title: The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders.
abstract: Congenital diarrheal disorders are rare, often fatal, diseases that are difficult to diagnose (often requiring biopsies) and that manifest in the first few weeks of life as chronic diarrhea and the malabsorption of nutrients. The etiology of congenital diarrheal disorders is diverse, but several are associated with defects in the predominant intestinal epithelial cell type, enterocytes. These particular congenital diarrheal disorders (CDD(ENT)) include microvillus inclusion disease and congenital tufting enteropathy, and can feature in other diseases, such as hemophagocytic lymphohistiocytosis type 5 and trichohepatoenteric syndrome. Treatment options for most of these disorders are limited and an improved understanding of their molecular bases could help to drive the development of better therapies. Recently, mutations in genes that are involved in normal intestinal epithelial physiology have been associated with different CDD(ENT). Here, we review recent progress in understanding the cellular mechanisms of CDD(ENT). We highlight the potential of animal models and patient-specific stem-cell-based organoid cultures, as well as patient registries, to integrate basic and clinical research, with the aim of clarifying the pathogenesis of CDD(ENT) and expediting the discovery of novel therapeutic strategies.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Arend W
authors.initials: AW
authors.lastname: Overeem
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Posovszky
authors.affiliation: Department of Pediatrics, Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, 3000 CB Rotterdam, The Netherlands Department of Pediatrics, Leiden University Medical Center, Leiden University, 2300 RC Leiden, The Netherlands.
authors.forename: Edmond H M M
authors.initials: EH
authors.lastname: Rings
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Ben N G
authors.initials: BN
authors.lastname: Giepmans
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands s.c.d.van.ijzendoorn@umcg.nl.
authors.forename: Sven C D
authors.initials: SC
authors.lastname: van IJzendoorn
mesh_terms: D000012:Abetalipoproteinemia / Q000276:immunology; D000818:Animals; D002914:Chylomicrons / Q000502:physiology; D003967:Diarrhea / Q000151:congenital* / Q000503:physiopathology*; D003968:Diarrhea, Infantile / Q000276:immunology; D020895:Enterocytes / Q000166:cytology*; D019066:Facies; D005317:Fetal Growth Retardation / Q000276:immunology; D006201:Hair Diseases / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000276:immunology; D008055:Lipids / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000276:immunology / Q000502:physiology; D023421:Models, Animal; D009154:Mutation; D021381:Protein Transport; D012042:Registries; D013234:Stem Cells / Q000166:cytology
chemical_list: D002914:Chylomicrons; D008055:Lipids
keywords: Brush border; Cell polarity; Congenital diarrheal disorder; Enterocyte; Intracellular trafficking; Microvillus inclusion diseases