Bile bilirubin pigment analysis in disorders of bilirubin metabolism in early infancy

Background-Early and accurate diagnosis of Crigler-Najjar syndrome, which c auses prolonged unconjugated hyperbilirubinaemia in infancy, is important, as orthotopic liver transplantation is the definitive treatment. Aim-To determine whether bilirubin pigment analysis of bile in infants with prolonged unconjugated hyperbilirubinaemia provides useful diagnostic info rmation in the first 3 months of life. Methods-Retrospective review of patients with prolonged unconjugated hyperb ilirubinaemia referred to the liver unit, Birmingham Children's Hospital, f or the diagnosis of Crigler-Najjar syndrome. Bile bilirubin pigment composi tion was determined by high performance liquid chromatography. Initial diag noses were made based on the result of bile bilirubin pigment composition. Final diagnoses were made after reviewing the clinical course, response to phenobarbitone, repeat bile bilirubin pigment composition analysis, and gen etic studies. Results-Between 1992 and 1999, nine infants aged less than 3 months of age with prolonged hyperbilirubinaemia underwent bile bilirubin pigment analyse s. Based on these, two children were diagnosed with Crigler-Najjar syndrome (CNS) type 1, six with CNS type 2, and one with Gilbert's syndrome. Five c hildren whose initial diagnosis was CNS type 2 had resolution of jaundice a nd normalisation of serum bilirubin after discontinuing phenobarbitone, and these cases were thought to be normal or to have Gilbert's syndrome. One o f the initial cases of CNS type 1 responded to phenobarbitone with an 80% r eduction in serum bilirubin consistent with CNS type 2. In all, the diagnos es of six cases needed to be reviewed. Conclusions-Early bile pigment analysis, performed during the first 3 month s of Life, often shows high levels of unconjugated bilirubin or bilirubin m onoconjugates, leading to the incorrect diagnosis of both type 1 and type 2 Crigler-Najjar syndrome.