Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is a genetic condition that raises your risk for lung disease and other diseases.

AAT is a protein. If you do not make enough AAT, your lungs are more easily damaged from cigarette smoking or fumes and dust from the environment. This can lead to serious lung diseases, such as chronic obstructive pulmonary disease, or COPD. AAT deficiency may also cause a liver disease called cirrhosis. This is more common in children who have AAT deficiency. This topic focuses on AAT deficiency that leads to lung disease.

AAT deficiency runs in families. Many people do not know that they have it, but early diagnosis can help prevent serious lung disease. Talk to your doctor if you have a family member who has AAT deficiency or who was diagnosed with COPD in their 40s or 50s. Also, talk to your doctor if you have symptoms such as a chronic (ongoing) cough, shortness of breath, wheezing, or liver disease.

Currently, AAT deficiency has no cure, but a treatment called augmentation therapy may help slow lung damage. You may also need oxygen therapy, pulmonary rehabilitation, or medicines to treat complications. Your doctor may also talk to you about healthy lifestyle changes, such as quitting smoking and avoiding secondhand smoke and other fumes.

Explore this Health Topic to learn more about alpha-1 antitrypsin deficiency, our role in research and clinical trials to improve health, and where to find more information.

Causes - Alpha-1 Antitrypsin Deficiency

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 genes. 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.

How AAT deficiency is inherited. In this image, both parents have a normal AAT gene and a mutated AAT gene (called being a carrier). Each child has a 25% chance of inheriting two normal genes, a 50% chance of being a being carrier, and a 25% chance of inheriting two mutated AAT genes (and having AAT deficiency).
How AAT deficiency is inherited. In this image, both parents have a normal AAT gene and a mutated AAT gene (called being a carrier). Each child has a 25% chance of inheriting two normal genes, a 50% chance of being a being carrier, and a 25% chance of inheriting two mutated AAT genes (and having AAT deficiency).

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.

Risk Factors - Alpha-1 Antitrypsin Deficiency

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.

Screening and Prevention - Alpha-1 Antitrypsin Deficiency

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.

Signs, Symptoms, and Complications - Alpha-1 Antitrypsin Deficiency

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.

Signs and symptoms
- Alpha-1 Antitrypsin Deficiency

Symptoms of AAT deficiency include:

  • Chronic (ongoing) cough
  • Feeling tired (fatigue)
  • Repeat lung infections
  • Shortness of breath or problems breathing
  • Wheezing

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.

Complications
- Alpha-1 Antitrypsin Deficiency

AAT deficiency can lead to:

Early diagnosis can help you prevent serious complications by avoiding risk factors such as smoking.

Diagnosis - Alpha-1 Antitrypsin Deficiency

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.

Medical history and physical exam
- Alpha-1 Antitrypsin 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.

Diagnostic tests
- Alpha-1 Antitrypsin Deficiency

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.

  • A blood test can check the level of AAT protein in your blood. If the level is lower than normal, it is likely that you have AAT deficiency.
  • A genetic test is the most certain way to check for AAT deficiency and should be done to confirm the results of the blood test and find the mutation in the AAT gene. A genetic counselor can help you understand what to expect from a genetic test and what your results mean.

Lung tests
- Alpha-1 Antitrypsin Deficiency

If you have a lung disease related to AAT deficiency, your doctor may recommend pulmonary (lung) function tests and imaging tests such as a chest CT scan.

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.

Treatment - Alpha-1 Antitrypsin Deficiency

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:

  • Medicines called inhaled bronchodilators and inhaled steroids. These medicines help open your airways and make breathing easier. They are also used to treat asthma and COPD.
  • Oxygen therapy
  • Pulmonary rehabilitation, which involves treatment by a team of experts at a special clinic. You will learn how to manage your condition and function at your best.
  • A lung transplant, which may be an option if you have very severe breathing problems and have a good chance of surviving the transplant surgery

Living With - Alpha-1 Antitrypsin Deficiency

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.

Manage your condition
- Alpha-1 Antitrypsin Deficiency

Regular follow-up care is important to help you manage your health.

  • Talk with your doctor about how often you should schedule medical visits. You may need regular pulmonary (lung) function tests or imaging tests to monitor your condition.
  • Get flu and pneumococcal vaccines to protect you from illnesses that may worsen your condition.
  • Take all your medicines as prescribed and follow your treatment plan.
  • If you have a lung infection, get treatment right away. You also should get treatment right away for any breathing problems.

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.

Make healthy lifestyle changes
- Alpha-1 Antitrypsin Deficiency

Your doctor may talk to you about making healthy lifestyle changes, which can help you function at your best.

  • Quit smoking. If you smoke, quit. If you do not smoke, do not start. Smoking is the leading risk factor for life-threatening lung disease if you have AAT deficiency. Visit Smoking and Your Heart and the NHLBI’s Your Guide to a Healthy Heart. These resources include basic information about how to quit smoking. For free help and support to quit smoking, you can call the National Cancer Institute’s Smoking Quitline at 1-877-44U-QUIT (1-877-448-7848).
  • Avoid secondhand smoke and other lung irritants, such as dust, fumes, or toxins. 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.
  • Choose healthy foods. Choose vegetables, fruits, whole grains, fat-free or low-fat dairy products, fish, lean meats, poultry, eggs, nuts, seeds, soy products, legumes, and vegetable oils (except coconut and palm oils). Also, limit sodium (salt), saturated and trans fats, added sugars, and alcohol. Talk with your doctor about whether it's safe for you to drink alcohol. For more information about healthy eating, go to NHLBI’s Dietary Approaches to Stop Hypertension (DASH) eating plan.
  • Get regular physical activity. Talk with your doctor about how much and what types of activity are safe for you. For more information about physical activity, go to the U.S. Department of Health and Human Services’ Physical Activity Guidelines for Americans or our Physical Activity and Your Heart Health Topic.
  • Manage stress. Learning how to manage stress, relax, and cope with problems can improve your emotional and physical health. Relaxation techniques—such as meditation, yoga, breathing exercises, and muscle relaxation—can help you cope with stress.
  • Get enough good quality sleep. The recommended amount for adults is 7 to 9 hours of sleep a day.

