Inborn errors of bile acid metabolism and their diagnostic confirmation by means of mass spectrometry

Abstract

Bile acids are amphipathic molecules formed from cholesterol in the liver by two main pathways, the neutral and the acidic. Biosynthesis of bile acids generates bile A¯¬â€sow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids play an important role as biological detergents that make possible intestinal absorption of lipids and fat-soluble vitamins but also as metabolic regulators of lipid, glucose, and energy homeostasis. Several enzymatic steps and subcellular compartiments are involved in the biosynthesis of bile acids. In general, the synthetic pathways of bile acids consist of modification of the steroid nucleus, oxidation and cleavage of the corresponding side chain, and finally conjugation with the amino acids glycine or taurine. Genetic defects in one of these enzymes result in an accumulation of atypical bile acids or intermediates. These defects can cause beside others liver diseases that can vary from mild to very severe. Detection of elevated concentrations of unusual bile acids, intermediates and other endogenous metabolites can be performed by mass spectrometry. In this article, the most known inborn errors in bile acid metabolism and their mass spectrometric confirmation in biological fluids are concisely reviewed.