From the Liver Unit, Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom.
the Anatomical Pathology, Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom.
J Pediatr Gastroenterol Nutr. 2023 Jul 1;77(1):110-114. doi: 10.1097/MPG.0000000000003773. Epub 2023 Mar 14.
GLI-similar 3 (GLIS3) gene mutation heterozygosity is characterized by neonatal diabetes and hypothyroidism. It has wide phenotypic variability. Liver disease is prevalent, and its complications in some phenotypes are life-limiting. Transplantation and the pathogenesis of GLIS3 liver disease are not well explored in the literature. We report 2 cases of children with GLIS3 mutations with chronic liver disease who required liver transplantation and we present a literature review discussing the pathogenic mechanisms and liver histology. Histology demonstrated predominantly biliary cirrhosis consistent with abnormal bile duct development. Both patients were considered for multi-organ transplantation (liver, pancreas with or without kidney) before receiving a liver transplant alone. Postoperative management can be challenging due to infection, renal disease, and brittle diabetes. GLIS3 mutations need to be added to the list of non-syndromic causes of bile duct paucity in the liver. Liver transplantation should be considered in patients with life-limiting complications related to liver disease.
GLI 相似因子 3 (GLIS3) 基因突变的杂合性表现为新生儿糖尿病和甲状腺功能减退症。它具有广泛的表型变异性。肝脏疾病很常见，某些表型的并发症会限制生命。文献中对 GLIS3 肝脏疾病的发病机制和发病机制研究甚少。我们报告了 2 例 GLIS3 基因突变导致慢性肝病需要进行肝移植的儿童病例，并对发病机制和肝脏组织病理学进行了文献复习。组织学表现为以胆管发育异常为主的胆汁性肝硬化。在接受单独肝移植之前，这两名患者均被考虑进行多器官移植（肝、胰腺伴或不伴肾）。由于感染、肾病和脆性糖尿病，术后管理可能具有挑战性。GLIS3 突变需要添加到非综合征性肝内胆管稀少的病因列表中。对于与肝脏疾病相关的具有生命限制并发症的患者，应考虑进行肝移植。
