AAT deficiency, or Alpha-1-antitrypsin deficiency, is a genetic condition caused by a lack of the protective protein, Alpha-1-antitrypsin (AAT), normally produced by the liver. For the vast majority of us who have sufficient amounts of AAT, this little protein plays a vital role in maintaining normal lung function. But for those who have AAT deficiency, the story takes on a different scenario.
In healthy individuals, the lungs contain neutrophil elastase, a natural enzyme that -- under normal circumstances -- helps the lungs digest damaged, aging cells and bacteria. This process promotes healing of the lung tissue. Unfortunately, these enzymes don't know when to stop, and eventually attack the lung tissue instead of helping it heal. That's where AAT comes in. By destroying the enzyme before it can cause damage to healthy lung tissue, the lungs proceed to function normally. When there is not enough AAT, lung tissue will continue to be destroyed sometimes leading to emphysema.
How Can I Inherit AAT Deficiency?
When a child is born, he inherits two sets of AAT genes, one from each parent. The child will only have AAT deficiency if both sets of AAT genes are abnormal. If only one AAT gene is abnormal and the other is normal, then the child will be a "carrier" of the disease, but will not actually have the disease itself. If both sets of genes are normal, then the child will not be afflicted with the disease, nor will he be a carrier.
If you have been diagnosed with AAT deficiency, it is important that you talk with your doctor about having other people in your family tested for the disease, including each of your children. If you do not have children, your doctor may recommend that you seek genetic counseling before you make that decision.
For more information contact the Alpha-1 Foundation Website or call their patient hotline: 1-800-245-6809.
AAT deficiency has been identified in virtually every population, culture and ethnic group. The American Lung Association estimates that there are an estimated 100,000 people in the United States who were born with AAT deficiency. Among the majority of these individuals, AAT related emphysema may be prevalent. Moreover, since AAT deficiency is often either under-diagnosed or misdiagnosed, as many as 3% of all emphysema cases related to AAT deficiency are never detected.
Worldwide, 116 million people are carriers of AAT deficiency. Of these, approximately 25 million live in the United States. While carriers do not actually have the disease themselves, they can pass the disease on to their children. With this in mind, the World Health Organization (WHO) recommends that all people with COPD, as well as adults and teenagers with asthma, be tested for AAT deficiency.
The risk of developing AAT related emphysema significantly increases for people who smoke. The American Lung Association states that smoking not only increases your risk for emphysema if you have AAT deficiency, but it can also decrease your lifespan by as much as 10 years.
Signs and Symptoms of AAT Deficiency
Because AAT related emphysema sometimes takes a backseat to more easily recognized forms of COPD, much effort has been made over the years to find ways to distinguish it. According to Chest, two major features of emphysema related to severe AAT deficiency should prompt suspicion of AAT related emphysema.
First, emphysema symptoms in non-AAT deficient individuals usually don't occur until the sixth or seventh decade of life. According to the American Lung Association, this is not true for people who have AAT related emphysema. For these people, the onset of symptoms occurs much earlier, often between the ages of 32 to 41.
Another important feature that differentiates AAT related emphysema from its non-AAT deficient counterpart is the location in the lungs where the disease most frequently appears. In those who have AAT deficiency related emphysema, the disease is more prevalent in the lower part of the lungs, whereas in non-AAT related emphysema, the disease affects the upper lung region. Both of these features can help your health care provider make an accurate diagnosis.
The most common signs and symptoms of AAT deficiency emphysema are:
- Chronic cough and increased mucus production
- Recurring chest colds
- Swelling of the abdomen or legs
- Decreased exercise tolerance
- Non-responsive asthma or year-round allergies
- Unexplained liver problems or elevated liver enzymes
A simple blood test can tell your doctor if you have AAT deficiency. Because of the importance of early diagnosis, the University of South Carolina has developed a program, with the help of the Alpha-1 Foundation, that allows for free, confidential testing to those at risk for the disease.
Early diagnosis is critical because smoking cessation and early treatment may help slow the progression of AAT related emphysema.
For more information about testing, please contact the Alpha-1 Research Registry at the Medical University of South Carolina at 1-877-886-2383 or visit the Alpha-1 Foundation.
Read more about how a diagnosis of AAT deficiency is made and who should be tested.
For people who have begun to show symptoms of AAT related emphysema, replacement (augmentation) therapy, may be a treatment option that can help protect the lungs against the destructive enzyme, neutrophil elastase.
Replacement therapy consists of giving a concentrated form of AAT that is derived from human plasma. It raises the AAT level in the bloodstream. Once you start replacement therapy, however, you must undergo treatment for life. This is because if you stop, your lungs will return to their previous level of dysfunction and the neutrophil elastase will again start to destroy your lung tissue.
Not only does replacement therapy help slow the loss of lung function in people with AAT related emphysema, but it may also help to reduce the frequency of lung infections. In a study published in Chest, replacement therapy was shown to have a strong relationship with a significant reduction in the frequency and severity of lung infections associated with AAT related emphysema. The study concluded that while emphysema remains irreversible, less frequent, severe lung infections can help slow the progression of AAT related emphysema and lead to a higher quality of life.
For more information about AAT deficiency or replacement therapy, talk with your healthcare provider or visit the Alpha-1 Foundation.
American Lung Association. Alpha-1 Related Emphysemahttp://www.lungusa.org. November, 2006.
American Thoracic Society. American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency". ATS: December 2002. ERS: February, 2003.
Alpha-1 Foundation. http://www.alphaone.org/
Lieberman, J. "Augmentation Therapy Reduces Frequency of Lung Infections in Antitrypsin Deficiency: A New Hypothesis With Supporting Data". Chest 2000; 118; 1480-1485.
Stoller, J., M.D., FCCP. "Clinical Features and Natural History of Severe Alpha-1 Antitrypsin Deficiency". Chest 1997; 111: 123S-128S.