THE HEREDITARY HYPERBILIRUBINEMIAS

The presence of jaundice in the neonate, infant or young child present s a broad differential diagnosis. The 'disease' may be benign, as in b reast-milk jaundice, or potentially fatal, as in hereditary fructose i ntolerance. The cause of the jaundice may be a primary hepatic disorde r, such as extrahepatic biliary atresia, or secondary to a non-hepatic cause, such as haemolysis or sepsis. There may be significant hepatic injury and dysfunction, as in fulminant viral hepatitis, or simply el evation of plasma bilirubin, as in Gilbert's syndrome. In this chapter we will discuss the familial hyperbilirubinaemia syndromes. This dive rse group of disorders is characterized by hepatic dysfunction in the absence of hepatocellular injury. The first section of the chapter wil l discuss the unconjugated hyperbilirubinaemias: Crigler-Najjar syndro me I, Crigler-Najjar syndrome II and Gilbert's syndrome. The discovery of the gene for bilirubin uridine diphosphate glucuronosyltransferase has increased our understanding of the genetic heterogeneity and clin ical presentation of the Crigler-Najjar syndromes. The remainder of th e chapter will discuss the conjugated hyperbilirubinaemias: Rotor synd rome and Dubin-Johnson syndrome. These rare diseases share many clinic al features; however, they can be readily distinguished by biochemical markers in the urine and bile.