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Kelainan elektrolit berulang pada pasien dengan kecurigaan Sindrom Gitelman



Abstract

Pendahuluan: Sindrom Gitelman merupakan tubulopati yang terjadi akibat mutasi pada gen Solute Carrier Family 12 Member 3 (SLC12A3), yang mengkode thiazide-sensitive natrium chloride co-transporter (NCCT) pada membran apikal sel tubulus distal. Sindrom ini bersifat autosomal resesif yang ditandai dengan hipokalemia, alkalosis metabolik, hipomagnesemia, dan hipokalsiuria. Gejala yang sering muncul adalah kram dan kelemahan mulai dari keterbatasan aktivitas ringan hingga berat.

Laporan kasus: Laki-laki usia 19 tahun datang dengan keluhan lemas disertai kaku otot seluruh anggota gerak dan leher, mual, muntah, nyeri kepala, dan nyeri ulu hati. Pasien memiliki riwayat rawat inap tiga kali dengan keluhan serupa. Pada pemeriksaan fisik ditemukan tanda vital dalam batas normal, serta adanya tanda Chvostek. Pemeriksaan darah lengkap dalam batas normal. Pemeriksaan elektrolit menunjukan kadar natrium 118 mmol/L, kalium 2,16 mmol/L, dan klorida 74 mmol/L. Pasien sudah berulang kali melakukan pemeriksaan elektrolit dengan hasil hipokalemia. Delapan bulan sebelumnya, pasien dirawat akibat penurunan kesadaran dengan gambaran alkalosis metabolik, hipokalemia (2,59 mmol/L), hipomagnesemia (0,76 mg/dL) dan hipokalsemia (8,2 mg/dL). Pemeriksaan fungsi ginjal, urinalisis, dan elektrokardiografi dalam batas normal. Berdasarkan keluhan, riwayat penyakit, dan pemeriksaan penunjang berupa hipokalemia berulang, alkalosis metabolik, dan hipomagnesemia, maka dicurigai suatu Sindrom Gitelman. Pasien diterapi dengan kalium klorida (KCl) intravena 50 mEq dalam natrium klorida (NaCl) 0,9% 500 cc dengan laju 20 tetes per menit, tablet KCl 600 mg tiap 8 jam, kapsul garam dapur 500 mg tiap 12 jam, omeprazole serta ondansetron intravena sesuai keluhan. Pasien dirawat inap satu hari dan dipulangkan setelah kadar kalium terkoreksi (3,1 mmol/L) dan keadaan klinis membaik. Pemeriksaan analisis DNA untuk penegakan diagnosis tidak dilakukan karena keterbatasan fasilitas dan biaya.

Kesimpulan: Sindrom Gitelman merupakan tubulopati yang bersifat autosomal resesif ditandai dengan hipokalemia, alkalosis metabolik, hipomagnesemia, dan hipokalsiuria. Tatalaksana sindrom ini tergantung pada klinis dan gangguan laboratorium. Suplemen natrium, kalium, dan magnesium merupakan terapi yang paling sering dibutuhkan.

 

Introduction: Gitelman syndrome is a tubulopathy that occurs due to mutations in the Solute Carrier Family 12 Member 3 (SLC12A3) gene, which encodes thiazide-sensitive sodium chloride co-transporter (NCCT) in the apical membrane of distal tubule cells. This autosomal recessive syndrome characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalsiuria. Common symptoms are cramps and weakness ranging from mild to severe limitation of activity.

Case Report: a 19 years-old-man present a general weakness accompanied by muscle stiffness throughout the limbs and neck, nausea, vomiting, headache, and heartburn. The patient had a history of hospitalization three times with similar complaints. Normal vital signs and Chvostek's sign were found on physical examination. Complete blood count was within normal limits. Electrolyte examination showed sodium 118 mmol/L, potassium 2.16 mmol/L, and chloride 74 mmol/L. The patient had repeated episode of hypokalemia. In the previous eight months, he was admitted due to decreased of consciousness with metabolic alkalosis, hypokalemia (2.59 mmol/L), hypomagnesemia (0.76 mg/dL) and hypocalcemia (8.2 mg/dL). Kidney function, urinalysis, and electrocardiography within normal limits. Based on complaints, medical history, and the results of investigations a Gitelman syndrome was suspected. The patient was treated with 50 mEq intravenous KCL in 500cc NaCl 0,9% at a rate of 20 drops per minute, 600 mg KCl tablets every 8 hours, 500 mg table salt capsules every 12 hours, intravenous omeprazole and ondansetron as needed. The patient discharged after the potassium level was corrected (3.1 mmol/L) and improved clinical condition. Follow-up examination in the form of DNA analysis was not carried out due to limited facilities and funding.

