Bilirubin Metabolism in Congenital Nonhemolytic Jaundice

Abstract

Extract: A Negro female with congenital nonhemolytic jaundice (Crigler-Najjar syndrome) was studied over a period of 15 months. During this period the plasma bilirubin concentration averaged 20.6 mg/100 ml. Administration of phenobarbital did not lower the bilirubin concentration. Studies with isotopically labeled bilirubin showed that phenobarbital had not increased the fractional rate of elimination of bilirubin, and the patient's bilirubin production rate while receiving phenobarbital therapy (3.5 mg/kg/24 hr) was not increased over that seen in normal individuals (3.8 \pm 0.6 mg/kg/24 hr, mean \pm sd). Multicompartmental analysis of the patient's labeled bilirubin clearance data, as well as that from two other reported cases of congenital nonhemolytic jaundice, did not furnish new information on pathways of bilirubin catabolism but did demonstrate that the fractional transfer rate of bilirubin from plasma to liver for all three subjects (0.42–0.87 hr-1) was reduced compared with the range seen in normal individuals (0.9–2.0 hr-1). This finding may reflect saturation of either the hepatic uptake process or intracellular binding sites, in the face of a serum bilirubin concentration 20–40 times normal. Menthol conjugation in the patient's parents was normal, unlike reported findings in parents of children with congenital nonhemolytic jaundice unresponsive to phenobarbital therapy. Labeled bilirubin clearances in the parents demonstrated an abnormality in the mother's pattern of clearance, whereas the father's clearance was normal. The patient was found to excrete normal amounts of testosterone conjugated with glucuronic acid, demonstrating that the defect in glucuronide conjugation does not include all physiological compounds. Speculation: Plasma clearance studies with labeled bilirubin can aid in the investigation of modes of inheritance of unconjugated hyperbilirubinemia.