https://pubmed.ncbi.nlm.nih.gov/36917836/

J Pediatr Gastroenterol Nutr. 2023 Mar 15.
doi: 10.1097/MPG.0000000000003773.Online ahead of print.

Liver disease in GLIS 3 mutations - Transplant considerations and bile duct paucity on explant histology

Michael R Couper 1, Rachel M Brown 2, Girish Gupte 1, M Thamara P R Perera 1, Chayarani Kelgeri 1

Abstract
GLI-similar 3 (GLIS3) gene mutation heterozygosity is characterised 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 two 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. Post-operative 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.