Alpha-1 Antitrypsin Deficiency

What is alpha-1 antitrypsin deficiency (Alpha-1)?

Alpha-1 antitrypsin deficiency (also referred to as Alpha-1) is caused by mutations in the SERPINA1 gene on chromosome 14. This gene codes for an enzyme called alpha-1 antitrypsin. It is made in the liver and released into the blood, ultimately to protect the lungs from attack by an enzyme called neutrophil elastase. Neutrophil elastase is made by white blood cells in response to infection or irritants, to digest damaged tissue in the lungs.

When SERPINA1 is mutated, the abnormal alpha-1 antitrypsin protein gets stuck in the liver and is unable to pass into the bloodstream. Without protection from this protein, the lungs are left vulnerable to attack by neutrophil elastase. The accumulation of alpha-1 antitrypsin can also damage the liver.

How do people get Alpha-1?

Alpha-1 is an autosomal recessive disorder. A child must inherit one abnormal gene from each parent to develop the disease. If a child inherits a normal gene from one parent and an abnormal gene from the other, he or she will only be a carrier. Carriers produce lower-than-normal levels of the alpha-1 antitrypsin protein, but they still have enough of it to protect their lungs.

Autosomal Recessive

What are the symptoms of Alpha-1?

Alpha-1 antitrypsin deficiency damages the tiny air sacs (alveoli) in the lungs. When the alveoli are damaged, the lungs aren't able to expand and contract well enough for the person to breathe normally. Patients may feel short of breath, and they may cough or wheeze. As the lungs deteriorate, many patients develop lung diseases, such as emphysema, asthma, or chronic bronchitis.

About 10% of infants and 15% of adults with the disorder also have liver damage, which can develop into the chronic disease cirrhosis. In rare cases, patients may develop hard and painful lumps under their skin, called panniculitis.

How do doctors diagnose Alpha-1?

Alpha-1 antitrypsin deficiency is often misdiagnosed because its symptoms look a lot like the symptoms of asthma, bronchitis, or smoking-induced emphysema. Doctors can test for the disorder by checking a sample of the patient's blood for abnormal alpha-1 antitrypsin levels. To measure lung and liver function, doctors may also do chest x-rays, pulmonary (lung) function tests, lung volume measurements, and blood tests to check liver function.


How is Alpha-1 treated?

Doctors try to increase the amount of alpha-1 antitrypsin in a patient's blood with augmentation therapy. Each week, the patient is given injections of alpha-1 antitrypsin from the blood of healthy donors. Although augmentation therapy does not cure alpha-1-antitrypsin deficiency, it can slow its progression.

Researchers are currently experimenting with gene therapy, in which the patient is given the healthy gene using a modified virus. Unlike the viruses that make us sick, this special virus 'infects' the patient's cells and causes them to start making the normal protein.

To control bronchial symptoms, doctors prescribe asthma medications, such as inhaled steroids or bronchodilators. Patients in the late stages of the disease may have so much lung or liver damage that they need an organ transplant.

Interesting facts about Alpha-1

Alpha-1 is more prevalent among caucasians, affecting 1 in 2,500. In fact, it is one of the most common autosomal recessive disorders among this population. This disorder is hard to spot because people are often not diagnosed until middle adulthood. An estimated 95% of people who have alpha-1 antitrypsin deficiency have never been diagnosed.

Patients with this disorder need to stay away from tobacco, because smoking worsens the disease. Smoke damages the lungs by increasing secretion of neutrophil elastase and by inhibiting alpha-1 antitrypsin.

More information

Alpha-1 Association
The Alpha-1 Association Genetic Counseling Center provides confidential genetic counseling to the Alpha-1 community. It is also an expert resource for health care professionals. The toll-free phone number is 1-800-785-3177.

American Lung Association

American Liver Foundation


383 Colorow Dr, Salt Lake City, Utah 84108

APA format:
Genetic Science Learning Center (2014, June 22) Alpha-1 Antitrypsin Deficiency. Learn.Genetics. Retrieved May 04, 2016, from
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Chicago format:
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