Prevalence of Alpha-1 Antitrypsin Deficiency (AATD) in a General Population of Northern Italy: A Descriptive Analysis

Background. Alpha-1 antitrypsin deficiency (AATD) is an under-diagnosed hereditary disorder that predisposes individuals to lung and liver disease. While its prevalence is higher in Northern Europe, data from specific, isolated populations in other regions are scarce. Methods. This study assessed the prevalence of pathogenic SERPINA1 variants in the adult population of Ponte di Legno, a secluded town in the Italian Alps. A cross sectional screening was conducted on March 5–6, 2022. Asymptomatic adult residents were invited to undergo spirometry and provided venous blood samples for serum AAT and CRP measurement, while buccal swabs were collected from all participants for genotyping. Genotyping was performed using a validated multiplex Luminex xMAP assay detecting 14 common and rare SERPINA1 variants, with isoelectric focusing and Sanger sequencing for further characterization when required. Results: Ninety‑one subjects were enrolled (median age 61 years; 37.4% male). Five individuals (5.5%) carried pathogenic SERPINA1 variants: one PiMS heterozygote (1.1%), two PiMZ heterozygotes (2.2%), and two individuals homozygous for the rare PiMheerlen variant (2.2%). Median serum AAT levels were significantly lower in carriers of deficient alleles compared with PiMM individuals (100 mg/dL vs. 125 mg/dL, p = 0.0218). Conclusions: This population‑based screening revealed a notable prevalence of AATD carriers in a geographically isolated Italian community, including two cases of the rare Pi*Mheerlen variant. These findings underscore the value of targeted screening programs to identify at‑risk individuals who may benefit from counseling and clinical monitoring, and suggest that AATD may be more common than previously recognized in specific populations.