AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases.
chenodeoxycholic acid
cholic acid
inborn errors of bile acid metabolism
neonatal cholestasis
oxysterol 7α-hydroxylase deficiency
Journal
Pediatrics and neonatology
ISSN: 2212-1692
Titre abrégé: Pediatr Neonatol
Pays: Singapore
ID NLM: 101484755
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
05
02
2019
revised:
22
05
2019
accepted:
28
06
2019
pubmed:
25
7
2019
medline:
21
8
2020
entrez:
25
7
2019
Statut:
ppublish
Résumé
Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population. Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1. Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 -2016, three had ∆ Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population.
Sections du résumé
BACKGROUND
Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population.
METHODS
Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1.
RESULTS
Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 -2016, three had ∆
CONCLUSION
Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population.
Identifiants
pubmed: 31337596
pii: S1875-9572(19)30095-6
doi: 10.1016/j.pedneo.2019.06.009
pii:
doi:
Substances chimiques
Bile Acids and Salts
0
Oxidoreductases
EC 1.-
Steroid Hydroxylases
EC 1.14.-
Cytochrome P450 Family 7
EC 1.14.14.23
CYP7B1 protein, human
EC 1.14.14.29
3-oxo-5 beta-steroid delta 4-dehydrogenase
EC 1.3.99.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-83Informations de copyright
Copyright © 2019. Published by Elsevier B.V.