Diagnosis and management of Crigler-Najjar syndrome

Crigler-Najjar syndrome (CNS) results from a mutation in one of the five exons of the gene coding for the enzyme bilirubin-UDP-glucuronosyltransferase by exon 1*1 and exons 2-5 of the UDP-glucuronosyltransferase 1 locus, the bilirubin glucuronidating isoform of UDP-glucuronosyltransferase. CNS type 2 is caused by a single base pair mutation leading to a decreased but not totally absent enzyme activity. In these patients the enzyme remains responsive to phenobarbital induction therapy and their bile contains low amounts of bilirubin mono- and diglucuronides. In CNS type 1 the enzyme activity is completely absent. CNS type 1 patients do not respond to phenobarbital and their bile does not contain more than traces of bilirubin conjugates. In 1997 we reported a World Registry on the treatment of patients with CNS type 1. Data were collected on 57 patients, of whom 21 (37%) had been transplanted at the time of data collection. Some 15 patients (26%) had brain damage, in 7 of whom the brain damage was mild and they received a liver transplant. Patients with brain damage at transplantation were significantly older than those without brain damage (14.3 vs 5.9 years). Before transplantation the serum bilirubin level of CNS type 1 patients should be kept below 350 mu mol/l with daily phototherapy. Oral calcium supplementation makes phototherapy more efficient. Gene therapy has been performed successfully in the Gunn rat, an animal model for this disease. Liver cell transplantation has recently been done in a child with CNS type 1.