Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs' negative haemolytic anaemia.

We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs' negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum gamma-glutamyl transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we detected large amounts of 1 beta-hydroxylated bile acids, especially 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-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 urinary 1 beta-hydroxylated bile acids gradually decreased as the disease progressed. At the end-stage, we detected large amounts of 7 alpha,12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The ratio of 7 alpha,12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end-stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of delta 4-3-oxo bile acids is increased.