Danish children with ZZ-homozygous alpha-1 antitrypsin deficiency are more affected on liver parameters than children with heterozygosity

Abstract

Aim: The longitudinal health status of Danish children with alpha-1 antitrypsin deficiency had never previously been characterised. This study aimed to assess the changes in growth, lung and liver function through childhood in these children.

Methods: Danish children diagnosed between 2005 and 2020 with pathogenic variants in the Serpin family A member 1 gene were included. Retrospective data on growth, lung and liver parameters were obtained from local databases. Anthropometric Z-scores and composite liver scores were computed. Growth and blood results were analysed using robust linear mixed models.

Results: The study included 184 children (68 with ZZ-homozygosity, 116 with heterozygosity). The median follow-up time was 7 years [IQR 3.75-9.00] for children with ZZ-homozygosity and 0.5 years [IQR 0.0-2.0] for children with heterozygosity. Both groups had low weight-for-height Z-scores at diagnosis but experienced catch-up growth during the first year of life. In addition, children with ZZ-homozygosity had higher serum concentrations of γ-glutamyl transferase and alanine aminotransferase throughout childhood, when compared with children with heterozygosity. Data proved insufficient to assess lung function properly.

Conclusion: Children with ZZ-homozygosity were more affected on serum liver parameters throughout childhood when compared with children with heterozygosity. Both groups experienced catch-up growth during the first year of life.

Keywords: alpha-1 antitrypsin deficiency; children; fibrosis; liver function; weight-for-height Z-scores.