Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome

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• 作者：Karim Bouchireb (1)
  Olivia Boyer (1)
  Lamisse Mansour-Hendili (3) (4)
  Arnaud Garnier (2)
  Laurence Heidet (1)
  Patrick Niaudet (1)
  Remi Salomon (1)
  Rosa Vargas Poussou (3) (5)
  
  1. Assistance Publique-H么pitaux de Paris ; Service de N茅phrologie P茅diatrique ; Centre de R茅f茅rence des Maladies R茅nales H茅r茅ditaires (MARHEA) ; H么pital Necker-Enfants Malades ; 149 rue de S猫vres ; Paris ; 75015 ; France
  3. Assistance Publique-H么pitaux de Paris ; Service de G茅n茅tique ; H么pital Europ茅en Georges Pompidou ; Paris ; France
  4. Facult茅 de M茅decine ; Universit茅 Paris Descartes ; Paris ; France
  2. Service de N茅phrologie P茅diatrique et m茅decine interne ; H么pital d鈥橢nfants ; Toulouse ; France
  5. INSERM ; UMR970 ; centre de recherch茅 cardio-vasculaire ; Paris ; France
  
• 关键词：Polyuria ; Polydipsia ; Hypokalemia ; Fanconi syndrome ; Gitelman syndrome
• 刊名：BMC Pediatrics
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：377 KB
• 参考文献：1. Gitelman, HJ, Graham, JB, Welt, LG (1966) A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians 79: pp. 221-235
  2. Simon, DB, Nelson-Williams, C, Bia, MJ, Ellison, D, Karet, FE, Molina, AM, Vaara, I, Iwata, F, Cushner, HM, Koolen, M, Gainza, FJ, Gitleman, HJ, Lifton, RP (1996) Gitelman鈥檚 variant of Bartter鈥檚 syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet 12: pp. 24-30 CrossRef
  3. Naesens, M, Steels, P, Verberckmoes, R, Vanrenterghem, Y, Kuypers, D (2004) Bartter鈥檚 and Gitelman鈥檚 syndromes: from gene to clinic. Nephron Physiol 96: pp. 65-78 CrossRef
  4. Mastroianni, N, Bettinelli, A, Bianchetti, M, Colussi, G, De Fusco, M, Sereni, F, Ballabio, A, Casari, G (1996) Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome. Am J Hum Genet 59: pp. 1019-1026
  5. Vargas-Poussou, R, Dahan, K, Kahila, D, Venisse, A, Riveira-Munoz, E, Debaix, H, Grisart, B, Bridoux, F, Unwin, R, Moulin, B, Haymann, JP, Vantyghem, MC, Rigothier, C, Dussol, B, Godin, M, Nivet, H, Dubourg, L, Tack, I, Gimenez-Roqueplo, AP, Houillier, P, Blanchard, A, Devuyst, O, Jeunemaitre, X (2011) Spectrum of mutations in Gitelman syndrome. J Am Soc Nephrol 22: pp. 693-703 CrossRef
  6. Nakhoul, F, Nakhoul, N, Dorman, E, Berger, L, Skorecki, K, Magen, D (2012) Gitelman鈥檚 syndrome: a pathophysiological and clinical update. Endocrine 41: pp. 53-57 CrossRef
  7. Cruz, DN, Shaer, AJ, Bia, MJ, Lifton, RP, Simon, DB (2001) Gitelman鈥檚 syndrome revisited: an evaluation of symptoms and health-related quality of life. Kidney Int 59: pp. 710-717 CrossRef
  8. Balavoine, AS, Bataille, P, Vanhille, P, Azar, R, No毛l, C, Asseman, P, Soudan, B, W茅meau, JL, Vantyghem, MC (2011) Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome. Eur J Endocrinol 165: pp. 665-673 CrossRef
  9. Bettinelli, A, Bianchetti, MG, Girardin, E, Caringella, A, Cecconi, M, Appiani, AC, Pavanello, L, Gastaldi, R, Isimbaldi, C, Lama, G (1992) Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. J Pediatr 120: pp. 38-43 CrossRef
  10. Herrero-Morin, JD, Rodriguez, J, Coto, E, Gil-Pe帽a, H, Alvarez, V, Espinosa, L, Loris, C, Gil-Calvo, M, Santos, F (2011) Gitelman syndrome in Gypsy paediatric patients carrying the same intron 9鈥?鈥?聽G鈥?鈥塗 mutation. Clinical features and impact on quality of life. Nephrol Dial Transplant 26: pp. 151-155 CrossRef
  11. Berl, T, Linas, SL, Aisenbrey, GA, Anderson, RJ (1977) On the mechanism of polyuria in potassium depletion. The role of polydipsia. J Clin Invest 60: pp. 620-625 CrossRef
  12. Marples, D, Frokiaer, J, Dorup, J, Knepper, MA, Nielsen, S (1996) Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex. J Clin Invest 97: pp. 1960-1968 CrossRef
  13. Vigano, C, Amoruso, C, Barretta, F, Minnici, G, Albisetti, W, Syr猫n, ML, Bianchetti, MG, Bettinelli, A (2013) Renal phosphate handling in Gitelman syndrome鈥搕he results of a case-control study. Pediatr Nephrol 28: pp. 65-70 CrossRef
  14. Emery, C, Young, RM, Morgan, DB, Hay, AW, Tete-Donker, D, Rubython, J (1984) Tubular damage in patients with hypokalaemia. Clin Chim Acta 140: pp. 231-238 CrossRef
  15. Watanabe, T (2005) Proximal renal tubular dysfunction in primary distal renal tubular acidosis (dRTA). Pediatr Nephrol 20: pp. 86-88 CrossRef
  16. Tasic, V, Korneti, P, Gucev, Z, Hoppe, B, Blau, N, Cheong, HI (2008) Atypical presentation of distal renal tubular acidosis in two siblings. Pediatr Nephrol 23: pp. 1177-1181 CrossRef
  17. Ceri, M, Unverdi, S, Altay, M, Unverdi, H, Kurultak, I, Y谋lmaz, R, Ensari, A, Duranay, M (2011) Focal segmental glomerulosclerosis in association with Gitelman syndrome. Int Urol Nephrol 43: pp. 905-907 CrossRef
  18. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/201/prepub
  
