Alpha-1-Antitrypsin Deficiency
Basic Information
Definition
Alpha-1-antitrypsin (A1AT) deficiency is an inherited autosomal recessive disease caused by homozygosity for the mutant type “Z” A1AT protein. A1AT deficiency is the most common genetic cause of liver disease in children and panacinar emphysema in adults.
Epidemiology & Demographics
• The incidence of A1AT deficiency (PiZZ) in most populations is 1 in 1600 to 1 in 2000 live births.
• The prevalence of A1AT deficiency (PiZZ) in the United States is 1 in 4800; an additional 1 in 600 individuals is heterozygous for the Z allele.
• From 10% to 15% of all PiZZ homozygotes develop clinically significant liver disease during the first 30 years of life.
• Liver disease most commonly presents in infancy (as neonatal cholestasis), but may also present as chronic liver disease in childhood or adulthood.
Clinical Presentation
• Increased anteroposterior diameter of chest, prolonged expiratory phase, clubbing, hyperresonant lung fields, poor air exchange (not apparent until late in second decade)
Etiology
• A1AT deficiency results in synthesis of a defective A1AT protein that cannot be excreted from the hepatocytes.
• Liver disease is caused by accumulation of abnormal protein polymers in the hepatocytes; in some patients this may be aggravated by an additional defect in the ability to break down the abnormal protein.
• Lung disease (pulmonary emphysema) is caused by a lack of active A1AT in the lung, leading to uninhibited proteolytic destruction of the connective tissue backbone.
