Wang Sheng-Nan, Fu Yu-Juan, Lu Xiao-Lan, Miao Shi-Jian, Zhang Ping, Wang Lin, Huang Ying, Wang Yu-Huan
Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China.
Department of Pathology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital (Shao Yifu Hospital), Hangzhou, China.
Transl Pediatr. 2024 Aug 31;13(8):1486-1495. doi: 10.21037/tp-24-97. Epub 2024 Aug 28.
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 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.
先天性簇绒性小肠病（CTE）是儿童顽固性先天性腹泻的罕见病因，常导致依赖肠外营养（PN）。我们旨在报告中国患者中的新突变，并阐述中国CTE的临床、组织病理学和分子特征。
我们报告3例经全外显子测序（WES）和MOC31[上皮细胞粘附分子（EPCAM）单克隆抗体]免疫组化诊断的CTE病例。3例患者的主要表现为水样腹泻和生长发育迟缓。3例患者的上消化道内镜检查均显示十二指肠黏膜绒毛萎缩。组织学检查发现绒毛异常，2例患者有局灶性簇绒。通过MOC31免疫组化，所有3例患者均显示EPCAM表达完全缺失。通过分子分析鉴定出5个新突变，包括c.319delG、c.505_507delGAG、c.491+1G>C、c.60del（p.F20Lfs*17）和c.353G>A。在我们的综述中，9项研究的11例患者中有18种不同突变，其中12种突变仅报告过1次。在中国，73%的患者为复合杂合子，大多数致病变异位于第3外显子。所有患者均出现先天性腹泻，因生长发育迟缓需要PN支持，即使腹泻有所改善。11例患者中，3例（27%）死亡。
CTE罕见且致命，内镜检查缺乏特征性改变。CTE患者需要通过组织学检查和基因检测进行早期诊断，以提高生存率。
