Abstract Rationale Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition that can cause lung, liver, and skin disease. The disease-causing variant Z (p.Glu366Lys) causes severe serum deficiency of this important antiprotease. This can lead to poorer health outcomes in patients with AATD, including chronic obstructive pulmonary disease (COPD) and liver cirrhosis. AATD is recognized as a rare disease, yet 1 in 25 Irish people carry the Z allele. Hence, the development and maintenance of a national registry is essential for improved understanding of the condition. Methods Alpha-1 Foundation Ireland coordinates the Irish national AATD registry and collaborates with the National Centre of Expertise for AATD at Beaumont Hospital. To date, 777 individuals in Ireland have joined the registry. The main AATD phenotypes represented include ZZ, MZ, SZ, SS, MS and rarer phenotypes. This includes 298 severely deficient ZZ individuals, followed by 252 MZ and 142 SZ moderate AATD genotypes. In this study, we present clinical features of this population including age at diagnosis, smoking exposure, lung and liver health across a range of genotypes. Results 63% of the severely deficient ZZ AATD individuals are ever smokers with only 0.05% (n = 12) reporting active smoking. An initial review revealed that 45% of ZZ individuals had a baseline pulmonary function test result indicative of COPD with a forced expiratory volume in one second (FEV1) ranging from 16-142% predicted. Results from CT thorax shows that 60% of ZZ individuals had evidence of emphysema and/or bronchiectasis when initially diagnosed with AATD whereas only 40% of moderately deficient MZ individuals presented with AATD related lung disease. Liver health was evaluated by Fibroscan assessment at routine clinical reviews. This revealed that 54% of severely deficient ZZ individuals have liver steatosis assessed using a Controlled Attenuation Pattern (CAP) score 248dB/m and 32% showed evidence of fibrosis with abnormal kilopascal scores 7.1 kPa. Of note, we include 3 cases of panniculitis secondary to AATD which have responded successfully to intravenous augmentation therapy. Skin manifestations of AATD are under-recognized and this is supported by a growing number of case reports. Improved awareness of the diverse extra-pulmonary manifestations of AATD can lead to better patient outcomes. Conclusion Further development of the National AATD Registry in Ireland will increase our knowledge of AATD, allow assessment of patient suitability for clinical trials of emerging therapies and allow for longitudinal assessment of lung and liver health in this uniquely susceptible cohort. This abstract is funded by: None
Bedri et al. (Fri,) studied this question.