Homozygous (PiZZ phenotype) α -antitrypsin (α -AT) deficiency is a relatively common genetic disorder, affecting 1 in 3000 live births [1]. It is an autosomal codominant disorder associated with 85–90% reduction in serum concentrations of α -AT. A single amino acid substitution results in an abnormally folded protein that is unable to traverse the secretory pathway. The mutant α antitrypsin Z (α -ATZ) protein is retained in the endoplasmic reticulum (ER) rather than secreted into the blood and body fluids. Antitrypsin is an approximately 55kDa secretory glycoprotein that inhibits destructive neutrophil proteases, elastase, cathepsin G, and proteinase 3. Plasma α AT is derived predominantly from the liver and increases three- to five-fold 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 by Sveger and coworkers [2, 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 orthotopic liver transplantation. It also causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in adults [4].

Original languageEnglish
Title of host publicationLiver Disease in Children, Fourth Edition
PublisherCambridge University Press
Number of pages1
ISBN (Electronic)9781139012102
ISBN (Print)9781107013797
StatePublished - Jan 1 2011


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