Congenital tufting enteropathy (CTE) is a rare autosomal recessive inherited disorder caused by mutations in the epithelial cell adhesion molecule (EpCAM) gene, characterized by severe diarrhea and growth failure. Between December 2017 and December 2023, eight patients diagnosed with CTE at our hospital were retrospectively analyzed for their clinical and genetic features, alongside a comprehensive literature review. All patients presented with severe malnutrition and growth failure upon admission. Parenteral nutrition (PN) with high caloric intake was required for all patients to achieve growth catch-up. A total of 142 patients with EpCAM mutations were reviewed, including 137 previously reported cases and five newly identified patients described in this study. Among the 114 CTE patients with detailed treatment information, 108 patients received PN therapy, with six patients successfully weaned off PN. Additionally, 19 patients underwent intestinal transplantation (IT). Outcome analysis revealed that 30 patients (27.3%) died, including five post-IT deaths. A total of 68 EpCAM mutations were identified, with most located in exon 3. The most frequently reported variant was c.499dup C. In this study, four novel mutations were detected in our patients. This study provides a comprehensive overview of the clinical and genetic characteristics of CTE, enhancing the understanding of its phenotype and genotype, particularly in Asian patients.

Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Congenital diarrhea and enteropathies (CODEs) constitute a group of rare genetic disorders characterized by severe diarrhea and malabsorption in the neonatal period or early infancy. Timely diagnosis and treatment is essential to prevent life-threatening complications, including dehydration, electrolyte imbalance, and malnutrition. This review offers a simplified approach to the diagnosis of CODEs, with a specific focus on microvillus inclusion disease (MVID), congenital tufting enteropathy (CTE), congenital chloride diarrhea (CLD), and congenital sodium diarrhea (CSD). Patients with CODEs typically present with severe watery or occasionally bloody diarrhea, steatorrhea, dehydration, poor growth, and developmental delay. Therefore, it is crucial to thoroughly evaluate infants with diarrhea to rule out infectious, allergic, or anatomical causes before considering CODEs as the underlying etiology. Diagnostic investigations for CODEs encompass various modalities, including stool tests, blood tests, immunological studies, endoscopy and biopsies for histology and electron microscopy, and next-generation sequencing (NGS). NGS plays a pivotal role in identifying the genetic mutations responsible for CODEs. Treatment options for CODEs are limited, often relying on total parenteral nutrition for hydration and nutritional support. In severe cases, intestinal transplantation may be considered. The long-term prognosis varies among specific CODEs, with some patients experiencing ongoing intestinal failure and associated complications. In conclusion, the early recognition and accurate diagnosis of CODEs are of paramount importance for implementing appropriate management strategies. Further research and advancements in genetic testing hold promise for enhancing diagnostic accuracy and exploring potential targeted therapies for these rare genetic disorders.

This article aims to evaluate the effects of growth hormone (GH) therapy in a case with congenital tufting enteropathy (CTE). CTE is a rare autosomal recessive enteropathy that typically presents with persistent diarrhea. In this case, a 13-year-old girl presented with a diagnosis of CTE. Due to short stature, GH therapy was considered. Pre- and post-treatment evaluations were conducted for height, growth rate, and motor skills. As a result, an increase in growth rate and improvement in motor skills were observed with GH therapy. These findings suggest that the potential of GH therapy is to increase growth and improve the quality of life in patients with CTE. Further studies are needed to evaluate the long-term effects of GH therapy and its efficacy in broader patient groups.

The causes of intractable diarrhoea in infancy are varied, and can be classified into enteropathic and non-enteropathic groups. Congenital tufting enteropathy (CTE) is a rare cause of enteropathic form of intractable diarrhoea in infants requiring nutritional supplementation. We herein report a case of CTE in a one-year-old female child who presented with recurrent abdominal distension, frequent watery diarrhoea and marked stunted growth soon after birth. A systematic clinical, laboratory and pathological evaluation brought out the etiology, followed by genotypic confirmation. Histological examination revealed mild villous abnormality with presence of epithelial tufts both in the villous and crypt surface, in the duodenum and rectal biopsies supported by complete loss of MOC31 staining. Deep sequencing revealed homozygous 3' splice mutation at intron 5 of the EPCAM gene (c.556-14A>G). She was given TPN support and discharged with weight gain under home-based parenteral nutrition supplement. This case brings out the need for a multidisciplinary team approach to reveal underlying the cause of infantile intractable diarrhoea and report a favorable outcome with nutritional supplementation.