Conclusion: Gitelman syndrome is an autosomal recessive tubulopathy characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. Management of this syndrome in accordance with clinical and laboratory abnormalities that occur. The most frequently needed therapy are sodium, potassium, and magnesium supplement.

Keywords: Gitelman syndrome hypokalemia hypomagnecemia metabolic alkalosis

References

  1. Van der Merwe PDT, Rensburg MA, Haylett WL, Bardien S, Davids MR. Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings. BMC Nephrol. 2017;18(1):38–38. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/28125972
  2. Blanchard A, Bockenhauer D, Bolignano D, Calò LA, Cosyns E, Devuyst O, et al. Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International. 2017;91(1):24–33. Diakses pada: http://dx.doi.org/10.1016/j.kint.2016.09.046
  3. Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C. Gitelman syndrome: pathophysiological and clinical aspects. QJM. 2010;103(10):741–8. Diakses pada: http://dx.doi.org/10.1093/qjmed/hcq123
  4. Hsu Y-J, Yang S-S, Chu N-F, Sytwu H-K, Cheng C-J, Lin S-H. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure. Nephrology Dialysis Transplantation. 2008;24(4):1170–5. Diakses pada: http://dx.doi.org/10.1093/ndt/gfn619
  5. Riveira-Munoz E, Chang Q, Godefroid N, Hoenderop JG, Bindels RJ, Dahan K, et al. Transcriptional and Functional Analyses ofSLC12A3Mutations: New Clues for the Pathogenesis of Gitelman Syndrome. Journal of the American Society of Nephrology. 2007;18(4):1271–83. Diakses pada: http://dx.doi.org/10.1681/asn.2006101095
  6. Knoers NVAM, Levtchenko EN. Gitelman syndrome. Orphanet J Rare Dis. 2008;3:22–22. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/18667063
  7. de Jong JC, Van der Vliet WA, Van den Heuvel LPWJ, Willems PHGM, Knoers NVAM, Bindels RJM. Functional Expression of Mutations in the Human NaCl Cotransporter: Evidence for Impaired Routing Mechanisms in Gitelman’s Syndrome. Journal of the American Society of Nephrology. 2002;13(6):1442–8. Diakses pada: http://dx.doi.org/10.1097/01.asn.0000017904.77985.03
  8. Simon DB, Nelson-Williams C, Johnson Bia M, Ellison D, Karet FE, Morey Molina A, et al. Gitelman’s variant of Barter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na–Cl cotransporter. Nature Genetics. 1996;12(1):24–30. Diakses pada: http://dx.doi.org/10.1038/ng0196-24
  9. Takeuchi Y, Mishima E, Shima H, Akiyama Y, Suzuki C, Suzuki T, et al. Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome. J Am Soc Nephrol. 2014/07/24 ed. 2015;26(2):271–9. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/25060058
  10. Vargas-Poussou R, Dahan K, Kahila D, Venisse A, Riveira-Munoz E, Debaix H, et al. Spectrum of mutations in Gitelman syndrome. J Am Soc Nephrol. 2011/03/17 ed. 2011;22(4):693–703. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/21415153
  11. Lin S-H, Shiang J-C, Huang C-C, Yang S-S, Hsu Y-J, Cheng C-J. Phenotype and Genotype Analysis in Chinese Patients with Gitelman’s Syndrome. The Journal of Clinical Endocrinology & Metabolism. 2005;90(5):2500–7. Diakses pada: http://dx.doi.org/10.1210/jc.2004-1905
  12. Santos F, Gil-Peña H, Blázquez C, Coto E. Gitelman syndrome: a review of clinical features, genetic diagnosis and therapeutic management. Expert Opinion on Orphan Drugs. 2016;4(10):1005–9. Diakses pada: http://dx.doi.org/10.1080/21678707.2016.1223542
  13. Tavira B, Gómez J, Santos F, Gil H, Alvarez V, Coto E. A labor- and cost-effective non-optical semiconductor (Ion Torrent) next-generation sequencing of the SLC12A3 and CLCNKA/B genes in Gitelman’s syndrome patients. Journal of Human Genetics. 2014;59(7):376–80. Diakses pada: http://dx.doi.org/10.1038/jhg.2014.37
