Disease Status at Diagnosis in Danish Children with α1-antitrypsin Deficiency

Objectives: The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with alpha(1)-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 alpha(1)-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 alpha-1-antitrypsin deficiency (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. Conclusions: 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.

Automated summary

The aim of this study was to assess the state of disease at the time of diagnosis in Danish children with alpha(1)-antitrypsin deficiency. The results showed that homozygous children had higher concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared to heterozygotes at diagnosis.