Crigler-Najjar syndrome: a case report

Background: Crigler-Najjar syndrome (CN) clinically manifests as intense unconjugated hyperbilirubinemia without evidence of hemolysis. At present, over 90 genetic variations such as mutations, insertions, or deletions have been described in the five exons of the UDP-glucuronosyltransferase (UGT1A1) gene responsible for defect of bilirubin conjugation. Objective: To report a case of a female CN type I child who presented with unconjugated hyperbilirubinemia, normal liver function tests, and normal ultrasonographic images of the liver. Results: Peak total bilirubin in this patient was 27.6 mg/dL. She developed kernicterus despite prolonged daily home phototherapy. Exons 1-5 of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the UGT1A1 gene was screened for mutations by direct DNA sequencing. Molecular genetic analysis showed that this patient was homozygous for a nonsense mutation at nucleotide number 715 (715C -> T) in exon 1 resulting in the replacement of glutamine (CAG, amino acid 239) by a stop codon (TAG). Conclusion: Detection of this genetic defect is essential for gene therapy and can be used as a prenatal screening test to identify the affected offspring.