Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome

Ring, Troels; Knoers, Nine V A M; Oh, Man S.; Halperin, Mitchell L.

doi:10.1007/s00467-002-0898-y

Cited by 18 publications

(7 citation statements)

References 23 publications

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“…Indeed, despite the small size of our study, significant differences were observed between the three groups concerning blood potassium, chloride, magnesium, supine aldosterone and 24 h urine chloride and magnesium levels. However, hypomagnesaemia and hypocalciuria were not constant, which is in line with other previous studies in which the absence of hypomagnesaemia reached 20-40% and the absence of hypocalciuria 26% (24)(25)(26)(27)(28). Indeed, numerous factors can interfere with urinary calcium excretion, such as calcium, salt and protein intake; age; vitamin D level and other gene polymorphisms such as the CaSR gene (29).…”

Section: Discussionsupporting

confidence: 88%

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Balavoine

Bataille

Vanhille

et al. 2011

European Journal of Endocrinology

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Introduction: Gitelman syndrome (GS) is a tubulopathy caused by SLC12A3 gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria. Aim: The aim of this study was to assess the prevalence of SLC12A3 gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment. Methods: Clinical, biological and genetic data were recorded in 26 patients. Results: Screening for the SLC12A3 gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (PZ0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8G0.3, 3.5 G0.5 and 3.2G0.3 before treatment to 3.2G0.5, 3.7G0.6 and 3.7G0.3 mmol/l with treatment in groups with two (PZ0.003), one and no mutated alleles respectively. Conclusion: In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.

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Section: Discussionsupporting

confidence: 88%

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Balavoine

Bataille

Vanhille

et al. 2011

European Journal of Endocrinology

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“…Although the coexistence of hypomagnesemia and hypocalciuria is typical for NCCT deficiency, it is neither a specific nor universal finding. Clinical observations in NCCT-deficient patients disclosed intraindividual and interindividual variations in urinary Ca 2ϩ concentrations, which can be attributed to gender, age-related conditions of bone metabolism, intake of Mg 2ϩ supplements, changes in water diuresis and urinary osmolality, respectively (68,91). Likewise, hypomagnesemia might not be present from the beginning.…”

Section: Thiazide-sensitive Na ϩ -Cl ϫ Cotransportermentioning

confidence: 99%

Salt handling in the distal nephron: lessons learned from inherited human disorders

Jeck¹,

Schlingmann²,

Reinalter³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

111

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The molecular basis of inherited salt-losing tubular disorders with secondary hypokalemia has become much clearer in the past two decades. Two distinct segments along the nephron turned out to be affected, the thick ascending limb of Henle's loop and the distal convoluted tubule, accounting for two major clinical phenotypes, hyperprostaglandin E syndrome and Bartter-Gitelman syndrome. To date, inactivating mutations have been detected in six different genes encoding for proteins involved in renal transepithelial salt transport. Careful examination of genetically defined patients ("human knockouts") allowed us to determine the individual role of a specific protein and its contribution to the overall process of renal salt reabsorption. The recent generation of several genetically engineered mouse models that are deficient in orthologous genes further enabled us to compare the human phenotype with the animal models, revealing some unexpected interspecies differences. As the first line treatment in hyperprostaglandin E syndrome includes cyclooxygenase inhibitors, we propose some hypotheses about the mysterious role of PGE(2) in the etiology of renal salt-losing disorders.

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“…263800) is an autosomal-recessively inherited renal tubular disorder characterized by low plasma potassium and magnesium levels, reduced calcium excretion, metabolic alkalosis and increased renin activity associated with normal blood pressure levels. Hypocalciuria and hypomagnesemia are typical features of patients with GS; however, they are not constant findings in GS [1]. In a majority of patients, the GS phenotype is caused by mutations in the SLC12A3 gene (MIM No.…”

Section: Introductionmentioning

confidence: 99%

Novel <i>SLC12A3</i> Mutations in Chinese Patients with Gitelman’s Syndrome

et al. 2008

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Background: Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman’s syndrome (GS), a disorder inherited as an autosomal recessive trait. In a minority of cases, GS-like phenotypes are caused by mutations in the CLCNKB gene. Methods: We searched for SLC12A3 and CLCNKB gene mutations in 13 Chinese patients (9 males and 4 females, age 35 ± 14 years) from 8 unrelated families with the clinical and biochemical features of GS. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Results: We identified 10 mutations distributed throughout the SLC12A3 gene. Seven are novel variants, including 4 missense mutations (Gly196Val, Cys430Gly, Gly439Val and Leu571Pro), 2 deletions (1384delG and 346–353delACTGATGG) and 1 in-frame insertion (997insCys). Three mutations were recurrent, including 2 missense mutations (Thr60Met and Asp486Asn) and 1 deletion (2883–2884delAG). The homozygous or heterozygous mutation Thr60Met was found in 8 of 13 patients. There were no mutations detected in the CLCNKB gene. Conclusions: Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify.

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Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome

Cited by 18 publications

References 23 publications

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Salt handling in the distal nephron: lessons learned from inherited human disorders

Novel <i>SLC12A3</i> Mutations in Chinese Patients with Gitelman’s Syndrome

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