Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
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Homozygous Missense Epithelial Cell Adhesion Molecule Variant in a Patient with Congenital Tufting Enteropathy and Literature Review

  • Guvenoglu, Merve (Department of Pediatric Genetics, Hacettepe University Faculty of Medicine) ;
  • Simsek-Kiper, Pelin Ozlem (Department of Pediatric Genetics, Hacettepe University Faculty of Medicine) ;
  • Kosukcu, Can (Department of Bioinformatics, Institute of Health Sciences, Hacettepe University) ;
  • Taskiran, Ekim Z. (Department of Medical Genetics, Hacettepe University Faculty of Medicine) ;
  • Saltik-Temizel, Inci Nur (Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hacettepe University Faculty of Medicine) ;
  • Gucer, Safak (Division of Pediatric Pathology, Department of Pediatrics, Hacettepe University) ;
  • Utine, Eda (Department of Pediatric Genetics, Hacettepe University Faculty of Medicine) ;
  • Boduroglu, Koray (Department of Pediatric Genetics, Hacettepe University Faculty of Medicine)
  • Received : 2022.04.20
  • Accepted : 2022.09.21
  • Published : 2022.11.15
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Abstract

Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

Keywords

Acknowledgement

The authors thank the patient's parents for their participation in the study. This study was supported by Hacettepe University Scientific Research Unit under the project entitled Hacettepe Exome Project (Grant ID: TAY 2015-7335).

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