α₁-Antitrypsin Deficiency, DNA Analysis

Alpha-1 antitrypsin deficiency is an autosomal recessive metabolic disorder with variable severity and age at onset. Signs and symptoms may include increased risk for chronic obstructive lung disease that typically manifests after age 30, liver disease, and liver cancer. Liver disease can be present in infancy as neonatal cholestasis (jaundice) or in adulthood as cirrhosis and fibrosis. Lung and liver disease may be accelerated by environmental exposures such as smoking and excessive alcohol use. Established treatments for COPD and emphysema are used to treat lung disease; lung and/or liver transplantation may be an option for those with severe disease. Intravenous augmentation therapy may be available for patients who meet criteria. The ZZ and SZ genotypes account for more than 95% of individuals with severe alpha-1 antitrypsin deficiency. To rule out other variants, further testing of symptomatic individuals heterozygous for one variant (S or Z) or with negative results may include phenotyping (PI typing), AAT level testing, and/or expanded genotyping. Genetic coordinators are available for health care providers to discuss results and for information on how to order additional testing, if desired, at 1-800-345-GENE.