Gitelman syndrome with a novel frameshift variant in SLC12A3 gene accompanied by chronic kidney disease and type 2 diabetes mellitus

Iio, Kenichiro; Mori, Takayasu; Bessho, Saki; Imai, Yosuke; Hatanaka, Masaki; Omori, Hiroki; Kouhara, Haruhiko; Chiga, Motoko; Sohara, Eisei; Uchida, Shinichi; Kaimori, Jun-Ya

doi:10.1007/s13730-021-00652-4

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…[15] In Table 3, We summarized the general characteristics of GS patients with T2DM in published articles. [21–26] Based on the results, the mutation sites in GS patients with T2DM are mostly located in the exon areas, and it is more common in Chinese male patients. Some patients were diagnosed with T2DM earlier than GS, so it is not clear whether the cause of T2DM in these patients is caused by GS.…”

Section: Discussionmentioning

confidence: 99%

Case report: Gitelman syndrome with diabetes: Confirmed by both hydrochlorothiazide test and genetic testing

et al. 2023

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Rationale: Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Hypokalemia, hypomagnesemia, and increased renin-angiotensin-aldosterone system (RAAS) activity can cause glucose metabolism dysfunction. The diagnosis of GS includes clinical diagnosis, genetic diagnosis and functional diagnosis. The gene diagnosis is the golden criterion while as functional diagnosis is of great value in differential diagnosis. The hydrochlorothiazide (HCT) test is helpful to distinguish GS from batter syndrome, but few cases have been reported to have HCT testing. Patient concerns: A 51-year-old Chinese woman presented to emergency department because of intermittent fatigue for more than 10 years. Diagnoses: Laboratory test results showed hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis. The HCT test showed no response. Using next-generation and Sanger sequencing, we identified 2 heterozygous missense variants (c.533C > T:p.S178L and c.2582G > A:p.R861H) in the SLC12A3 gene. In addition, the patient was diagnosed with type 2 diabetes mellitus 7 years ago. Based on these findings, the patient was diagnosed with GS with type 2 diabetic mellitus (T2DM). Interventions: She was given potassium and magnesium supplements, and dapagliflozin was used to control her blood glucose. Outcomes: After treatments, her fatigue symptoms were reduced, blood potassium and magnesium levels were increased, and blood glucose levels were well controlled. Lessons: When GS is considered in patients with unexplained hypokalemia, the HCT test can be used for differential diagnosis, and genetic testing can be continued to confirm the diagnosis when conditions are available. GS patients often have abnormal glucose metabolism, which is mainly caused by hypokalemia, hypomagnesemia, and secondary activation of RAAS. When a patient is diagnosed with GS and type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) can be used to control the blood glucose level and assist in raising blood magnesium.

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Section: Discussionmentioning

confidence: 99%

Case report: Gitelman syndrome with diabetes: Confirmed by both hydrochlorothiazide test and genetic testing

et al. 2023

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“…Besides the manifestations of renal tubulopathy, GS is also accompanied by proteinuria [2][3][4][5][6][7][8][9][10][11][12], renal dysfunction [7][8][9][13][14][15][16], and even renal failure requiring renal replacement [17][18][19]. To date, only 19 cases of GS with renal pathology data have been reported which indicated chronic tubulointerstitial injury [1,10,13,14,19], C1q nephropathy (C1qN), focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), severe podocyte detachment, diabetic nephropathy, and membranous nephropathy [2, 4-9, 12, 15, 16].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological Features of Gitelman Syndrome with Proteinuria and Renal Dysfunction

Zhang¹,

Peng²,

Zhao³

et al. 2023

Nephron

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Introduction. Gitelman syndrome (GS) is a rare renal tubular salt-wasting disorder. Besides kidney electrolytes loss, proteinuria and renal dysfunction were also observed. However, their incidence, risk factors, pathological features, and prognosis were unclear. Methods. We retrospectively reviewed 116 GS patients and analyzed their clinical, genetic, and pathological characteristics. We also systematically reviewed articles on GS with proteinuria and renal dysfunction. Results. Twenty-three GS patients had proteinuria (69.6%) and renal dysfunction (43.5%) with a mean age of 35.3 ±13.2 years and 65.2% were male. Compared to patients without proteinuria or renal dysfunction, these patients had elevated plasma angiotensin II level (440.2±351.7 vs. 253.2±187.4 pg/ml, P=0.031) and three times higher incidence of diabetes. The renal pathology of nine biopsied patients indicated hypertrophy of the juxtaglomerular apparatus (100%), chronic tubulointerstitial changes (66.7%), intrarenal vascular changes (66.7%), and glomerulopathy (55.6%). More extensive renin staining was observed in patients with GS than in the control group with glomerular minor lesion (P<0.001). During a median of 85 months (range, 11-205 months) follow-up for 19 out of the 23 GS-renal patients, the renal function was generally stable, except one died of cancer and one developed end-stage renal disease because of concomitant membranous nephropathy and IgA nephropathy. Conclusion. Proteinuria and renal dysfunction were more common than expected and might indicate glomerulopathy and vascular lesions besides a tubulointerstitial injury in GS. Renal function may maintain stable with effective therapy in most cases.

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Magnesium-oxide/potassium-chloride

2022

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Gitelman syndrome with a novel frameshift variant in SLC12A3 gene accompanied by chronic kidney disease and type 2 diabetes mellitus

Cited by 3 publications

References 22 publications

Case report: Gitelman syndrome with diabetes: Confirmed by both hydrochlorothiazide test and genetic testing

Case report: Gitelman syndrome with diabetes: Confirmed by both hydrochlorothiazide test and genetic testing

Clinicopathological Features of Gitelman Syndrome with Proteinuria and Renal Dysfunction

Magnesium-oxide/potassium-chloride

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