Clinical, hematologic, liver function and histologic examinations were performed in the majority of sixteen jaundiced patients with defective glucuronide formation in vivo and deficient hepatic glucuronyl transferase activity in vitro. Their bile pigments and response to administration of phenobarbital were also analyzed. One hundred eight members of the eleven families represented were also studied. The results indicate that chronic nonhemolytic unconjugated hyperbilirubinemia with hepatic glucuronyl transferase deficiency occurs in two forms which appear to be phenotypically homogeneous but are genotypically heterogeneous. Patients in group I usually had more severe hyperbilirubinemia and frequently had kernicterus. Their bile was essentially colorless and contained traces of unconjugated bilirubin only. The conjugation defect was transmitted as an autosomal recessive character and hyperbilirubinemia was unaffected by phenobarbital administration. Patients in group II generally had less severe hyper bilirubinemia without kernicterus. Their bile was pigmented and contained bilirubin glucuronide. The conjugation defect was transmitted in a different manner and appeared to be an autosomal dominant character. These patients responded dramatically to phenobarbital administration with disappearance of jaundice. The mechanism of the response to phenobarbital is uncertain although the evidence presented supports the view that enzyme induction may be occurring. The observed differences between groups I and II probably reflect differences in the structure of a single glucuronyl transferase or in the control of protein synthesis.
ASJC Scopus subject areas