https://pubmed.ncbi.nlm.nih.gov/36070551/

J Pediatr Gastroenterol Nutr. 2022 Sep 6.
doi: 10.1097/MPG.0000000000003604.Online ahead of print.

Disease status at diagnosis in Danish children with α1-antitrypsin deficiency

Christina Louise Winther 1, Sofie Nyrann 2, Rasmus Gaardskaer Nielsen 3, Morten Duno 4, Klaus Birkelund Johansen 5, Thora Wesenberg Helt 5, Vibeke Brix Christensen 6
Affiliations expand
PMID: 36070551

DOI: 10.1097/MPG.0000000000003604

Abstract

Objective: The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with ɑ1-antitrypsin deficiency as Denmark has a high prevalence of ZZ-homozygosity.

Methods: Children either heterozygous, compound heterozygous or homozygous for Z- and S- variants in the SERPINA1-gene were included. Clinical characteristics, SERPINA1-genotype and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T-tests and Wilcoxon-Mann Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α1-antitrypsin (S-AAT). The relationship between S-AAT concentration and genotype was assessed using logistic regression with GEE.

Results: The study included 183 of 225 children genetically tested for AATD. Of these, 36.6% were homozygous for the Z-variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ-homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S-AAT. Children under 6 months of age had higher total S-bilirubin concentrations than children over 6 months of age.

Conclusion: A low S-AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S-AAT concentration in children with prolonged neonatal jaundice.An infographic is available for this article at: http://links.lww.com/MPG/C926.