Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene

Abstract

Background and aims: Chronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics.

Methods: We enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed.

Results: 58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS.

Conclusions: This study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.

Keywords: Chinese; Chronic enteropathy associated with SLCO2A1 gene; SLCO2A1.

Fig. 1

Endoscopic images of patients diagnosed with CEAS. A-D, gastroscopic pictures of patient 3, showing fold thickening in gastric cardia (A), fundus of stomach (B), gastric body (C), and descending duodenum (D). E, an enteroscopic picture of patient 7 showing stenosis and ulceration of the middle ileum. F and G, colonoscopic pictures of patient 6 (F) and patient 11 (G) respectively, showing circular stenosis and ulceration of the terminal ileum. H, a colonoscopic picture of patient 1 showing stenosis and ulceration of the sigmoid colon

Fig. 2

Representative CTE images of CEAS patients. A-C, computed tomography enteroscopy (CTE) images of patient 1, showing wall thickening of gastric antrum (arrow in A), descending duodenum (arrow in B) and horizontal duodenum (arrow in C) with enhanced mucosa. D, the CTE image of patient 11, showing thickened intestinal wall of multi-segmental ileum, enhanced mucosa, short-segmental stenosis (indicated by white arrows), and dilated intestinal lumen between strictured segments. E, the CTE image of patient 1 showing diffuse wall thickening of ileum with enhanced mucosa and multiple stenosis of ileum highlighted by white arrows. F and G, CTE images of patient 3, showing diffusely thickened gastric wall, thickened plicae and mildly enhanced gastric wall (arrow in F), and slightly thickened colon wall as well (arrows in G)

Fig. 3

Histology of CEAS intraoperative pathological sections. Hematoxylin and Eosin staining. A and B, multiple superficial ulcers (scale bar, 5 mm). C, vasodilation and hyperemia of the small intestinal mucosa adjacent to ulcers (scale bar, 500 μm). D, hyperplasia of submucosal fibrous tissue (scale bar, 500 μm)

Fig. 4

Immunohistochemical staining of CEAS surgical pathological sections. Representative immunohistochemical staining of anti-CD31 and anti-SLCO2A1 of intraoperative pathological sections from patient 1, patient 7, patient 8 and negative control without CEAS respectively (scale bar, 100 μm)