Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy.
Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy.
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四肽重复结构域7A（TTC7A）种系突变患者的小儿胃肠道组织病理学：一种罕见的疾病，导致多个肠闭锁，严重的合并免疫缺陷和先天性肠胃疾病。
DOI：
10.1097/pas.0000000000001856
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发表时间：
2022-06-01
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TTC7A基因突变是先天性肠病的罕见病因，可导致严重的发病率。TTC7A缺乏导致肠上皮细胞的破坏。这种情况的组织病理学已在病例报告和临床研究中部分描述。本文描述了迄今为止报道的最大的经组织学检查证实的TTC7A突变队列的儿科胃肠道病理学的深入研究，并首次将研究结果与年龄和性别匹配的肠闭锁对照患者进行了比较，这些患者被认为与TTC7A突变无关。对7例已知TTC7A突变患者的内镜下黏膜活检和手术切除标本的苏木精和伊红染色切片进行回顾性检查。发现显微镜检查结果在从闭锁为主到上皮异常为主的范围内。与对照组相比，观察到几个独特的组织病理学特征。这些包括嗜酸性结肠炎和整个胃肠道的显著固有层嗜酸性粒细胞增多。在7名患者中的4名中观察到上皮的显著结构异常。5例肠闭锁患者表现为结肠粘膜肌层肥大和紊乱，伴肠壁内淡梭形细胞结节。后者的成分进一步阐明使用免疫组化，我们随后假设，他们代表闭塞的粘膜与残留的粘膜肌层。最后，在4名患者中观察到萎缩性胃炎。总之，本文所述的TTC7A突变相关肠病的独特组织病理学特征更充分地描述了存在先天性肠病或小肠结肠炎的婴儿中的这种新疾病实体。
Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene are a rare cause of congenital enteropathy that can result in significant morbidity. TTC7A deficiency leads to disruption of the intestinal epithelium. The histopathology of this condition has been partly described in case reports and clinical studies. This manuscript describes an in-depth investigation of the pediatric gastrointestinal pathology of the largest histologically examined cohort with confirmed TTC7A mutations reported to date and, for the first time, compared the findings to age- and sex-matched control patients with intestinal atresia not thought to be associated with TTC7A mutations. Hematoxylin and eosin-stained slides of endoscopically obtained mucosal biopsies and surgical resection specimens from seven patients with known TTC7A mutations were examined retrospectively. The microscopic findings were found to be on a spectrum from atresia-predominant to those with predominantly epithelial abnormalities. Several unique histopathologic characteristics were observed when compared to controls. These included neutrophilic colitis and prominent lamina propria eosinophilia throughout the gastrointestinal tract. Striking architectural abnormalities of the epithelium were observed in four of the seven patients. The five patients with intestinal atresia demonstrated hypertrophy and disorganization of the colonic muscularis mucosae accompanied by bland spindle cell nodules within the intestinal wall. The components of the latter were further elucidated using immunohistochemistry, and we subsequently hypothesize that they represent obliterated mucosa with remnants of the muscularis mucosae. Finally, atrophic gastritis was noted in four patients. In conclusion, the unique histopathologic characteristics of TTC7A mutation-associated enteropathy described herein more fully describe this novel disease entity in infants who present with congenital enteropathy or enterocolitis.