Congenital Cholestasis: Clinical and Ultrastructural Study

Abstract

Byler’s disease is a recessively inherited form of progressive intrahepatic cholestasis first described by Clayton in an extensive Amish kindred descended from Jacob Byler born in the United States in 1799 (2). Clinical manifestations are steatorrhea, conjugated hyperbilirubinemia which is initially intermittent and later persistent, pruritus, and hepatosplenomegaly. Alkaline phosphatase is elevated but serum cholesterol is normal. Serum bile acid levels are elevated and an increased level of lithocholic acid has been described in one patient. The transport maximum (Tm) for bromsulphalein and storage capacity (S) are both reduced. The liver architecture early in the disease is normal and normal numbers of interlobular bile ducts are present (6). Progressive hepatic cirrhosis occurs; the longest survivor was 14 3/12 years of age and had severe cirrhosis and mental and physical retardation (6). Defective excretion of conjugated bile salts and bilirubin across the canalicular membrane has been postulated (2, 6).

This work was supported in part by U.S. Public Health Service Grant RR-00123 from the General Clinical Research Centers Branch, National Institutes of Health.