PROFILE OF URINARY BILE-ACIDS IN FAMILIAL INTRAHEPATIC CHOLESTASIS WITH COOMBS NEGATIVE HEMOLYTIC-ANEMIA

We present two male siblings with intrahepatic cholestasis and prolong ed indirect hyperbilirubinaemia. Their familial intrahepatic cholestas is syndrome was characterized by Coombs' negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentratio ns of serum gamma-glutamyl transpeptidase and cholesterol. By gas chro matography-mass spectrometry, we detected large amounts of 1 beta-hydr oxylated bile acids, especially 1 beta,3 alpha,7 alpha,12 alpha-tetrah ydroxy-5 beta-cholan-24-oic acid (25.5-67.9% of total urine bile acids ) in the urine during phenobarbital therapy. However, the amount of ur inary 1 beta-hydroxylated bile acids gradually decreased as the diseas e progressed. At the end-stage, we detected large amounts of 7 alpha,1 2 alpha-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bil e acids). The ratio of 7 alpha,12 alpha-dihydroxy-3-oxochol-4-en-24-oi c acid to cholic acid in the urine was 0.8. We conclude that in infant s with end-stage liver failure, the microsomal hydroxylation of bile a cids is impaired and the excretion of Delta(4)-3-ore bile acids is inc reased.