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Pediatric Nephrology
Published in: Pediatric Nephrology 7/2017

Open Access 01-07-2017 | Review

Genetic causes of hypomagnesemia, a clinical overview

Authors: Daan H. H. M Viering, Jeroen H. F. de Baaij, Stephen B. Walsh, Robert Kleta, Detlef Bockenhauer

Published in: Pediatric Nephrology | Issue 7/2017

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Abstract

Magnesium is essential to the proper functioning of numerous cellular processes. Magnesium ion (Mg2+) deficits, as reflected in hypomagnesemia, can cause neuromuscular irritability, seizures and cardiac arrhythmias. With normal Mg2+ intake, homeostasis is maintained primarily through the regulated reabsorption of Mg2+ by the thick ascending limb of Henle’s loop and distal convoluted tubule of the kidney. Inadequate reabsorption results in renal Mg2+ wasting, as evidenced by an inappropriately high fractional Mg2+ excretion. Familial renal Mg2+ wasting is suggestive of a genetic cause, and subsequent studies in these hypomagnesemic families have revealed over a dozen genes directly or indirectly involved in Mg2+ transport. Those can be classified into four groups: hypercalciuric hypomagnesemias (encompassing mutations in CLDN16, CLDN19, CASR, CLCNKB), Gitelman-like hypomagnesemias (CLCNKB, SLC12A3, BSND, KCNJ10, FYXD2, HNF1B, PCBD1), mitochondrial hypomagnesemias (SARS2, MT-TI, Kearns–Sayre syndrome) and other hypomagnesemias (TRPM6, CNMM2, EGF, EGFR, KCNA1, FAM111A). Although identification of these genes has not yet changed treatment, which remains Mg2+ supplementation, it has contributed enormously to our understanding of Mg2+ transport and renal function. In this review, we discuss general mechanisms and symptoms of genetic causes of hypomagnesemia as well as the specific molecular mechanisms and clinical phenotypes associated with each syndrome.
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Metadata
Title
Genetic causes of hypomagnesemia, a clinical overview
Authors
Daan H. H. M Viering
Jeroen H. F. de Baaij
Stephen B. Walsh
Robert Kleta
Detlef Bockenhauer
Publication date
01-07-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 7/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3416-3

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