25. Alpha-1-antitrypsin deficiency as an incidental diagnosis at autopsy

Abstract

Alpha-1-antitrypsin (AAT) is the main protease inhibitor in human serum with highly efficient actions against several enzymes including neutrophil elastase. It is encoded by the SERPINA1 gene and is produced and secreted by hepatocytes. AAT deficiency (AATD) results from mutations in this the SERPINA1 gene causing misfold-ing of the encoded protein. The altered protein then accumulates in the endoplasmic reticulum of hepatocytes resulting in hepatic injury. Lack of circulating AAT results in unregulated action of protease enzymes which may damage some tissues. A common clinical manifestation of this damage is chronic obstructive pulmonary disease (COPD) and AATD is thought to contribute to 1–2% of cases. AATD is rare but is one of the most common and clinically relevant genetic conditions in Caucasian adults. It is thought to be significantly underdiagnosed and there is often a considerable delay in diagnosis. However, early diagnosis can affect the course of treatment and allow for the commencement of preventative measures to limit disease progression. Thus recognition of AATD in an individual can have significant impact for family members. This report presents a case of AATD diagnosed at autopsy as an incidental finding and highlights the role of the autopsy pathologist in the diagnosis of disease which is not related to the cause of death.