Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease

J Gastroenterol. 2018 Aug;53(8):907-915. doi: 10.1007/s00535-017-1426-y. Epub 2018 Jan 8.

Abstract

Background: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations in the SLCO2A1 gene and characterized by multiple small intestinal ulcers of nonspecific histology. SLCO2A1 is also a causal gene of primary hypertrophic osteoarthropathy (PHO). However, little is known about the clinical features of CEAS or PHO.

Methods: Sixty-five Japanese patients recruited by a nationwide survey of CEAS during 2012-2016 were enrolled in this present study. We reviewed the clinical information of the genetically confirmed CEAS patients.

Results: We identified recessive SLCO2A1 mutations at 11 sites in 46 patients. Among the 46 patients genetically confirmed as CEAS, 13 were men and 33 were women. The median age at disease onset was 16.5 years, and parental consanguinity was present in 13 patients (28%). Anemia was present in 45 patients (98%), while a single patient experienced gross hematochezia. All patients showed relatively low inflammatory markers in blood tests (median CRP 0.20 mg/dl). The most frequently involved gastrointestinal site was the ileum (98%), although no patient had mucosal injuries in the terminal ileum. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.

Conclusions: The clinical features of CEAS are distinct from those of Crohn's disease. Genetic analysis of the SLCO2A1 gene is therefore recommended in patients clinically suspected of having CEAS.

Keywords: Chronic nonspecific multiple ulcers of the small intestine; Crohn’s disease; Pachydermoperiostosis; Primary hypertrophic osteoarthropathy; Prostaglandin transporter.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Anemia / complications
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Chronic Disease
  • Consanguinity
  • Crohn Disease / diagnosis
  • Diagnosis, Differential
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • Intestinal Diseases / blood
  • Intestinal Diseases / complications
  • Intestinal Diseases / diagnosis*
  • Intestinal Diseases / genetics*
  • Intestine, Small
  • Loss of Function Mutation
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Osteoarthropathy, Primary Hypertrophic / complications*
  • Sex Factors
  • Stomach Diseases / blood
  • Stomach Diseases / complications
  • Stomach Diseases / diagnosis
  • Stomach Diseases / genetics
  • Ulcer / blood
  • Ulcer / complications
  • Ulcer / diagnosis*
  • Ulcer / genetics*
  • Young Adult

Substances

  • Organic Anion Transporters
  • SLCO2A1 protein, human
  • C-Reactive Protein