A Family with Gitelman Syndrome with Asymptomatic Phenotypes while Carrying Reported SLC12A3 Mutations

Ishikawa, Moena; Tada, Yumi; Tanaka, Hiromu; Morii, Wataru; Inaba, Masako; Takada, Hidetoshi; Mori, Takayasu; Noguchi, Emiko

doi:10.1159/000507845

Cited by 2 publications

(3 citation statements)

References 13 publications

(28 reference statements)

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“…However, we have not found electrolyte alterations characteristic of GS in our proband. Thus, the phenotypic effect of such missense variants is difficult to evaluate, and some pathogenic variants may not be sufficient to cause phenotypic changes related to GS [ 27 , 28 , 29 , 30 , 31 ], although, we cannot rule out that modifier genes are involved in the onset of GS or that phenotypic changes caused by this compound heterozygous would be apparent later in life. Indeed, our proband had a reduced eGFR at the time of the first evaluation, and this fact could in part mask the electrolyte alterations of GS ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…GS is clinically characterized by hypomagnesemia, hypochloremic metabolic alkalosis, hypokalemia, hypereninemia, and hyperaldosteronism with normal or low blood pressure and salt loss [ 27 ]. Most of patients with GS present during childhood or early adulthood, however, it has high clinical variability, and some patients may not have GS features [ 27 , 28 , 29 , 30 , 31 ]. We here report a patient with ADPKD and coexisting masked KS and GS, based on genetic studies and clinical features.…”

Section: Introductionmentioning

confidence: 99%

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Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

Peces

Mena

et al. 2022

Genes

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic hereditary renal disease, promoting end-stage renal disease (ESRD). Klinefelter syndrome (KS) is a consequence of an extra copy of the X chromosome in males. Main symptoms in KS include hypogonadism, tall stature, azoospermia, and a risk of cardiovascular diseases, among others. Gitelman syndrome (GS) is an autosomal recessive disorder caused by SLC12A3 variants, and is associated with hypokalemia, hypomagnesemia, hypocalciuria, normal or low blood pressure, and salt loss. The three disorders have distinct and well-delineated clinical, biochemical, and genetic findings. We here report a male patient with ADPKD who developed early chronic renal failure leading to ESRD, presenting with an intracranial aneurysm and infertility. NGS identified two de novo PKD1 variants, one known (likely pathogenic), and a previously unreported variant of uncertain significance, together with two SLC12A3 pathogenic variants. In addition, cytogenetic analysis showed a 47, XXY karyotype. We investigated the putative impact of this rare association by analyzing possible clinical, biochemical, and/or genetic interactions and by comparing the evolution of renal size and function in the proband with three age-matched ADPKD (by variants in PKD1) cohorts. We hypothesize that the coexistence of these three genetic disorders may act as modifiers with possible synergistic actions that could lead, in our patient, to a rapid ADPKD progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

Peces

Mena

et al. 2022

Genes

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“…Usually, normokalemia is difficult to be achieved even with high-dose potassium replacement in patients with Gitelman syndrome. However, the phenotype in Gitelman syndrome can have a wide spectrum from normokalemia 14 to severe hypokalemia resistant to treatment. This phenotypic variability is the possible explanation for the achievement of normokalemia only with spironolactone in this patient.…”

Section: Managementmentioning

confidence: 99%

A novel mutation of SLC12A3 gene causing Gitelman syndrome

Silva

Pathmanathan

Sumanatilleke

et al. 2022

SAGE Open Medical Case Reports

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A 48-year-old patient with a history of diabetes mellitus, presented to a surgical ward with abdominal pain. She was found to have hypokalemia. Her younger sister had passed away due to sudden cardiac death at the age of 25 years. Further evaluation revealed an elevated trans-tubular potassium gradient suggestive of renal potassium loss, normal blood pressure, hypomagnesemia, hypocalciuria, and alkalosis. Moreover, there was evidence of secondary hyperaldosteronism. Genetic studies revealed two heterozygous mutations of the SLC12A3 gene, including a novel mutation which has not been reported before anywhere in the world. She was treated with intravenous potassium supplementation and was later converted to oral potassium and oral magnesium supplementation with spironolactone. Her potassium and magnesium levels normalized and glycaemic control also improved. Hypokalemia and hypomagnesemia found in Gitelman syndrome may be associated with insulin resistance and correction of electrolytes can lead to better glycaemic control.

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A Family with Gitelman Syndrome with Asymptomatic Phenotypes while Carrying Reported SLC12A3 Mutations

Cited by 2 publications

References 13 publications

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

A novel mutation of SLC12A3 gene causing Gitelman syndrome

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