HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Figure All Versions of this Article: EJE-09-0271v1 161/2/275    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Miao, Z. Articles by Shao, L. Search for Related Content PubMed PubMed Citation Articles by Miao, Z. Articles by Shao, L.

Coexistence of normotensive primary aldosteronism in two patients with Gitelman's syndrome and novel thiazide-sensitive Na–Cl cotransporter mutations

Divisions of¹ , Endocrinology and Metabolism² Nursing, Affiliated Hospital of Qingdao University School of Medicine, No. 16, Jiangsu Road, Qingdao 266003, People's Republic of China³ Department of Cell Physiology, Institute of Cellular Signalling, University Medical Center Nijmegen, Nijmegen 9101, The Netherlands⁴ Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA⁵ Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China⁶ Division of Nephrology, Affiliated Hospital of Qingdao University School of Medicine, No. 16, Jiangsu Road, Qingdao 266003, People's Republic of China

(Correspondence should be addressed to L Shao at Division of Nephrology, Affiliated Hospital of Qingdao University School of Medicine; Email: shaoleping{at}medmail.com.cn)

Background: Primary aldosteronism (PA) is the most common form of secondary hypertension, while Gitelman's syndrome (GS) is the most common inherited renal tubular disease. However, coexistence of these two diseases has never been previously reported.

Aim and subjects: The aim of our study was to describe the association of GS and PA in two unrelated patients and compare their clinical presentation with a group of patients with GS.

Methods: Ten subjects suspected to have only GS were assigned to the control group. Saline infusion test was used to confirm the diagnosis of PA. GS was confirmed by sequencing of the causal genes (SLC12A3 and CLCNKB) and functional analyses in Xenopus laevis oocytes.

Results: Confirmatory tests, gene analysis, and functional studies demonstrated the coexistence of GS and PA in both patients. In total, nine novel SLC12A3 gene variants, including seven missense mutations, one splice mutation, and one frameshift deletion, were found in 12 subjects. Four mutations (p.T60M, p.T304M, p.T465P, and p.N611T) harbored by the two patients with both PA and GS were revealed to be loss-of-function variants. Although both patients were normotensive, neither of them had normal nocturnal dip.

Conclusions: Two rare diseases GS and PA may occasionally coexist in one subject. In these patients, salt depletion and volume constriction might explain the absence of hypertension normally seen in PA patients. However, the protective mechanism against hypertension via down-regulation of renal sodium handling was probably not sufficient in those patients, since their normal circadian rhythm of blood pressure was disrupted.