Disease Status at Diagnosis in Danish Children with α 1 -antitrypsin Deficiency
Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition..
OBJECTIVES: The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with α 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 α 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:75 |
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| Enthalten in: |
Journal of pediatric gastroenterology and nutrition - 75(2022), 5 vom: 01. Nov., Seite 629-634 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Winther, Christina Louise [VerfasserIn] |
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| Anmerkungen: |
Date Completed 01.11.2022 Date Revised 03.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1097/MPG.0000000000003604 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345876741 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. | ||
| 520 | |a OBJECTIVES: The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with α 1 -antitrypsin deficiency as Denmark has a high prevalence of ZZ-homozygosity | ||
| 520 | |a 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 α 1 -antitrypsin (S-AAT). The relationship between S-AAT concentration and genotype was assessed using logistic regression with GEE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Nyrann, Sofie |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Rasmus Gaardskaer |e verfasserin |4 aut | |
| 700 | 1 | |a Duno, Morten |e verfasserin |4 aut | |
| 700 | 1 | |a Johansen, Klaus Birkelund |e verfasserin |4 aut | |
| 700 | 1 | |a Helt, Thora Wesenberg |e verfasserin |4 aut | |
| 700 | 1 | |a Brix Christensen, Vibeke |e verfasserin |4 aut | |
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