Alpha1-antitrypsin deficiency is a hereditary disorder in which a lack or low level of the enzyme alpha1-antitrypsin damages the lungs and liver.
Alpha1-antitrypsin is an enzyme produced by the liver that inhibits the action of other enzymes called proteases. Proteases break down proteins as part of normal tissue repair. Alpha1-antitrypsin protects the lungs from the damaging effects of proteases.
Alpha1-antitrypsin deficiency results from an inherited mutation in the gene that controls production and release of the enzyme. There are many subtypes of alpha1-antitrypsin deficiency, but in all, levels of active enzyme in the blood are insufficient, the enzyme is structurally abnormal (and thus functions poorly), or both. Whites are affected more often than blacks or Asians.
The most common problems caused by the deficiency are
If the enzyme is structurally abnormal, it may clump in the liver, causing the liver to malfunction. In some people, liver malfunction leads to cirrhosis (see Cirrhosis and Related Disorders: Cirrhosis) and to an increased risk of liver cancer.
The low levels of alpha1-antitrypsin allow proteases to damage the lungs, resulting in emphysema (see Chronic Obstructive Pulmonary Disease (COPD): Chronic Obstructive Pulmonary Disease). Emphysema is more common (and worse) in people who smoke. Emphysema in nonsmokers is often caused by alpha1-antitrypsin deficiency.
Disorders of other organs sometimes occur. These disorders include inflammation of fat under the skin (panniculitis), life-threatening hemorrhage, aneurysms, ulcerative colitis, vasculitis, and kidney disease.
Symptoms may first appear during infancy, childhood, or adulthood. About 20% of affected people have symptoms during infancy. Affected infants develop yellowing of the skin and the whites of the eyes (jaundice) and an enlarged liver during the first week of life. Jaundice disappears at about age 2 to 4 months. However, about 20% of these infants later develop cirrhosis, and some die before reaching adulthood.
Adults commonly develop emphysema, with progressively increasing shortness of breath, difficulty breathing, coughing, and wheezing. Emphysema rarely develops before age 25. It develops earlier and is more severe in smokers than in nonsmokers. The severity of symptoms also varies depending on the form of the deficiency, other disorders people have, environmental exposure to lung irritants, and other factors. If people have never smoked, their symptoms tend to be moderate, and most have a normal life expectancy.
Even if they did not have liver problems during infancy, about 10% of adults develop cirrhosis, which may eventually lead to liver cancer.
People with panniculitis have painful, tender bumps or discolored patches on the lower abdomen, buttocks, and thighs. The bumps may feel hard to the touch.
Alpha1-antitrypsin deficiency is suspected in the following:
Because the deficiency is inherited, doctors usually ask whether any family members have had emphysema or cirrhosis with no known cause.
The deficiency is often confirmed by genetic testing, which also can determine the specific form of the deficiency. Doctors also usually do blood tests to measure the level of alpha1-antitrypsin.
People who smoke are advised to stop. Bronchodilators such as albuterol may help ease breathing and relieve cough. Lung infections that develop are treated promptly.
Alpha1-antitrypsin may be given by vein to replace the deficient enzyme. It is collected from a group of donors and screened for bloodborne disorders. Thus, it is expensive and is most beneficial to people who have only moderate symptoms due to emphysema and do not smoke. This treatment is thought to prevent further damage but does not reverse damage already done.
If people are younger than 60 and have severe symptoms, lung transplantation may be done. A few medical centers sometimes do transplantations in highly selected people as old as 70.
Taking alpha1-antitrypsin does not treat or prevent liver damage because liver damage is caused by production of an abnormal enzyme, not by enzyme deficiency. If the liver is severely damaged, liver transplantation may be done (see Transplantation: Liver Transplantation). The transplanted liver does not become damaged because the alpha1-antitrypsin it produces is normal and thus does not accumulate in the liver.
Doctors may give corticosteroids, antimalarial drugs, or certain antibiotics (tetracyclines) to relieve inflammation. But whether these drugs are effective is unclear.
Last full review/revision December 2008 by Robert A. Wise, MD