A1AT

Alpha-1 antitrypsin (A1AT) is a glycoprotein and serine protease inhibitor produced mainly by hepatocytes in the liver and released into the bloodstream. It functions to protect tissues, especially in the lungs, from enzymes such as neutrophil elastase released during inflammation.

A1AT is encoded by the SERPINA1 gene. Common alleles include M (normal), S, and Z. The combination of alleles determines the protease inhibitor (Pi) phenotype; PiMM is typical, while PiZZ and PiSZ deficiencies are associated with reduced circulating A1AT and increased disease risk. The Z allele causes misfolded protein that accumulates in liver cells, lowering serum levels and potentially causing liver disease.

Severe A1AT deficiency predisposes to early-onset panacinar emphysema, particularly in the lower lungs, and to liver disease ranging from neonatal cholestasis to cirrhosis and, in some cases, hepatocellular carcinoma. Symptoms may include shortness of breath, chronic cough, and wheezing, with onset often in adulthood but variable among individuals.

Diagnosis involves a blood test to measure A1AT levels, followed by genotyping or phenotyping to identify SERPINA1 variants. Clinically, testing is considered in patients with unexplained COPD or liver disease, a family history of A1AT deficiency, or compatible symptoms.

Management focuses on reducing lung injury and managing symptoms. This includes avoidance of smoking and lung irritants, vaccination, and standard therapies for airway disease as indicated. For individuals with PiZZ or other deficient genotypes and significant lung disease, intravenous augmentation therapy with purified A1AT can slow emphysema progression. Liver disease may require monitoring or transplantation in severe cases. Prevalence varies by population and the condition is often underdiagnosed.