Clinical features in patients with severe Alpha-1 antitrypsin deficiency due to rare genotypes.

Alpha-1 Antitrypsin Deficiency (AATD) is a co-dominant condition associated with an increased risk of lung and liver disease. Since it is commonly thought that 95% of severe cases of AATD have PIZZ genotype, most studies about AATD have been focused on the Z variant. Nevertheless, over 500 single nucleotide variations in the gene have been identified. We investigated the clinical presentation of subjects with severe AAT deficiency due to rare genotypes of the gene. We enrolled patients from the Italian Registry for AATD (RIDA1) with the following inclusion criteria: diagnosis of severe AATD; age >18 years; full clinical data available at diagnosis; three years of follow-up respiratory function data. A total of 281 patients were enrolled from the RIDA1 Registry and subdivided into 3 cohorts: PIZZ genotype (n = 160), PISZ genotype (n = 54), and rare genotypes PIR (n = 67). We did not observe any statistical differences among the cohorts regarding sex, smoking habits, occupational exposure and age at diagnosis. Patients with severe AATD due to rare genotypes have clinical characteristics and respiratory profiles similar to PIZZ subjects, and differed from the PISZ patient group. Early and accurate diagnosis of PI*R subjects is therefore important for their appropriate clinical management.