Genetic disorder with an autosomal inheritance pattern and codominant expression of alleles.
Pulmonary and hepatic manifestations include emphysema, COPD, and cirrhosis.
Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) and necrotizing panniculitis are infrequent complications but can prompt diagnosis.
Plasma AAT levels, protein phenotyping (called Pi-typing), and protein genotyping may be necessary for diagnosis. Rare alleles may require gene sequencing.
Intravenous AAT augmentation therapy benefits some patients.
Alpha-1 antitrypsin (AAT) deficiency is an autosomal codominant genetic disorder (i.e., 1 allele is inherited from each parent and each allele is expressed equally) resulting from AAT allele mutations at the protease inhibitor (PI) locus. PI* allele mutations cause ineffective activity of the specific protease inhibitor alpha-1 antitrypsin, which is the enzyme responsible for neutralizing neutrophil elastase and preventing inflammatory tissue damage in the lungs. Variants of the enzyme may also polymerize and accumulate in the liver, resulting in hepatic failure. Alpha-1 antitrypsin is also known as alpha-1 proteinase inhibitor.
History and exam
Pulmonary and Critical Care
University of Chicago
DKH has served as a consultant for CSL Behring: manufacturer of AAT replacement therapy. Has lectured for CSL Behring, Grifols, and Shire: manufacturers of AAT replacement therapy. Research sponsored by Shire: manufacturer of AAT replacement therapy.
Dr D. Kyle Hogarth would like to gratefully acknowledge Dr Paul J. Hutchison, a previous contributor to this monograph. PJH declares that he has no competing interests.
Assistant Professor of Medicine
David Geffen School of Medicine at UCLA
JD declares that she has no competing interests.
Chair of Quality
Pulmonary Hypertension Clinic
Pulmonary Education and Rehabilitation
Department of Pulmonary, Allergy and Critical Care
Cleveland Clinic Florida
FR has been a consultant and speaker and has received funding from Baxter Healthcare and CSL Behring.
Consultant Chest Physician
Aberdeen Royal Infirmary
GPC declares that he has no competing interests.
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