title: α1-Antitrypsin deficiency.
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.
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Greene
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Marciniak
authors.affiliation: Department of Pediatrics, Saint Louis University, St Louis, Missouri, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Teckman
authors.affiliation: Department of Internal Medicine and Therapeutics Pneumology Unit, University of Pavia, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarotti
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Brantly
authors.affiliation: UCL Respiratory, Division of Medicine, University College London, London, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: Education Institute and Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: James K
authors.initials: JK
authors.lastname: Stoller
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
mesh_terms: D057210:Delayed Diagnosis / Q000009:adverse effects / Q000401:mortality; D004417:Dyspnea / Q000209:etiology; D004646:Emphysema / Q000209:etiology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000209:etiology; D009000:Monocytes / Q000378:metabolism; D009154:Mutation / Q000276:immunology / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin