiency currently has no cure, but there are treatments to slow lung damage and treat its complications. Treatment is best managed by a team that includes a primary care doctor, pulmonologist (lung specialist), gastroenterologist (GI specialist), and geneticist (specialist in genetic conditions). People who have AAT deficiency and develop related liver or skin diseases will be referred to doctors who treat those diseases.
You may need a lifelong treatment called augmentation therapy. In this treatment, you receive the AAT protein, obtained from blood donors, through a vein to raise levels of the protein in your lungs. This helps slow down lung damage. Side effects of this treatment are rare and may include a mild fever, headaches, nausea, and dizziness.
If you have complications from AAT deficiency, you may also need:
If you already know you have AAT deficiency, you probably also have a related lung or liver disease. Ongoing medical care and lifestyle changes can help you manage your health. Your doctor may also talk to you about making healthy lifestyle changes such as quitting smoking, avoiding secondhand smoke and other lung irritants, and getting annual flu and pneumonia vaccines.
Regular follow-up care is important to help you manage your health.
If you have COPD, your doctor may recommend regular monitoring for heart disease, asthma, depression, and diabetes. COPD can increase your risk for these conditions or make them worse.
Your doctor may talk to you about making healthy lifestyle changes, which can help you function at your best.
Living with AAT deficiency may cause fear, anxiety, depression, and stress. Talk about how you feel with your healthcare team. Talking to a professional counselor also can help. Your doctor may also talk to you about:
Learn about the following ways the NHLBI continues to translate current research into improved health for people who have AAT deficiency. Research on this topic is part of the NHLBI’s broader commitment to advancing lung diseases scientific discovery.
Learn about some of the pioneering research contributions we have made over the years that have improved clinical care.
In support of our mission, we are committed to advancing AAT deficiency research in part through the following ways.
Learn about exciting research areas the NHLBI is exploring about AAT deficiency.
To learn more about clinical trials at the NIH Clinical Center or to talk to someone about a study that might fit your needs, call the Office of Patient Recruitment 800-411-1222.
After reading our Alpha-1 Antitrypsin Deficiency Health Topic, you may be interested in additional information found in the following resources.