Alpha-1 Antitrypsin Deficiency (AATD)

Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder with significant clinical variability, affecting both the liver and lungs. It occurs due to mutations in the SERPINA1 gene, which leads to reduced levels or dysfunctional forms of the alpha-1 antitrypsin (AAT) protein. This protein plays a crucial role in protecting the lungs from enzymatic damage and maintaining normal liver function.

Clinically, AATD can manifest as hepatic dysfunction from infancy to adulthood and as chronic obstructive lung disease, primarily emphysema and bronchiectasis, typically in individuals over 30 years. Additional complications include panniculitis and C-ANCA-positive vasculitis. The severity and presentation of AATD symptoms can vary widely among individuals and even within families.

A key factor in the progression of lung disease in AATD is smoking, which accelerates the development of chronic obstructive pulmonary disease (COPD). Non-smokers may lead a normal life but are not immune to potential lung and liver diseases. While emphysema is rare in children with AATD, liver disease can manifest early as neonatal cholestasis, with the risk increasing with age. In adults, liver diseases such as cirrhosis, fibrosis, and an increased risk for hepatocellular carcinoma can occur, even in the absence of earlier liver problems.

Diagnosis of AATD is based...