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Intractable diarrhea of infancy with epithelial and basement membrane abnormalities
O Goulet1, M Kedinger, N Brousse
1Department of Gastroentérologie et Nutrition, Hôpital Necker, Strasbourg, France.
Insights
This study identifies a severe neonatal diarrhea with specific intestinal abnormalities. These findings in children highlight potential basement membrane changes contributing to intractable infant diarrhea.
Area of Science:
- Pediatric Gastroenterology
- Gastrointestinal Pathology
- Neonatal Medicine
Background:
- Intractable diarrhea in neonates presents a significant clinical challenge.
- Similar clinical and histopathologic features suggest a distinct enteropathy.
- Neonatal onset diarrhea necessitates early diagnosis and management.
Purpose of the Study:
- To characterize a unique form of intractable neonatal diarrhea.
- To investigate the histopathologic features of intestinal biopsies.
- To examine basement membrane abnormalities in affected children.
Main Methods:
- Analysis of clinical histories and intestinal biopsies from six children.
- Histopathologic examination of duodenal and jejunal tissue.
- Immunohistochemical staining for basement membrane components (laminin, heparan sulfate proteoglycan).
Main Results:
- Identified intractable watery diarrhea of neonatal onset.
- Histopathology revealed villous atrophy, epithelial dysplasia, and abnormal regenerative cryptae.
- Demonstrated altered deposition of laminin and heparan sulfate proteoglycan in the basement membrane.
Conclusions:
- Described a distinct neonatal enteropathy characterized by specific histopathologic and basement membrane changes.
- These basement membrane modifications may be linked to epithelial abnormalities and disease severity.
- The condition requires permanent total parenteral nutrition due to its intractable nature.
Abstract:
We describe a form of intractable diarrhea in six children (four girls) with similar clinical histories and identical histopathologic features. The children had watery diarrhea of neonatal onset requiring total parenteral nutrition. Two had siblings who had died of diarrhea in the first year of life; two others are sisters. Repeated duodenal or jejunal biopsies revealed villous atrophy with normal or hyperplastic and regenerative cryptae, normal cellularity of the lamina mesenterii propria, and no signs of T-cell activation. The main histologic features are epithelial dysplasia with focal crowding and disorganization of the surface enterocytes, pseudocystic formation of the glands, and abnormal regenerative cryptae. The basement membrane components were studied with polyclonal antibodies on frozen specimens, and were compared with biopsy specimens from patients with celiac disease or autoimmune enteropathy. Relative to the control subjects, there was faint and irregular deposition of laminin at the epithelium-lamina mesenterii propria interface, whereas deposits of heparan sulfate proteoglycan were large and lamellar. The primary or secondary nature of these modifications of the basement membrane remains to be determined, but the modifications might be related to epithelial abnormalities and to the severity of this neonatal diarrhea, which resisted all treatment and necessitated permanent total parenteral nutrition.