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Editor—α1-antitrypsin (PI), the major inhibitor of neutrophil elastase in the lower respiratory tract, is a highly polymorphic glycoprotein synthesised in the liver that has several rare gene products in which serum protein levels are reduced or even undetectable.1 Early onset pulmonary emphysema, resulting from unopposed elastase activity, and neonatal cholestasis probably resulting from the retention of the defective protein in the liver,2 are the two most common clinical manifestations of PI deficiency and are mainly associated with PI*Z, the most common deficient allele. In addition, other rare alleles occasionally associated with liver injury have been shown to share with PI*Z an increased tendency for intracellular accumulation. Recently, a complete intracellular transport block has been reported for a newly identified3 4 defective Pro369Ser allele (Mwürzburg) by in vitro expression studies in human cell cultures. Adenovirus mediated transfer of the mutant gene into the mouse reproduced the consequences of this block and no traceable amounts of the variant protein could be detected in the plasma after in vivo recombinant expression.3 However, no detectable intrahepatocytic PI inclusions were found in the mice expressing the Mwürzburg mutant3 and no liver biopsy material has yet been presented from patients with this defective allele.
Case report
We report a carrier of the Mwürzburg allele with evidence for in vivo intrahepatic accumulation of …