Case report of a novel alpha1-antitrypsin null variant in Türkiye: Q0RIZE.

BACKGROUND: Alpha1-antitrypsin (AAT) is a serine protease inhibitor that serves as a counterbalance to the activity of elastases, e.g., neutrophil elastase in lung tissue. AAT deficiency (AATD) is a rare disorder usually arising from mutations to the SERPINA1 gene that codes for AAT. The most common AATD alleles are S and Z which produce ~ 40% and ~ 90% reductions in serum AAT, respectively. Rare genetic variants (> 500 identified) can also be associated with mild to severe AATD. RESULTS: This report describes a novel mutation of SERPINA1 producing AATD, which we have designated, Q0RIZE. This mutation was identified in a 44-year-old woman admitted with massive hemoptysis and treated with bronchial artery embolization. Computed tomography revealed centriacinar and panacinar emphysema with prominent air entrapment, atelectasis, and localized bronchiectasis. Serum AAT was < 0.27 g/L (below detection limit). Genetic analysis showed homozygous deletion of exons I to III. CONCLUSIONS: Although many SERPINA1 variants have been identified, variants with large deletions and identified in a homozygous individual, as seen in this case with Q0RIZE, are uncommon. AATD is an underdiagnosed and undertreated disease. Wider screening of COPD patients could result in earlier diagnosis and treatment that could preserve lung function.

An Alpha-1 Antitrypsin Deficiency Screening Study in Patients with Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Asthma in Turkey.

Purpose: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition characterized by decreased serum alpha-1 antitrypsin (AAT) levels. We aim to identify AATD in patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, or asthma and to report the frequency of AAT variants in Turkey. Patients and Methods: This non-interventional, multicenter, prospective study was conducted between October 2021 and June 2022. Adult patients with COPD, bronchiectasis, asthma, liver symptoms, or family members with AATD were included. Demographic and clinical characteristics, pulmonary diagnosis, respiratory symptoms, and AAT serum levels were assessed. Whole blood samples were collected as dried blood spots, and the most common AATD mutations were simultaneously tested by allele-specific genotyping. Results: A total of 1088 patients, mainly diagnosed with COPD (92.7%) and shortness of breath (78.7%), were assessed. Fifty-one (5%) were found to have AATD mutations. Fifteen (29.4%) patients had Pi*S or Pi*Z mutations, whereas 36 (70.6%) patients carried rare alleles Pi*M malton (n=18, 35.3% of mutations), Pi*I (n=8, 16%), Pi*P lowell (n=7, 14%), Pi*M heerlen (n=2, 4%), and Pi*S iiyama (n=1, 2%). The most common heterozygous combinations were Pi*M/Z (n=12, 24%), and Pi*M/M malton (n=11, 22%). Ten patients with severe AATD due to two deficiency alleles were identified, two with the Pi*Z/Z genotype, four with the genotype Pi*M malton/M malton, three with Pi*Z/M malton, and one with Pi*Z/M heerlen. Conclusion: Our results identified AATD mutations as a genetic-based contributor to lung disease in patients with COPD or bronchiectasis and assessed their frequency in a population of Turkish patients.

Post-marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections.

Secondary hypogammaglobulinemia is one of the factors responsible for the increased susceptibility to infection in patients with chronic lymphocytic leukemia (CLL). This study assessed the therapeutic results, concomitant medication and tolerance of administering 5% intravenous immunoglobulin, secondary immunodeficiency and recurrent serious bacterial infections. A single center, post-marketing, observational clinical study was performed on 10 patients with a variety of hematological malignancies (CLL, follicular non-Hodgkin lymphoma, IgM-secreting immunocytoma, IgA plasmacytoma and myelodysplastic syndrome/non-Hodgkin lymphoma) who had been infused with IVIG from June 1994 to May 2009. The clinical benefit of IVIG was assessed by comparing the incidence of bacterial infections before and after starting this therapy. Plasma immunoglobulin concentrations and relevant hematological variables were recorded. For safety assessment, adverse events were monitored. The standard IVIG dosage was approximately 0.35 g/kg body weight every 3-4 weeks. Most patients had normal IgG trough values of >600 mg/dL during the IVIG treatment period. The rate of bacterial infections was reduced from 2.4 per patient in the 3 months before IVIG to 0.7 (0-1.5) per patient per year during IVIG treatment. All patients received concomitant medication, mainly anticancer and anti-anemia therapy (100%). No serious adverse events related to IVIG were observed. The frequency of at least one minor adverse reaction was 1.44% (8/556 infusions). In conclusion, the investigated IVIG preparation was well tolerated and clinically beneficial in reducing the long term rate of serious bacterial infections in patients receiving concomitant treatment for malignant diseases.