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Year 2021, Volume: 34 Issue: 3, 254 - 259, 27.10.2021

Sercin Guven Ibrahim Gokce Ceren Alavanda Neslihan Cıcek Ece Bodur Demırcı Mehtap Sak Serim Pul Ozde Nisa Turkkan Nurdan Yıldız Pinar Ata Harika Alpay

https://doi.org/10.5472/marumj.1012351

Abstract

References

  • [1] Besouw MTP, Kleta R, Bockenhauer D. Bartter and Gitelman syndromes: Questions of class. Pediatr Nephrol 2020 ;35:1815- 24. https://doi.org/10.1007/s00467.019.04371-y
  • [2] Seyberth HW. Pathophysiology and clinical presentations of salt-losing tubulopathies. Pediatr Nephrol 2016; 31:407-18 https://doi.org/10.1007/s00467.015.3143-1
  • [3] Simon DB, Nelson-Williams C, Bia MJ. et al. Gitelman’s variant of Bartter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet 1996; 12: 24-30. https://doi. org/10.1038/ng0196-24
  • [4] Kamel KS, Harvey E, Douek K, Parmar MS, Halperin ML. Studies on the pathogenesis of hypokalemia in Gitelman’s syndrome: Role of bicarbonaturia and hypomagnesemia. Am J Nephrol 1998;18:42-9.
  • [5] Ring T, Knoers N, Oh MS, Halperin ML. Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome. Pediatr Nephrol 2002;17:612-16. https://doi.org/10.1159/000013303
  • [6] Simon DB, Bindra RS, Mansfield TA. et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet 1997 ;17:171-8.
  • [7] Messa HL, de Oliveira Achili Ferreira JC, Andreia Rangel- Santos, Vaisbich MH. Genetic spectrum of Brazilian suspected Bartter Syndrome Patients. https://doi.org/10.21203/ rs.3.rs-35560/v1(preprint)
  • [8] Sahbani D, Strumbo B, Tedeschi S, et al. Functional study of novel Bartter’s Syndrome mutations in ClC-Kb and rescue by the accessory subunit Barttin toward personalized medicine. Front Pharmacol 2020 ;11:327. https://doi.org/10.3389/ fphar.2020.00327
  • [9] Coto E, Rodriguez J, Jeck N, et al. A new mutation (intron 9 +1 G>T) in the SLC12A3 gene is linked to Gitelman syndrome in Gypsies. Kidney Int 2004 ;65:25-9. https://doi.org/10.1111/ j.1523-1755.2004.00388.x
  • [10] Mastroianni N, Bettinelli A, Bianchetti M, et al. Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome. Am J Hum Genet 1996 ;59:1019-26. http://www.ncbi.nlm.nih.gov/pmc/articles/ pmc1914834
  • [11] Syrén ML, Tedeschi S, Cesareo L, et al. Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Cotransporter in Italian patients with Gitelman syndrome. Hum Mutat 2002 ;20:78. doi: 10.1002/humu.9045. Erratum in: Hum Mutat 2002 ;20:321 https://doi.org/10.1002/humu.9045
  • [12] Colussi G, Bettinelli A, Tedeschi S, et al. A thiazide test for the diagnosis of kidney tubular hypokalemic disorders. Clin J Am Soc Nephrol 2007;2:454-60. https://doi.org/10.2215/ cjn.02950906
  • [13] Zelikovic I. Hypokalaemic salt-losing tubulopathies: an evolving story. Nephrol Dial Transplant 2003;18:1696-700. https://doi.org/10.1093/ndt/gfg249
  • [14] Jeck N, Konrad M, Peters M, Weber S, Bonzel KE, Seyberth HW. Mutations in the chloride channel gene, CLCNKB,leadingto a mixed Bartter-Gitelman phenotype. Pediatr Res 2000; 48:754- 8. https://doi.org/10.1203/00006.450.200012000-00009
  • [15] Peters M, Jeck N, Reinalter S, et al. Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med 2002; 112: 183-90.
  • [16] Bettinelli A, Bianchetti MG, Girardin E, et al. Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. J Pediatr 1992;120: 38-43. https://doi.org/10.1016/ s0022-3476(05)80594-3
  • [17] Nozu K, Iijima K, Kanda K, et al. The pharmacological characteristics of molecular-based inherited salt-losing tubulopathies. J Clin Endocrinol Metab 2010;95:511-8. https:// doi.org/10.1210/jc.2010-0392
  • [18] Lee BH, Cho HY, Lee H, et al. Genetic basis of Bartter syndrome in Korea. Nephrol Dial Transplant 2012;27:1516- 21. https://doi.org/10.1093/ndt/gfr475
  • [19] Vargas-Poussou R, Dahan K, Kahila D, et al. Spectrum of mutations in Gitelman syndrome. J Am Soc Nephrol 2011; 22:693-703. https://doi.org/10.1681/asn.201.009.0907
  • [20] Zelikovic I, Szargel R, Hawash A, et al. A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes. Kidney Int 2003; 63:24-32. https://doi. org/10.1046/j.1523-1755.2003.00730.x
  • [21] Seys E, Andrini O, Keck M, et al. Clinical and genetic spectrum of Bartter Syndrome type 3 J Am Soc Nephrol 2017;28:2540- 52. https://doi.org/10.1681/asn.201.610.1057
  • [22] Bettinelli A, Borsa N, Bellantuono R, et al. Patients with biallelic mutations in the chloride channel gene CLCNKB: longterm management and outcome. Am J Kidney Dis 2007; 49: 91-8 https://doi.org/10.1053/j.ajkd.2006.10.001
  • [23] Puricelli E, Bettinelli A, Borsa N, et al. Long-term follow-up of patients with Bartter syndrome type I and II. Nephrol Dial Transplant 2010; 25: 2976-81 https://doi.org/10.1093/ndt/ gfq119
  • [24] Brochard K, Boyer O, Blanchard A, et al. Phenotype–genotype correlation in antenatal and neonatal variants of Bartter syndrome. Nephrol Dial Transplant 2009; 24: 1455-64 https:// doi.org/10.1093/ndt/gfn689
  • [25] García Castaño A, Pérez de Nanclares G, Madariaga L, et al. Renal Tube Group: Poor phenotypegenotype association in a large series of patients with Type III Bartter syndrome. PLoS One 2017 ;12:e0173581. https //doi: 10.1371/journal. pone.0173581
  • [26] Han Y, Lin Y, Sun Q, Wang S, Gao Y, Shao L . Mutation spectrum of Chinese patients with Bartter syndrome. Oncotarget 2017;8:101614-22. https://doi.org/10.18632/ oncotarget.2135

Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?

Year 2021, Volume: 34 Issue: 3, 254 - 259, 27.10.2021

Sercin Guven Ibrahim Gokce Ceren Alavanda Neslihan Cıcek Ece Bodur Demırcı Mehtap Sak Serim Pul Ozde Nisa Turkkan Nurdan Yıldız Pinar Ata Harika Alpay

https://doi.org/10.5472/marumj.1012351

Abstract

Objective: Classical Bartter syndrome (cBS) and Gitelman syndrome (GS) are genotypically distinct, but there is a phenotypic overlap
among these two diseases, which can complicate the accurate diagnosis without genetic analysis. This study aimed to evaluate the
correlation between clinical and genetic diagnoses among patients who have genetically defined cBS and GS.
Patients and Methods: The study included 18 patients with homozygous/compound heterozygous CLCNKB (NM_000085) (n:10/18)
and SLC12A3 (NM_000339) (n:8/18) mutations. Biochemical, clinical and radiological data were collected at presentation and at the
last visit.
Results: In cBS group age at diagnosis, median plasma potassium and chloride concentrations were significantly lower and median
plasma HCO3 and blood pH values were significantly higher. Patients with GS had significantly lower median plasma magnesium
concentrations and urinary calcium/creatinine ratio. One child with GS had normocalciuria, two children with cBS had hypocalciuria
and hypomagnesemia. Low estimated glomerular filtration rate (eGFR) (ml/dk/1.73m2) and growth failure were more evident in cBS
group. In patients with cBS, nine different CLCNKB gene mutations were detected, five of them were novel. Novel mutations were:
one nonsense (c.66G>A, p.Trp22*), one missense (c.499G>A, p.Gly167Ser) and three splice-site (c.867-2delA; c.499-2insG; c.1930-
2A>C) mutations. In patients with GS, six different SLC12A3 gene mutations were found.
Conclusions: It may not always be possible to clinically distinguish cBS from GS. We suggest to perform a genotypic classification if
genetic analysis is possible.

