Gitelman Syndrome: a Сlinical and Molecular Overview
DOI:
https://doi.org/10.22141/2307-1257.0.3.13.2015.74915Keywords:
Gitelman syndrome, renal tubulopathy/tubular disorder, SLC12A3 gene, Na -Cl– cotransporter, hypokalemia, hypocalciuria, metabolic alkalosis, chondrocalcinosis, tetanyAbstract
Gitelman syndrome (OMIM #263800) is an autosomal recessive renal tubular disorder due to loss of function mutations of SLC12A3 gene, encoding the thiazide-inhibitable, electroneutral Na+-Cl– cotransporter (NCC) of the distal convoluted tubule. Clinical consequences include chronic normotensive hypokalemic alkalosis, hypomagnesemia, hypocalciuria, polyuria/nocturia, chronic asthenia, muscular cramps, chondrocalcinosis and rarely cardiac arrhythmias.
Impaired reabsorption of glomerular filtrate through NCC drives compensatory reabsorption of Na+ in more distal tubular segments (connecting and cortical collecting tubules) via both the «electrogenic» channel ENa (which also enhances tubular secretion of potassium and protons, explaining the hypokalemic alkalosis), and pendrin-dependent electroneutral NaCl reabsorption. Thus volume depletion is seldom severe in these patients.
There exists wide variability and severity of clinical symptoms between subjects, ranging from an almost asymptomatic disease to a severely disabling one. More than 400 SLC12A3 mutations have been so far described, evenly distributed along the protein sequence and without any hot spot. Mutation detection rate by gene sequencing actually is about 80 %. There are no genotype-phenotype correlations.
Commonly considered a benign condition, Gitelman syndrome may be associated with reduced quality of life, increased medicalization and high hospitalization rate.
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Copyright (c) 2015 Maria Luisa Querques, Federica Ravera, Alberto Menegotto, Giacomo Colussi
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