  14. Mejía N, Santos F, Claverie-Martín F, García-Nieto V, Ariceta G, Castaño L. RenalTube: a network tool for clinical and genetic diagnosis of primary tubulopathies. European Journal of Pediatrics. 2013;172(6):775–80. Diakses pada: http://dx.doi.org/10.1007/s00431-013-1934-6
  15. Dimitri V, Priyono D. Jurnal Kesehatan Andalas. 2019; 8(4) Gitelman Syndrome. Jurnal Kesehatan Andalas. 2020;8(4). Diakses pada: http://dx.doi.org/10.25077/jka.v8i4.1122
  16. Rose BD, Post T. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5th ed. New York: McGraw-Hill Education; 2001. 1008 p.
  17. Pachulski RT, Lopez F, Sharaf R. Gitelman’s Not-So-Benign Syndrome. New England Journal of Medicine. 2005;353(8):850–1. Diakses pada: http://dx.doi.org/10.1056/nejmc051040
  18. Peters M, Jeck N, Reinalter S, Leonhardt A, Tönshoff B, Klaus G ünter, et al. Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. The American Journal of Medicine. 2002;112(3):183–90. Diakses pada: http://dx.doi.org/10.1016/s0002-9343(01)01086-5
  19. Tang NLS, Hui J, To KF, Ng HK, Hjelm NM, Fok TF. Severe hypokalemic myopathy in Gitelman’s syndrome. Muscle & Nerve. 1999;22(4):545–7. Diakses pada: http://dx.doi.org/10.1002/(sici)1097-4598(199904)22:4<545::aid-mus25>3.0.co;2-w
  20. Cheng N-L, Kao M-C, Hsu Y-D, Lin S-H. Novel thiazide-sensitive Na-Cl cotransporter mutation in a Chinese patient with Gitelman’s syndrome presenting as hypokalaemic paralysis. Nephrology Dialysis Transplantation. 2003;18(5):1005–8. Diakses pada: http://dx.doi.org/10.1093/ndt/gfg073
  21. El Beltagi A, Norbash A, Vattoth S. Novel brain MRI abnormalities in Gitelman syndrome. Neuroradiol J. 2015/10/06 ed. 2015;28(5):523–8. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/26443301
  22. Ji W, Foo JN, O’Roak BJ, Zhao H, Larson MG, Simon DB, et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet. 2008/04/06 ed. 2008;40(5):592–9. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/18391953
  23. Fujimura J, Nozu K, Yamamura T, Minamikawa S, Nakanishi K, Horinouchi T, et al. Clinical and Genetic Characteristics in Patients With Gitelman Syndrome. Kidney Int Rep. 2018;4(1):119–25. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/30596175
  24. Nakhoul F, Nakhoul N, Dorman E, Berger L, Skorecki K, Magen D. Gitelman’s syndrome: a pathophysiological and clinical update. Endocrine. 2011;41(1):53–7. Diakses pada: http://dx.doi.org/10.1007/s12020-011-9556-0
  25. Berry MR, Robinson C, Karet Frankl FE. Unexpected clinical sequelae of Gitelman syndrome: hypertension in adulthood is common and females have higher potassium requirements. Nephrol Dial Transplant. 2013/01/17 ed. 2013;28(6):1533–42. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/23328711
  26. Fukuyama S, Hiramatsu M, Akagi M, Higa M, Ohta T. Novel Mutations of the Chloride Channel Kb Gene in Two Japanese Patients Clinically Diagnosed as Bartter Syndrome with Hypocalciuria. The Journal of Clinical Endocrinology & Metabolism. 2004;89(11):5847–50. Diakses pada: http://dx.doi.org/10.1210/jc.2004-0775
  27. Zelikovic I, Szargel R, Hawash A, Labay V, Hatib I, Cohen N, et al. A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes. Kidney International. 2003;63(1):24–32. Diakses pada: http://dx.doi.org/10.1046/j.1523-1755.2003.00730.x
  28. Barathidasan GS, Krishnamurthy S, Karunakar P, Rajendran R, Ramya K, Dhandapany G, et al. Systemic lupus erythematosus complicated by a Gitelman-like syndrome in an 8-year-old girl. CEN Case Rep. 2019;9(2):129–32. Diakses pada: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148407/
  29. Saxena R, Mahajan T, Mohan C. Lupus nephritis: current update. Arthritis Res Ther. 2011;13(5):240. Diakses pada: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308062/
