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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency
Gastroenterology, Volume 144, No. 5, Year 2013
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Description
Background & Aims: The final step in bile acid synthesis involves conjugation with glycine and taurine, which promotes a high intraluminal micellar concentration to facilitate lipid absorption. We investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some with growth failure or transient neonatal cholestatic hepatitis. Methods: We identified the genetic defect that causes this disorder using mass spectrometry analysis of urine, bile, and serum samples and sequence analysis of the genes encoding bile acid-CoA:amino acid N-acyltransferase (BAAT) and bile acid-CoA ligase (SLC27A5). Results: Levels of urinary bile acids were increased (432 ± 248 μmol/L) and predominantly excreted in unconjugated forms (79.4% ± 3.9%) and as sulfates and glucuronides. Glycine or taurine conjugates were absent in the urine, bile, and serum. Unconjugated bile acids accounted for 95.7% ± 5.8% of the bile acids in duodenal bile, with cholic acid accounting for 82.4% ± 5.5% of the total. Duodenal bile acid concentrations were 12.1 ± 5.9 mmol/L, which is too low for efficient lipid absorption. The biochemical profile was consistent with defective bile acid amidation. Molecular analysis of BAAT confirmed 4 different homozygous mutations in 8 patients tested. Conclusions: Based on a study of 10 pediatric patients, genetic defects that disrupt bile acid amidation cause fat-soluble vitamin deficiency and growth failure, indicating the importance of bile acid conjugation in lipid absorption. Some patients developed liver disease with features of a cholangiopathy. These findings indicate that patients with idiopathic neonatal cholestasis or later onset of unexplained fat-soluble vitamin deficiency should be screened for defects in bile acid conjugation. © 2013 AGA Institute.
Authors & Co-Authors
Setchell, Kenneth D.R.
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Heubi, James E.
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Shah, Sohela
United States, San Francisco
Ucsf Medical Center
Lavine, Joel Edward
United States, New York
Columbia University
Suskind, David
United States, Seattle
University of Washington School of Medicine
Al-Edreesi, Mohammed
Saudi Arabia, Dhahran
Johns Hopkins Aramco Healthcare
Potter, Carol
United States, Columbus
The Ohio State University
Russell, David Warwick
United States, Dallas
Ut Southwestern Medical School
O'Connell, Nancy C.
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Wolfe, Brian
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Jha, Pinky
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Zhang, Wujuan
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Bove, Kevin E.
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Knisely, Alexander S.
United Kingdom, London
King's College Hospital
Hofmann, Alan F.
United States, La Jolla
University of California, San Diego
Rosenthal, Philip Jon
United States, San Francisco
Ucsf Medical Center
Bull, Laura N.
United States, San Francisco
Ucsf Medical Center
Statistics
Citations: 90
Authors: 17
Affiliations: 9
Identifiers
Doi:
10.1053/j.gastro.2013.02.004
ISSN:
00165085
e-ISSN:
15280012
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health