Alpha-1 Antitrypsin Deficiency-associated Liver Disease

Alpha-1 antitrypsin (AAT) deficiency (AATD) is a rare inherited condition that can lead to liver disease (AATLD) in children and liver and lung disease in adults. The disorder is caused by mutations in the SERPINA1 gene, which provides instructions for making the AAT protein. In people with AATLD, the liver produces an abnormal version of the AAT protein, which is prone to aggregation in the liver. This accumulation of mutated AAT in the liver can lead to liver disease. Individuals with AATLD also have an increased risk of having lung disease.

Research suggests that people who have the pair of gene variants called “ZZ” are most commonly identified as having AATLD. Recent epidemiology research indicates that approximately 120,000 individuals in Europe and 63,000 individuals in the U.S. carry this ZZ genotype; the genotype occurs most frequently in individuals of Northern European descent. Although most individuals with this pair will not develop liver disease, some will. It is estimated that 10% or more of individuals with the ZZ genotype may have AATLD, and recent research suggests that AATLD is both underrecognized and underdiagnosed.