Diagnosis and management of Crigler-Najjar syndrome
Diagnosis and management of Crigler-Najjar syndrome
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DOI：
10.1007/pl00014330
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发表时间：
1999-12-01
影响因子：
3.6
通讯作者：
Jansen, PLM
中科院分区：
文献类型：
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作者：
Jansen, PLM
Crigler-Najjar综合征（CNS）由编码胆红素-UDP-葡萄糖醛酸基转移酶的基因的5个外显子之一突变引起，突变为UDP-葡萄糖醛酸基转移酶1基因座的外显子1*1和外显子2-5，UDP-葡萄糖醛酸基转移酶的胆红素葡萄糖醛酸化亚型。CNS 2型由单碱基对突变引起，导致酶活性降低但并非完全缺失。在这些患者中，酶对苯巴比妥诱导治疗仍有反应，其胆汁中含有少量的胆红素单葡萄糖醛酸和二葡萄糖醛酸。在CNS 1型中，酶活性完全不存在。CNS 1型患者对苯巴比妥无反应，其胆汁中不含超过痕量的胆红素结合物。1997年，我们报告了一项关于CNS 1型患者治疗的世界登记研究。收集了57例患者的数据，其中21例（37%）在数据收集时已接受移植。大约15名患者（26%）有脑损伤，其中7名脑损伤轻微，他们接受了肝移植。移植时有脑损伤的患者明显比没有脑损伤的患者年龄大（14.3岁vs 5.9岁）。移植前CNS 1型患者的血清胆红素水平应保持在350 μ mol/l以下，每日进行光疗。口服钙补充剂使光疗更有效。基因治疗已成功地进行了古恩大鼠，这种疾病的动物模型。肝细胞移植最近已经完成了一个孩子与中枢神经系统1型。
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.