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

Summary 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...

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Bibliographic Details
Published in:Journal of inherited metabolic disease 2008-02, Vol.31 (1), p.21-34
Main Authors: 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.
Format: Article
Language:English
Subjects:
alpha 1-Antitrypsin - chemistry
alpha 1-Antitrypsin - genetics
alpha 1-Antitrypsin Deficiency - complications
alpha 1-Antitrypsin Deficiency - genetics
alpha 1-Antitrypsin Deficiency - physiopathology
Animals
Autophagy - physiology
Biochemistry
Biological and medical sciences
Errors of metabolism
Human Genetics
Humans
Internal Medicine
Liver Diseases - etiology
Liver Diseases - genetics
Liver Diseases - therapy
Lung Diseases - etiology
Lung Diseases - genetics
Lung Diseases - therapy
Medical genetics
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Models, Biological
Pediatrics
Protein Conformation
Protein Folding
Proteins and glycoproteins
Review
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Summary:Summary 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.
ISSN:0141-8955
1573-2665
DOI:10.1007/s10545-007-0748-y