Emphysema is a chronic progressive lung disease characterised by abnormal permanent enlargement of airspaces as a result of destruction of alveolar walls.1 Most patients develop emphysema as a consequence of smoking but 1–2% of patients with emphysema develop the condition as a result of a genetic deficiency of the plasma proteinase inhibitor α₁-antitrypsin. The two common deficiency variants of α₁-antitrypsin, S and Z, result from point mutations in the α₁-antitrypsin gene2-4 and are named on the basis of their slower electrophoretic mobility on isoelectric focusing analysis compared with the normal M allele.5 S α₁-antitrypsin (²⁶⁴Glu→Val) is found in up to 28% of Southern Europeans and, although it results in plasma α₁-antitrypsin levels that are 60% of the M allele, it is not associated with any pulmonary sequelae. The Z variant (³⁴²Glu→Lys) results in a more severe deficiency that is characterised, in the homozygote, by plasma α₁-antitrypsin levels of 10% of the normal M allele and by levels of 60% in the MZ heterozygote (50% from the M allele and 10% from the Z allele). The Z mutation results in the accumulation of α₁-antitrypsin in the rough endoplasmic reticulum of the liver (fig 1A) and predisposes the homozygote to juvenile hepatitis, cirrhosis,6 and hepatocellular carcinoma.7 Z α₁-antitrypsin inclusions are associated with abnormal liver function tests in over 90% of Z homozygotes in the first year of life but only 10–15% of these develop the prolonged cholestatic jaundice that can progress to cirrhosis and the requirement for hepatic transplantation.6 ,8