Alpha-1 antitrypsin deficiency is an inherited disease that can be a risk factor for developing emphysema and can also cause liver disease. The condition occurs when the gene that makes a protective blood protein called alpha-1 antitrypsin, or AAT, is defective. Normally, AAT is made in the liver and then travels through the bloodstream to the lungs, where it keeps lung tissue healthy by neutralizing an enzyme called neutrophil elastase, which normally fights off infections and helps clean up dead lung tissue. When the AAT gene is defective, AAT accumulates in the liver and can’t make its way to the lungs. Without enough AAT, neutrophil elastase doesn’t stop working when an infection is cleared, but instead keeps going, attacking the walls of fragile air sacks in the lungs called alveoli, which are responsible for exchanging oxygen from the air we breath for carbon dioxide in the blood. When the alveoli are damaged, oxygen and carbon dioxide cannot be exchanged as efficiently, and emphysema is the result. Cigarette smoking greatly increases the amount and rate of this damage, because smoking causes more inflammation in the lungs, leading to the production of more neutrophil elastase.

In most cases, Alpha-1 restricts its damaging effects to the lungs. In some cases, however, the amount of AAT accumulated in the liver becomes so large that liver damage results. Scientists estimate this occurs in about 10 percent of infants born with the severe form of the disease. However, adults with Alpha-1 may also experience liver problems, including cirrhosis or, in rare cases, liver cancer.

Created: September 2003
Updated: May 25, 2005