Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization.

CONTEXT: We previously demonstrated that deficiency of the prostaglandin transporter (SLCO2A1) is a cause of primary hypertrophic osteoarthropathy (PHO). However, its clinical and metabolic characteristics have not been well defined.

OBJECTIVE: The objective of the study was to expand this mutational spectrum to better delineate the SLCO2A1 deficiency phenotype and investigate the clinical and metabolic characteristics of a cohort of subjects with PHO.

DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURE: Eleven affected individuals and their available healthy family members from 9 unrelated Chinese families with PHO (7 of which were previously undescribed) were clinically studied. The SLCO2A1 gene was screened and analyzed. Urinary levels of prostaglandin E₂ (PGE₂) and prostaglandin E metabolite (PGE-M) were measured using competitive ELISAs. The serum levels of total T, estradiol, sex hormone-binding protein, LH, FSH, and fasting gastrin were detected.

RESULTS: Nine different SLCO2A1 mutations were identified in affected individuals in the 7 previously undescribed families, 7 of which (Glu165X, Ala286GlnfsX35, Gln356AlafsX77, Gly369Asp, Gly379Glu, Glu465Lys, and c.861+2T>C) were novel. The urinary levels of PGE₂ and PGE-M were much higher in the SLCO2A1-deficient individuals and decreased with age. There was no relationship between sex hormones and PGE₂ or PGE-M. There was no significant difference in the levels of fasting serum gastrin between PHO patients with watery diarrhea and their relatives.

CONCLUSIONS: The present findings broaden the allelic spectrum of SLCO2A1 mutations. The urinary levels of PGE₂ and PGE-M in the SLCO2A1-deficient individuals decreased with age. The measurement of the excreted PGE₂ and PGE-M may have implications in the differential diagnosis, treatment, and follow-up of PHO.