Ebrahimi Ammar, Rahim Fakher
Department of Medical Biotechnology, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.
Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Endocr Metab Immune Disord Drug Targets. 2018;18(3):201-211. doi: 10.2174/1871530318666171213153130.
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.
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.
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.
In spite of remaining safety and efficiency issues, gene therapy promises to be a realistic treatment modality for CNS during the future decade.
克里格勒-纳贾尔综合征（CNS，OMIM：218800）是先天性代谢缺陷的典型疾病，也是一种罕见的遗传病，估计每百万活产儿中的发病率为0.6 - 1.0。CNS亚型的区分通常基于临床标准，如对苯巴比妥治疗的反应以及其他分子和功能特征。
鉴定四个新的致病突变以及分析UGT1A1基因错义突变的残余活性对临床诊断有用，并且可能揭示酶活性方面的新见解，而致病突变的鉴定将加速对新确诊的CNS患者的遗传咨询。
光疗、原位肝移植、肝细胞移植和基因治疗是对抗该综合征的治疗选择和候选方法。由于在小动物模型中基因治疗有前景的报道，基因治疗方法有望继续进行临床前研究，以开发安全有效的CNS治疗方法。使用重组病毒（如腺病毒）的基因转移载体已成功应用于将UGT1A1基因转移到CNS Gunn大鼠模型的肝脏中。
尽管仍存在安全性和有效性问题，但基因治疗有望在未来十年成为CNS切实可行的治疗方式。
