A new deficient variant of alpha1-antitrypsin (MDUARTE). Inability to detect the heterozygous state by antitrypsin phenotyping

Abstract

A new molecular variant of alpha1-antitrypsin was discovered in the family of a woman with severe antitrypsin deficiency and bullous emphysema. The variant resembles the Z variant in most respects in that it results in severe antitrypsin deficiency with the homozygous state and intermediate deficiency with the heterozygous state, and is associated with diastase-resistant, periodic acid-Schiff-positive globules in the liver cells. It differs from the usual Z variant, however, by having normal mobility on acid-starch electrophoresis so that the heterozygous state with the normal M form cannot be distinguished by phenotyping procedures on either acid-starch or alkaline-agarose electrophoresis. The variant has been labeled MDUARTE. A review of phenotype patterns in all patients previously classified as having a homozygous ZZ phenotype reveals extra, fast-moving bands on acid-starch suggestive of an MDUARTEZ heterozygous state in 7.9 per cent of such cases. When intermediate antitrypsin deficiency occurs in the presence of a normal phenotype pattern, one must consider that the patient has inherited either a null gene for antitrypsin synthesis or an MDUARTE variant.