ISSN: 1859 - 2872
Gitelman syndrome caused by a rare homozygous mutation in the SLC12A3 gene: A case report
Main Article Content
Keywords
Gitelman syndrome, hypokalemia, SLC12A3 gene
Abstract
Gitelman syndrome is a rare hereditary renal tubular disease characterized by hypokalemic metabolic alkalosis with significant hypomagnesemia and low urinary calcium excretion. The disease is caused by biallelic inactivating mutations in the SLC12A3 gene, which encodes NaCl cotransporters and magnesium in the thiazide-sensitive segment of the distal tubule. We reported a clinical case of a 31-year-old male patient diagnosed with Gilteman syndrome by genetic testing, a mutation in the SLC12A3 gene at position NM_001126108.2: c.1145C>T, homozygous mutation. Although this mutation is still controversial, with clinically relevant evidence, bioinformatics tools, and reports from previous authors, we support reclassifying this mutation from a form of uncertainty to the group of pathogenic mutations. Treatments with potassium and magnesium replacement and mineralocorticoid receptor antagonist supplements bring remarkable results to patients.
Article Details
References
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3. Bettinelli A, Bianchetti MG, Girardin E et al (1992) Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. The Journal of Pediatrics. 120(1): 38-43. doi:10.1016/S0022-3476(05)80594-3.
4. Knoers NV, Levtchenko EN (2008) Gitelman syndrome. Orphanet J Rare Dis 3:22. doi: 10.1186/1750-1172-3-22.
5. Blanchard A, Bockenhauer D, Bolignano D et al (2017) Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International. 91(1): 24-33. doi:10.1016/j.kint.2016.09.046.
6. Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB, Yale Gitelman’s and Bartter’s Syndrome Collaborative Study Group (2002) Gitelman’s syndrome revisited: An evaluation of symptoms and health-related quality of life. Kidney Int 59(2): 710-717. doi:10.1046/j.1523-1755.2001.059002710.x.
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8. Tammaro F, Bettinelli A, Cattarelli D, Cavazza A, Colombo C, Syrén ML, Tedeschi S, Bianchetti MG (2010) Early appearance of hypokalemia in Gitelman syndrome. Pediatric nephrology (Berlin, Germany) 25(10):2179-2182. doi: 10.1007/s00467-010-1575-1.
9. Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C (2010) Gitelman syndrome: pathophysiological and clinical aspects*. QJM: An International Journal of Medicine 103(10):741-748. doi:10.1093/qjmed/hcq123.
10. Cheng CJ, Shiang JC, Hsu YJ, Yang SS, Lin SH (2007) Hypocalciuria in patients with Gitelman syndrome: Role of blood volume. Am J Kidney Dis 49(5): 693-700. doi:10.1053/j.ajkd.2007.02.267.
11. Voets T, Nilius B, Hoefs S et al (2004) TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 279(1): 19-25. doi:10.1074/jbc.M311201200.
12. Diaz G (2021) Gitelman Syndrome Pathophysiology Gitelman Syndrome GrepMed. June 23, 2021. Accessed October 6, 2024. https://grepmed.com/images/13188/pathophysiology-nephrology-gitelman-syndrome-diagnosis.
13. Takeuchi Y, Mishima E, Shima H, Akiyama Y, Suzuki C, Suzuki T, Kobayashi T, Suzuki Y, Nakayama T, Takeshima Y, Vazquez N, Ito S, Gamba G, Abe T (2014) Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome. J Am Soc Nephrol 26(2): 271-279. doi: 10.1681/ASN.2013091013.
14. Balavoine AS, Bataille P, Vanhille P et al (2011) Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome. Eur J Endocrinol 165(4): 665-673. doi:10.1530/EJE-11-0224.
15. Luo JW, Meng XR, Yang X, Liang JX, Hong FY, Zheng XY, Li WH (2017) Analysis of mutations of two Gitelman syndrome family SLC12A3 genes and proposed treatments using Chinese medicine. Chin J Integr Med 23(6):461-468. doi:10.1007/s11655-016-2461-x.
16. Baldane S, Ipekci SH, Celik S, Gundogdu A, Kebapcilar L (2015) Hypokalemic paralysis due to thyrotoxicosis accompanied by Gitelman’s syndrome. Indian J Nephrol 25(2): 103-105. doi:10.4103/0971-4065.140719.
17. Berry MR, Robinson C, Karet Frankl FE (2013) Unexpected clinical sequelae of Gitelman syndrome: hypertension in adulthood is common and females have higher potassium requirements. Nephrol Dial Transplant. 28(6):1533-1542. doi:10.1093/ndt/gfs600.
18. Zeng Y, Li P, Fang S, et al (2019) Genetic Analysis of SLC12A3 Gene in Chinese Patients with Gitelman Syndrome. Med Sci Monit 25: 5942-5952. doi:10.12659/MSM.916069.
19. Ji W, Foo JN, O’Roak BJ et al (2008) Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 40(5):592-599. doi:10.1038/ng.118.
20. Gallagher H, Soar J, Tomson C (2016) New guideline for perioperative management of people with inherited salt-wasting alkaloses. Br J Anaesth 116(6): 746-749. doi:10.1093/bja/aew102.
21. Larkins N, Wallis M, McGillivray B, Mammen C (2014) A severe phenotype of Gitelman syndrome with increased prostaglandin excretion and favorable response to indomethacin. Clin Kidney J 7(3): 306-310. doi:10.1093/ckj/sfu029.
22. Brambilla G, Perotti M, Perra S, Dell’Oro R, Grassi G, Pincelli AI (2013) It is never too late for a genetic disease: a case of a 79-year-old man with persistent hypokalemia. J Nephrol 26(3): 594-598. doi:10.5301/jn.5000256.
