Available online 13 November 2022

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare disorder characterized by multiple small intestine ulcers. Patients with CEAS typically present with chronic anemia and gastrointestinal bleeding. Besides CEAS, SLCO2A1 mutations cause primary hypertrophic osteoarthropathy (PHO) which is considered as an extraintestinal manifestation in CEAS patients. Since CEAS and Crohn’s disease are clinically indistinguishable, patients are often misdiagnosed with Crohn’s disease. Herein, we describe a 4-year-old Turkish girl with CEAS due to homozygous pathogenic variant (c.656C > T) in SLCO2A1 with concomitant hereditary fructose intolerance (HFI) caused by homozygous pathogenic variant (c.1005C > G) in ALDOB. Prompt restriction of fructose, sucrose and sorbitol resulted in hepatomegaly regression and mild amelioration of patient’s symptoms. Despite budesonide and azathioprine treatments, patient’s protein losing enteropathy and chronic anemia did not improve. Although previous CEAS cases were reported from East Asian countries, it is likely to occur in people from other geographic areas. CEAS seems to be underdiagnosed and high index of suspicion is required for the diagnosis of this rare entity. Patients with prior diagnosis of Crohn’s disease with no response to immunosuppressive treatment or anti-TNF therapy should be re-evaluated for possible CEAS diagnosis.

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare autosomal recessive clinical entity caused by loss of function mutations in solute carrier organic anion transporter family member 2A1 (SLCO2A1) [1]. CEAS, first described as ‘’chronic nonspecific multiple ulcers of the small intestine (CNSU)’’ in 1968, is characterized by multiple small intestine ulcers presenting as chronic anemia and gastrointestinal bleeding. Patients typically present with diarrhea, abdominal pain, and weight loss, thus most commonly misdiagnosed as Crohn’s disease [2]. Age of CEAS onset varies widely from 1 to 69 years with a mean onset in adolescence. The majority of CEAS cases reported previously were from Asian countries like Japan, Korea, and China.

SLCO2A1 encodes for the transmembrane prostaglandin transporter which mediates prostaglandins reuptake into cells where they get degraded by cytoplasmic 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Functional impairment of prostaglandin transporter results in systemic PGE2 levels elevation [3], [4]. Although prostaglandin E2 has protective effects on mucosa via prostaglandin receptor EP3/EP4 pathway, elevated levels result in multiple mucosal ulcers in CEAS patients [5]. Mutations in SLCO2A1 have been reported in cases of primary hypertrophic osteoarthropathy (PHO), thus CEAS patients may present with PHO features like digital clubbing, periostosis or pachyderma. SLCO2A1 mutations associated with chronic enteropathy show female predominance while those associated with PHO are more predominant in males [1].

Herein, we report a 4-year-old Turkish girl with CEAS and concomitant hereditary fructose intolerance (HFI). The coincidence of these two rare disorders has not been reported before. To the best of our knowledge, this is the first CEAS report from Europe.

A 4-year-old girl who was the second child born with a birthweight of 3325 g by term caesarean section to first degree consanguineous parents. She received breast milk for the first two years of life while complementary foods were started at the age of 4 months. Medical history revealed recurrent vomiting episodes after initiation of complementary foods. Her developmental milestones were normal.

At the age of 10 months, the patient developed diarrhea, intermittent bloody stool and abdominal

Prostaglandin-associated enteropathy is a clinicopathological term of many disorders characterized by impaired prostaglandin homeostasis including CEAS, cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), and NSAID-induced enteropathy. Capsule endoscopy and balloon-assisted enteroscopy enable endoscopic evaluation of small intestine ulcers. CEAS is characterized by multiple asymmetric circular or oblique ulcers that are restricted to the mucosa or the submucosa with clear margins [6].

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This study was conducted in accordance with the Decleration of Helsinki. A written informed consent for publication was provided by patient’s parents on her last visit. Ethical approval was waived by ethics committee as our report does not include patient’s images or personal information. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Both Utku Dönger and Khaled Warasnhe contributed equally to the manuscript.

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© 2022 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.