Alpha-1 Antitrypsin Deficiency
What is alpha-1 antitrypsin deficiency (Alpha-1)?
Alpha-1 antitrypsin (AAT) is a protein made mainly by your liver, which then moves it into your bloodstream. This protein protects your lungs and other organs from the harmful effects of irritants and infections.
Alpha-1 is a rare genetic (inherited) disorder in which people have low levels of AAT in their bloodstream. This disorder can increase your risk of developing lung and liver diseases, including emphysema (damaged air sacs in the lungs) and cirrhosis (liver scarring). The low level of AAT means that lungs are not protected, and the liver is injured by the build-up of the protein there.
Alpha-1 can cause lung problems in adults and liver problems in both adults and children. Some of these conditions can be life-threatening.
How common is alpha-1 antitrypsin deficiency (Alpha-1)?
Alpha-1 is not common. Alpha-1 occurs in about one of every 3,500 people in the U.S. However, the condition is not well-recognized and is under-diagnosed. People with alpha-1 often experience long delays between their first symptom and initial diagnosis, so asking specifically whether lung or liver symptoms could be due to alpha-1 antitrypsin deficiency may prompt earlier diagnosis.
Who is affected by alpha-1 antitrypsin deficiency (Alpha-1)?
Alpha-1 occurs in males and females equally. It is most common in white people of Central or Northern European heritage.
Symptoms and Causes
What causes alpha-1 antitrypsin deficiency (Alpha-1)?
Mutations (changes) in the gene that produces the AAT protein cause Alpha-1. In people with the most common abnormal type of Alpha-1 (called ZZ type), AAT proteins are misshapen. These proteins can’t pass from the liver into the bloodstream, so the number of AAT proteins in the blood is low and the amount of AAT in the liver cells is increased.
When people have low AAT levels in the bloodstream, there isn’t enough AAT protein to protect the lungs and other organs from the effects of infection or irritants. Low levels of AAT can cause conditions such as emphysema and bronchitis (inflammation of the linings of the lungs). Your risk of developing lung problems with Alpha-1 increases a lot if you smoke.
Additionally, when AAT is unable to move out of the liver, it can build up and cause damage and scarring to the liver cells. This damage can lead to disorders such as cirrhosis and liver cancer.
Alpha-1 is a genetic condition, meaning a parent passes it to a child. Severe forms of the condition develop in people who get the abnormal gene from both parents. People who get an abnormal gene from just one parent are carriers, meaning they can pass the gene to their children. They also have a small risk of developing lung disease, especially if they smoke, and of liver disease.
What are the symptoms of alpha-1 antitrypsin deficiency (Alpha-1)?
Some people with Alpha-1 do not develop related diseases and have no symptoms. You might never know you have the disorder. People who have symptoms usually notice them between ages 20 and 50.
People with lung diseases caused by Alpha-1 have symptoms like those caused by chronic obstructive pulmonary disease (COPD). Shortness of breath especially with exertion, is most common. COPD is a group of lung conditions with symptoms that can include:
- Allergies that last all year.
- Extreme tiredness.
- Frequent chest colds.
- Shortness of breath.
- Unexplained weight loss.
Some adults with Alpha-1, and about 10% of infants with Alpha-1, develop liver disease. Signs and symptoms of liver diseases caused by Alpha-1 may include:
- Easy bruising.
- Jaundice (yellowing of the skin and eyes).
- Swelling in the belly or legs from fluid.
- Vomiting blood.
Diagnosis and Tests
How is alpha-1 antitrypsin deficiency (Alpha-1) diagnosed?
Doctors often first diagnose people with Alpha-1 as having asthma, because the disorders share many symptoms, especially shortness of breath. If you don’t respond to asthma treatment, your doctor may order several tests to diagnose Alpha-1. Alternatively, you might ask your doctor whether Alpha-1 could be causing you symptoms and request being tested. These can include:
- Blood test: A doctor takes a sample of your blood to measure your levels of AAT and your Alpha-1 type (i.e., which, if any, abnormal genes for Alpha-1 you have) as well as other substances.
