Disorders of Bile Acid Synthesis and Biliary Transport

  • Hugh A. Lemonde
  • Paul Gissen
  • Peter T. ClaytonEmail author


Bile acids have well established roles as drivers of bile flow and as the catabolic end products of cholesterol metabolism, but bile acids and their metabolic precursors are increasingly recognised as important regulators of other pathways. Inborn errors have been identified in each of the main stages of bile acid synthesis (modification of sterol nucleus, side chain and conjugation) and also in a variety of steps in bile acid transport. Manifestations of these disorders reflect the lack of functional bile acids and build-up of their potentially toxic precursors. Examples include progressive liver dysfunction with fat soluble vitamin malabsoprtion, progressive neurological deterioration, hereditary spastic paraplegia and mild statin resistant hypercholesterolaemia.

Bile acids and there precursors can be detected in a variety of biological fluids including blood, urine, bile and CSF. They represent a considerable diagnostic challenge due to their natural heterogeneity. The characterisation of abnormal bile acids in these fluids has relied heavily on mass spectrometry. Single stage mass spectrometry of urine with minimal sample preparation can provide a rapid tool for the detection of abnormal patterns of bile acids sufficient to diagnose most inborn errors. Further characterisation of unusual bile acids can be achieved by gas-chromatography mass spectrometry or liquid chromatography linked to tandem mass spectrometry. Disorders of bile acid transport do not result in the production of abnormal bile acid patterns and require genetic characterisation.

Treatment for most of the disorders of bile acid synthesis is the replacement of the primary bile acids by oral administration of chenodeoxycholic and/or cholic acid. This supplies functional bile acids and has the benefit of negative feedback inhibition of potentially toxic bile acid intermediates. This is a highly effective treatment for those disorders presenting with hepatic impairment, as long as it is instigated prior to irreversible liver damage (which requires liver transplantation). Chenodeoxycholic acid has also been shown to improve neurological outcomes in patients with cerebrotendinousxanthomatosis.


Bile Acid Chenodeoxycholic Acid Hereditary Spastic Paraplegia Bile Acid Synthesis Bile Acid Metabolism 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hugh A. Lemonde
    • 1
  • Paul Gissen
    • 1
  • Peter T. Clayton
    • 1
    Email author
  1. 1.Institute of Child HealthUniversity College London and Great Ormond Street HospitalLondonUK

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