Abstract
Introduction: Alpha1-antitrypsin (A1AT) deficiency is an autosomal co-dominant disease related to SERPINA-1 gene mutations predisposing to pulmonary emphysema and/or liver disease.
Aim: to examine the genotype and phenotype of a Greek cohort of A1AT-deficiency patients.
Methods: This multicenter study enrolled A1AT-deficiency patients under augmentation treatment from 8 centers in Greece.
Results: 23 adult patients, 61% male, 17.4% non-smokers, diagnosed at a median age (IQR) of 47(42-58) years with A1AT levels of 0.24 (0.04-0.4) g/L were identified. Indications for A1AT measurement were severe obstructive pulmonary disease at the age < 45 years (82%), recurrent respiratory tract infections and emphysema/bronchiectasis at an older age. Upon initiation of therapy, patients presented with a median (IQR) FEV1 % pred, FEV1/FVC% and DLCO% pred of 37.5 (29-50), 47.3 (37-60) and 32.6 (29.9-52.7) respectively. Genetic testing revealed only 13 (56.5%) patients with the commonest worldwide PI*ZZ genotype whereas 10 (43.5%) patients were homozygous or compound heterozygous for extremely rare and null alleles including PI*Q0-Bellingham, PI*Q0-Amersfoort, PI*Q0-Granitefalls, PI*MHeerlen and PI*MProcida. Rare and null variants were related to very low A1AT levels compared to Z variants (p=0.001).
Conclusion: In contrast with the literature, where Z and S are the most common A1AT-deficiency alleles, the present study reveals extremely rare deleterious variants in Greek A1AT-deficiency patients under augmentation treatment. Further examination of phenotype-genotype associations and outcome is expected to unveil their clinical significance in the future.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3324.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020