Novel SLCO2A1compound heterozygous mutation causing primary hypertrophic osteoarthropathy with Bartter-like hypokalemia in a Chinese family
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Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia.
Clinical manifestations were collected and genetic analyses were performed in the PHO family.
The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family.
The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.
KeywordsPrimary hypertrophic osteoarthropathy Prostaglandin E2 Hypokalemia SLCO2A1 Gene mutation
The authors thank the patients for their involvements in this study. This study was supported by the National Natural Science Foundation of China (No. 81670714), the Beijing Natural Science Foundation (No. 7121012), the Scientific Research Foundation of Beijing Medical Development (No. 2007-3029), National Key Program of Clinical Science (WBYZ2011-873), and the CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-3-003), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Nos. 2017PT32020, 2018PT32001), Clinical Research Fund for Endocrine Disease Research Project of Chinese Medical Association (No. 13050790464) and Youth Fund of Peking Union Medical College Hospital (No. 2013019).
Compliance with ethical standards
Conflict of interest
All authors state that they have no conflicts of interest.
This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of Ethics Committee of PUMCH and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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