Take care of your mental health
- Alpha-1 Antitrypsin Deficiency

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:

  • Taking medicines or undergoing other treatments that can improve your quality of life
  • Joining a patient support group, which may help you adjust to living with AAT deficiency. You can see how other people have managed their condition, as well as similar symptoms. Talk with your doctor about local support groups or check with an area medical center.
  • Seeking support from family and friends, which may help relieve stress and anxiety. Let your loved ones know how you feel and what they can do to help you.

Research for Your Health

The NHLBI is part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discoveries to improve health and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders including alpha-1 antitrypsin (AAT) deficiency. Learn about current and future NHLBI efforts to improve health through research and scientific discovery.

Improving health with current research
- Alpha-1 Antitrypsin Deficiency

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.

  • Increasing and Sustaining Research to Reduce the Burden of COPD. AAT deficiency can lead to COPD. The NHLBI, with input from federal and nonfederal partners, developed a COPD National Action Plan to guide stakeholders nationwide in their efforts to reduce the burden of COPD. The NHLBI’s Learn More Breathe Better program seeks to increase the awareness and understanding of COPD and encourage people at risk to get tested. The NHLBI also supported a 2010 workshop where researchers and experts made recommendations to guide research into COPD caused by AAT deficiency. View Short of Breath, But Still Fighting and Genetics of COPD for more information.
  • Improving Understanding of the Disease. In 1988, the NHLBI established the Alpha1-Antitrypsin Deficiency Registry (AADR). The aim of this registry was to study the symptoms, treatments, response to treatment, and quality of life of people living with AAT deficiency. This research showed that augmentation therapy helps slow down lung damage caused by AAT deficiency. The AADR has also helped plan clinical trials to develop new treatments. Data from the AADR is available through our Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Researchers can find and request available resources on BioLINCC's secure website.
  • Advancing Treatments for Alpha-1 Antitrypsin Deficiency. The NHLBI has funded research to develop and improve augmentation therapy to treat AAT deficiency. The Institute has also supported the development of genetic therapies to help people who have AAT deficiency make alpha-1 antitrypsin protein. Other studies the NHLBI funds are examining the safety and effectiveness of lung transplants in people who have severe lung damage caused by AAT deficiency. The research funded has improved current treatment options while spearheading progress being made toward a cure.
  • Improving the Diagnosis of AAT Deficiency. The NHLBI funded pioneering research to make it easier to diagnose AAT deficiency. The research helped streamline tests to screen for and diagnose this condition both by blood tests to measure alpha-1 antitrypsin levels and by genetic tests to identify mutations that may cause AAT deficiency.
  • Understanding Lung Function in People Who Have Alpha-1 Antitrypsin Deficiency. The NHLBI has funded research to better understand how AAT deficiency affects how the lungs work. This research has led to advances in methods to measure how well a person’s lungs are working and to predict the decline of lung function, improving clinical care for people who have this condition.

Advancing research for improved health
- Alpha-1 Antitrypsin Deficiency

In support of our mission, we are committed to advancing AAT deficiency research in part through the following ways.

Participate in NHLBI Clinical Trials

We lead or sponsor studies relevant to alpha-1 antitrypsin deficiency. See if you or someone you know is eligible to participate in our clinical trials and observational studies.

Trials at the NIH Clinical Center

Causes and progression of chronic lung disease

This study aims to develop a better understanding of lung disorders. This study also identifies patients who are eligible to participate in other research studies. To participate in this study, you must be between 7 and 90 years old and have symptoms of lung disease. This study is located in Bethesda, Maryland, at the NIH Clinical Center.

Genes involved in development of lung diseases

This study will investigate the genes involved in the breathing process and in the development of lung diseases such as asthma or sarcoidosis to improve understanding of the role they play. To participate in this study, you or your child must be between 2 and 90 years old and have been diagnosed and living with a lung disease. This study is located in Bethesda, Maryland, at the NIH Clinical Center.

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.

Are you an adult who is healthy or has lung disease?

This study aims to collect blood, urine, and airway samples from healthy volunteers and from people who have lung disease. Researchers will use the samples to study genes and proteins that may be involved in lung disease. To participate in this study, you must be at least 18 years old or older. This study is located in New York, New York.

More Information

After reading our Alpha-1 Antitrypsin Deficiency Health Topic, you may be interested in additional information found in the following resources.

Non-NHLBI resources
- Alpha-1 Antitrypsin Deficiency

Last updated

RELATED NEWS

Microscope view of the lungs
|
Research Feature
Might pave the way for new and improved treatments for a wide variety of respiratory diseases Maps may be great tools for helping you find your way around unfamiliar places, but in the future, a new type of map well might help save your life. Welcome to the Molecular Atlas of Lung Development Program, or LungMAP, a historic effort to help...