Clinical Profile in Patients with Severe Alpha-1 Antitrypsin Deficiency due to Rare Mutations

Alpha-1 antitrypsin (A1AT) deficiency is a clinically underdiagnosed genetic condition due to mutations involving SERPINA1 gene and resulting in quantitative and/or qualitative alterations of A1AT. Despite the two variants, Z and S alleles, account for the majority of deficient cases, up to now more than 120 variants have been identified. In recent years many national registries across the world have focused their work on rare variants which have led to important discoveries. Among the severe cases of A1AT deficiency as many as 23% of individuals were found to be affected by at least one rare variant in the Italian population, 6.3% in Spanish and 9.5% in Portuguese populations. Despite expected continuation of the increase in frequency of rare genotypes, the clinical data remains scarce. This factor importantly limits the possibility of inclusion of patients with severe A1AT deficiency caused by genotypes other than PI*ZZ, PI*Z/Null and PI*Null/Null in the disease-specific treatment programme. The work studies how the clinical profiles of individuals affected by the rare genotypes differ from the most common deficient genotype, the PI*ZZ.