Gene mutations and clinical manifestations of alpha-1 antitrypsin deficiency in Czech patients - a pilot study

Alpha-1 antitrypsin deficiency (AATD) is a rare genetically associated disease with different clinical manifestations dependent on serum level of alpha-1 antitrypsin (AAT) and AAT gene mutations. Pathological mutations of AAT gene (located on 14th chromosome) are associated with its insufficient production or dysfunction. Early onset emphysema and COPD is the most common lung AATD manifestation. Another lung injury can also be present. We evaluated AAT serum levels in few patients with COPD or other airway obstruction, emphysema and recurrent respiratory infections. If AAT serum level was low, gene mutation testing (by MassArray) followed up. Mutations were tested also in 4 young men with spontaneous pneumothorax (PNO). Altogether 19 patients (10 male, 9 female, mean age 44 years) were enrolled; 6 of them (33 %) were past or current smokers. We evaluated the presence of two of the most frequent mutations of AAT gene – „Z“ and „S“alleles and their association with clinical phenotypes. Severe AATD (serum level less than protective 0.5 g/l) was observed in 3 patients. In two of them it was associated with emphysema and reduced lung functions (patients currently on augmentation therapy), the 3rd patient had liver disease. Emphysema was more frequent in smokers. All patients with very low AAT serum level had „Z“ alleles. Any other found were asthma, bronchiectasis, lymphadenopathy or pulmonary nodules. Alleles „Z“ or „S“ were detected also in all young men with spontaneous PNO and normal AAT serum level. Our pilot study shows that AATD testing should be extended from COPD and early onset emphysema patients also to other risk groups. Supported by a grant IGA UP: LF 2023 007