Abstract
ABSTRACT: A 9-wk-old infant with familial giant cell hepatitis and severe intrahepatic cholestasis had low plasma concentrations of chenodeoxycholic acid and cholic acid and elevated plasma concentrations of5β-cholestane-3α,7α,12α,25-tetrol, 5β-cholestane-3α,7α,12α,24-tetrol, and 5β-cholest-24-ene-3α,7α,12α-triol. Analysis of the urine by fast atom bombardment mass spectromctry and by gas chromatography-mass spectrometry after treatment with Helix pomatia glucuronidase/sulfatase showed that the major cholanoids in urine were the glucuronides of 5β-cholestane-3α,7α,12α,24S, 25-pentol, 5β-cholestane-3α,7α,12α,25-tetrol, and 5β-cholestane-3α,7α,12α,24-tetrol. These results are consistent with an inborn error of the 25-hydroxylase pathway for bile acid synthesis, specifically one of the enzymes responsible for conversion of 5β-cholestane-3α,7α,12α,24S, 25-pentol to cholic acid and acetone. Treatment with chenodcoxycholic acid was tried on two occasions. On the first it appeared to precipitate a rise in bilirubin, on the second the liver function tests improved and the improvement was maintained when the treatment was modified to a combination of chenodeoxycholic acid and cholic acid and finally, cholic acid alone. Despite the normalization of liver function tests, a liver biopsy at 1.25 y showed an active cirrhosis. Nonetheless, the child is thriving at the age of 3.5 y, whereas an affected sibling died at 13 mo.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Clayton, P., Casteels, M., Mieli-Vergani, G. et al. Familial Giant Cell Hepatitis with Low Bile Acid Concentrations and Increased Urinary Excretion of Specific Bile Alcohols: A New Inborn Error of Bile Acid Synthesis?. Pediatr Res 37, 424–431 (1995). https://doi.org/10.1203/00006450-199504000-00007
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-199504000-00007
This article is cited by
-
Hepatotoxicity due to chenodeoxycholic acid supplementation in an infant with cerebrotendinous xanthomatosis: implications for treatment
European Journal of Pediatrics (2016)
-
Bile acid‐CoA ligase deficiency—a new inborn error of bile acid metabolism
Journal of Inherited Metabolic Disease (2012)
-
Disorders of bile acid synthesis
Journal of Inherited Metabolic Disease (2011)
-
Mechanisms of Disease: inborn errors of bile acid synthesis
Nature Clinical Practice Gastroenterology & Hepatology (2008)