Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study

Abstract

Background-aim Alpha-1-antitrypsin deficiency (AATD) is an autosomal recessive disorder characterized by the reduced alpha-1-antitrypsin (AAT) level in blood. In pediatric patients, it is dominantly tested as a cause of liver disease, while specific lung diseases might be potentially regarded as additional indications. Measurement of AAT concentration is useful as a first-line test, although decreased level may be also encountered in certain acquired conditions. Our aim was to determine the interpretative cut-off for AAT concentration i.e. level below which the presence of common AATD-associated alleles might be suspected. Methods We included 37 subjects with clinical indications or familiar history of AATD: 19 males and 18 females, aged between 2 months and 19 years. Immunonephelometry was used for measurement of AAT concentration in serum and PCR-reverse allele specific hybridization assay for detection of Z and S alleles, which are considered as the common AATD-associated alleles. Kruskal-Wallis test and ROC analysis were applied in statistical evaluation. Results Three cases of AATD (ZZ genotype) and 14 carriers (13 heterozygous for Z and one for S allele) were detected. AAT concentration (median (min-max)) measured in AATD cases (0.35 (0.31–0.39) g/L), carriers (0.81 (0.56–1.41) g/L) and patients with no Z and S allele (1.20 (0.91–2.24) g/L) were significantly different (P b .001). Four carriers (three heterozygous for Z and one for S allele) had AAT concentration in the reference range (0.9–2.0 g/L). We identified the level 1.03 g/L as the most appropriate cut-off to distinguish group comprising both cases of AATD and carriers from patients in whom no common AATD-associated allele was present. Corresponding AUC value (95% Confidence interval (CI)) was 0.929 (0.795–0.987) (P b .001). Sensitivity and specificity (95% CI) reached 94.1 (71.3–99.9)% and 90.0 (68.3–98.8)% respectively. Conclusions In pediatric patients AAT concentration below 1.03 g/L may be regarded as a potential cut-off indicating the presence of common AATD-associated alleles in homo-or heterozygous form. Nevertheless, this preliminary finding needs confirmation in a larger study.