Familial Giant Cell Hepatitis with Low Bile Acid Concentrations and Increased Urinary Excretion of Specific Bile Alcohols: A New Inborn Error of Bile Acid Synthesis?

摘要

A 9-wk-old infant with familial giant cell hepatitis and severe intrahepatic cholestasis had low plasma concentrations of chenodeoxycholic acid and cholic acid and elevated plasma concentrations of5β-cholestane-3α,7α,12α,25-tetrol, 5β-cholestane-3α,7α,12α,24-tetrol, and 5β-cholest-24-ene-3α,7α,12α-triol. Analysis of the urine by fast atom bombardment mass spectromctry and by gas chromatography-mass spectrometry after treatment with Helix pomatia glucuronidase/sulfatase showed that the major cholanoids in urine were the glucuronides of 5β-cholestane-3α,7α,12α,24S, 25-pentol, 5β-cholestane-3α,7α,12α,25-tetrol, and 5β-cholestane-3α,7α,12α,24-tetrol. These results are consistent with an inborn error of the 25-hydroxylase pathway for bile acid synthesis, specifically one of the enzymes responsible for conversion of 5β-cholestane-3α,7α,12α,24S, 25-pentol to cholic acid and acetone. Treatment with chenodcoxycholic acid was tried on two occasions. On the first it appeared to precipitate a rise in bilirubin, on the second the liver function tests improved and the improvement was maintained when the treatment was modified to a combination of chenodeoxycholic acid and cholic acid and finally, cholic acid alone. Despite the normalization of liver function tests, a liver biopsy at 1.25 y showed an active cirrhosis. Nonetheless, the child is thriving at the age of 3.5 y, whereas an affected sibling died at 13 mo.