• 刊物主题：Pediatrics; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2431

文摘

Background Gitelman syndrome is an autosomal recessive tubulopathy characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The majority of patients do not present with symptoms until late childhood or adulthood, and the symptoms are generally mild. We report here the first case of Gitelman syndrome presenting with the biological features of Fanconi syndrome and an early polyuria since the neonatal period. We discuss in this article the atypical electrolytes losses found in our patient, as well as the possible mechanisms of severe polyuria. Case presentation A 6-year-old Caucasian girl was admitted via the Emergency department for vomiting, and initial laboratory investigations found hyponatremia, hypokalemia, metabolic acidosis with normal anion gap, hypophosphatemia, and hypouricemia. Urinalysis revealed Na, K, Ph and uric acid losses. Thus, the initial biological profile was in favor of a proximal tubular defect. However, etiological investigations were inconclusive and the patient was discharged with potassium chloride and phosphorus supplementation. Three weeks later, further laboratory analysis indicated persistent hypokalemia, a metabolic alkalosis, hypomagnesemia, and hypocalciuria. We therefore sequenced the SLC12A3 gene and found a compound heterozygosity for 2 known missense mutations. Conclusions Gitelman syndrome can have varying and sometimes atypical presentations, and should be suspected in case of hypokalemic tubular disorders that do not belong to any obvious syndromic entity. In this case, the proximal tubular dysfunction could be secondary to the severe hypokalemia. This report emphasizes the need for clinicians to repeat laboratory tests in undiagnosed tubular disorders, especially not during decompensation episodes.