Case report of a novel alpha1-antitrypsin null variant in Türkiye: Q0.

Background: 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.

Results: This report describes a novel mutation of SERPINA1 producing AATD, which we have designated, Q0. 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.

Conclusions: Although many SERPINA1 variants have been identified, variants with large deletions and identified in a homozygous individual, as seen in this case with Q0 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.