Keywords

Bartter syndrome Gitelman syndrome Kidney tubuler disease Hypokalemic metabolic alkalosis

References

  • [1] Besouw MTP, Kleta R, Bockenhauer D. Bartter and Gitelman syndromes: Questions of class. Pediatr Nephrol 2020 ;35:1815- 24. https://doi.org/10.1007/s00467.019.04371-y
  • [2] Seyberth HW. Pathophysiology and clinical presentations of salt-losing tubulopathies. Pediatr Nephrol 2016; 31:407-18 https://doi.org/10.1007/s00467.015.3143-1
  • [3] Simon DB, Nelson-Williams C, Bia MJ. et al. Gitelman’s variant of Bartter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet 1996; 12: 24-30. https://doi. org/10.1038/ng0196-24
  • [4] Kamel KS, Harvey E, Douek K, Parmar MS, Halperin ML. Studies on the pathogenesis of hypokalemia in Gitelman’s syndrome: Role of bicarbonaturia and hypomagnesemia. Am J Nephrol 1998;18:42-9.
  • [5] Ring T, Knoers N, Oh MS, Halperin ML. Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome. Pediatr Nephrol 2002;17:612-16. https://doi.org/10.1159/000013303
  • [6] Simon DB, Bindra RS, Mansfield TA. et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet 1997 ;17:171-8.
  • [7] Messa HL, de Oliveira Achili Ferreira JC, Andreia Rangel- Santos, Vaisbich MH. Genetic spectrum of Brazilian suspected Bartter Syndrome Patients. https://doi.org/10.21203/ rs.3.rs-35560/v1(preprint)
  • [8] Sahbani D, Strumbo B, Tedeschi S, et al. Functional study of novel Bartter’s Syndrome mutations in ClC-Kb and rescue by the accessory subunit Barttin toward personalized medicine. Front Pharmacol 2020 ;11:327. https://doi.org/10.3389/ fphar.2020.00327
  • [9] Coto E, Rodriguez J, Jeck N, et al. A new mutation (intron 9 +1 G>T) in the SLC12A3 gene is linked to Gitelman syndrome in Gypsies. Kidney Int 2004 ;65:25-9. https://doi.org/10.1111/ j.1523-1755.2004.00388.x
  • [10] Mastroianni N, Bettinelli A, Bianchetti M, et al. Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome. Am J Hum Genet 1996 ;59:1019-26. http://www.ncbi.nlm.nih.gov/pmc/articles/ pmc1914834
  • [11] Syrén ML, Tedeschi S, Cesareo L, et al. Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Cotransporter in Italian patients with Gitelman syndrome. Hum Mutat 2002 ;20:78. doi: 10.1002/humu.9045. Erratum in: Hum Mutat 2002 ;20:321 https://doi.org/10.1002/humu.9045
  • [12] Colussi G, Bettinelli A, Tedeschi S, et al. A thiazide test for the diagnosis of kidney tubular hypokalemic disorders. Clin J Am Soc Nephrol 2007;2:454-60. https://doi.org/10.2215/ cjn.02950906
  • [13] Zelikovic I. Hypokalaemic salt-losing tubulopathies: an evolving story. Nephrol Dial Transplant 2003;18:1696-700. https://doi.org/10.1093/ndt/gfg249
  • [14] Jeck N, Konrad M, Peters M, Weber S, Bonzel KE, Seyberth HW. Mutations in the chloride channel gene, CLCNKB,leadingto a mixed Bartter-Gitelman phenotype. Pediatr Res 2000; 48:754- 8. https://doi.org/10.1203/00006.450.200012000-00009
  • [15] Peters M, Jeck N, Reinalter S, et al. Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med 2002; 112: 183-90.
  • [16] Bettinelli A, Bianchetti MG, Girardin E, et al. Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. J Pediatr 1992;120: 38-43. https://doi.org/10.1016/ s0022-3476(05)80594-3
  • [17] Nozu K, Iijima K, Kanda K, et al. The pharmacological characteristics of molecular-based inherited salt-losing tubulopathies. J Clin Endocrinol Metab 2010;95:511-8. https:// doi.org/10.1210/jc.2010-0392
  • [18] Lee BH, Cho HY, Lee H, et al. Genetic basis of Bartter syndrome in Korea. Nephrol Dial Transplant 2012;27:1516- 21. https://doi.org/10.1093/ndt/gfr475
  • [19] Vargas-Poussou R, Dahan K, Kahila D, et al. Spectrum of mutations in Gitelman syndrome. J Am Soc Nephrol 2011; 22:693-703. https://doi.org/10.1681/asn.201.009.0907
  • [20] Zelikovic I, Szargel R, Hawash A, et al. A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes. Kidney Int 2003; 63:24-32. https://doi. org/10.1046/j.1523-1755.2003.00730.x
  • [21] Seys E, Andrini O, Keck M, et al. Clinical and genetic spectrum of Bartter Syndrome type 3 J Am Soc Nephrol 2017;28:2540- 52. https://doi.org/10.1681/asn.201.610.1057
  • [22] Bettinelli A, Borsa N, Bellantuono R, et al. Patients with biallelic mutations in the chloride channel gene CLCNKB: longterm management and outcome. Am J Kidney Dis 2007; 49: 91-8 https://doi.org/10.1053/j.ajkd.2006.10.001
  • [23] Puricelli E, Bettinelli A, Borsa N, et al. Long-term follow-up of patients with Bartter syndrome type I and II. Nephrol Dial Transplant 2010; 25: 2976-81 https://doi.org/10.1093/ndt/ gfq119
  • [24] Brochard K, Boyer O, Blanchard A, et al. Phenotype–genotype correlation in antenatal and neonatal variants of Bartter syndrome. Nephrol Dial Transplant 2009; 24: 1455-64 https:// doi.org/10.1093/ndt/gfn689
  • [25] García Castaño A, Pérez de Nanclares G, Madariaga L, et al. Renal Tube Group: Poor phenotypegenotype association in a large series of patients with Type III Bartter syndrome. PLoS One 2017 ;12:e0173581. https //doi: 10.1371/journal. pone.0173581
  • [26] Han Y, Lin Y, Sun Q, Wang S, Gao Y, Shao L . Mutation spectrum of Chinese patients with Bartter syndrome. Oncotarget 2017;8:101614-22. https://doi.org/10.18632/ oncotarget.2135
There are 26 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Articles
Authors

