11 Scopus citations


Homozygous PIZZ α1-antitrypsin (α1-AT) deficiency is a relatively common genetic disorder, affecting 1 in 1600 to 1 in 2000 live births [1, 2]. It is an autosomal codominant disorder associated with 85–90% reduction in serum concentrations of α1-AT. A single amino acid substitution results in an abnormally folded protein that is unable to traverse the secretory pathway. The mutant α1-ATZ protein is retained in the endoplasmic reticulum (ER) rather than secreted into the blood and body fluids. α1-Antitrypsin is an approximately 55-kDa secretory glycoprotein that inhibits destructive neutrophil proteases, elastase, cathepsin G, and proteinase 3. Plasma α1-AT is derived predominantly from the liver and increases three- to fivefold during the host response to tissue injury or inflammation. It is the archetype of a family of structurally related circulating serine protease inhibitors called serpins. Nationwide prospective screening studies done by Sveger [1, 3] in Sweden have shown that only 8–10% of the PIZZ population develops clinically significant liver disease over the first 20 years of life. Nevertheless, this deficiency is the most frequent genetic cause of liver disease in children and the most frequent genetic disease for which children undergo orthotropic liver transplantation. It also has been associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma in adults [4]. Although the condition does not affect children, many α1-AT-deficient individuals develop destructive lung disease and emphysema.

Original languageEnglish
Title of host publicationLiver Disease in Children, Third Edition
PublisherCambridge University Press
Number of pages27
ISBN (Electronic)9780511547409
ISBN (Print)9780521856577
StatePublished - Jan 1 2007


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