Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic (inherited) condition – it is passed from parents to their children through their genes. Alpha-1 may result in serious lung disease in adults and/or liver disease at any age.
For each trait a person inherits, there are usually two genes; one gene comes from each parent. People with Alpha-1 have received two abnormal alpha-1 antitrypsin genes. One of these abnormal genes came from their mother and one from their father.
The abnormal Alpha-1 genes
There are many types of abnormal alpha-1 antitrypsin genes. The most common abnormal genes are called S and Z. Normal genes are called M. A person who does not have Alpha-1 will have two M genes (MM).
People identified with Alpha-1 most commonly have two Z genes (ZZ). Current evidence suggests that there are about 100,000 people with Alpha-1 (ZZ) in the United States. Another deficient gene combination is SZ, although people with this gene combination are less likely to get lung or liver problems than those with two Z genes.
Alpha-1 occurs when there is a lack of a protein in the blood called alpha-1 antitrypsin, or AAT. AAT, the alpha-1 protein, is mainly produced by the liver. The main function of AAT is to protect the lungs from inflammation caused by infection and inhaled irritants such as tobacco smoke.
The low level of AAT in the blood occurs because the AAT is abnormal and cannot be released from the liver at the normal rate. This leads to a build-up of abnormal AAT in the liver that can cause liver disease and a decrease of AAT in the blood that can lead to lung disease.
The most common signs and symptoms of disease caused by Alpha-1
Symptoms related to the lung:
- Shortness of breath
- Chronic bronchitis, which is cough and sputum (phlegm) production that lasts for a long time
- Recurring chest colds
- Less exercise tolerance
- Asthma that can’t be completely reversed with aggressive medical treatment
- Year-round allergies
Symptoms related to the liver:
- Unexplained liver disease or elevated liver enzymes
- Eyes and skin turning yellow (jaundice)
- Swelling of the abdomen (ascites) or legs
- Vomiting blood (from enlarged veins in the esophagus or stomach)
Who gets Alpha-1 lung or liver disease?
- Alpha-1 has been identified in nearly all populations and ethnic groups. It is estimated that about 1 in every 2,500 Americans have Alpha-1.
- People with Alpha-1 may remain healthy throughout their lives. Early diagnosis and avoiding risk factors, such as cigarette smoking, can help prevent Alpha-1 from causing disease.
- An estimated 19 million people in the United States have one normal and one defective alpha-1 gene. People with one normal gene and one defective gene (for example MZ) are called “carriers”. Carriers may pass the defective gene on to their children.
- Alpha-1 can lead to lung destruction and is often first diagnosed as asthma or smoking-related Chronic Obstructive Pulmonary Disease (COPD).
Alpha-1 cannot be diagnosed by symptoms or by a medical examination alone; you need to get a simple, reliable blood test to know for sure.
- Alpha-1 is the most common known genetic risk factor for emphysema.
- Up to 3% of all people diagnosed with COPD may have undetected Alpha-1.
- Alpha-1 can also lead to liver disease. The most serious liver diseases are cirrhosis and liver cancer.
- The World Health Organization (WHO), American Thoracic Society (ATS), and the European Respiratory Society (ERS) recommend that everyone with COPD be tested for Alpha-1.
Testing for Alpha-1
The Alpha-1 Foundation supports testing for those at risk for Alpha-1. In response to concerns surrounding testing, privacy and the benefit of an early diagnosis, the Medical University of South Carolina (MUSC), with the support of the Alpha-1 Foundation, developed a free and confidential opportunity for testing. This is a research study called the Alpha-1 Coded Testing (ACT) Study.
The Foundation also established the Alpha-1 Research Registry at MUSC to encourage research, the development of new treatments and a cure for Alpha-1. The Registry is a confidential database made up of both Alphas and Alpha-1 carriers.
The Alpha-1 Genetic Counseling Center is also located at MUSC. The genetic counselor is available to provide support and information to patients, caregivers, and healthcare professionals.
For information on all these programs, see Get Tested.
See Participate in Research Programs to learn how to participate in the ACT Study and be tested for Alpha-1; to join the Research Registry; or to learn more about the Foundation’s research programs.