PMID- 36070551
OWN - NLM
STAT- MEDLINE
DCOM- 20221101
LR  - 20230203
IS  - 1536-4801 (Electronic)
IS  - 0277-2116 (Linking)
VI  - 75
IP  - 5
DP  - 2022 Nov 1
TI  - Disease Status at Diagnosis in Danish Children with alpha 1 -antitrypsin Deficiency.
PG  - 629-634
LID - 10.1097/MPG.0000000000003604 [doi]
AB  - 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.
CI  - Copyright (c) 2022 by European Society for European Society for Pediatric 
      Gastroenterology, Hepatology, and Nutrition and North American Society for 
      Pediatric Gastroenterology, Hepatology, and Nutrition.
FAU - Winther, Christina Louise
AU  - Winther CL
AD  - From the Department of Pediatrics and Adolescent Medicine, Rigshospitalet, 
      Denmark.
FAU - Nyrann, Sofie
AU  - Nyrann S
AD  - the Copenhagen University, Copenhagen, Denmark.
FAU - Nielsen, Rasmus Gaardskaer
AU  - Nielsen RG
AD  - the Department of Paediatrics, Odense University Hospital, OdensenDenmark.
FAU - Duno, Morten
AU  - Duno M
AD  - the Department of Clinical Genetics, Rigshospitalet, Denmark.
FAU - Johansen, Klaus Birkelund
AU  - Johansen KB
AD  - the Department of Paediatrics and Adolescent Medicine, Aarhus University 
      Hospital, Denmark.
FAU - Helt, Thora Wesenberg
AU  - Helt TW
AD  - the Diagnostic Centre, Rigshospitalet, Denmark.
FAU - Brix Christensen, Vibeke
AU  - Brix Christensen V
AD  - From the Department of Pediatrics and Adolescent Medicine, Rigshospitalet, 
      Denmark.
LA  - eng
PT  - Journal Article
DEP - 20220906
PL  - United States
TA  - J Pediatr Gastroenterol Nutr
JT  - Journal of pediatric gastroenterology and nutrition
JID - 8211545
RN  - 0 (alpha 1-Antitrypsin)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Infant, Newborn
MH  - Child
MH  - Humans
MH  - Infant
MH  - Cross-Sectional Studies
MH  - *alpha 1-Antitrypsin Deficiency/diagnosis/genetics/complications
MH  - alpha 1-Antitrypsin/genetics
MH  - Genotype
MH  - Bilirubin
MH  - Denmark/epidemiology
COIS- The authors report no conflicts of interest.
EDAT- 2022/09/08 06:00
MHDA- 2022/11/02 06:00
CRDT- 2022/09/07 16:04
PHST- 2022/09/08 06:00 [pubmed]
PHST- 2022/11/02 06:00 [medline]
PHST- 2022/09/07 16:04 [entrez]
AID - 00005176-202211000-00015 [pii]
AID - 10.1097/MPG.0000000000003604 [doi]
PST - ppublish
SO  - J Pediatr Gastroenterol Nutr. 2022 Nov 1;75(5):629-634. doi: 
      10.1097/MPG.0000000000003604. Epub 2022 Sep 6.