α1-Antitrypsin deficiency

Catherine M. Greene, Stefan J. Marciniak, Jeffrey Teckman, Ilaria Ferrarotti, Mark L. Brantly, David A. Lomas, James K. Stoller, Noel G. McElvaney

Research output: Contribution to journalArticle

Abstract

α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development.

Original languageEnglish
Article number16051
JournalNature Reviews Disease Primers
Volume2
DOIs
Publication statusPublished - Jul 28 2016

ASJC Scopus subject areas

  • Medicine(all)

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    Greene, C. M., Marciniak, S. J., Teckman, J., Ferrarotti, I., Brantly, M. L., Lomas, D. A., Stoller, J. K., & McElvaney, N. G. (2016). α1-Antitrypsin deficiency. Nature Reviews Disease Primers, 2, [16051]. https://doi.org/10.1038/nrdp.2016.51