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. It classically causes emphysema (i.e. chronic obstructive pulmonary disease) in patients who are young and non-smokers.

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
• heterozygous: PiMZ
  • evidence base is conflicting re: risk of emphysema
  • however, if non-smoker low risk of developing emphysema but may pass on A1AT gene to children
• 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
• spirometry: obstructive picture

Management

• no smoking
• supportive: bronchodilators, physiotherapy