Article
Gastroenterology & Hepatology
Barun Das, Kevin Okamoto, John Rabalais, Jocelyn A. Young, Kim E. Barrett, Mamata Sivagnanam
Summary: Mutant mice with CTE-associated EpCAM mutations showed altered intestinal cell differentiation, leading to an increase in absorptive cells at the expense of major secretory cells. Although the proportion of absorptive enterocytes increased, they lacked key functional properties, underlying pathogenic features of CTE such as malabsorption and diarrhea. Treatment with a Notch signaling inhibitor increased the numbers of major secretory cell types in mutant enteroids.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Yougen Zhan, Stephen C. Ward, Maria Isabel Fiel, Julie Teruya-Feldstein, Eileen M. McKay, Fumiko Dekio
Summary: The study found disrupted apical-basal polarity of cholangiocytes and ductopenia in patients with Tufting enteropathy (TE). EpCam was shown to play a role in maintaining the integrity of biliary epithelium, and there was evidence of disrupted development of hepatic reparative cells in TE patients.
LIVER INTERNATIONAL
(2021)
Article
Pediatrics
Hasret Ayyildiz Civan, Coleen Leitner, Iris Oestreicher, Anna-Maria Schneider, Malte Cremer, Johannes A. Mayr, Rainer Rossi, Thomas Mueller, Andreas R. Janecke
Summary: Tufting enteropathy is caused by recessive EPCAM mutations, resulting in congenital diarrhea and disorganization of enterocytes. The study found that patients with TE experienced adequate weight gain with PN but often had stunted growth, with diagnosis typically being delayed.
Article
Genetics & Heredity
Yusriya Al Rawahi, Omar Al Sunaidi, Mohammed Al-Masqari, Adawiya Al Jamei, Dafalla Rahamtalla, Almundher Al-Maawali
Summary: Biallelic SPINT2 pathogenic variants can cause congenital diarrhea and enteropathy, but this study reported a case where the patient only presented with diarrhea symptoms and had no additional extra-intestinal features. The patient was found to have a novel homozygous variant in the SPINT2 gene, and in vitro functional studies confirmed the loss of inhibitory activity of intestinal serine proteases caused by this variant.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Medicine, General & Internal
Barun Das, Mamata Sivagnanam
Summary: Congenital tufting enteropathy (CTE) is an autosomal recessive disease of infancy that causes severe intestinal failure, and insight into the pathogenesis and predicted mechanisms of the disease may contribute to future therapeutic options.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Weihui Yan, Yongtao Xiao, Yunyi Zhang, Yijing Tao, Yi Cao, Kunhui Liu, Wei Cai, Ying Wang
Summary: This study enhances our understanding of the clinical manifestations and molecular genetics of neonatal-onset watery diarrhea. Early diagnosis through genomic analysis is possible for infants with atypical histological features. The discovery of novel mutations in the EPCAM and MYO5B genes provides further evidence for the association of genetic mutations with neonatal-onset diarrhea, with c.269_270 dupAA being the most frequent SLC26A3 mutation in China to date.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Review
Pediatrics
Parijat R. R. Tripathi, Anshu Srivastava
Summary: Chronic diarrhea in children presents diagnostic and management challenges. The causes and mechanisms vary depending on the age group, with congenital or genetic factors more common in neonates and infections, allergies, and immune-mediated mechanisms more common in childhood. Proper history taking and physical examination are essential for determining further diagnostic evaluations. The approach to managing chronic diarrhea should be tailored to the age group and the underlying pathophysiology. Diagnostic tests such as serological tests, imaging, endoscopy, histopathology, and genetic evaluation may be necessary to establish a definitive diagnosis. Treatment aims to stabilize the patient, provide nutritional support, and address the specific underlying cause, which can range from simple dietary exclusions to complex interventions such as small bowel transplant. Timely referral to specialists is crucial for effective evaluation and management, reducing the risk of complications and improving outcomes.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Pediatrics
Mohsin Raj Mantoo, Rohan Malik, Prasenjit Das, Rajni Yadav, Tripti Nakra, Pandu Chouhan
Summary: Congenital diarrhea and enteropathies (CODEs) are monogenic disorders causing early onset of intractable diarrhea. Diagnosis and management of these disorders have been improved with the availability of commercial next generation genetic testing. The authors shared their experience with 4 cases, suggesting a stepwise approach to diagnosis and management in the Indian context.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Article
Agriculture, Dairy & Animal Science
Denise S. Riggers, Corinne Gurtner, Martina Protschka, Denny Boettcher, Wolf von Bomhard, Gottfried Alber, Karsten Winter, Joerg M. Steiner, Romy M. Heilmann
Summary: This study investigates the expression of S100A8/A9 and S100A12 proteins in the intestine of cats with intestinal inflammation and lymphoma. It found that calgranulins-positive cells correlated with inflammatory changes and clinical severity, suggesting a role in both diseases. Further understanding of calgranulins in these feline diseases may lead to better diagnostics and treatments.
