Editor—Crigler-Najjar syndrome types 1 and 2 (CN1 and CN2) are inherited as autosomal recessive conditions and are characterised by severe non-haemolytic unconjugated hyperbilirubinaemia. CN1 is the most severe form, in which a virtual absence of hepatic bilirubin-uridinediphosphoglucuronate glucuronosyltransferase (UGT1A1) (PIR Accession A31340) activity results in serum bilirubin levels of 340-685 μmol/l or higher (normal 1.7-17.1 μmol/l).1 A milder variant of this disorder, termed CN2, is associated with intermediate levels of hyperbilirubinaemia (120-340 μmol/l) as a result of an incomplete deficiency of hepatic UGT1A1 activity. Usually, the residual UGT1A1 activity can be induced by phenobarbital administration, resulting in partial amelioration of jaundice.2 A third type of inherited unconjugated hyperbilirubinaemia, termed Gilbert's syndrome, is associated with mild, fluctuating hyperbilirubinaemia, ranging from normal levels to up to 85 μmol/l.3 Hepatic UGT1A1 activity is reduced to approximately 30% of normal in Gilbert's syndrome. In all three forms of inherited hyperbilirubinaemia, other hepatic functions are unaffected and the liver is morphologically normal.4 Before the institution of routine phototherapy, CN1 used to be uniformly lethal because of bilirubin encephalopathy (kernicterus).5 6 Although phototherapy has prolonged survival, it becomes progressively ineffective around puberty.6 7 Hepatocyte transplantation has resulted in partial amelioration of jaundice,8 9 but at present liver transplantation remains the only definitive therapy.10 11Kernicterus is much less common in CN2, and does not occur in Gilbert's syndrome.

UGT1A1 is one of the several UGT isoforms that are expressed from theUGT1A gene locus,12 located in human chromosome 2q37.13 The locus contains four exons at the 3′ end (exons 2, 3, 4, and 5), which are used in several UGT1A isoform mRNAs and encode the identical carboxy-terminal half of these enzymes. Upstream to these common region exons are a series of unique exons (exon …