Sercin Guven This is me

Ibrahim Gokce This is me

Ceren Alavanda This is me

Neslihan Cıcek This is me

Ece Bodur Demırcı This is me

Mehtap Sak This is me

Serim Pul This is me

Ozde Nisa Turkkan This is me

Nurdan Yıldız This is me

Pinar Ata This is me

Harika Alpay This is me

Publication Date October 27, 2021
Published in Issue Year 2021 Volume: 34 Issue: 3

Cite

APA Guven, S., Gokce, I., Alavanda, C., Cıcek, N., et al. (2021). Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?. Marmara Medical Journal, 34(3), 254-259. https://doi.org/10.5472/marumj.1012351
AMA Guven S, Gokce I, Alavanda C, Cıcek N, Bodur Demırcı E, Sak M, Pul S, Turkkan ON, Yıldız N, Ata P, Alpay H. Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?. Marmara Med J. October 2021;34(3):254-259. doi:10.5472/marumj.1012351
Chicago Guven, Sercin, Ibrahim Gokce, Ceren Alavanda, Neslihan Cıcek, Ece Bodur Demırcı, Mehtap Sak, Serim Pul, Ozde Nisa Turkkan, Nurdan Yıldız, Pinar Ata, and Harika Alpay. “Differential Diagnosis of Classical Bartter Syndrome and Gitelman Syndrome: Do We Need Genetic Analysis?”. Marmara Medical Journal 34, no. 3 (October 2021): 254-59. https://doi.org/10.5472/marumj.1012351.
EndNote Guven S, Gokce I, Alavanda C, Cıcek N, Bodur Demırcı E, Sak M, Pul S, Turkkan ON, Yıldız N, Ata P, Alpay H (October 1, 2021) Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?. Marmara Medical Journal 34 3 254–259.
IEEE S. Guven, “Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?”, Marmara Med J, vol. 34, no. 3, pp. 254–259, 2021, doi: 10.5472/marumj.1012351.
ISNAD Guven, Sercin et al. “Differential Diagnosis of Classical Bartter Syndrome and Gitelman Syndrome: Do We Need Genetic Analysis?”. Marmara Medical Journal 34/3 (October 2021), 254-259. https://doi.org/10.5472/marumj.1012351.
JAMA Guven S, Gokce I, Alavanda C, Cıcek N, Bodur Demırcı E, Sak M, Pul S, Turkkan ON, Yıldız N, Ata P, Alpay H. Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?. Marmara Med J. 2021;34:254–259.
MLA Guven, Sercin et al. “Differential Diagnosis of Classical Bartter Syndrome and Gitelman Syndrome: Do We Need Genetic Analysis?”. Marmara Medical Journal, vol. 34, no. 3, 2021, pp. 254-9, doi:10.5472/marumj.1012351.
Vancouver Guven S, Gokce I, Alavanda C, Cıcek N, Bodur Demırcı E, Sak M, Pul S, Turkkan ON, Yıldız N, Ata P, Alpay H. Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?. Marmara Med J. 2021;34(3):254-9.
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