Alpha-1 Antitrypsin Deficiency

What is Alpha-1 Antitrypsin Deficiency (Alpha-1)?

Alpha-1 is a genetic disorder that affects the lungs and sometimes the liver. Even though it is one of the most common genetic disorders, Alpha-1 can be hard to diagnose. One challenge is that most people with Alpha-1 are healthy for at least the first few decades of their lives. For many, symptoms do not appear until middle adulthood. Another challenge is that the effects of the disorder look a lot like other conditions. Lung symptoms can mimic asthma, bronchitis, or smoking-induced emphysema. Liver symptoms can mimic cirrhosis. This often leads to misdiagnosis and a delay in treatment. In the United States, more than 90% of people with Alpha-1 never learn that they have it.

Affected gene

The affected gene in Alpha-1 is SERPINA1, on chromosome 14. This gene codes for a protein called alpha-1 antitrypsin (AAT). People with the disorder have two non-working copies (alleles) of the gene; they make little or no working AAT protein.

AAT protein is normally made in the liver and released into the blood stream. From there, it can travel throughout the body—most importantly to the lungs. When we breathe in irritants like viruses or smoke, AAT protects the lungs from damage.

In people with Alpha-1, very little or no AAT protein makes it to the lungs. The lungs are left unprotected. Some people who have Alpha-1 make a sticky version of AAT protein that builds up in the liver. Not only do their lungs become damaged, but the sticky AAT protein can also harm the liver.

People with Alpha-1 inherit two non-working copies (alleles) of the SERPINA1 gene: one from each parent. Not everyone with two non-working alleles will develop the symptoms of Alpha-1. Yet they are still considered to have a genetic disorder because their AAT levels are low, or deficient.

Alpha-1 antitrypsin protein is active in the lungs, where it protects them from damage. Without the protein, the lungs slowly accumulate damage over the course of a lifetime.


From the perspective of having the genetic disorder, Alpha-1 mostly follows an autosomal recessive inheritance pattern: it takes two non-working alleles to cause the disorder.

From the perspective of the amount of AAT protein that is made, a person's two SERPINA1 alleles are co-dominant: protein is made from both.

Symptoms and features of Alpha-1

Many people with Alpha-1 develop emphysema (left). The tiny air sacs in the lungs, called alveoli, are damaged. This makes the air spaces in the lungs larger, decreases the surface area of the lungs, and makes breathing difficult. Some people with Alpha-1 make a version of AAT protein that builds up inside of liver cells (right).

The effects of Alpha-1 can be very different from person to person. The effects depend mostly on the specific gene variants (alleles) that a person has.

The main feature of Alpha-1 is damage to the tiny air sacs (alveoli) in the lungs. When the alveoli are damaged, the lungs have a harder time taking in oxygen. This can cause shortness of breath, coughing, or wheezing. Over time, people with Alpha-1 may develop lung diseases, such as asthma, emphysema, chronic bronchitis, or COPD (Chronic Obstructive Pulmonary Disease). Lung disease can appear as early as age 30. These conditions are life-threatening, with symptoms that get worse over time.

Certain SERPINA1 gene variants (alleles) can also cause liver damage. These alleles code for a sticky version of AAT protein that builds up in liver cells. Liver problems include liver cancer, liver failure, and cirrhosis (a chronic liver disease). Liver symptoms can appear at any time, affecting infants, children, and adults.

In rare cases, hard and painful lumps may form under the skin. This is called panniculitis.

Treating and managing Alpha-1

To manage their health, people with Alpha-1 can use a combination of lifestyle behaviors and medical approaches. Lifestyle behaviors are aimed at keeping the body as strong and healthy as possible. Medical approaches are aimed at preventing and managing infections, and easing symptoms.

Carriers of one disease-causing allele may have a higher-than-average risk for lung and liver disease. But usually it also takes an unhealthy environmental factor—such as obesity or cigarette smoking—for disease to develop. Carriers should follow the recommended lifestyle behaviors below and stay up-to-date on their vaccinations. Carriers should also talk to their doctors if they see warning signs of disease.

Lifestyle behaviors

  • Limit tobacco smoke and air pollution. Lung irritants cause inflammation (and increase levels of neutrophil elastase) and block the protective effects of AAT.
  • Develop an exercise program. A stronger body has more stamina.
  • Limit drinking alcohol. This is especially important in people who have alleles that can affect the liver.
  • Eat a nutritious diet.
  • Limit stress.

Tobacco smoke is especially harmful to people with Alpha-1.

Medical approaches

  • Vaccinate against influenza, pneumonia, and hepatitis. These preventable illnesses can damage the lungs or liver.
  • Aggressively treat lung infections. This can decrease inflammation and prevent lung damage.
  • Asthma medications, such as bronchodilators, can ease lung symptoms.
  • Corticosteroids can reduce lung inflammation.
  • Supplemental oxygen.
  • Protein therapy (also called augmentation therapy) can help to slow lung damage. It involves injecting working AAT protein into the blood stream.
  • Lung surgery can be helpful in some cases.
  • In later stages of disease, if the lungs or liver become heavily damaged, people with Alpha-1 may receive an organ transplant.

Alpha-1 is a potential target for genetic technology. One approach is gene therapy, in which a modified virus delivers a working copy of the SERAPINA1 gene into the patient's cells.

Vaccinating against preventable illnesses can help to protect the lungs and liver.

More information

The Alpha-1 Foundation provides confidential testing and genetic counseling to the Alpha-1 community. It is also an excellent resource both for the public and for health care professionals.

American Thoratic Society
American Lung Association
American Liver Foundation


The Alpha-1 Foundation (December 2015). Alpha-1 Antitrypsin Deficiency Healthcare Provider's Guide, version 2.0. Accessed 3/10/2018 at

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