Gitelman's syndrome: a pathophysiological and clinical update

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• 作者：Farid Nakhoul (1) (5)
  Nakhoul Nakhoul (1)
  Evgenia Dorman (3)
  Liron Berger (3)
  Karl Skorecki (3) (4)
  Daniella Magen (2) (3) (4)
  
• 关键词：Gitelman’s syndrome ; Hypokalemia–hypomagnesemia
• 刊名：Endocrine
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：41
• 期：1
• 页码：53-57
• 全文大小：288KB
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  6. A.J. Shaher, Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes. Am. J. Med. Sci. 322, 316-32 (2001) CrossRef
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  12. A. Noriko, T. Nakayama, Y. Tehira, A. Haketa, M. Yabuki, T. Sekiyama, C. Nakane, H. Mano, K. Matsumoto, Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman’s syndrome. Endocrine 31, 149-53 (2007) CrossRef
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• 作者单位：Farid Nakhoul (1) (5)
  Nakhoul Nakhoul (1)
  Evgenia Dorman (3)
  Liron Berger (3)
  Karl Skorecki (3) (4)
  Daniella Magen (2) (3) (4)
  
  1. Nephrology & Hypertension Division, Faculty of Medicine, Baruch-Padeh Poryia Medical Center, Lower Galilee, Israel
  5. Faculty of Medicine, Bar-Ilan University, Tel-Aviv, Israel
  3. Laboratory of Molecular Medicine, Technion-Haifa, Israel
  4. Rambam Health Care Campus, Faculty of Medicine, Technion-Haifa, Israel
  2. Pediatric Nephrology Unit, Technion-Haifa, Israel
  

文摘

Gitelman’s syndrome (GS), also known as familial hypokalemic hypomagnesemia, is a rare autosomal recessive hereditary salt-losing tubulopathy, characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria, which is usually caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive sodium chloride contrasporter. Because 18-0% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements must account for unidentified mutations. The clinical manifestations of GS are highly variable in terms of age at presentation, severity of symptoms, and biochemical abnormalities. Molecular analysis in our sibling’s patients revealed compound heterozygous mutations in the coding region of SLC12A3 as underlying their disease. Such compound heterozygosity can result in disease phenotype for such loss of function mutations in the absence of homozygosis through consanguineous inheritance of mutant alleles, identical by descent. Missense mutations account for approximately 70% of the mutations in GS, and there is a predisposition to large rearrangements caused by the presence of repeated sequences within the SLC12A3. We report two adult male siblings of Jewish origin with late onset GS, who presented in their fifth decade of life with muscle weakness, hypokalemia, hypomagnesaemia, and metabolic alkalosis. Rapid clinical and biochemical improvement was achieved by replacement therapy with potassium and magnesium.