α1-Antitrypsin deficiency

Nat Rev Dis Primers. 2016 Jul 28;2:16051. doi: 10.1038/nrdp.2016.51.

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.

Publication types

  • Review

MeSH terms

  • Delayed Diagnosis / adverse effects
  • Delayed Diagnosis / mortality
  • Dyspnea / etiology
  • Emphysema / etiology
  • Epithelial Cells / metabolism
  • Humans
  • Liver Diseases / etiology
  • Monocytes / metabolism
  • Mutation / immunology
  • Mutation / physiology
  • Neutrophils / metabolism
  • Smoking / adverse effects
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency / complications*
  • alpha 1-Antitrypsin Deficiency / epidemiology
  • alpha 1-Antitrypsin Deficiency / physiopathology*

Substances

  • SERPINA1 protein, human
  • alpha 1-Antitrypsin

Supplementary concepts

  • alpha-1-Antitrypsin Deficiency, Autosomal Recessive