AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Ju-Yin Chen (Author), Jia-Feng Wu (Author), Akihiko Kimura (Author), Hiroshi Nittono (Author), Bang-Yu Liou (Author), Chee-Seng Lee (Author), Ho-Sheng Chen (Author), Yu-Chun Chiu (Author), Yen-Hsuan Ni (Author), Steven Shinn-Forng Peng (Author), Wang-Tso Lee (Author), I-Jung Tsai (Author), Mei-Hwei Chang (Author), Huey-Ling Chen (Author)
Format: Book
Published: Elsevier, 2020-02-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!

MARC

LEADER 00000 am a22000003u 4500
001 doaj_bc23a19a3e6d4a19a24bb123280ed82d
042 |a dc 
100 1 0 |a Ju-Yin Chen  |e author 
700 1 0 |a Jia-Feng Wu  |e author 
700 1 0 |a Akihiko Kimura  |e author 
700 1 0 |a Hiroshi Nittono  |e author 
700 1 0 |a Bang-Yu Liou  |e author 
700 1 0 |a Chee-Seng Lee  |e author 
700 1 0 |a Ho-Sheng Chen  |e author 
700 1 0 |a Yu-Chun Chiu  |e author 
700 1 0 |a Yen-Hsuan Ni  |e author 
700 1 0 |a Steven Shinn-Forng Peng  |e author 
700 1 0 |a Wang-Tso Lee  |e author 
700 1 0 |a I-Jung Tsai  |e author 
700 1 0 |a Mei-Hwei Chang  |e author 
700 1 0 |a Huey-Ling Chen  |e author 
245 0 0 |a AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases 
260 |b Elsevier,   |c 2020-02-01T00:00:00Z. 
500 |a 1875-9572 
500 |a 10.1016/j.pedneo.2019.06.009 
520 |a 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 ∆4-3-oxosteroid 5β-reductase deficiency with AKR1D1 mutations, and three had oxysterol-7α-hydroxylase deficiency with CYP7B1 mutation. Two patients with ∆4-3-oxosteroid 5β-reductase deficiency were successfully treated with cholic acid. The three unrelated infants with oxysterol 7α-hydroxylase deficiencies had the same p.R112X homozygous CYP7B1 mutation. Two had mild renal or neurological involvement. Among 608 healthy control subjects, the allele frequency of the heterozygous mutation for p.R112X was 2/1216 (0.16%). The only surviving patient with oxysterol 7α-hydroxylase deficiency recovered from liver failure after chenodeoxycholic acid (CDCA) treatment beginning at 3 months of age. 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. Key Words: chenodeoxycholic acid, cholic acid, inborn errors of bile acid metabolism, neonatal cholestasis, oxysterol 7α-hydroxylase deficiency 
546 |a EN 
690 |a Pediatrics 
690 |a RJ1-570 
655 7 |a article  |2 local 
786 0 |n Pediatrics and Neonatology, Vol 61, Iss 1, Pp 75-83 (2020) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S1875957219300956 
787 0 |n https://doaj.org/toc/1875-9572 
856 4 1 |u https://doaj.org/article/bc23a19a3e6d4a19a24bb123280ed82d  |z Connect to this object online.