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Hereditary etiologies of hypomagnesemia


Magnesium ions are essential to all living cells. As the second most abundant intracellular cation, magnesium has a crucial role in fundamental metabolic processes such as DNA and protein synthesis, oxidative phosphorylation, enzyme function, ion channel regulation, and neuromuscular excitability. After presenting an overview of magnesium homeostasis, we review the etiologies of hypomagnesemia, with an emphasis on hereditary causes.

Key Points

  • Magnesium deficiency is probably more prevalent than is recognized; this condition has been linked to common disorders such as diabetes, hypertension and cardiovascular disease

  • Hypomagnesemia is frequently associated with other electrolyte abnormalities such as hypokalemia and hypocalcemia; patients present with symptoms of increased neuromuscular excitability

  • Hypomagnesemia can cause severe, potentially fatal, cardiac arrhythmias

  • In most cases, hypomagnesemia results from acquired forms of renal and/or intestinal magnesium wasting

  • Hereditary causes of hypomagnesmia are rare; patients usually become symptomatic during the first two decades of life

  • Recent advances in characterization of hereditary magnesium disorders has enhanced understanding of renal and intestinal magnesium transport mechanisms

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Figure 1: Magnesium transport in the thick ascending limb of the loop of Henle is passive and paracellular, perhaps mediated by paracellin-1 (claudin-16) and claudin-19.
Figure 2: The distal convoluted tubule reabsorbs Mg2+ via an active transcellular route.


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Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Correspondence to Amir Said Alizadeh Naderi.

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Naderi, A., Reilly, R. Hereditary etiologies of hypomagnesemia. Nat Rev Nephrol 4, 80–89 (2008).

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