Gitelman syndrome with early onset – a case report and literature news
More details
Hide details
Katedra i Klinika Nefrologii Pediatrycznej, Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu
Katarzyna Kiliś-Pstrusińska   

Katedra i Klinika Nefrologii Pediatrycznej, Uniwersytet Medyczny we Wrocła-wiu, ul. Borowska 213, 50-556 Wrocław
Ann. Acad. Med. Siles. 2017;71:99–103
Gitelman syndrome (GS) is caused by genetic mutation resulting in dysfunction of the thiazide-sensitive sodium-chloride cotransporter located in the distal convoluted tubule. The disease usually produces the first visible symptoms during adolescence or adulthood. This paper describes the case of a boy who developed the first symptoms at the age of 6 and was diagnosed when 16.

At the time of admission of the 16-year-old boy, the following information was provided: the child suffered from upper limb muscle cramps recurring every few weeks since the age of six. Lower limb and orbicularis oris muscle cramps were also observed. In addition, during fever, the patient presented additional symptoms: numbness of the face and limbs. The patient was treated in an ED with anxiolytics and magnesium. Two weeks before admission he developed diarrhea and fever, followed the next day by severe muscle cramps with forced limb position and finally short term loss of consciousness. The boy was admitted to the local hospital where laboratory tests showed hypokalemia, hypomagnesemia and metabolic alkalosis, and then was transferred to the Clinic of Paediatric Nephrology. Blood tests confirmed earlier results and in addition revealed hypochloremia and increased plasma renin activity. The urine tests had following results: basic pH, decreased specific gravity, increased excretion of potassium and magnesium and reduced excretion of calcium. Blood pressure and abdomen USG were normal. Genetic testing was performed and two heterozygous mutations: 2221 G→A (Gly741Arg) and 1315 G→A (Gly439Ser) were found in the SLC12A3 gene.

GS may occur early in life and produce only short passing episodes when symptoms are observable. The presence of the mentioned symptoms requires considering tubulopathy during diagnosis. If not diagnosed and not treated, GS may lead in the long term to somatic complications and a decreased quality of life.

Blanchard A., Bockenhauer D., Bolignano D., Calò L.A., Cosyns E., Devuyst O., Ellison D.H., Karet Frankl F.E., Knoers N.V., Konrad M., Lin S.H., Vargas-Poussou R. Gitelman Syndrome: Consensus and Guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2017; 91(1): 24–33.
van der Merwe P.D., Rensburg M.A., Haylett W.L., Bardien S., Davids M.R. Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings. BMC Nephrol. 2017; 18: 38.
Ganguli A., Veis J.H. Hyponatremia – A rare complication of Gitelman's syndrome. Indian J. Nephrol. 2017; 27: 74–77.
Berry M.R., Robinson C., Karet Frankl F.E. Unexpected Clinical Sequelae of Gitelman Syndrome : Hypertension in Adulthood Is Common and Females Have Higher Potassium Requirements. Nephrol. Dial. Transplant. 2013; 28: 1533–1542.
Tseng M.H., Yang S.S., Hsu Y.J., Fang Y.W., Wu C.J., Tsai J.D., Hwang D.Y., Lin S.H. Genotype, phenotype, and follow-up in Taiwanese patients with salt-losing tubulopathy associated with SLC12A3 mutation. J Clin Endocrinol Metab. 2012; 97(8): E1478-E1482.
Tammaro F., Bettinelli A., Cattarelli D., Cavazza A., Colombo C., Syrén M.L., Tedeschi S., Bianchetti M.G. Early appearance of hypokalemia in Gitelman syndrome. Pediatr Nephrol. 2010; 25: 2179–2182.
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; 7: 306–310.
Cruz D.N., Shaer A.J., Bia M.J.,Lifton R.P., Simon D.B. Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life. Kidney Int. 2001; 59: 710–717.
Vargas-Poussou R., Dahan K., Kahila D., Venisse A., Riveira-Munoz E., Debaix H., Grisart B., Bridoux F., Unwin R., Moulin B., Haymann J.P., Vantyghem M.C., Rigothier C., Dussol B., Godin M., Nivet H., Dubourg L., Tack I., Gimenez-Roqueplo A.P., Houillier P., Blanchard A., Devuyst O., Jeunemaitre X. Spectrum of mutations in Gitelman syndrome. J. Am. Soc. Nephrol. 2011; 22: 693–703.
Glaudemans B., Yntema H.G., San-Cristobal P., Schoots J., Pfundt R., Kamsteeg E.J., Bindels R.J., Knoers N.V., Hoenderop J.G., Hoefsloot L.H. Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome. Eur. J. Hum. Genet. 2012; 20: 263–270.
Urbanová M., Reiterová J., Rysavá R., Merta M. Genetic Analysis of Gitelman Syndrome Patients from the Czech Republic and Slovakia – Three Novel Mutations Found. Kidney Blood Press Res. 2006; 29: 360–365.
Nozu K., Nozu Y., Nakanishi K., Konomoto T., Horinouchi T., Shono A., Morisada N., Minamikawa S., Yamamura T.1, Fujimura J., Nakanishi K., Ninchoji T., Kaito H., Morioka I., Taniguchi-Ikeda M., Vorechovsky I., Iijima K. Cryptic exon activation in SLC12A3 in Gitelman syndrome. J. Hum. Genet. 2017; 62: 335–337.
van der Made C.I., Hoorn E.J., de la Faille R., Karaaslan H., Knoers N.V., Hoenderop J.G., Vargas Poussou R., de Baaij J.H. Hypomagnesemia as First Clinical Manifestation of ADTKD-HNF1B: A Case Series and Literature Review. Am. J. Nephrol. 2015; 42: 85–90.
Lo Y.-F., Nozu K., Iijima K., Morishita T, Huang C.C., Yang S.S., Sytwu H.K., Fang Y.W., Tseng M.H., Lin S.H. Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman’s syndrome. Clin. J. Am. Soc. Nephrol. 2011; 6: 630–639.
Blanchard A., Vargas-Poussou R., Vallet M., Caumont-Prim A., Allard J., Desport E., Dubourg L., Monge M., Bergerot D., Baron S., Essig M., Bridoux F., Tack I., Azizi M. Indomethacin, Amiloride, or Eplerenone for Treating Hypokalemia in Gitelman Syndrome. J. Am. Soc. Nephrol. 2015; 26: 468–475.
Calo L.A., Caielli P. Gitelman’s syndrome and pregnancy: new potential pathophysiological influencing factors, therapeutic approach and materno-fetal outcome. J. Matern. Fetal Neonatal Med. 2012; 25: 1511–1513.
Khosravi M., Walsh S.B. The long-term complications of the inherited tubulopathies: an adult perspective. Pediatr. Nephrol. 2015; 30: 385–395.