  30. Hsieh S-C, Tsai C-Y, Yu C-L. Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems. OARRR. 2016;8:81–91. Diakses pada: https://www.dovepress.com/potential-serum-and-urine-biomarkers-in-patients-with-lupus-nephritis--peer-reviewed-fulltext-article-OARRR
  31. Cavanaugh C, Perazella MA. Urine Sediment Examination in the Diagnosis and Management of Kidney Disease: Core Curriculum 2019. American Journal of Kidney Diseases. 2019;73(2):258–72. Diakses pada: https://www.ajkd.org/article/S0272-6386(18)30873-4/abstract
  32. Gitelman Syndrome Collaborative Study Group. Expert consensus for the diagnosis and treatment of patients with Gitelman syndrome. Zhonghua Nei Ke Za Zhi. 2017;56(9):712–6. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/28870047/
  33. Huang C-L, Kuo E. Mechanism of Hypokalemia in Magnesium Deficiency. Journal of the American Society of Nephrology. 2007;18(10):2649–52. Diakses pada: http://dx.doi.org/10.1681/asn.2007070792
  34. Ranade VV, Somberg JC. Bioavailability and Pharmacokinetics of Magnesium After Administration of Magnesium Salts to Humans. American Journal of Therapeutics. 2001;8(5):345–57. Diakses pada: http://dx.doi.org/10.1097/00045391-200109000-00008
  35. Kim G-H, Han JS. Therapeutic Approach to Hypokalemia. Nephron. 2002;92(1):28–32. Diakses pada: http://dx.doi.org/10.1159/000065374
  36. Phillips DR, Ahmad KI, Waller SJ, Meisner P, Karet FE. A serum potassium level above 10 mmol/l in a patient predisposed to hypokalemia. Nature Clinical Practice Nephrology. 2006;2(6):340–6. Diakses pada: http://dx.doi.org/10.1038/ncpneph0201
  37. AGUS ZS. Hypomagnesemia. Journal of the American Society of Nephrology. 1999;10(7):1616–22. Diakses pada: http://dx.doi.org/10.1681/asn.v1071616
  38. Knoers NVAM. Gitelman Syndrome. Advances in Chronic Kidney Disease. 2006;13(2):148–54. Diakses pada: http://dx.doi.org/10.1053/j.ackd.2006.01.014
  39. Colussi G, Rombolà G, De Ferrari ME, Macaluso M, Minetti L. Correction of Hypokalemia with Antialdosterone Therapy in Gitelman’s Syndrome. American Journal of Nephrology. 1994;14(2):127–35. Diakses pada: http://dx.doi.org/10.1159/000168701
  40. Ito Y, Yoshida M, Nakayama M, Tsutaya S, Ogawa K, Maeda H, et al. Eplerenone Improved Hypokalemia in a Patient with Gitelman’s Syndrome. Internal Medicine. 2012;51(1):83–6. Diakses pada: http://dx.doi.org/10.2169/internalmedicine.51.5723
  41. Brambilla G, Perotti M, Perra S, Dell’Oro R, Grassi G, Pincelli AI. It is never too late for a genetic disease: a case of a 79-year-old man with persistent hypokalemia. Journal of Nephrology. 2013;26(3):594–8. Diakses pada: http://dx.doi.org/10.5301/jn.5000256
  42. Larkins N, Wallis M, McGillivray B, Mammen C. A severe phenotype of Gitelman syndrome with increased prostaglandin excretion and favorable response to indomethacin. Clin Kidney J. 2014/04/04 ed. 2014;7(3):306–10. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/25852896
  43. Liaw LC, Banerjee K, Coulthard MG. Dose related growth response to indometacin in Gitelman syndrome. Arch Dis Child. 1999;81(6):508–10. Diakses pada: https://pubmed.ncbi.nlm.nih.gov/10569969
  44. Mayan H, Gurevitz O, Farfel Z. Successful treatment by cyclooxyenase-2 inhibitor of refractory hypokalemia in a patient with Gitelman’s syndrome. Clinical Nephrology. 2002;58(07):73–6. Diakses pada: http://dx.doi.org/10.5414/cnp58073
  45. Morton A. Eplerenone in the treatment of Gitelman’s syndrome. Internal Medicine Journal. 2008;38(5):377–377. Diakses pada: http://dx.doi.org/10.1111/j.1445-5994.2008.01664.x

How to Cite

Wijaya, B. S., & Karya, K. W. S. (2021). Kelainan elektrolit berulang pada pasien dengan kecurigaan Sindrom Gitelman. Intisari Sains Medis, 12(3), 777–784. https://doi.org/10.15562/ism.v12i3.1082
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