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.

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.

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.

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

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.