Alpha1-antitrypsin deficiency—a liver disease causing emphysema

Abstract

Acid starch gel electrophoresis and two dimensional immuno-electrophoresis have been used to recognize genetic variants of human α 1 -antitrypsin; 9 phenotypes have so far been found. They are inherited by a series of autosomal codominant alleles. One in 750 New Zealanders has a severe serum deficiency of this protein associated with the phenotypes SZ and ZZ. One in 9 has a less severe deficiency (phenotype MZ or MS). Severely deficient individuals usually develop emphysema with basal bullae often by age 40, but several of 16 cases with emphysema studied are elderly with mild disease. Patients heterozygous for the Z gene (phenotype MZ) also have an increased incidence of emphysema, usually of later onset, but we have observed several cases under 40. The other manifestation of severe α-antitrypsin deficiency is liver disease. Three children studied had prolonged neonatal cholestasis going on, in the eldest one, to cirrhosis. Symptomatic adult liver disease is less common. The emphysema patients may have asymptomatic liver disease. Histologically the liver tissues show PAS-staining intracellular granules. The deposits fluoresce with conjugated antiserum to α 1 -antitrypsin and electron microscopy shows amorphous material in the rough endoplasmic reticulum of the liver cells. This abnormal antitrypsin is not released into the blood and leaves the lungs vulnerable to attack by sputum proteases. Severe antitrypsin deficiency should be considered in the differential diagnosis of liver disease. MZ heterozygotes also show liver granules but the extent of their predisposition to liver disease remains to be defined.