Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
J Pediatr. 2018 May;196:161-167.e1. doi: 10.1016/j.jpeds.2017.12.058. Epub 2018 Feb 28.
To clarify the clinical, pathologic, and genetic features of neonatal Dubin-Johnson syndrome.
Ten patients with neonatal Dubin-Johnson syndrome were recruited from 6 pediatric centers in Japan between September 2013 and October 2016. Clinical and laboratory course, macroscopic and microscopic liver findings, and molecular genetic findings concerning ATP-binding cassette subfamily C member 2 (ABCC2) were retrospectively and prospectively examined.
All neonates exhibited cholestasis, evident as prolonged jaundice with or without acholic stools and elevations of serum direct bilirubin as well as γ-glutamyltransferase or total bile acids. Only 38% (3 of 8) of patients who underwent liver biopsy showed a grossly black liver or melanin-like pigment deposits in hepatocytes; their biopsies were performed in early infancy. Immunohistochemically, all liver specimens showed no expression of multidrug resistance-associated protein 2 but increased expression of the bile salt export pump protein. Homozygous or compound heterozygous pathogenic variants of ABCC2 were identified in all patients, representing 11 distinct pathogenic variants including 2 not previously reported.
Immunohistochemical staining of the liver for multidrug resistance-associated protein 2 and molecular genetic analysis of ABCC2 are crucial for accurate diagnosis of neonatal Dubin-Johnson syndrome.
阐明新生儿型杜宾-约翰逊综合征的临床、病理和遗传特征。
2013 年 9 月至 2016 年 10 月期间，从日本的 6 个儿科中心招募了 10 名新生儿型杜宾-约翰逊综合征患者。回顾性和前瞻性检查了临床和实验室病程、肝脏大体和显微镜下表现以及与 ATP 结合盒亚家族 C 成员 2（ABCC2）相关的分子遗传学发现。
所有新生儿均表现为胆汁淤积，表现为持续黄疸，伴有或不伴有白陶土样粪便和血清直接胆红素以及 γ-谷氨酰转移酶或总胆汁酸升高。仅 38%（8 例中的 3 例）接受肝活检的患者显示肝脏大体上呈黑色或肝细胞中有黑色素样色素沉着；他们的活检是在婴儿早期进行的。免疫组织化学染色显示，所有肝脏标本均无多药耐药相关蛋白 2 的表达，但胆汁盐输出泵蛋白的表达增加。所有患者均发现 ABCC2 存在纯合子或复合杂合致病性变异，代表了包括 2 种以前未报道过的 11 种不同的致病性变异。
肝脏多药耐药相关蛋白 2 的免疫组织化学染色和 ABCC2 的分子遗传学分析对于新生儿型杜宾-约翰逊综合征的准确诊断至关重要。
