Alpha-1 antitrypsin deficiency is caused by an inherited gene mutation.
Infants may develop jaundice and liver damage.
Cirrhosis can develop during childhood.
Adults commonly develop emphysema, with shortness of breath, wheezing, and coughing, and some adults develop cirrhosis.
Tests that measure the amount of the enzyme in the blood and that detect the gene mutations are used for diagnosis.
People with emphysema take drugs to improve breathing and sometimes receive infusions of alpha-1 antitrypsin by vein.
Some people need lung or liver transplants.
Alpha-1 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. Alpha-1 antitrypsin protects the lungs from the damaging effects of proteases.
Alpha-1 antitrypsin deficiency results from an inherited mutation in the gene that controls production and release of the enzyme. There are many subtypes of alpha-1 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 people of Asian or Hispanic ancestry.
The most common problems caused by the deficiency are
Emphysema (a form of chronic obstructive pulmonary disease, or COPD)
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 and to an increased risk of liver cancer.
The low levels of alpha-1 antitrypsin allow proteases to damage the lungs, resulting in emphysema. Emphysema is more common (and worse) in people who smoke. Emphysema in nonsmokers can be caused by alpha-1 antitrypsin deficiency.
Disorders of other organs sometimes occur. These disorders include inflammation of fat under the skin (panniculitis), life-threatening bleeding, aneurysms, ulcerative colitis, vasculitis, and kidney disease.
Symptoms may first appear during infancy, childhood, or adulthood. About 10 to 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.
Alpha-1 antitrypsin deficiency is suspected in the following:
Infants who have typical symptoms
Smokers who develop emphysema before age 45
Nonsmokers who develop emphysema at any age
People with an unexplained liver disorder
People who develop panniculitis
People with a family history of emphysema or unexplained cirrhosis
People with a family history of alpha-1 antitrypsin deficiency
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 alpha-1 antitrypsin.
People who smoke are advised to stop. Bronchodilators, drugs that relax the muscles around the small airways and thus widen the airways, such as albuterol may help ease breathing and relieve cough. Lung infections that develop are treated promptly.
Alpha-1 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.
Taking alpha-1 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. The transplanted liver does not become damaged because the alpha-1 antitrypsin it produces is normal and thus does not accumulate in the liver.
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