Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin (A1AT) deficiency is a common inherited condition caused by a lack of a protease inhibitor (Pi) normally produced by the liver. The role of A1AT is to protect cells from enzymes such as neutrophil elastase.

Genetics

• located on chromosome 14
• inherited in an autosomal recessive / co-dominant fashion*
• alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow
• normal = PiMM
• homozygous PiSS (50% normal A1AT levels)
• homozygous PiZZ (10% normal A1AT levels)

Features

• patients who manifest disease usually have PiZZ genotype
• lungs: panacinar emphysema, most marked in lower lobes
• liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children

Investigations

• A1AT concentrations

Management

• no smoking
• supportive: bronchodilators, physiotherapy
• intravenous alpha1-antitrypsin protein concentrates
• surgery: volume reduction surgery, lung transplantation

*trusted sources are split on which is a more accurate description