Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.
K D Setchell, … , R J Sokol, D W Russell
K D Setchell, … , R J Sokol, D W Russell
Published November 1, 1998
Citation Information: J Clin Invest. 1998;102(9):1690-1703. https://doi.org/10.1172/JCI2962.
View: Text | PDF
Research Article Article has an altmetric score of 19

Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.

  • Text
  • PDF
Abstract

We describe a metabolic defect in bile acid synthesis involving a deficiency in 7alpha-hydroxylation due to a mutation in the gene for the microsomal oxysterol 7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis. The defect, identified in a 10-wk-old boy presenting with severe cholestasis, cirrhosis, and liver synthetic failure, was established by fast atom bombardment ionization-mass spectrometry, which revealed elevated urinary bile acid excretion, a mass spectrum with intense ions at m/z 453 and m/z 510 corresponding to sulfate and glycosulfate conjugates of unsaturated monohydroxy-cholenoic acids, and an absence of primary bile acids. Gas chromatography-mass spectrometric analysis confirmed the major products of hepatic synthesis to be 3beta-hydroxy-5-cholenoic and 3beta-hydroxy-5-cholestenoic acids, which accounted for 96% of the total serum bile acids. Levels of 27-hydroxycholesterol were > 4,500 times normal. The biochemical findings were consistent with a deficiency in 7alpha-hydroxylation, leading to the accumulation of hepatotoxic unsaturated monohydroxy bile acids. Hepatic microsomal oxysterol 7alpha-hydroxylase activity was undetectable in the patient. Gene analysis revealed a cytosine to thymidine transition mutation in exon 5 that converts an arginine codon at position 388 to a stop codon. The truncated protein was inactive when expressed in 293 cells. These findings indicate the quantitative importance of the acidic pathway in early life in humans and define a further inborn error in bile acid synthesis as a metabolic cause of severe cholestatic liver disease.

Authors

K D Setchell, M Schwarz, N C O'Connell, E G Lund, D L Davis, R Lathe, H R Thompson, R Weslie Tyson, R J Sokol, D W Russell

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1983 Total
Citations: 2 4 4 6 11 8 8 12 13 4 4 10 14 13 11 14 16 8 8 15 10 9 22 18 16 15 9 1 1 286
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2013 (14)

Title and authors Publication Year
Comprehensive Physiology
BJ Wilkins, M Pack
Comprehensive Physiology 2013
Comprehensive Physiology
BJ Wilkins, M Pack
Comprehensive Physiology 2013
Comprehensive Physiology
BJ Wilkins, M Pack
Comprehensive Physiology 2013
Comprehensive Physiology
BJ Wilkins, M Pack
Comprehensive Physiology 2013
Macrophage PPAR gamma Co-activator-1 alpha participates in repressing foam cell formation and atherosclerosis in response to conjugated linoleic acid
C McCarthy, NT Lieggi, D Barry, D Mooney, M Gaetano, WG James, S McClelland, MC Barry, L Escoubet-Lozach, AC Li, CK Glass, DJ Fitzgerald, O Belton
EMBO Molecular Medicine 2013
Human cytochromes P450 in health and disease
DW Nebert, K Wikvall, WL Miller
Philosophical Transactions of the Royal Society B: Biological Sciences 2013
Cytochromes p450: roles in diseases
IA Pikuleva, MR Waterman
The Journal of biological chemistry 2013
Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes
E Szalowska, G Stoopen, MJ Groot, PJ Hendriksen, AA Peijnenburg
BMC Medical Genomics 2013
Sulphatation does not appear to be a protective mechanism to prevent oxysterol accumulation in humans and mice
J Acimovic, A Lövgren-Sandblom, M Olin, Z Ali, M Heverin, R Schüle, L Schöls, B Fischler, P Fickert, M Trauner, I Björkhem
PloS one 2013
A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns
AE DeBarber, J Luo, M Star-Weinstock, S Purkayastha, MT Geraghty, J Chiang, LS Merkens, AS Pappu, RD Steiner
Journal of lipid research 2013
Sulphatation Does Not Appear to Be a Protective Mechanism to Prevent Oxysterol Accumulation in Humans and Mice
J Acimovic, A Lövgren-Sandblom, M Olin, Z Ali, M Heverin, R Schüle, L Schöls, B Fischler, P Fickert, M Trauner, I Björkhem, JM Lobaccaro
PloS one 2013
The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis
NJ Cherrington, TE Estrada, HA Frisk, MJ Canet, RN Hardwick, B Dvorak, K Lux, MD Halpern
AJP Gastrointestinal and Liver Physiology 2013
The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition: a randomized clinical trial
S Savini, R DAscenzo, C Biagetti, G Serpentini, A Pompilio, A Bartoli, PE Cogo, VP Carnielli
The American journal of clinical nutrition 2013
Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases
N Blau, M Duran, KM Gibson, CD Vici
2013

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Referenced in 7 patents
Referenced in 1 Wikipedia pages
101 readers on Mendeley
See more details