• Vani Mulkareddy and Jesse Roman.
• Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine and The Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA, USA.
• Am. J. Med. Sci. 2024 Jul 1; 368 (1): 181-8.

AbstractAlpha 1 antitrypsin deficiency is a widely under recognized autosomal codominant condition caused by genetic mutations in the SERPINA 1 gene, which encodes for alpha 1 antitrypsin (AAT), a serine protease inhibitor. The SERPINA 1 gene contains 120 variants and mutations in the gene may decrease AAT protein levels or result in dysfunctional proteins. This deficiency leads to unopposed protease activity in tissues, thereby promoting pulmonary and hepatic disease. The most common genotype associated with pulmonary disease is the ZZ genotype, and the most frequent pulmonary manifestation is emphysema. Although its pathophysiology may differ from cigarette smoking related chronic obstructive pulmonary disease, smoking itself can hasten lung decline in alpha 1 antitrypsin deficiency (AATD). The diagnosis of AATD is made through AAT protein testing along with genotyping. AATD patients with obstructive airflow limitation may qualify for intravenous augmentation with AAT. However, there is ongoing research to allow for earlier detection and treatment. This review describes in general terms the genetic mechanisms of AATD; its pathogenesis and the impact of cigarette smoke; and its clinical manifestations, diagnosis, treatment, and prognosis. We hope to stimulate research in the field, but mostly we wish to enhance awareness to promote early diagnosis and treatment in those eligible for intervention.Copyright © 2024. Published by Elsevier Inc.

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