Qin YZ, Liu YM, Wang Y, You C, Li LN, Zhou XY, Lv WM, Hong SH, Xiao LX. Novel compound heterozygous mutation of SLC12A3 in Gitelman syndrome co-existent with hyperthyroidism: A case report and literature review. World J Clin Cases 2022; 10(21): 7483-7494 [PMID: 36158002 DOI: 10.12998/wjcc.v10.i21.7483]
Corresponding Author of This Article
Li-Xia Xiao, MD, Associate Chief Physician, Department of Endocrinology, The First Affiliated Hospital of Gannan Medical University, No. 128 Jinling Road, Ganzhou 341000, Jiangxi Province, China. xlx981107@163.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Yong-Zhang Qin, Yang Wang, Xue-Yan Zhou, Wei-Min Lv, Shi-Hua Hong, Li-Xia Xiao, Department of Endocrinology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
Yan-Ming Liu, Department of Endocrinology, The First People’s Hospital of Nankang District, Ganzhou 341400, Jiangxi Province, China
Cong You, Long-Nian Li, Department of Dermatology and Venereology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
Author contributions: Qin YZ, Liu YM, and Wang Y contributed equally to this work; Qin YZ and Xiao LX contributed to the design and conception of the study; Wang Y, You C, Li LN, Zhou XY, and Lv WM contributed to data collection; Qin YZ and Liu YM contributed to writing the original draft; Hong SH and Xiao LX revised the manuscript; and all the authors approved the final version of the manuscript.
Supported bythe Science and Technology Plan of Health Commission of Jiangxi Province, No. 202130648; and the Science and Technology Research Project of Department of Education of Jiangxi Province, No. GJJ201522.
Informed consent statement: The present study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Gannan Medical University (Ethics Approval Number: LLSC-2021092201) in accordance with the tenets of the Declaration of Helsinki. The patient provided written informed consent for publication of this case report.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Xia Xiao, MD, Associate Chief Physician, Department of Endocrinology, The First Affiliated Hospital of Gannan Medical University, No. 128 Jinling Road, Ganzhou 341000, Jiangxi Province, China. xlx981107@163.com
Received: December 4, 2021 Peer-review started: December 4, 2021 First decision: January 25, 2022 Revised: January 27, 2022 Accepted: May 27, 2022 Article in press: May 27, 2022 Published online: July 26, 2022 Processing time: 219 Days and 0.3 Hours
Abstract
BACKGROUND
Gitelman syndrome (GS) is a rare inherited autosomal recessive tubulopathy, characterized clinically by hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis, and is caused by an inactivating mutation in SLC12A3. GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism. It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia, which is difficult to correct.
CASE SUMMARY
A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo. However, the patient’s serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism. GS was confirmed by whole exome and Sanger sequencing. Gene sequencing revealed compound heterozygous mutations of c.488C>T (p.Thr163Met), c.2612G>A (p.Arg871His), and c.1171_1178dupGCCACCAT (p.Ile393fs) in SLC12A3. Protein molecular modeling was performed to predict the effects of the identified missense mutations. All three mutations cause changes in protein structure and may result in abnormal protein function. All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.
CONCLUSION
We have identified a novel compound heterozygous mutation in SLC12A3. The present study provides new genetic evidence for GS.
Core Tip: In the present study, we report a patient with hyperthyroidism who was diagnosed with Gitelman syndrome (GS) through genome sequencing. We identified a novel compound heterozygous mutation in SLC12A3. Protein molecular modeling was performed to predict the effects of the identified missense mutations, which cause changes in protein structure and may result in abnormal protein function. All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.