- Imaging tests: Tests such as X-rays and CT scans help doctors confirm identifying signs of Alpha-1 in the lungs. These tests can show the location of any damage and how severe it is.
- Genetic tests: Your doctor may study a blood sample to identify abnormal genes associated with Alpha-1.
Management and Treatment
What are the treatments for alpha-1 antitrypsin deficiency (Alpha-1)?
Treatment for Alpha-1 depends on the type of disease it causes. Your treatment options might include:
- Augmentation therapy: Doctors increase your AAT levels with donated AAT. If you have emphysema due to Alpha-1, augmentation therapy may be considered and you may be recommended to receive weekly or monthly infusions (injections into a vein). This treatment may continue for the rest of your life.
- Lung transplant: A new, healthy lung from a lung transplant can relieve respiratory problems.
- Medication: Steroids and other drugs called bronchodilators can help make it easier for you to breathe by opening airways in the lungs.
- Oxygen therapy: Receiving extra oxygen through a mask or tube in the nostrils can help you breathe more comfortably.
- Pulmonary rehabilitation: Exercises and behavioral changes can relieve breathing problems to improve your daily functioning. Such therapy allows you to do more with the lung function that you have.
What are the complications associated with alpha-1 antitrypsin deficiency (Alpha-1)?
Complications of Alpha-1 depend on the disease it causes:
- Lungs: If you develop lung disease, complications may include emphysema or bronchiectasis (damage to the walls of the airways in your lungs).
- Liver: If Alpha-1 causes liver disease, you may experience swelling of your abdomen and legs, have a higher risk of infections, or develop liver scarring or cancer.
- Skin: In rare cases, some people with Alpha-1 develop a skin disease called panniculitis. This condition can cause painful red lumps in the skin. The lumps may break open and discharge liquid or pus.
How can you prevent alpha-1 antitrypsin deficiency (Alpha-1)?
Because it is inherited (you’re born with it), you can’t prevent Alpha-1. But having the disorder does not mean you’ll develop any of the diseases related to it.
You can reduce your risk of developing emphysema caused by Alpha-1 by not smoking and not using e-cigarettes. You can lower your risk by avoiding being exposed to tobacco smoke and other lung irritants, such as the chemicals produced by vaping. Use safety equipment (like face masks) if you need them for your job. Avoiding breathing in irritating dusts is important, especially for people with dusty jobs, like coal mining, steel mill work, etc.
If you have a family member with Alpha-1 and want to have children, you may want to speak with a genetic counselor. The counselor can help you learn about the risks of passing the disorder to your biological child.
Who is at risk of developing alpha-1 antitrypsin deficiency (Alpha-1)?
People are at higher risk for Alpha-1 if they have a family member with the disorder.
Outlook / Prognosis
What is the prognosis (outlook) for people with alpha-1 antitrypsin deficiency (Alpha-1)?
With ongoing treatment and support, you can live an active and fulfilling life with Alpha-1. The prognosis for people with Alpha-1 varies depending on the person and the severity of the related disease.
Many people with Alpha-1, especially those who do not smoke, do not develop serious complications. They have a normal life expectancy. Other people may develop more serious conditions as a result of the disorder.
Getting the right treatment for diseases caused by Alpha-1 can help you live a longer, healthier life. Treatment can also ease symptoms to improve your quality of life.
When should I see a healthcare provider about alpha-1 antitrypsin deficiency (Alpha-1)?
Contact your healthcare provider if you or your child experiences symptoms of Alpha-1. If you or your child has unexplained lung or liver disease, your doctor may want to do a blood test to see if Alpha-1 is the cause. Always contact your healthcare provider if you or your child develops new or worrisome signs or symptoms of disease.
What questions should I ask my healthcare provider about alpha-1 antitrypsin deficiency (Alpha-1)?
If you or your child has Alpha-1, ask your provider:
- How serious is this case of Alpha-1?
- What caused the disorder?
- What might happen with our health in the future?
- What type of treatment is best?
- How will it affect daily life?
What resources are available for people with alpha-1 antitrypsin deficiency (Alpha-1)?
You may find helpful information from one or more of the following organizations: