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Abstract: SA-PO519

The Dominant Cause of Cramping Muscles

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1002 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Clinical


  • Blum, Christina L., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Watson, Maura A., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Joshi, Megha Raj, Walter Reed National Military Medical Center, Bethesda, Maryland, United States

Magnesium (Mg2+) is the second most abundant intracellular cation. The human body contains about 24g of Mg2+ with normal serum concentration 1.7-2.5mg/dL. Mg2+ influences neuromuscular excitability, mitochondrial function and cellular proliferation. Clinical hypomagnesemia (hypoMg2+) ranges from asymptomatic to cramping, seizures and death. Investigating the cause of hypoMg2+ assists prompt management and prevents life threatening complications.

Case Description

A 37 year-old male with no significant medical or family history was hospitalized in 2015 for fatigue, profound diarrhea and dehydration. Labs revealed hypoMg2+ and supplementation was started; an extensive workup did not reveal an etiology. He continued to have muscle fasciculation, fatigue, cramping and decreased stamina despite taking Mg2+ 1064mg and two Phos-Nak packets twice daily (phos 8mmol/packet). Calcium was 8.9mg/dL, (alb 3.9g/dL), Mg2+ 1.1mg/dL, phosphorous 3.1mg/dL, urine calcium <5mg/dL and Mg2+ 8.2mg/dL with fractional excretion of Mg 13%. After a trial of amiloride 20mg daily; his Mg2+ remained 1.1mg/dL, potassium 3.5, and phos 2.9. He discontinued amiloride and resumed high dose Mg2+ supplements. Genetic testing revealed a pathogenic variant on gene FXYD2 c.121G>A, p.Gly41Arg.


Isolated dominant hypoMg2+, FXYD2 c.121G>A, p.Gly41Arg, an autosomal dominant Gitelman-like hypoMg2+, is a rare genetic cause of hypoMg2+ affecting the subunit of Na+-K+-ATPase protein of the distal convoluted tubule. The γ-subunit is misrouted and the α- and β-subunit of the Na+-K+-ATPase cannot form, resulting in reduction of Na+-K+-ATPase activity decreasing Mg2+ uptake and increasing renal Mg2+ losses. The average Mg2+ concentration with this mutation is of 1.142mg/dL (0.47mM). Incidence unknown. The gene was discovered in 2000 in 3 Dutch families (29 patients) who presented with tetany, muscle weakness, chondrocalcinosis, excessive thirst, polyuria and less commonly epilepsy, kidney failure, or arrhythmias. Treatment is Mg2+ supplementation. Genetic testing is an important tool for early diagnosis and prompt management. Ongoing research in hereditary hypoMg2+ is needed to further our understanding of FXYD2 mutations.

The views expressed are those of the authors and do not reflect the official policy of the Department of the Army/Navy/Air Force, the Department of Defense, or the United States government.