Journal of Inherited Metabolic Disease

, Volume 31, Issue 1, pp 21–34 | Cite as

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

  • C. M. GreeneEmail author
  • S. D. W. Miller
  • T. Carroll
  • C. McLean
  • M. O’Mahony
  • M. W. Lawless
  • S. J. O’Neill
  • C. C. Taggart
  • N. G. McElvaney


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.


Endoplasmic Reticulum Stress Unfold Protein Response High Resolution Compute Tomography Human Neutrophil Elastase A1AT Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • C. M. Greene
    • 1
    Email author
  • S. D. W. Miller
    • 1
  • T. Carroll
    • 1
  • C. McLean
    • 1
  • M. O’Mahony
    • 1
  • M. W. Lawless
    • 1
    • 2
  • S. J. O’Neill
    • 1
  • C. C. Taggart
    • 1
    • 3
  • N. G. McElvaney
    • 1
  1. 1.Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research CentreBeaumont HospitalDublin 9Ireland
  2. 2.Hepatology Research Division, Institute of Molecular Medicine, Trinity Health Science Building, Trinity CollegeSt. James HospitalDublin 8Ireland
  3. 3.School of Medicine and DentistryQueen’s University BelfastBelfastNorthern Ireland

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