Clinical and Genetic Characteristics of Korean Patients Diagnosed with Chronic Enteropathy Associated with SLCO2A1 Gene: A KASID Multicenter Study

Abstract

Background/Aims Chronic enteropathy associated with SLCO2A1 gene (CEAS), an inherited disease characterized by nonspecific intestinal ulcers, has emerged in the Japanese population via loss-of-function mutations in the SLCO2A1 gene. We aimed to investigate the clinical and genetic characteristics of Korean patients diagnosed with CEAS. Methods From July 2018 to July 2021, we performed Sanger sequencing of the SLCO2A1 gene in 46 patients with chronic intestinal ulcers. CEAS was confirmed based on known SLCO2A1 mutations. We summarized the clinical characteristics of patients with confirmed CEAS. Results Fourteen out of 46 patients (30.4%) had genetically confirmed CEAS, and two SLCO2A1 variants were detected (splicing site variant c.940+1G>A and nonsense mutation [p.R603X] in SLCO2A1 ). Twelve patients (85.7%) were females and the median age at diagnosis of CEAS was 44.5 years. All patients presented with abdominal pain, and 13 patients (92.9%) presented with anemia (median hemoglobin, 9.6 g/dL). Ten patients (71.4%) had hypoalbuminemia (median, 2.7 g/dL). The most commonly involved site was the ileum (13/14, 92.9%). Manifestations of primary hypertrophic osteoarthropathy (PHO), such as digital clubbing, pachydermia, and periostosis were observed in five patients (28.6%) and two male patients and one female patient satisfied all major PHO diagnostic criteria. Conclusions The clinical and genetic characteristics of Korean patients with confirmed CEAS were similar to those reported in the literature. CEAS should be considered in the differential diagnosis for patients with unexplained chronic nonspecific ulcers of the small intestine.

A Novel Chronic Enteropathy Associated with SLCO2A1 Gene Mutation: Enterography Findings in a Multicenter Korean Registry

“…Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a recently recognized, rare, chronic enteropathy characterized by multiple ulcerations and strictures in the small bowel. It is caused by loss-of-function mutations in the SLCO2A1 gene [ 1 2 3 4 5 ]. Since the first report from Japan in 2015 [ 1 ], only a few dozen cases have been reported worldwide.…”

“…Since the first report from Japan in 2015 [ 1 ], only a few dozen cases have been reported worldwide. These cases were mostly from northeast Asia [ 2 3 4 5 6 7 ]. CEAS usually affects adolescents or middle-aged females and presents with abdominal pain associated with anemia and hypoalbuminemia [ 2 3 4 5 ].…”

“…These cases were mostly from northeast Asia [ 2 3 4 5 6 7 ]. CEAS usually affects adolescents or middle-aged females and presents with abdominal pain associated with anemia and hypoalbuminemia [ 2 3 4 5 ]. It predominantly involves the small bowel and often excludes the colorectal region [ 3 5 7 ].…”

“…It predominantly involves the small bowel and often excludes the colorectal region [ 3 5 7 ]. Studies on CEAS have focused on describing its clinical characteristics, including laboratory findings, genetic findings, and relationships with other diseases [ 2 3 4 5 ], with no published studies on the radiological findings/diagnosis of the disease. CEAS is frequently misdiagnosed as Crohn’s disease because of overlaps in clinical manifestations and unfamiliarity with CEAS owing to its novelty and rarity [ 1 3 ].…”

“…CEAS is frequently misdiagnosed as Crohn’s disease because of overlaps in clinical manifestations and unfamiliarity with CEAS owing to its novelty and rarity [ 1 3 ]. However, since it is intractable to medications for Crohn’s disease, recognizing the possibility of CEAS and recommending early diagnostic genetic testing are critical to avoid unmatched treatments [ 2 4 8 ].…”