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      A case of Gitelman syndrome: our experience with a patient treated in clinical practice on a local island

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          Abstract

          Background: Gitelman syndrome (GS) is an autosomal recessive salt-losing renal tubulopathy resulting from mutations in the thiazide-sensitive Na-Cl cotransporter ( NCC) gene. Notably, lack of awareness regarding GS and difficulty with prompt diagnosis are observed in clinical practice, particularly in rural settings.

          Case presentation: We report a case of a 48-year-old man with GS who presented to a local clinic on a remote island. Occasional laboratory investigations incidentally revealed a reduced serum potassium level of 2.6 mmol/L. A careful medical interview revealed episodes of intermittent paralysis of the lower extremities and muscular weakness for >30 years. Subsequent laboratory investigations revealed hypomagnesemia, hypocalciuria, and hypokalemic metabolic alkalosis. Based on the patient’s history, clinical presentation, and laboratory investigations, we suspected GS. Genetic testing revealed a rare homozygous in-frame 18 base insertion in the NCC gene that might have resulted from the founder effect, consequent to his topographically isolated circumstances.

          Conclusion: More case studies similar to our study need to be added to the literature to gain a deeper understanding of the functional consequences of this mutation and to establish optimal management strategies for this condition, particularly in rural clinical settings.

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          Most cited references33

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          Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

          Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
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            A new familial disorder characterized by hypokalemia and hypomagnesemia.

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              Spectrum of mutations in Gitelman syndrome.

              Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene. Copyright © 2011 by the American Society of Nephrology
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                Author and article information

                Journal
                J Rural Med
                J Rural Med
                JRM
                Journal of Rural Medicine : JRM
                The Japanese Association of Rural Medicine
                1880-487X
                1880-4888
                20 November 2019
                November 2019
                : 14
                : 2
                : 258-262
                Affiliations
                [1 ]Department of Clinical Oncology, Jichi Medical University, Japan
                [2 ]Setouchi-Cho Hekichi Clinic, Japan
                [3 ]Division of Nephrology, Department of Internal Medicine, Amami Central Hospital, Japan
                [4 ]Department of Nephrology, Tokyo Medical and Dental University, Japan
                [5 ]Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Japan
                Author notes
                Correspondence: Takashi Chinen, Department of Clinical Oncology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi 329-0498, Japan. E-mail: takashi.chinen@ 123456gmail.com
                Article
                3014
                10.2185/jrm.3014
                6877917
                e9d36d06-ebd3-4adb-81c9-590d8cfff0f9
                ©2019 The Japanese Association of Rural Medicine

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: http://creativecommons.org/licenses/by-nc-nd/4.0/ ).

                History
                : 07 March 2019
                : 31 May 2019
                Categories
                Case Report

                gitelman syndrome,thiazide-sensitive na-cl cotransporter,hypomagnesemia,hypokalemic metabolic alkalosis,proteinuria

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