The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2016-01-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/9/1/1 |
| _version_ | 1828972386150514688 |
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| author | Arend W. Overeem Carsten Posovszky Edmond H. M. M. Rings Ben N. G. Giepmans Sven C. D. van IJzendoorn |
| author_facet | Arend W. Overeem Carsten Posovszky Edmond H. M. M. Rings Ben N. G. Giepmans Sven C. D. van IJzendoorn |
| author_sort | Arend W. Overeem |
| collection | DOAJ |
| description | 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 (CDDENT) 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 CDDENT. Here, we review recent progress in understanding the cellular mechanisms of CDDENT. 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 CDDENT and expediting the discovery of novel therapeutic strategies. |
| first_indexed | 2024-12-14T13:27:05Z |
| format | Article |
| id | doaj.art-ab6387d924d743c180cbd7d7b10dff49 |
| institution | Directory Open Access Journal |
| issn | 1754-8411 1754-8403 |
| language | English |
| last_indexed | 2024-12-14T13:27:05Z |
| publishDate | 2016-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-ab6387d924d743c180cbd7d7b10dff492022-12-21T22:59:48ZengThe Company of BiologistsDisease Models & Mechanisms1754-84111754-84032016-01-019111210.1242/dmm.022269022269The role of enterocyte defects in the pathogenesis of congenital diarrheal disordersArend W. Overeem0Carsten Posovszky1Edmond H. M. M. Rings2Ben N. G. Giepmans3Sven C. D. van IJzendoorn4 Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, Germany Department of Pediatrics, Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, 3000 CB Rotterdam, The Netherlands Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands 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 (CDDENT) 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 CDDENT. Here, we review recent progress in understanding the cellular mechanisms of CDDENT. 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 CDDENT and expediting the discovery of novel therapeutic strategies.http://dmm.biologists.org/content/9/1/1Brush borderCell polarityCongenital diarrheal disorderEnterocyteIntracellular traffickingMicrovillus inclusion diseases |
| spellingShingle | Arend W. Overeem Carsten Posovszky Edmond H. M. M. Rings Ben N. G. Giepmans Sven C. D. van IJzendoorn The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders Disease Models & Mechanisms Brush border Cell polarity Congenital diarrheal disorder Enterocyte Intracellular trafficking Microvillus inclusion diseases |
| title | The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders |
| title_full | The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders |
| title_fullStr | The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders |
| title_full_unstemmed | The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders |
| title_short | The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders |
| title_sort | role of enterocyte defects in the pathogenesis of congenital diarrheal disorders |
| topic | Brush border Cell polarity Congenital diarrheal disorder Enterocyte Intracellular trafficking Microvillus inclusion diseases |
| url | http://dmm.biologists.org/content/9/1/1 |
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