Alpha-1 antitrypsin deficiency (AATD) is an inherited genetic disorder that is most commonly caused by a G-to-A point mutation in the SERPINA1 gene. This mutation results in the production of insufficient levels of circulating M-AAT protein, which protects the lungs from proteolytic enzymes, and aggregation of misfolded Z-AAT protein in hepatocytes. This leads to lung and liver disease. Individuals with AATD carry Z mutations on both SERPINA1 alleles; this is known as the PiZZ genotype.
Augmentation therapy via delivery of functional AAT protein is currently the only treatment option for AATD-associated lung disease and requires weekly intravenous infusions. There are no treatments for AATD-associated liver disease, besides liver transplantation.
