Loss of Consciousness and Hypokalemia in an Elderly Man with a Mutation of the Thiazide-sensitive Na-Cl Cotransporter Gene

Abstract

Abstract. An 80-year-old man was referred to our department for evaluation of repetitive loss of consciousness and faintness with hypokalemia. He had relatively low blood pressure, hypomagnesemia, hypocalciuria and chondrocalcinosis in the knee, clinically suggesting Gitelman's syndrome. A renal clearance study could not be carried out due to the patient's age and complications of the heart. Sequence analysis of the gene of thiazide-sensitive Na-Cl cotransporter (TSC) showed a heterozygous missense mutation from C to T at 1712 base pairs from the translation start site, with resultant changes in codon 569 from alanine to valine (A569V). Treatment with oral administration of potassium chloride improved all the symptoms. Although Gitelman's syndrome has been considered to be autosomal recessive, cases of only heterozygous mutation detected have recently been reported. Therefore, the mutation found in this patient may be responsible for Gitelman's syndrome.

Gitelman syndrome DD thiazide diuretics abuse

“…It is a rare inherited autosomal recessive renal disorder with decreased tubulary resorption of Na + , Cl -, Mg 2+ and K + [3][4][5][7][8][9][10][11][12][13][14][15][16][17][18]. The prevalence of GS has been reported between 1:40000 to 1:52500 [6,12,19].…”

“…GS underlies one or more genetic mutations of the NCCT gene (SLC12A3-Gen/16q13) [3][4][5][6][7]9,10,[12][13][14][16][17][18][19][20][21]. By now, more than 100 mutations of the SLC12A3 gene (associated with GS) have been identified [6,10,12,13,16,17,21].…”

“…By now, more than 100 mutations of the SLC12A3 gene (associated with GS) have been identified [6,10,12,13,16,17,21]. Although an inherited autosomal recessive succession has been reported, 30-40% of patients showed mutations at only one allele of the SLC12A3 gene [10,11].…”

“…GS is frequently overlooked at its beginning [4,12]. The symptoms include adynamia, loss of muscle strength, fatigue, vertigo, hypotension, muscle spasm, tetania and paraesthesia [2,4,[6][7][8]10,12,13,16,19,20]. Other rare symptoms are abdominal pain, nausea, vomiting and fever [4,12,13].…”

“…These criteria include normal urine concentrating ability of the kidneys and normal GFR, hypomagnesaemia <0,65mmol/l, hypokalemia <3,6mmol/l and hypocalciuria <0,1mmol/mmol creatinine [10,13,14,23]. Hypomagnesaemia and hypocalciuria have a high probability for the diagnosis [6].…”