Alpha1-antitrypsin deficiency: a twenty-five years' experience.

Purpose Analyze the natural history of AATD subjects identified during the twenty-five years’ experience of the Referral Center of Spedali Civili, Brescia (Italy). Methods Retrospective clinical analysis of patients referred to our Center since January 1996 up to January 2020. The inclusion criterion was a diagnosis of AATD via genotyping or protein phenotyping. Results 1021 patients were included (53% males). At the time of diagnosis, mean AAT serum level was 79±27 mg/dL. We diagnosed 825 simple heterozygotes (genotype PiMZ 65%), 117 compound heterozygotes (genotype PiSZ 54%) and 79 homozygotes (genotype PiZZ 82%); 151 (15%) patients were carriers of rare variants, especially Mmalton (35). Index cases (diagnosed due to diseases correlated with AATD) were 223 (22%), 70 of them suffered from emphysema. Among non-index cases, family history for AATD was the most common cause of diagnosis (70%). Augmentation therapy was prescribed in 38 patients; no adverse drug reactions were observed. FEV1 annual decline (mL/year) and the annual trend of blood transaminases have been evaluated. Conclusions Z-AAT resulted the most common variant, although many rarer ones are present. Experienced Referral Centers are crucial for AATD correct management and to carry out a timely diagnosis. Our final data regarding natural history of AATD will let clinicians better understand the prognosis of AATD, supporting them to make the better medical decision. Clinical implications This research increases the knowledge on AATD natural history and its optimal management.