Learn About Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin (AAT) deficiency is a rare genetic disorder that is passed on in families and affects the lungs, liver and skin. When this condition affects the lungs, it causes emphysema, a part of COPD (chronic obstructive pulmonary disease) along with chronic bronchitis.
- Alpha-1-antitrypsin (AAT) is a protein that keeps an enzyme called elastase, produced by white blood cells to fight infection in check.
- In alpha-1 antitrypsin deficiency, AAT levels are reduced, allowing elastase enzymes to increase. This results in the destruction of lung tissue and the development of emphysema.
- AAT deficiency is inherited. Severe disease is more likely to occur in people who receive an abnormal gene from both parents.
- People with AAT deficiency may have a normal lifespan, although those who smoke cigarettes have a faster decline in lung function and develop earlier lung disease.
What Is AAT Deficiency?
AAT deficiency is a genetic disorder in which the body’s ability to produce a protein called alpha-1 antitrypsin (AAT) is reduced, resulting in damage to the lungs and other organs.
How AAT Deficiency Affects Your Body
When AAT levels are reduced or absent, the balance between AAT and elastase is thrown off. This means that elastase can cause damage. Normally, this enzyme plays an important role in fighting infection, but too much of it can harm healthy tissue. It causes damage to the lining and alveoli of the lung, resulting in emphysema, or permanent enlargement of the lung’s airways. This can cause problems with exchange of gas and clearance of mucus from the lung. Additionally, AAT deficiency can affect the liver, leading to poor function and increasing the risk of cirrhosis and liver cancer. In the first three decades of life, liver disease is more common than lung disease. In some individuals, AAT deficiency may cause frequent red, painful nodules on the skin.
How Serious Is AAT Deficiency?
There are different severity levels of AAT deficiency. This depends on the type of gene alteration that is inherited from each parent. The normal gene from each parent is called an M. The gene alteration that is most abnormal is Z. A patient that inherits a Z from each parent is the most at risk for disease as compared to those that receive an abnormal gene from only one parent. Those with severe deficiency are at higher risk of life-threatening complications such as liver failure and lung damage, and may require a liver or lung transplant in the late stages of disease. Individuals with AAT deficiency who smoke or are exposed to environmental pollutants are at increased risk for developing lung disease. However, non-smoking individuals with AAT especially with a less severe gene alteration can have a more normal life span.
AAT Symptoms, Causes and Risk Factors
Individuals with AAT deficiency may have a wide variety of symptoms. Symptoms can appear early in life or may not begin until a person is 50 or 60 years old.
What Are the Symptoms of AAT Deficiency?
Symptoms by affected organ:
- Shortness of breath, excessive cough with phlegm/sputum production, wheezing. These symptoms can persist and lead to a decrease in exercise capacity and a persistent low energy state or tiredness. Symptoms may occur chronically or with acute infections of the respiratory tract. Occasionally a person with AAT deficiency may have chest pain that increases when breathing in. This can be due to a life-threating collapsed lung.
- Tiredness, loss of appetite, weight loss, swelling of the feet or belly, yellowish discoloration of the skin (jaundice) or white part of the eyes, vomiting of blood, or blood in stools.
- Warm, red, painful lumps under the skin
What Causes AAT Deficiency?
AAT deficiency is a hereditary (or inherited) condition. AAT deficiency happens when one or both parents pass an abnormal gene to their child. Based on inherited 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?
The primary AAT deficiency risk factor is inheritance of the abnormal gene from one or both parents. Not every individual with AAT deficiency develops emphysema. People with AAT deficiency 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 a history of repeated lung infections, are at an increased risk of developing lung disease early in life.
When to See Your Doctor
The symptoms mentioned above may occur with but are not specific to AAT deficiency. You should consult your doctor if you have any of the symptoms above. However, if you are a young to middle-aged person with these symptoms, or have a family history of liver or lung disease, you should see your doctor to discuss testing for AAT deficiency.
Diagnosing and Treating AAT Deficiency
If you are a younger than average individual with emphysema or liver disease, your doctor may decide to test you for AAT deficiency with a blood test. Not every individual with AAT deficiency will require treatment especially if they have one of the less severe genetic alterations to the AAT gene.
What to Expect
In most individuals with AAT deficiency, lung disease does not occur until the age of 30 or 40 years. Smokers with AAT deficiency develop disease 10 or more years earlier than non-smokers. Liver disease does not occur in every individual with AAT deficiency; however, it usually occurs by age 40.
How AAT Deficiency Is Diagnosed
All individuals with COPD or emphysema, regardless of age or ethnicity should be tested for AAT deficiency. Your doctor may order a screening blood test to check the level of alpha-1 antitrypsin in your body. An AAT level below 57mg/dl is usually considered lower than normal. If levels are low, genetic testing (from a blood test) may be performed to identify the abnormal gene that was passed to you from your parents. If you haven’t already had a lung function test or spirometry to measure your breathing ability this will likely be performed. You will also likely have a chest X-ray or CT scan of your lungs, blood testing of liver function, and in some cases an ultrasound of the liver. If you have low levels of AAT but normal liver and lung function tests, you may not need treatment; however, you will be monitored with repeat testing over time.
