Mutant Neurogenin-3 in Congenital Malabsorptive Diarrhea

• Published in: The New England journal of medicine Vol. 355; no. 3; pp. 270 - 280
• Main Authors: Wang, Jiafang, Cortina, Galen, Wu, S. Vincent, Tran, Robert, Cho, Jang-Hyeon, Tsai, Ming-Jer, Bailey, Travis J, Jamrich, Milan, Ament, Marvin E, Treem, William R, Hill, Ivor D, Vargas, Jorge H, Gershman, George, Farmer, Douglas G, Reyen, Laurie, Martín, Martín G
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 20.07.2006
• Subjects: Amino Acid Sequence; Base Sequence; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological and medical sciences; Chronic Disease; Diarrhea; Diarrhea - congenital; Diarrhea - genetics; Diarrhea - pathology; Enteroendocrine Cells - pathology; Fatal Outcome; General aspects; Humans; Infant, Newborn; Intestine, Small - pathology; Malabsorption Syndromes - complications; Malabsorption Syndromes - genetics; Malabsorption Syndromes - pathology; Male; Medical research; Medical sciences; Molecular Sequence Data; Mutation, Missense; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Patients; Promoter Regions, Genetic; Proteins; Xenopus; Medicine; Diarrhea; Digestive diseases; Intestinal disease; Mutation; Congenital
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa054288

This study shows that mutations in the neurogenin-3 gene are associated with a virtual absence of enteroendocrine cells and with malabsorptive diarrhea. Neurogenin-3 is critical to the differentiation of enteroendocrine cells, and the presence of these cells is required for absorption of nutrients by enterocytes. Mutations in the neurogenin-3 gene are associated with a virtual absence of enteroendocrine cells and with malabsorptive diarrhea. Patients with congenital diarrhea generally present within the first weeks after birth with severe, life-threatening watery diarrhea that can be classified as either secretory or malabsorptive in nature. 1 Routine clinical evaluation, including intestinal biopsy, may be used to further categorize the diarrhea according to the severity of the inflammation and to assess the integrity of the crypt–villus axis and the architecture of the epithelial layer. On the basis of both clinical and pathological characteristics, various specialized formulas may be used to minimize the diarrheal symptoms, although some children require extended periods of intravenous nutrition to sustain normal growth and development. . . .