Two cases of siblings with Gitelman's syndrome accompanied by Hypokalemia

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 130-162-Neuroendocrinology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-159
Ichiro Mori*, Koichiro Taguchi, Kazuo Kajita, Hiroyuki Morita and Tatsuo Ishizuka
Gifu University Graduate School of Medicine, Gifu, Japan
Introduction: Gitelman’s syndrome (GS), which was discovered by Gitelman, Greham and Welt in 1966, is characterized by hypokalemia, hypomagnesaemia, hypocalciuria and metabolic alkalosis. Patients are usually found during early childhood or adulthood. Typical clinical symptoms include muscle spasms, muscle paralysis, nocturia, and hypotension. Mild hypokalemia is a common finding in the clinical setting. However, severe hypokalemia presenting periodic paralysis is fairly rare. Hypokalemic salt-losing tubulopathies have been reported to constitute a distinct set of inherited renal disorder. GS is associated with inactivating mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na+–Clcotransporter (NCCT) that is expressed in the apical membrane of the cells lining distal convoluted tubules (DCT). Furthermore, gene mutations related to the defective ion transporters or channels have also been defined. Here, we describe two cases of siblings with Gitelman’s syndrome accompanied by Hypokalemia. Case report: Case1: 49-year-old Japanese man presented with a history of dermatomyositis and chronic thyroiditis with latent hypothyroidism (positive thyroglobulin antibody, TSH 5.09μIU/ml (0.35-4.94), FT4 1.33 ng/dl (0.70-1.48)).  He was hospitalized for glucocorticoid treatment. Laboratory examination indicated low serum potassium and magnesium levels (3.2 mEq/l (3.5-4.8) and 1.4mg/dl (1.6-2.3)), respectively, and normal serum calcium level (8.5mg/dl(8.5-10.5)). Urinary examination indicated low urinary calcium level. Calculated transtubular potassium gradient (TTKG) was 4.5. Plasma renin activity (PRA) was high (20.0 ng/ml/hr (0.2-2.7)), and plasma aldosterone concentration (PAC) was normal (94.2 pg/ml (30-160)). Metabolic alkalosis (pH 7.43, HCO3- 26.9 mmol/l, pCO2 41.1 mmHg) was observed. He was treated with potassium chloride, and finally, his potassium level became normal. Case2: 53-year-old Japanese woman (elder sister of Case 1) presented with a history of hypokalemia and experienced periodic paralysis twice with normal blood pressure. Laboratory examinations showed as follows: K3.2 mEq/l, Mg 2.0mg/dl, Ca 9.5mg/dl, urinary Ca not detectable, TTKG 11.7, PRA 5.4ng/ml/hr, PAC 133pg/ml. Metabolic alkalosis (pH 7.43, HCO3- 27.7 mmol/l, pCO2 42.6 mmHg) was observed. Based on their symptoms and laboratory data, GS was suspected. Genetic analysis of SLC12A3 gene indicated heteromissense mutations Leu858His in Exon 22 and Ser976Phe in Exon 25 with compound heterozygote in both cases were detected. Conclusion: GS is the autosomal recessive inheritance disorder showing a mutation in SLC12A3, and it is necessary to suspect it for hypokalemic patients with characteristic evidence.

Nothing to Disclose: IM, KT, KK, HM, TI

*Please take note of The Endocrine Society's News Embargo Policy at