Clinical evolution of rare variants of Alpha1 Antitrypsin deficiency in Romania

Abstract

Alpha-1 Antitrypsin deficiency (AATD) is a genetic inherited autosomal dominant condition, characterized by decreased serum and pulmonary level of alpha-1 antitrypsin, affecting the lung, liver, rarely skin, associated with an increased risk of emphysema and chronic obstructive pulmonary disease (COPD) early in life, under 40. Under the minimum protection value of Alpha-1 Antitrypsin (AAT) (11 μmol/L or 80 mg /dL), neutrophil elastase may cause the alveolar septa destruction with the early appearance of pulmonary emphysema. Although, AAT is a highly pleomorphic glycoprotein, due by mutations Z and S of approximately 120 alleles. At least 30 AAT alleles other than PI*Z or PI*S were described in literature, some of them as single cases. The prevalence of rare genotypes, other than PI*ZZ or PI*SZ, is between 11% and 21.3%. These rare genotypes were recorded in areas with low prevalence of PI*Z. Rare genotypes of AATD with low plasma levels are Mprocida, Mpalermo, Q0isola di procida, Q0trastevere, Mmalton, Harleen, etc. These evolve clinically with severe emphysema with early onset between 30-40 years. The use in screening programs of gene sequencing for exons 2-5 of SERPINA-1, when genotyping demonstrates the absence of the Z and S alleles, will allow in the coming years to identify several cases of rare variants. Rare variants of alpha1 antitrypsin should be considered on the same risk for emphysema as PI*ZZ.