How AAT Deficiency Is Treated
If you are diagnosed with AAT deficiency, your doctor may or may not suggest treatment based on the results of other testing and severity of your symptoms.
- If you have no symptoms – you may be advised to return for regular follow up. You should restrict alcohol consumption, get regular exercise and control your weight. You may be asked to get a pneumonia vaccine every 5 years and flu vaccine every year.
- If you have lung disease – If you smoke, you must stop smoking—call the Lung HelpLine at 1-800-LUNGUSA to get help quitting. Additionally, treatment may include prescribed inhaled medications to control symptoms of emphysema, referral to a pulmonary rehabilitation program, and antibiotics and inhaled corticosteroids to control symptoms of flare ups, infections or exacerbations if needed. If you are not a current smoker and your lung function is rapidly declining, you may be considered eligible for AAT replacement therapy. Replacement therapy will increase blood levels of AAT, but currently it is not clear that it leads to longer-term improvements in lung function or survival. Replacement therapy is given intravenously. Some patients with advanced lung disease may be referred for lung volume reduction surgery (LVRS) or lung transplantation.
- If you have liver disease – you will undergo frequent monitoring of liver function and in severe cases, you may be referred for liver transplantation.
Living with AAT Deficiency
What to Expect
Patients who are diagnosed with AAT deficiency before symptoms occur usually have better outcomes than those who are diagnosed at later stages after symptoms occur. People who smoke have a higher likelihood of developing lung disease at an earlier age and are more seriously affected.
Managing AAT Deficiency
AAT deficiency may or may not limit your long-term survival. Once diagnosed, several steps can be taken to control disease symptoms and result in a normal life. It is important to stop smoking and avoid exposure to secondhand smoke. Additionally, you should protect yourself from environmental dusts or workplace exposure to toxic substances. It is important to exercise regularly, eat healthfully, and maintain optimal weight. If you have symptoms of emphysema, use your prescribed treatment. If you have a lower exercise tolerance due to lung symptoms, you should consider enrolling in a pulmonary rehabilitation program, offered at many locations. In patients with severe emphysema, surgical treatment to reduce the size of over-expanded lungs or referral for lung transplantation may be offered. Apart from this, it is important to limit excessive alcohol use, as it can harm your liver. In certain cases, you may be offered AAT replacement therapy. AAT replacement is a costly treatment, and individuals who use it may experience side effects, making it unavailable as an option for some individuals.
The Lung Association recommends patients and caregivers join our Living with Lung Disease Support Community to connect with others facing this disease. You can also call the Lung Association’s Lung HelpLine at 1-800-LUNGUSA to talk to a trained respiratory professional who can help answer your questions and connect you with support.
More information about AAT deficiency can be found at Alpha1.org.
It is estimated that there are between 80,000 to 100,000 individuals affected by AAT deficiency in the United States. You will be referred to an AAT specialist by your primary care doctor. 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. There are 80 affiliated support groups that provide support to alpha-1 families, caregivers, and information about pre- and post-transplant care. Support groups are available in most states. In addition, several others local foundations offer support groups a well.
Questions to Ask Your Doctor about AAT Deficiency
1. How is AAT deficiency diagnosed?
In individuals who are suspected to have AAT, your doctor 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 will be performed.
2. Can patients with AAT deficiency have a normal life span?
Yes, it is possible that some individuals with AAT deficiency may have a normal life span. Those who are non-smokers are more likely to retain normal lung function long term.
3. What lifestyle changes should I make if I am diagnosed with AAT deficiency?
- Stop smoking and avoid secondhand smoke exposure.
- Avoid exposure to dust or fumes.
- Eat well and exercise regularly
- Limit alcohol consumption.
- Avoid herbal supplements or unlabeled medicines without consulting your doctor.
4. Who should be given AAT replacement therapy?
If your doctor determines that your lung function is declining, you may be offered AAT replacement therapy. AAT therapy can cause side effects, is expensive, and usually requires prior authorization from your insurance company. The manufacturer may offer programs to provide therapy at little or no cost to you.
5. How do I manage my breathing symptoms?
Your shortness of breath may be a result of emphysema. If you are a smoker, you should stop smoking. Your doctor may prescribe inhalers for emphysema or check you for other conditions that can affect your breathing, such as heart disease. Your oxygen levels will also be checked and if found to be low, you may benefit from oxygen therapy.
6. Is it safe to exercise if I have AAT-related emphysema?
Your doctor will recommend an exercise plan that is good for you. You may also be referred to a pulmonary rehabilitation program. In general, it is good for patients with emphysema to remain as active as possible and perform regular exercises.
7. Will I need a lung transplant or advanced therapies to control my symptoms?
If your doctor determines that your lung function is declining quickly and you have breathing problems that are not controlled with currently approved therapies, you may be referred for evaluation for lung volume reduction surgery or lung transplantation.
8. Do I have to get any special vaccinations if I have been diagnosed with AAT?
Based on your lung function and age, your doctor may prescribe the pneumonia vaccines (Prevnar 13 and Pneumovax). However, you should always get the annual flu vaccine.
Keith M. Wille, MD, FCCP
Nirmal S. Sharma, MD
Date Last Reviewed