Intermediate Alpha-1 Antitrypsin Deficiency Can Play a Role in Pulmonary Exacerbation?

Abstract

Background: Alpha-1 antitrypsin deficiency is generally suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic delays or are misdiagnosed, for example, with COPD, asthma, or airway hyperresponsiveness because of the nonspecific nature of respiratory symptoms recognised with Alpha-1 antitrypsin deficiency (AATD). These pathologies develop in homozygous patients (both compromised alleles) with severely deficient protein; however, they are also frequently observed in heterozygous patients (only one compromised allele) for the gene mutation with a more or less deficient protein and functional anatomical damage of varying severity depending on the type of mutation and the exposure to environmental risk factors and/or professional that can trigger the repeated injurious inflammatory process. Case Description: We describe two cases of late diagnosis of alpha-1 antitrypsin deficiency, with many exacerbations and intermediate level of alpha-1 antitrypsin. Due to the peculiar clinical history, and the PLowell rare mutation, although intermediate AATD, the patients were subjected to replacement therapy and they obtained clinical improvement. Discussion: Both the cases carried a heterozygous PLowell mutation representing two interesting and rare examples of clinical cases with double heterozygosity. The presence in the other AAT allele of the S-mutation in the first case and a concomitant presence of another mutation in the cystic fibrosis gene in the second case contributed to the protease-antiprotease imbalance and, despite intermediate AATD, was the probable cause of the numerous exacerbations. Conclusion: Alpha-1 antitrypsin deficiency should always be suspected in patients with respiratory disease and an unclear or complex clinical history. It may be useful to recognize and evaluate treatment even outside the established parameters, in selected cases.