The New England Journal of MedicineMagnesium Disorders

Recent advances in understanding magnesium homeostasis have highlighted the intricate regulation of magnesium balance by the intestine, bone, and kidneys, with implications for managing hypomagnesemia and its associated electrolyte disorders.

Magnesium is a critical electrolyte involved in various cellular functions and physiological processes, yet its disorders, particularly hypomagnesemia, often remain underdiagnosed in clinical practice. This comprehensive review goes over the mechanisms of magnesium homeostasis, the roles of magnesium transporters, and the clinical implications of magnesium deficiency, especially in patients with comorbidities or those undergoing specific drug therapies. By addressing both the genetic and acquired causes of hypomagnesemia, the article provides a detailed framework for evaluating and managing magnesium disorders in clinical settings.

Key Points:

• Magnesium’s Role in Health:
  • Magnesium is essential for ATP function and acts as a cofactor in numerous enzymatic reactions.
  • It regulates glucose, lipid, and protein metabolism, neuromuscular function, cardiac rhythm, vascular tone, hormone secretion, and circadian rhythm.
• Magnesium Homeostasis:
  • Normal serum magnesium levels in adults are 1.7 to 2.4 mg/dL.
  • Magnesium balance is tightly controlled by intestinal absorption, renal excretion, and bone storage.
• Prevalence of Hypomagnesemia:
  • Affects 3-10% of the general population, with higher prevalence in type 2 diabetes patients and hospitalized individuals, especially those in ICUs.
• Symptoms and Diagnosis:
  • Often asymptomatic or presents with nonspecific symptoms such as lethargy, muscle cramps, or weakness.
  • Diagnosis may be overlooked due to lack of routine serum magnesium measurement and its association with other electrolyte imbalances.
• Magnesium Transporters:
  • TRPM6 and TRPM7 are key magnesium transporters, with TRPM6 mutations linked to hypomagnesemia and secondary hypocalcemia.
  • Other transporters include solute carrier family 41, CNNM1-4, and MRS2.
• Causes of Hypomagnesemia:
  • Can result from inadequate dietary intake, gastrointestinal loss, reduced renal reabsorption, or redistribution of magnesium.
  • Drug-induced causes include antibiotics, diuretics, PPIs, and chemotherapies.
  • Non-drug causes include chronic alcohol use, type 2 diabetes, cardiovascular disease, and preeclampsia.
• Hereditary Hypomagnesemia:
  • Genetic mutations affecting magnesium transport pathways account for 80% of familial cases.
  • Common genetic causes include mutations in TRPM6, TRPM7, CNNM2, and others.
• Evaluation and Management:
  • Serum magnesium measurement is standard but may underestimate total body magnesium.
  • Diagnosis involves assessing dietary intake, urinary loss, and specific diagnostic tests like 24-hour magnesium excretion.
  • Treatment includes oral magnesium supplements, with organic salts being more effectively absorbed than inorganic salts.
  • Parenteral therapy is indicated for severe or refractory cases.
• Therapeutic Uses of Magnesium:
  • Effective in treating torsades de pointes, acute asthma exacerbations, and preeclampsia/eclampsia.
  • Mechanisms include calcium-channel blockade and modulation of bronchial smooth muscle and vascular tone.

“Hypomagnesemia should be corrected with magnesium replacement therapy in the form of the organic salt preparation. Although there is still much to be learned about magnesium and its regulation in health and disease, the field has advanced, and clinicians should be more attuned to the importance of magnesium in clinical medicine.”

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