Alpha-1 antitrypsin deficiency is a genetic condition that can cause lung and liver damage. Lung symptoms are usually similar to emphysema, including chronic cough, shortness of breath and wheezing. Treatments can reduce your risk of lung damage. Not smoking is the best way to reduce your risk of serious complications.
Alpha-1 antitrypsin deficiency (sometimes just called “Alpha-1”) is an inherited genetic disorder that causes low levels of a protein (AAT) that protects your lungs. Alpha-1 increases your risk of developing certain diseases, including emphysema (damaged air sacs in your lungs), cirrhosis (liver scarring) and panniculitis (an uncommon skin condition). Some of these conditions can be life-threatening.
Alpha-1 is sometimes referred to as “genetic COPD” or “genetic emphysema.”
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Alpha-1 antitrypsin deficiency affects people who have two copies of the SERPINA1 gene that makes an abnormal type of the Alpha-1 protein. Genes are the instructions for how your body should function.
These gene changes can cause your body to have low levels of AAT or no AAT in your lungs, and, depending on the changes, a buildup of AAT in your liver. Any of these changes can cause health issues. People with one abnormal copy of the gene and one normal copy (called Alpha-1 carriers) can also have symptoms and are at an increased risk of lung damage, especially if they smoke.
Alpha-1 is one of the most common genetic disorders among those with European ancestry, but it’s uncommon in people of non-European descent. One in 25 people of European descent have at least one abnormal copy of the gene for Alpha-1. In 1 in about 3,500 people in the U.S., both of their genes for AAT are abnormal, putting them at risk for severe organ damage. About 75% of people with two malfunctioning genes will eventually develop lung function issues.
Alpha-1 antitrypsin (AAT) is a protein that forms in your liver and moves through your bloodstream to your lungs. It’s the “off switch” for an enzyme called neutrophil elastase. Neutrophil elastase is important for fighting infections in your lungs, but it can also destroy your healthy lung tissue. After elastase has had time to help fight an infection, AAT shuts it off (inhibits) so it won’t damage your lungs.
If a gene mutation causes low levels of AAT or creates incorrectly formed AAT, you won’t have enough in your lungs to stop elastase, which will start breaking down the protein elastin in your lungs. Elastin gives strength to the small air sacs of your lungs (alveoli) and allows them to stretch and contract, like a rubber band. Without it, your alveoli lose their shape and become floppy. This makes it so you can’t breathe or get oxygen properly. This is a condition called emphysema.
Gene mutations that change the shape of AAT keep it from moving out of your liver. It builds up there and can cause scarring. Since it can’t get out of your liver, it’s not able to move to your bloodstream and your lungs.
Alpha-1 isn’t necessarily a terminal illness. Many people with Alpha-1, especially if they don’t smoke, can live a normal life span.
Lung diseases caused by Alpha-1 have symptoms similar to chronic obstructive pulmonary disease (COPD). Lung symptoms usually start between the ages of 30 and 50 and include:
About 10% of infants and 15% of adults with Alpha-1 develop liver disease. Signs and symptoms of liver disease may include:
Rarely, your first symptoms of Alpha-1 are painful, red bumps on your skin (panniculitis). These can move around on your body and may break open, leaking fluid or pus.
Everyone has two sets of genes (the instructions for how your body functions), one from each parent. Just like differences in these instructions can determine what color eyes or hair you have, they can also change how your body functions. Differences (mutations) in a specific gene cause Alpha-1 antitrypsin deficiency.
The SERPINA1 gene makes a protein called Alpha-1 antitrypsin (AAT) that protects your lungs from damage caused by another protein in your body (neutrophil elastase, which attacks infections in your lungs). There are many SERPINA1 mutations that can change how your body makes AAT. Some tell your body to make less AAT, some tell your body not to make any at all, and some cause AAT to form incorrectly so it can’t get to your lungs. Any of these can cause you to have too little AAT in your lungs to protect them.
If both copies of your SERPINA1 gene have mutations, you have Alpha-1 antitrypsin deficiency. Depending on the types of abnormal genes, you have a 75% chance of developing lung symptoms. If you have a mutation in just one of your copies of the gene (carrier), your body can usually make enough functioning AAT to protect your lungs. You’re still at an increased risk for lung damage and could eventually develop symptoms, especially if you smoke.
Carriers of abnormal Alpha-1 genes can pass the mutation on to their children. If both parents are carriers, their children have a 25% chance of having two abnormal genes and a 50% chance of being carriers (one abnormal copy and one normal copy). Since both genes contribute to how you make AAT rather than one being dominant, Alpha-1 antitrypsin deficiency is said to have a codominant inheritance.
A provider diagnoses Alpha-1 with blood tests. Because it has symptoms of other illnesses, sometimes it can take a long time to diagnose Alpha-1. You might be tested for Alpha-1 if you have liver symptoms or if you’ve received a COPD diagnosis. Tests and procedures your provider might perform include:
For those with lung conditions from Alpha-1, your provider can treat you with COPD medications and therapies, like bronchodilators and pulmonary rehabilitation. If you have emphysema due to very low levels of Alpha-1 in your blood, they may recommend augmentation therapy. Augmentation therapy delivers normal Alpha-1, collected and purified from blood donors, through an IV. Augmentation therapy can slow the progression of emphysema.
If Alpha-1 affects your liver, your provider may be able to treat some of the symptoms, but only a liver transplant can cure Alpha-1 by restoring normal AAT production.
Not smoking or drinking reduces your risk of lung and liver damage from Alpha-1. It’s recommended that you get vaccinated to help prevent viral hepatitis and pneumonia.
Depending on where Alpha-1 affects you, treatment options may include:
You should avoid alcohol if you have certain types of Alpha-1 or are a carrier. Alcohol can increase your chances of liver damage. You should also avoid medications that can cause liver damage. A provider can help you identify which medications to avoid.
Because it’s inherited (you get it from your parents and are born with it), you can’t prevent Alpha-1. But that doesn’t mean you’ll develop the diseases it can cause. Even with an Alpha-1 diagnosis, there are several things you can do to reduce your risk of organ damage, including:
Your provider can tell you what to expect in your specific situation. Some people with Alpha-1 never have symptoms or related organ damage, especially if they never smoke. Others can have life-threatening complications. Follow your provider’s recommendations to get the best outcome possible.
Complications of Alpha-1 can affect your lungs, liver or other organs and include:
The life expectancy of someone with Alpha-1 varies widely from person to person. Some people live a normal life span and some have life-threatening complications. Your prognosis will depend on:
The best way to take care of yourself with an Alpha-1 diagnosis is to avoid things that can damage your lungs or liver. This includes smoking, lung irritants, alcohol and certain medications. Follow your provider’s recommendations for other ways to stay healthy and manage your symptoms.
See your provider if you have symptoms of Alpha-1 or if a family member has Alpha-1. Early diagnosis is important, so if you have COPD or asthma, ask your provider if you should get an Alpha-1 test.
If you’ve been diagnosed with Alpha-1, see your provider if you have any new symptoms or questions about your care, or if you’re having trouble managing your symptoms.
A note from Cleveland Clinic
Some people with Alpha-1 have few or no symptoms, while others have life-threatening complications. Having honest conversations with your healthcare provider can help you understand what to expect in your specific case. Together, you can make a plan to improve your symptoms, reduce your risk of complications and have the best quality of life.
Last reviewed by a Cleveland Clinic medical professional on 10/18/2022.
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