Chalasani N, Chowdhury N R, Chowdhury J R, Boyer T D
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30320, USA.
Gastroenterology. 1997 Jun;112(6):2099-103. doi: 10.1053/gast.1997.v112.pm9178703.
Gilbert syndrome is a common genetic disorder associated with mild unconjugated hyperbilirubinemia and no clinical illness. In contrast, Crigler-Najjar syndrome types I and II are rare genetic disorders associated with severe unconjugated hyperbilirubinemia and a life-long risk of kernicterus. Patients with Gilbert syndrome have low levels of a normal form of uridinediphosphoglucuronate glucuronosyltransferase because of a defect in the promoter region of both alleles, whereas patients with Crigler-Najjar syndrome are homozygous for a defect that yields an abnormal form of the enzyme that has limited or no activity. This case report describes a young adult with Crigler-Najjar syndrome type II in whom kernicterus developed after a laparoscopic cholecystectomy. The development of kernicterus was the result of a largely preventable series of events that lead to an increase in the free fraction of his serum bilirubin. Analysis of his genetic defect showed that he was homozygous for the mutation associated with Gilbert syndrome and heterozygous for a second mutation in the open reading frame of one allele of the bilirubin uridinediphosphoglucuronate glucuronosyltransferase gene. The combined defect leads to severe hyperbilirubinemia and shows how seemingly benign genetic defects, when combined, can cause serious clinical disease.
吉尔伯特综合征是一种常见的遗传性疾病，与轻度非结合性高胆红素血症相关，且无临床疾病。相比之下，I型和II型克里格勒 - 纳贾尔综合征是罕见的遗传性疾病，与严重的非结合性高胆红素血症以及终身核黄疸风险相关。吉尔伯特综合征患者由于两个等位基因启动子区域存在缺陷，导致尿苷二磷酸葡萄糖醛酸葡萄糖醛酸转移酶正常形式的水平较低，而克里格勒 - 纳贾尔综合征患者是纯合子缺陷，产生一种异常形式的酶，其活性有限或无活性。本病例报告描述了一名患有II型克里格勒 - 纳贾尔综合征的年轻成年人，其在腹腔镜胆囊切除术后发生了核黄疸。核黄疸的发生是一系列在很大程度上可预防的事件导致其血清胆红素游离部分增加的结果。对其基因缺陷的分析表明，他对于与吉尔伯特综合征相关的突变是纯合子，并且在胆红素尿苷二磷酸葡萄糖醛酸葡萄糖醛酸转移酶基因一个等位基因的开放阅读框中存在第二个杂合突变。这种联合缺陷导致严重的高胆红素血症，并表明看似良性的基因缺陷组合在一起时如何能引发严重的临床疾病。
