Background: Crigler-Najjar syndrome (CNS, OMIM: 218800) is the paradigm of an inborn
error of metabolism and a rare genetic disease with an estimated incidence of 0.6–1.0 per million live
births. Discrimination between CNS subtypes is usually done on the basis of the clinical criteria, such
as response to phenobarbital treatment and other molecular and functional characteristics.
Methods: The identification of four novel pathogenic mutations and the analysis of residual activity of
missense in UGT1A1 gene are useful for clinical diagnosis, and may reveal a new insight in enzyme
activity, whereas the identification of pathogenic mutations will accelerate genetic counseling for
newly identified CNS patients.
Results: Phototherapy, orthotropic liver transplantation, liver cell transplantation and gene therapy are
treatment choices and candidates to fight back this syndrome. Due to the promising reports of gene
therapy in small animal models, gene therapy approaches are expected to continue in preclinical research
for developing safe and effective treatment of CNS. Gene transfer vectors using recombinant
viruses, such as Adenovirus have been applied successfully in transferring UGT1A1 gene to the liver of
Gunn rat model of CNS.
Conclusion: In spite of remaining safety and efficiency issues, gene therapy promises to be a realistic
treatment modality for CNS during the future decade.