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Gastroenterology. 2018 Jun;154(8):2045-2059.e6. doi: 10.1053/j.gastro.2018.03.067. Epub 2018 Apr 12.

Advances in Evaluation of Chronic Diarrhea in Infants.

Author information

1
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
2
Departments of Surgery and Pediatrics and the Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
3
Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
4
Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Department of Paediatrics and Biochemistry, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
5
Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: yaron.avitzur@sickkids.ca.
6
Department of Pediatrics, Division of Gastroenterology and Nutrition, Mattel Children's Hospital and the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Electronic address: MMartin@mednet.ucla.edu.

Abstract

Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa.

KEYWORDS:

Detection; Gastrointestinal Disorder; Inherited; Pediatric

PMID:
29654747
PMCID:
PMC6044208
DOI:
10.1053/j.gastro.2018.03.067
[Indexed for MEDLINE]
Free PMC Article

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