Bile acids and bile alcohols in two patients with Zellweger (cerebro-hepato-renal) syndrome.
The Zellweger cerebro-hepato-renal syndrome (CHRS) is a rare hereditary disease in which there is a generalized deficiency of peroxisomal function. Liver peroxisomes are important for the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid into cholic acid, and, consequently, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid and metabolites of this bile acid precursor accumulate in serum and bile of patients with CHRS. Little is known about the urinary excretion of bile acids in this disease. Using gas chromatography-mass spectrometry we have analyzed serum bile acids and urinary excretion of bile acids and bile alcohols in two Swiss male CHRS patients. As expected, serum concentrations and urinary excretions of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid and 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid were elevated, which is probably an obligatory finding in CHRS. In addition, the urinary excretion of 1,3,7,12-tetrahydroxy-5 beta-cholanoic acid (a very polar unusual bile acid) was increased (99-1556 nmol/24 h). In contrast, the excretion of the major urinary bile alcohol, 27-nor-5 beta-cholestane-3 alpha, 7 alpha,12 alpha,24,25-pentol was found to be normal. 3 alpha, 7 alpha,12 alpha-Trihydroxy-5 beta-C29-dicarboxylic acid, a metabolite of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid previously believed to be obligatory in CHRS, was found only in one of our patients.
D000015:Abnormalities, Multiple; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000032:analysis* / Q000378:metabolism; D001927:Brain Diseases / Q000235:genetics* / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002777:Cholestanols / Q000032:analysis* / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism; D002869:Chromosome Aberrations / Q000378:metabolism*; D025063:Chromosome Disorders; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D013577:Syndrome
D001647:Bile Acids and Salts; D002777:Cholestanols; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; D019826:Cholic Acid