Reviewed by Robert A. Sandhaus, MD, PhD, FCCP

The inherited condition alpha-1 antitrypsin deficiency can cause liver disease in children and adults.

Alpha-1 antitrypsin is a major protein in the blood that protects the lungs and other organs in the body from being damaged by our own inflammatory cells. It does this by inactivating enzymes released by white blood cells whose purpose is to destroy foreign invaders like viruses or bacteria or infected cells. Without alpha-1 antitrypsin to turn off the destructive power of these defensive enzymes, they start to chew up the bodies' normal proteins.

A person who has alpha-1 antitrypsin deficiency makes a defective version of this protein in the liver that tends to misfold, polymerize (forms long chains of many molecules bonded together), and accumulate within liver cells. When this happens, the alpha-1 antitrypsin polymers (chains) cannot be transported out of the liver cells where they are made. This has the dual effect of clogging liver cells and of not allowing delivery of the protein to organs like the lungs that need alpha-1 antitrypsin to function properly.


People at Risk

Although rare, alpha-1 antitrypsin deficiency, also known more simply as Alpha-1, is the most common genetic cause of severe liver disease in children. While the incidence of Alpha-1 in the US is about 1 in 2000 live births, less than 5 percent of babies born with Alpha-1 will have severe liver disease. Since Alpha-1 is a genetic condition, a person needs two copies of the faulty gene (one from each parent) to have the severe form of this condition.

There are over 20 million carriers of a single gene for alpha-1 antitrypsin deficiency in the U.S.  If there is concern about passing on Alpha-1 to your children, a genetic test is available to determine if you are a carrier. It is probably not necessary to get tested unless you or your family members have a history of Alpha-1, or of COPD, emphysema, or unexplained liver disease.

Clinical Trials

For more than 100 years, National Jewish Health has been committed to finding new treatments and cures for diseases. Search our clinical trials.