Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

C. M. Greene*, S. D W Miller, T. Carroll, C. McLean, M. O'Mahony, M. W. Lawless, S. J. O'Neill, C. C. Taggart, N. G. McElvaney

*Corresponding author for this work

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Abstract

Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called 'Z' mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols. © Springer Science+Business Media B.V. 2008.

Original languageEnglish
Pages (from-to)21-34
Number of pages14
JournalJournal of Inherited Metabolic Disease
Volume31
Issue number1
DOIs
Publication statusPublished - Feb 2008

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

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    Greene, C. M., Miller, S. D. W., Carroll, T., McLean, C., O'Mahony, M., Lawless, M. W., O'Neill, S. J., Taggart, C. C., & McElvaney, N. G. (2008). Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations. Journal of Inherited Metabolic Disease, 31(1), 21-34. https://doi.org/10.1007/s10545-007-0748-y