Article
Pediatrics
Jessica A. Eldredge, Michael R. Couper, Christopher P. Barnett, Lesley Rawlings, Richard T. L. Couper
Summary: Diacylglycerol O-acyltransferase 1 deficiency is a rare congenital diarrheal disorder with unusual phenotypes, including a macrophage activation syndrome-like response in one patient that was ameliorated with low dietary fat.
JOURNAL OF PEDIATRICS
(2021)
Article
Pediatrics
Shooq Alkhalifa, Aysha Darwish, Mohamed Awadh, Salman M. M. Alkhalifa, Abdulla Darwish
Summary: Congenital tufting enteropathy (CTE) is a rare autosomal recessive disorder caused by EPCAM gene mutation. It presents in early infancy as intractable diarrhea independent of breast or formula feeding, requiring life-long total parental nutrition or small bowel transplantation in severe cases. This study aims to review the literature on CTE, discuss its clinicopathological aspects, and distinguish it from other causes of congenital diarrheal disorders (CDDs).
CASE REPORTS IN PEDIATRICS
(2023)
Article
Pathology
Sonja Chen, Jeffrey D. Goldsmith, Rima Fawaz, Alyaa Al-Ibraheemi, Antonio R. Perez-Atayde, Sara O. Vargas
Summary: Congenital tufting enteropathy (CTE) is a rare heritable cause of intractable diarrhea due to EPCAM mutation. In affected patients, absent intestinal epithelial cell adhesion molecule (EpCAM) expression results in loss of MOC31 immunostaining. Hepatopathy in CTE patients may be difficult to separate from comorbid disease, but absent ductular reaction may be characteristic.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Pathology
Jiajie G. Lu, Shweta S. Namjoshi, Annie D. Niehaus, Shawn Tahata, Chung Un Lee, Lin Wang, Erin McDonnell, Melissa Seely, Martin G. Martin, Florette K. Hazard
Summary: In this article, a case of a rare inherited syndrome of congenital enteropathy is described. The patient presented with metabolic acidosis, lethargy, and watery stools. Further investigation revealed a novel pathogenic variant in the AP1S1 gene. Histopathologic analysis showed mild villous blunting, enterocytes with cytoplasmic vacuoles, and disrupted brush border.
PEDIATRIC AND DEVELOPMENTAL PATHOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Panpicha Sattasathuchana, Naris Thengchaisri, Yasushi Minamoto, Tomomi Minamoto, Jonathan A. Lidbury, Jan S. Suchodolski, Joerg M. Steiner
Summary: This study aimed to evaluate the diagnostic sensitivity of serum and fecal 3-bromotyrosine (3-BrY) concentrations in dogs with chronic inflammatory enteropathy (CIE) and compare the differences in 3-BrY concentrations among dogs with different gastrointestinal (GI) pathological changes. The results showed that dogs with CIE had increased 3-BrY concentrations in both serum and fecal samples, but the 3-BrY elevations may not accurately reflect the severity of gastrointestinal inflammation.
Article
Biology
Roman Szabo, Jerrold M. Ward, Ferruh Artunc, Thomas H. Bugge
Summary: This study reveals the overlapping functions of EPCAM and TROP2 in epithelial development in both intestinal and extraintestinal tissues. Loss of EPCAM results in developmental defects and decreased viability, while TROP2 deficiency exacerbates these defects. Importantly, TROP2 compensates for loss of EPCAM in stabilizing claudin-7 expression and cell membrane localization.