Alpha1-Antitrypsin Deficiency
Alpha1-antitrypsin deficiency is a hereditary disorder in which a lack of the enzyme alpha1-antitrypsin may cause lung and liver disease.
Alpha1-antitrypsin is an enzyme that the liver produces and secretes into the bloodstream. Certain tissues then take up this enzyme and, in turn, secrete it into fluids that they produce. Thus alpha1-antitrypsin is normally present in saliva, duodenal fluid (the fluid present in the first segment of the small intestine), lung secretions, tears, nasal secretions, and cerebrospinal fluid.
Alpha1-antitrypsin inhibits the action of enzymes that break down proteins (proteases). A lack or reduced level of alpha1-antitrypsin allows proteases to damage tissue, particularly in the lungs and liver. In alpha1-antitrypsin deficiency, the liver is unable to secrete (export) this enzyme, which then accumulates inside the liver cells, leading to their destruction. The disorder is usually identified in children, many of whom die before they reach adulthood. Therefore, this disorder is uncommon in adults.
Symptoms and Prognosis
About 25% of children with alpha1-antitrypsin deficiency develop cirrhosis and excessive pressure in the portal vein (the vein that carries blood from the intestines to the liver) and die before age 12. About 25% die by age 20. Another 25% have only minor liver abnormalities and survive into adulthood. The remaining 25% do not develop liver abnormalities and have no evidence of progressive disease.
Adults with alpha1-antitrypsin deficiency commonly develop emphysema, a lung disease that results in increasing shortness of breath. Less commonly, adults with this disorder develop cirrhosis, which may eventually lead to liver cancer.
Treatment
Replacement of the missing enzyme using synthetic alpha1-antitrypsin has shown some promise in the treatment of children, but liver transplantation (see Section 16, Chapter 187) remains the only fully successful treatment. Liver damage does not usually recur in the transplanted liver, which is able to produce and secrete alpha1-antitrypsin normally.
Treatment in adults is usually directed at the lung disease (see Section 4, Chapter 45). Measures include preventing lung infection and getting a person who smokes to stop smoking. Liver transplantation is also successful in adults.
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