Evidence for defective primary bile acid secretion in children with progressive familial intrahepatic cholestasis (Byler disease).

To clarify the relationship of progressive familial intrahepatic cholestasis (Byler disease) to bile acid metabolism, we analysed, by high performance liquid chromatography, the bile acid composition of serum and bile in seven children with Byler disease and in eight control children with other cholestatic diseases. In serum, total bile acid concentration was increased in patients with Byler disease (0.30 +/- 0.05 mmol/l) and in control patients (0.21 +/- 0.08 mmol/l). Cholate (C) and chenodeoxycholate (CDC) comprised the major proportion of total bile acids in patients with Byler disease as in control patients. Hyocholate (HC) was only detected in patients with Byler disease and lithocholate was only present in control children. In bile, total bile acid concentration was very low in patients with Byler disease (1.1 +/- 1.4 mmol/l) compared to control patients (88.9 +/- 83.2 mmol/l). C and CDC were the major bile acids in control patients, whereas C and HC comprised the major proportion of bile acids in patients with Byler disease. These results suggest the existence of a defect of primary bile acid secretion in Byler disease characterized by the presence of high concentration of bile acids in serum and absence or very low concentration of bile acids in bile.