2. Kardalas E, Paschou SA, Anagnostis P, Muscogiuri G, Siasos G, Vryonidou A (2018) 2018 Hypokalemia: a clinical update. Endocr Connect 7(4): 135-146. doi:10.1530/EC-18-0109.
3. Bettinelli A, Bianchetti MG, Girardin E et al (1992) Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. The Journal of Pediatrics. 120(1): 38-43. doi:10.1016/S0022-3476(05)80594-3.
4. Knoers NV, Levtchenko EN (2008) Gitelman syndrome. Orphanet J Rare Dis 3:22. doi: 10.1186/1750-1172-3-22.
5. Blanchard A, Bockenhauer D, Bolignano D et al (2017) Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International. 91(1): 24-33. doi:10.1016/j.kint.2016.09.046.
6. Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB, Yale Gitelman’s and Bartter’s Syndrome Collaborative Study Group (2002) Gitelman’s syndrome revisited: An evaluation of symptoms and health-related quality of life. Kidney Int 59(2): 710-717. doi:10.1046/j.1523-1755.2001.059002710.x.
7. Parmar MS, Muppidi V, Bashir K (2024) Gitelman Syndrome. In: StatPearls. StatPearls Publishing; 2024. Accessed October 6, 2024. http://www.ncbi.nlm.nih.gov/books/NBK459304/.
8. Tammaro F, Bettinelli A, Cattarelli D, Cavazza A, Colombo C, Syrén ML, Tedeschi S, Bianchetti MG (2010) Early appearance of hypokalemia in Gitelman syndrome. Pediatric nephrology (Berlin, Germany) 25(10):2179-2182. doi: 10.1007/s00467-010-1575-1.
9. Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C (2010) Gitelman syndrome: pathophysiological and clinical aspects*. QJM: An International Journal of Medicine 103(10):741-748. doi:10.1093/qjmed/hcq123.
10. Cheng CJ, Shiang JC, Hsu YJ, Yang SS, Lin SH (2007) Hypocalciuria in patients with Gitelman syndrome: Role of blood volume. Am J Kidney Dis 49(5): 693-700. doi:10.1053/j.ajkd.2007.02.267.
11. Voets T, Nilius B, Hoefs S et al (2004) TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 279(1): 19-25. doi:10.1074/jbc.M311201200.
12. Diaz G (2021) Gitelman Syndrome Pathophysiology Gitelman Syndrome GrepMed. June 23, 2021. Accessed October 6, 2024. https://grepmed.com/images/13188/pathophysiology-nephrology-gitelman-syndrome-diagnosis.
13. Takeuchi Y, Mishima E, Shima H, Akiyama Y, Suzuki C, Suzuki T, Kobayashi T, Suzuki Y, Nakayama T, Takeshima Y, Vazquez N, Ito S, Gamba G, Abe T (2014) Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome. J Am Soc Nephrol 26(2): 271-279. doi: 10.1681/ASN.2013091013.
14. Balavoine AS, Bataille P, Vanhille P et al (2011) Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome. Eur J Endocrinol 165(4): 665-673. doi:10.1530/EJE-11-0224.
15. Luo JW, Meng XR, Yang X, Liang JX, Hong FY, Zheng XY, Li WH (2017) Analysis of mutations of two Gitelman syndrome family SLC12A3 genes and proposed treatments using Chinese medicine. Chin J Integr Med 23(6):461-468. doi:10.1007/s11655-016-2461-x.
16. Baldane S, Ipekci SH, Celik S, Gundogdu A, Kebapcilar L (2015) Hypokalemic paralysis due to thyrotoxicosis accompanied by Gitelman’s syndrome. Indian J Nephrol 25(2): 103-105. doi:10.4103/0971-4065.140719.
17. Berry MR, Robinson C, Karet Frankl FE (2013) Unexpected clinical sequelae of Gitelman syndrome: hypertension in adulthood is common and females have higher potassium requirements. Nephrol Dial Transplant. 28(6):1533-1542. doi:10.1093/ndt/gfs600.
18. Zeng Y, Li P, Fang S, et al (2019) Genetic Analysis of SLC12A3 Gene in Chinese Patients with Gitelman Syndrome. Med Sci Monit 25: 5942-5952. doi:10.12659/MSM.916069.
19. Ji W, Foo JN, O’Roak BJ et al (2008) Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 40(5):592-599. doi:10.1038/ng.118.
20. Gallagher H, Soar J, Tomson C (2016) New guideline for perioperative management of people with inherited salt-wasting alkaloses. Br J Anaesth 116(6): 746-749. doi:10.1093/bja/aew102.
21. Larkins N, Wallis M, McGillivray B, Mammen C (2014) A severe phenotype of Gitelman syndrome with increased prostaglandin excretion and favorable response to indomethacin. Clin Kidney J 7(3): 306-310. doi:10.1093/ckj/sfu029.
22. Brambilla G, Perotti M, Perra S, Dell’Oro R, Grassi G, Pincelli AI (2013) It is never too late for a genetic disease: a case of a 79-year-old man with persistent hypokalemia. J Nephrol 26(3): 594-598. doi:10.5301/jn.5000256.
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Published
Dec 30, 2024
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How to Cite
QuỳnhL. T., ThắngL. M., NhànL. B., ThuýN. T., LoanV. T., NhungP. T. H., MạnhN. V., LinhN. T. T., HàL. T., & PhượngN. T. (2024). Gitelman syndrome caused by a rare homozygous mutation in the SLC12A3 gene: A case report. Tạp Chí Y Dược lâm sàng 108, 19(8). https://doi.org/10.52389/ydls.v19i8.2485