Unconjugated hyperbilirubinemia. Physiologic evaluation and experimental approaches to therapy

The plasma concentration of unconjugated bilirubin is determined by the rate at which newly synthesized bilirubin enters the plasma (bilirubin turnover) and the rate of irreversible bilirubin removal by the liver (hepatic bilirubin clearance). Measurement of each of these variables by kinetic studies with radiolabeled bilirubin permits a precise classification of cases of unconjugated hyperbilirubinemia into those due to increased bilirubin turnover (for example, hemolysis), those due to decreased bilirubin clearance (for example, Gilbert's syndrome), and those in which both mechanisms operate. The ability to quantitate hepatic bilirubin clearance makes it possible to detect Gilbert's syndrome even in the presence of concomitant hemolysis. Of the hereditary disorders of bilirubin metabolism, Gilbert's syndrome is common but innocuous, whereas Crigler Najjar syndrome is rare but devastating. An unusual case of Crigler Najja syndrome is described in which bilirubin encephalopathy developed at age 18. Various modalities used in an attempt to reduce her plasma bilirubin concentration by either increasing bilirubin clearance or reducing bilirubin turnover are described.