Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (or just “Alpha-1”) is a genetic disorder that increases your risk of developing lung disease and liver damage. It happens when a gene change causes low levels of alpha-1 antitrypsin (AAT), a protein that protects your lungs from damage. It can also cause a buildup of AAT in your liver.

If you have Alpha-1, you’re at increased risk for:

• Emphysema (damaged air sacs in your lungs) and other lung conditions, like bronchiectasis
• Liver scarring
• Panniculitis (inflammation of fat under your skin)

Some of these conditions can be life-threatening. Alpha-1 is sometimes called “genetic COPD” (chronic obstructive pulmonary disease) or “genetic emphysema.”

Symptoms of Alpha-1 antitrypsin deficiency

The most common symptoms of Alpha-1 affect your lungs, including:

• Shortness of breath, especially with exercise or exertion
• Wheezing, or a whistling sound when you breathe
• Chronic cough, often with mucus
• Extreme tiredness
• Frequent chest colds

Lung symptoms usually start between the ages of 30 and 50, but can also start later.

Some people with Alpha-1 develop liver disease, either as infants or in adulthood. Symptoms could include:

• Yellow or gray skin and eyes (jaundice)
• Itchy skin
• Swelling in your legs or abdomen
• Throwing up blood

Rarely, the first symptom of Alpha-1 is painful, red bumps on your skin.

Alpha-1 antitrypsin deficiency causes

A gene change you’re born with causes Alpha-1. Changes in the SERPINA1 gene affect how your body makes Alpha-1 antitrypsin (AAT) proteins. Some changes cause AAT to form incorrectly, some tell your body to make less AAT and some tell your body not to make any at all.

AAT 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. After elastase has had time to do its job, AAT shuts it off. This prevents elastase from accidentally damaging healthy tissues in your lungs.

Improperly formed AAT can’t move out of your liver. It builds up there and can cause scarring. It’s also not able to move to your bloodstream and your lungs to do its job.

If you have low levels of AAT or AAT that can’t get out of your liver, you won’t have enough in your lungs to stop elastase. Elastase will start breaking down the protein elastin in your lungs. Elastin gives strength to the small air sacs of your lungs (alveoli). It allows them to stretch and contract, like a rubber band. Without it, your alveoli lose their shape and become floppy (emphysema). This makes it so you can’t breathe or get oxygen properly.

Risk factors

Alpha-1 antitrypsin deficiency is most common in people of European ancestry. People who have two malfunctioning copies of the SERPINA1 gene are at high risk for lung disease. Smoking increases this risk.

You can also have symptoms if you have one abnormal copy of the gene and one normal copy. If you have one abnormal copy of the gene, you’re at an increased risk of lung damage, especially if you smoke or breathe in harmful substances. One in 25 people of European descent has at least one abnormal copy of the gene for Alpha-1.

Alpha-1 is an inherited condition. That means that you can pass the gene changes that cause it to your biological children. This is true if one or both copies of your SERPINA1 genes have changes.

Complications

Complications of Alpha-1 include:

• Progressive lung conditions (like COPD or asthma)
• Permanent damage to your airways (emphysema, bronchiectasis)
• High blood pressure in the arteries leading from your heart to your lungs (pulmonary hypertension)
• Liver scarring
• Liver cancer
• Heart, liver or respiratory failure
• Inflammation of the fat under your skin

How doctors diagnose Alpha-1

Healthcare providers diagnose Alpha-1 with blood tests. Because it shares symptoms with other illnesses, sometimes it can take a long time to diagnose. Your provider might test you for it if you have liver symptoms or if you have COPD.

Your provider might do tests or procedures to measure AAT levels, determine how well your lungs or liver are working, and identify damage to your lungs or liver. Tests could include:

• Blood tests, including genetic testing
• Chest X-rays and CT scans
• Pulmonary function tests
• Liver ultrasound or elastography
• Liver biopsy

If you have Alpha-1, your provider may also recommend testing for hepatitis C.

How is Alpha-1 antitrypsin deficiency treated?

Depending on how Alpha-1 affects you, treatment options may include:

• Augmentation therapy: Your provider can increase AAT levels by giving you supplemental, normal AAT (collected and purified from blood donors). You receive augmentation therapy directly into a vein (IV infusion). This can’t reverse lung damage, but it can prevent future damage. It doesn’t prevent liver damage from Alpha-1.
• Medication: Inhaled corticosteroids and bronchodilators can make it easier to breathe by reducing inflammation and opening your airways.
• Oxygen therapy: If your oxygen levels are low, your provider may prescribe supplemental oxygen.
• Pulmonary rehabilitation: Breathing exercises and physical therapy can make breathing easier.
• Smoking cessation therapy: If you smoke, your provider can recommend therapies to help you quit.
• Lung transplant: If your lungs are severely damaged, you might be eligible for a lung transplant. Getting a healthy lung can help improve your quality of life, but it won’t cure Alpha-1.
• Liver transplant: If your liver is badly scarred, your provider may recommend a liver transplant. A healthy liver should make normal AAT.

When should I see my healthcare provider?

Early diagnosis is important. Talk to your provider about testing if you have:

• Liver or lung symptoms
• A family member with Alpha-1
• COPD, asthma or bronchiectasis

If you’ve been diagnosed with Alpha-1, see your provider if you:

• Have any new symptoms
• Have questions about your care
• Are having trouble managing your symptoms

What can I expect if I have Alpha-1?

Some people with Alpha-1 never have symptoms or related organ damage, especially if they never smoke. Others can have life-threatening complications. Your provider can tell you what to expect in your specific situation. Working with your provider can help you manage any conditions you have to stay as healthy as possible.

What is the life expectancy of someone with alpha-1 antitrypsin deficiency?

The life expectancy of someone with Alpha-1 varies widely from person to person. It may not affect how long you live. But some people have life-threatening complications. Your prognosis will depend on:

• How early you’re diagnosed
• The type of Alpha-1 you have and how it affects you
• The amount of organ damage you have at diagnosis
• How well your lungs are working
• How quickly lung or liver disease is getting worse
• If you smoke, whether or not you continue to smoke after diagnosis

How can I prevent Alpha-1?

Because you’re born with the gene changes that cause it, you can’t prevent Alpha-1. But not everyone with Alpha-1 goes on to have lung and liver conditions. There are several things you can do to reduce your risk of organ damage. These include:

• Don’t smoke or vape. Avoid secondhand exposure to tobacco smoke.
• Avoid lung irritants. Use safety equipment (like a respirator mask) if you work with chemicals or dust.
• Avoid alcohol use. You should limit or completely avoid alcohol use if you have certain types of Alpha-1 that can cause liver damage. You shouldn’t drink alcohol if you already have liver damage.
• Ask your provider before taking medications or supplements that can affect your liver, like acetaminophen (Tylenol®). Read labels on prescription and over-the-counter medications, vitamins and supplements for warnings about liver damage.
• Ask your provider what vaccines they recommend. Getting certain vaccinations can protect you against respiratory illnesses, like the flu, pneumonia and COVID-19, and liver infections, like hepatitis A and B.
• Wash your hands frequently. Take additional precautions — like wearing a mask during cold and flu season — to avoid getting sick with illnesses that can cause lung inflammation.
• If a family member has Alpha-1, talk to your provider about getting tested. Having a family member with Alpha-1 increases your risk of having it.

If you have Alpha-1 or are a carrier and want to have children, you may want to speak with a genetic counselor. They can help you understand the risk of passing genetic changes to your child.