Ammar Ebrahimi and Fakher Rahim* Pages 201 - 211 ( 11 )
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.
Crigler-najjar syndrome (CNS), in born error of metabolism (IEM), genetic disease, pathogenic mutations, gene therapy, recombinant viruses.
Department of Medical Biotechnology, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz