Case report of a novel alpha1-antitrypsin null variant in Türkiye: Q0_RİZE

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that serves as a counterbalance to the activity of elastases, e.g., neutrophil elastase in lung tissue. AAT deficiency (AATD) is a rare disorder usually arising from mutations to the SERPINA1 gene that codes for AAT. The most common AATD alleles are S and Z which produce ~ 40% and ~ 90% reductions in serum AAT, respectively. Rare genetic variants (> 500 identified) can also be associated with mild to severe AATD.

This report describes a novel mutation of SERPINA1 producing AATD, which we have designated, Q0_RİZE. This mutation was identified in a 44-year-old woman admitted with massive hemoptysis and treated with bronchial artery embolization. Computed tomography revealed centriacinar and panacinar emphysema with prominent air entrapment, atelectasis, and localized bronchiectasis. Serum AAT was < 0.27 g/L (below detection limit). Genetic analysis showed homozygous deletion of exons I to III.

Although many SERPINA1 variants have been identified, variants with large deletions and identified in a homozygous individual, as seen in this case with Q0_RIZE, are uncommon. AATD is an underdiagnosed and undertreated disease. Wider screening of COPD patients could result in earlier diagnosis and treatment that could preserve lung function.