Alpha-1 Antitrypsin Deficiency

Last Updated 05/20/2020

Authors:Keith M. Wille, MD, FCCP; Nirmal S. Sharma, MD

About Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is a rare genetic disorder. It is passed on in families and affects the lungs, liver, and skin. When this condition affects the lungs, it can cause emphysema, a type of chronic obstructive pulmonary disease (COPD), and chronic bronchitis.

Key facts about AAT
  • AAT is a protein. It controls an enzyme called elastase. White blood cells produce elastase to fight infection.
  • In AAT deficiency, AAT levels are lower than normal, which allows elastase enzymes to increase. This increase results in the destruction of lung tissue and the development of emphysema.
  • Having a shortage of ATT is inherited. Severe disease is more likely to occur in people who receive an abnormal gene from both parents.
  • People with a shortage of ATT may have a normal lifespan. However, those who smoke cigarettes have a faster decline in lung function. They also develop earlier lung disease.

How AAT deficiency affects your body

When AAT levels are low or you have none, there is no balance between AAT and elastase. Too much elastase can cause damage. Typically, this enzyme plays an important role in fighting infection. However, too much of it can harm healthy tissue.

Elastase causes damage to the lining and air sacs (called alveoli) of the lung. This results in emphysema, or permanent expansion of the airway to your lungs. Emphysema can cause problems with exchange of gas (such as oxygen and carbon dioxide) and clearing mucus from the lung.

AAT deficiency can affect the liver, leading to poor liver function. It also increases the risk of cirrhosis and liver cancer. Until you are 30 years old, liver disease is more common than lung disease.

In some people, AAT deficiency may cause frequent, red, painful lumps on the skin.

How serious is AAT deficiency?

There are different severity levels of AAT deficiency. This severity level depends on the type of gene change that you inherited from each of your parents.

The normal gene from each parent is called an M. The gene change that is most abnormal is Z. A person who inherits a Z from each parent is most at risk for disease. They are at a higher risk than someone who gets an abnormal gene from only 1 parent.

Those with severe deficiency are at higher risk of life-threatening complications, such as liver failure and lung damage. These people may require a liver or lung transplant in the late stages of disease. People with AAT deficiency who smoke or are exposed to environmental pollutants are at increased risk for developing lung disease. However, people who do not smoke and have AAT can have a more normal life span. This is especially true for those with a less severe gene change.

Symptoms of ATT Deficiency

People with AAT deficiency may have a variety of symptoms. Symptoms can appear early in life or may not begin until a person is 50 or 60 years old.

Symptoms by affected organ include the following:

  • Lungs:
    • Shortness of breath
    • Excessive cough, with phlegm production
    • Wheezing
      These symptoms can continue. They can lead to a decrease in ability to exercise and a feeling of low energy or tiredness. Symptoms may occur over a long period, or they may occur with sudden respiratory infections. Occasionally, a person with AAT deficiency may have chest pain that increases when breathing in. This can be because of a collapsed lung. This is a life-threatening problem. If this happens, get immediate emergency help.
  • Liver:
    • Tiredness
    • Loss of appetite
    • Weight loss
    • Swelling of the feet or belly
    • Yellowish skin (jaundice) or white part of the eyes
    • Vomiting of blood or blood in stools
  • Skin:
    • Warm, red, painful lumps under the skin

What causes AAT deficiency?

AAT deficiency is an inherited condition. It happens when one or both parents pass an abnormal gene to their child. Based on genes, AAT levels may be normal, reduced, or absent. When a child inherits an abnormal gene from each parent, it increases the severity of disease.

What are the risk factors for AAT deficiency?

The main AAT deficiency risk factor is receiving the abnormal gene from 1 or both parents. Not every person with AAT deficiency develops lung or liver disease.

Those who have an increased risk of lung disease early in life include people who:

  • Smoke cigarettes or are exposed to secondhand smoke;
  • Work or live in a dusty environment;
  • Have a family history of emphysema;
  • Have a personal history of asthma; or
  • Have a history of repeated lung infections.

Diagnosing ATT Deficiency

If you are a young person with emphysema or liver disease, your health care provider may order a blood test to check for AAT deficiency.

Not every person with AAT deficiency will require treatment. This is especially true if you have a less severe changes to the AAT gene.

Lung disease typically doesn’t occur until the age of 30 or 40 years for most people with ATT deficiency. Smokers with AAT deficiency develop disease 10 or more years earlier than nonsmokers. Liver disease does not occur in every individual with AAT deficiency. When it does occur, however, it usually does so by age 40.

How AAT deficiency is diagnosed

If you have COPD or emphysema, get tested for AAT deficiency.

To test you, your health care provider may order a blood test to check the level of AAT in your body.

If levels are low, your provider may order genetic testing using a blood test. This test shows whether you inherited the abnormal gene from your parents.

You may have a lung function test, or spirometry, to measure your breathing.

You will also likely have:

If you have low levels of AAT but normal liver and lung function tests, you may not need treatment. However, your health care team will monitor you. You will likely be tested again later.

When should you see your health care provider?

Talk to your health care provider if you have any of the symptoms noted here and they don’t go away.

If you’re a young to middle-aged person with these symptoms or you have a family history of liver or lung disease, talk to your provider about testing for AAT deficiency.

