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?

Abstract

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 of 5j3-cholestane-3a,7a, l2a,25-tetrol, 5/3-cholestane-3a,7a,12a,24£-tetrol, and 5j3-cholcst-24-ene-3a,7a,12a-triol. Analysis of the urine by fast atom bombardment mass spectrom­etry and by gas chromatography-mass spectrometry after treat­ment with Helix pomalia glucuronidase/sulfatase showed that the major cholanoids in urine were the glucuronidcs of 50-choIestane-3cY,7a,12o:,245,25-pentol, 5j3-cholestane-3a,7oβ12aβ25-tetrol, and 5j3-cholcstane-3a,7a,12a,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 5j3-cholestane-3a,7a,12a,245’,25-pentol to cholic acid and acetone. Treatment with chenodeoxycholic 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 lests. 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 f3 mo. © 1995 International Pediatric Research Foundation, Inc.