Background: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare hereditary disease caused by mutations in SLCO2A1 gene, encoding a prostaglandin transporter. CEAS resembles Crohn's disease (CD) in presenting multiple small intestinal ulcers. However, because immunosuppressive therapies such as corticosteroid and anti-tumor necrosis factor-alpha antibody therapies are ineffective for CEAS in contrast to CD, recognition and precise diagnosis of CEAS are critical to avoid unnecessary therapies.
Methods: Forty-one Japanese patients (10 male and 31 female) were diagnosed with CEAS by clinical findings and genetic analysis during a period of 2012 to 2016 and they were enrolled in this study. To identify the clinical features of CEAS, we reviewed the clinical information for the patients. In addition, because SLCO2A1 gene has also been reported as a causative gene of primary hypertrophic osteoarthropathy (PHO; OMIM 614441), we investigated whether CEAS patients had clinical manifestations of PHO.
Results: We found recessive SLCO2A1 mutations located at 11 sites. Among the identified SLCO2A1 mutations, a splice-site mutation of intron 7 (c.940+1G>A) was the most frequent, and 17 of the 41 patients were homozygous for this mutation (41%). Median age at onset was 17 (1 to 69) and parental consanguinity was present in 12 patients (29%). Anemia and abdominal pain were present in 40 (98%) and 16 (39%) patients, respectively. On the other hand, there were little inflammatory findings in blood tests (median CRP 0.16mg/dl). During the course of the disease, 27 patients (66%) had undergone one or more surgeries such as partial resection of the small intestine. The most frequently involved gastrointestinal site was ileum (98%), but there was no patient with ulcerations in the terminal ileum. The stomach and duodenum were affected in 11 (27%) and 18 (44%) patients, respectively. Although no patients had clinical manifestations of PHO that required treatment, mild digital clubbing or periostosis was present in 12 patients (29%). Moreover, 4 male patients fulfilled the major clinical criteria for PHO, having digital clubbing, periostosis, and pachydermia.
Conclusions: Although CEAS mimics CD, some clinical features of CEAS are different from those of CD, such as low inflammatory findings, terminal ileum-sparing ulcerations and extraintestinal manifestations. Genetic analysis should be considered if CEAS is clinically suspected.