Treating ATT Deficiency

Your treatment depends on the results of your tests. Your treatment also depends on the severity of your symptoms:

  • No symptoms. If you have no symptoms, your provider may ask you to return for regular follow-up visits. To stay healthy, don’t drink alcohol to excess, get regular exercise, and control your weight. You may be asked to get a pneumonia vaccine every 5 years and flu vaccine every year.
  • Lung disease. If you smoke, stop. Talk to your health care provider or call the American Lung Association Lung Helpline at 1-800-LUNGUSA to get help quitting. Your treatment may include medications to help control symptoms of emphysema. You may also take antibiotics and inhaled corticosteroids to control flare-ups, infections, or severe symptoms. Your provider may refer you to a lung rehabilitation program.
    If you aren’t a smoker and your lung function is rapidly declining, you may be eligible for AAT replacement therapy. This therapy increases the levels of AAT in your blood. It isn’t yet clear whether this therapy leads to longer-term improvements in lung function or survival. Replacement therapy is given intravenously (IV). Some people with advanced lung disease may be referred for lung volume reduction surgery (LVRS) or lung transplant.
  • Liver disease. Your provider will monitor your liver function. In severe cases, you may be referred for liver transplant.

People who are diagnosed with AAT deficiency before symptoms appear typically have better outcomes than those who are diagnosed after symptoms appear. People who smoke have a higher likelihood of developing lung disease at an earlier age. They are also more seriously affected.

Managing AAT deficiency

AAT deficiency may not limit your lifespan. You can take steps to control disease symptoms and live a normal life:

  • Stop smoking and avoid exposure to secondhand smoke. Protect yourself from environmental dusts or workplace exposure to toxic substances.
  • Exercise regularly, eat healthfully, and maintain optimal weight. Use your medications to control symptoms. If you have a lower exercise tolerance because of lung symptoms, consider enrolling in a lung rehabilitation program. These are offered at many locations.
  • If you have severe emphysema, talk to your provider about surgery to reduce the size of over-expanded lungs or lung transplant.
  • Limit alcohol use. Alcohol can harm your liver.
  • In certain cases, you may be offered AAT replacement therapy. AAT replacement therapy can be expensive and may have side effects. Talk to your health care provider about whether this is an option for you.

Resources

The American Lung Association recommends that patients and caregivers join its Living with Lung Disease support community to connect with others facing this disease. You can also call the American Lung Association’s Lung Helpline at 1-800-LUNGUSA to talk to a trained lung professional. They can help answer your questions and connect you with support.

For more information about AAT deficiency, visit Alpha1.org.

Between 80,000 and 100,000 people are estimated to be affected by AAT deficiency in the United States. If you have been diagnosed with ATT deficiency, you should go to an AAT specialist. If you have trouble traveling to the specialist, the Alpha-1 Foundation may offer travel vouchers to help. If you need support, the Alpha-1 Foundation support group network may be helpful.

More than 80 affiliated support groups provide support to alpha-1 families and caregivers. They also provide information about pre- and post-transplant care. Support groups are available in most states.

Frequently asked questions about AAT deficiency

  • Q. How is AAT deficiency diagnosed?

    A. Your provider will perform a screening blood test to check AAT levels in your body. If levels are found to be low, further testing of lung and liver function is performed.

  • Q. Can patients with AAT deficiency have a normal life span?

    A. Yes, it’s possible for those with AAT deficiency to have a normal lifespan. Nonsmokers are more likely to retain normal lung function.

  • Q. What lifestyle changes should I make if I am diagnosed with AAT deficiency?

    A. You can:

    • Stop smoking and avoid secondhand smoke exposure;
    • Avoid exposure to dust or fumes;
    • Eat well and exercise regularly;
    • Limit alcohol use; and
    • Consult your provider before taking herbal supplements or over-the-counter medicines.
  • Q. Who is a candidate for AAT replacement therapy?

    A. If your provider finds that your lung function is declining, you may be offered AAT replacement therapy. AAT therapy can cause side effects, is expensive, and usually requires approval from your insurance company. However, the manufacturer may offer programs to provide therapy at little or no cost to you.

  • Q. How do I manage my breathing symptoms?

    A. Your shortness of breath may be a result of emphysema. If you are a smoker, stop smoking. Your provider may prescribe inhalers for emphysema. He or she may check you for other conditions that can affect your breathing, such as heart disease. Your oxygen levels will also be checked. If your oxygen levels are low, you may benefit from oxygen therapy.

  • Q. Is it safe to exercise if I have AAT deficiency–related emphysema?

    A. Your provider will recommend an exercise plan that’s good for you. He or she may also refer you to a lung rehabilitation program. In general, it’s good for patients with emphysema to remain as active as possible and perform regular exercises.

  • Q. Will I need a lung transplant or advanced therapies to control my symptoms?

    A. If your provider determines that your lung function is declining quickly and you have breathing problems that are not controlled, he or she may refer you to be evaluated for LVRS or lung transplant.

  • Q. Do I have to get any special vaccinations if I have been diagnosed with AAT deficiency?

    A. Based on your lung function and age, your provider may prescribe pneumonia vaccines. However, you should always get the annual flu vaccine.