α1-Antitrypsin deficiency Agnieszka Bakuła, Piotr Socha, Joanna Pawłowska, Jerzy Socha Medical Science Review - Hepatologia 2006; 6 40-45 aaICID: 449237
Article type: Original article
IC™ Value: 3.59
Abstract provided by Publisher
α1-antitrypsin is a serine protease inhibitor (serpin) providing protection against proteolytic enzymes. It has important anti-inflammatory properties. α1-antitrypsin deficiency is a genetic disorder that predisposes to chronic liver disease and chronic obstructive pulmonary disease (COPD) and to emphysema. This deficiency is the most common inherited cause of liver disease in children, especially neonatal hepatitis syndrome. α1-antitrypsin deficiency is inherited as an autosomal recessive disorder for which more than 100 alleles have been identified. The most frequent mutation that causes severe α1-antitrypsin deficiency arises in the SERPINA1 gene (formerly known as PI) and gives rise to the Z allele. The SERPINA1 gene is located on the long arm of chromosome 14 (14q31-32.3). Deficiency occurs in 1 in 1600–2000 live births in North American and European populations, but it is much less common in other ethnic settings. The ZZ phenotype indicates individuals who are homozygous for the Z allele, mutations in which cause severe deficiency of α1-antitrypsin. In the case of ZZ α1-antitrypsin deficiency, the liver disease does not seem to be caused by the absence of protease inhibitory activity, but rather by the effect of the mutant α1-antitrypsin molecule retained in the endoplasmic reticulum of liver cells. Liver disease, including hepatitis, cirrhosis, and hepatoma, is due to such alleles as Z, Siiyama, and Mmalton. Cigarette smoking markedly increases the risk and rate of developing emphysema. Supplementation with vitamin E, a non-enzymatic scavenger, only during early infancy can prevent liver damage caused by powerful oxidants in patients with α1-AT deficiency.