Comparison of different algorithms in laboratory diagnosis of Alpha1-antitripsin deficiency

Background: Alpha1-antitrypsin deficiency (AATD) is an hereditary disorder which is under-recognized, probably because guidelines on best practice are not well established. In order to increase the efficiency of AATD testing in clinical laboratories, each center developed and evaluated integrative diagnostic algorithms. Objectives: Since an ideal algorithm of laboratory procedures for AATD detection has not been established, we decided to compare different existing practices. Methods: A systematic revision of literature allowed us to select five different algorithms for AATD diagnosis published on international journal. The diagnostic algorithms were retrospectively applied on 5783 sample previously processed in our laboratory by complete biochemical and molecular analysis. Receiver Operating Characteristic (ROC) curve was plotted to find the best threshold for AAT serum level for which we calculated the specificity, the sensitivity and the Negative Predictive Value (NPV). Results: The ROC curve identified a level of 110.8 mg/dL as the best cut-off value (sensitivity 76.8% and specificity 88.2%) for selecting patients to undergo genetic analysis. The results of the NPV and False Negative (FN) percentage of each algorithm applied to our cohort are reported in the table: Conclusions: The comparison of the selected algorithms underlines some differences regarding cut-off of AAT serum value and qualitative tests, which resulted in different diagnostic rates, as highlighted by NPV.