[Inborn errors of bile acid metabolism].
A review on inherited diseases caused by defects in the synthesis of bile acids is presented. In the first part the biochemical synthesis of bile acids from cholesterol, taking place in the liver, is described. Three consecutive events can be discerned: 1. modifications in the skeleton of cholesterol, 2. oxidation of the last carbon atom of the cholesterol side chain, 3. further oxidation of the side chain leading to shortening with three carbon atoms; this last step takes place in liver peroxisomes. In the second part a description of inborn errors (enzyme deficiencies) is given, which can occur in each of the above mentioned three steps, leading to serious aberrations. As a result abnormal metabolites, i.e. bile acids or sterols, are present in serum or urine, which can be detected using advanced analytical techniques like gas chromatography or mass spectrometry, leading to diagnosis. In contrast to defects in the first or third step in bile acid synthesis, giving rise to disorders already shortly after birth, symptoms of the disease cerebrotendinous xanthomatosis, caused by a defect in the second step, are only noticeable several years after birth. A number of these diseases can be treated successfully, but for peroxisomal defects no useful therapy exists.
Stellaard
F
F
Researchlaboratorium, afd. Kindergeneeskunde, Academisch Ziekenhuis Groningen.
Wolthers
B G
BG
D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism*; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism; D004798:Enzymes / Q000172:deficiency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D010088:Oxidoreductases / Q000172:deficiency; D014973:Xanthomatosis / Q000378:metabolism
D001647:Bile Acids and Salts; D004798:Enzymes; D002784:Cholesterol; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases
Inborn errors van het galzuurmetabolisme.