Abstract Background Chronic enteropathy associated with SLCO2A1 variants (CEAS) is a rare, autosomal recessive disorder marked by early-onset iron deficiency anaemia, hypoalbuminaemia, and chronic protein-losing enteropathy. These clinical symptoms are accompanied by superficial annular ulcers limited to the small bowel. SLCO2A1 encodes the transmembrane protein OATP2A1, which facilitates prostaglandin E2 (PGE2) transport and clearance. Mutations result in diminished PGE2 uptake, leading to elevated circulating levels that disrupt epithelial integrity and trigger ulceration. We describe a 28-year-old woman with consanguineous parents, presenting in childhood with refractory iron-deficiency anaemia and severe hypoalbuminaemia. Endoscopy and cross-sectional imaging revealed multiple stricturing, circumferential small bowel ulcers resembling Crohn’s disease. In August 2025, she suffered a severe relapse, requiring admission for supportive care and assessment of profound hypoalbuminaemia. Serum albumin was 9 g/L, and gross oedema was present to the waist. Therapeutic interventions included corticosteroids and anti-TNF immunosuppression, alongside supportive care with iron and human albumin infusions. Corticosteroids induced only transient remission, while anti-TNF therapy yielded marginal benefit, with drug levels difficult to maintain due to hypoalbuminaemia and protein loss. Supportive care stabilised the patient and allowed her to return to work, but inflammatory remission has not been sustained. Methods Due to the critical presentation, urgent singleton whole genome sequencing was undertaken (R14 test indication, via the NHS South West genomic laboratory hub). Results Singleton whole genome sequencing on DNA extracted from blood revealed homozygosity for a novel SLCO2A1 NM₀05630. 3 splice donor site variant of uncertain significance, c. 625 + 5GA. To further characterise this, peripheral blood mRNA sequencing was undertaken, demonstrating an in-frame deletion of 76 amino acids: r. 398₆25del, corresponding to exclusion of Exon 4 and predicting p. (Gly133Ser209delinsAla). This was confirmed to be due to SLCO2A1 c. 625 + 5GA. Loss of function of the protein would be predicted, which could be consistent with a severe protein-losing enteropathy phenotype. Conclusion Early genetic testing is essential for diagnosing CEAS, enabling tailored management. Broad access to genomic diagnostics, as provided by the NHS genomic test directory, is crucial for identification of monogenic causes of early-onset enteropathy and for optimising patient outcomes. Conflict of interest: Al-Hakim, Bahij: No conflict of interest Burkitt Wright, Emma: No conflict of interest Head, Nicholas: No conflict of interest Dr. Burkitt, Michael David: No conflict of interest
Al-Hakim et al. (Thu,) studied this question.