A NEW CAUSE OF PROGRESSIVE INTRAHEPATIC CHOLESTASIS - 3-BETA-HYDROXY-C-27-STEROID DEHYDROGENASE ISOMERASE DEFICIENCY/

There have been a few reports of infants with severe neonatal cholesta sis related to a defect in primary bile acid synthesis. To assess the importance of such deficiency among children with progressive intrahep atic cholestasis (Byler disease), screening for inborn errors in bile acid Synthesis was performed by fast atom bombardment ionization-mass spectrometry of urine samples from 30 affected children. Bile acid ana lysis revealed a specific fast atom bombardment ionization-mass spectr ometry profile for 3 beta-hydroxy-C-27 steroid dehydrogenase/isomerase deficiency in five children who had jaundice, hepatosplenomegaly, and fatty Stools beginning at ages ranging from 4 to 46 months. None of t hem had pruritus. Liver function tests showed persistently normal seru m gamma-glutamyltransferase activity, low serum cholesterol and vitami n E levels, normal serum bile acid concentrations despite raised serum bilirubin levels, and decreased prothrombin time and clotting factor V. In four of the cases a similar disease was observed in siblings. Li ver function returned to normal after oral ursodeoxycholic acid therap y. We conclude that 3 beta-hydroxy-C-27-steroid dehydrogenase/isomeras e deficiency should be considered when idiopathic cholestatic liver di sease with clinical features akin to Byler disease is characterized by the association of normal serum gamma-glutamyltransferase activity, n ormal serum bile acid concentration, absence of pruritus, and a return to normal liver function during ursodeoxycholic acid therapy. Early i dentification of these children is essential because they benefit from bile acid therapy and might thus avoid the need for liver transplanta tion.