Magnesium is an essential cofactor required for normal activity of hundreds of enzymes.
It plays important roles in cardiovascular and neuromuscular functions, among others.
Changes in magnesium concentrations may also affect the levels of potassium and calcium.
In the body, most of magnesium is located in bones and soft tissues. Only about 1 to 2% is present in
blood plasma. Magnesium level in the blood is maintained within a normal range by regulating
intestinal absorption, exchange with bones, and renal excretion. Of these, renal magnesium
reabsorption is the major control factor. In the kidney, serum magnesium is filtered
into the glomerular filtrate, but most of it is promptly reabsorbed back to the
blood. Reabsorption occurs mainly in the proximal convoluted tubule (PCT), the thick ascending loop
of Henle (TAL), and the distal convoluted tubule (DCT). A number of ion channels, transporters,
as well as tight-junction proteins, are responsible for magnesium transport in different
parts of the nephron. Mutations affecting these factors are known to cause several hereditary
syndromes involving magnesium imbalances. Normal serum magnesium levels are between
1.46 and 2.68 mg/dL. Hypomagnesemia is defined as a serum magnesium level of less than 1.46 mg/dL.
However, patients are typically asymptomatic until this number drops below 1.2 mg/dL.
Hypomagnesemia may result from one or more of the following mechanisms: shift of magnesium from
extracellular fluid into cells or bone, reduced dietary intake, reduced intestinal absorption,
increased gastrointestinal loss, and increased renal excretion.
Hypomagnesemia due to redistribution may occur during refeeding of starved patients, treatment of
metabolic acidosis, in hungry bone syndrome, acute pancreatitis, or alcohol withdrawal syndrome.
Hypomagnesemia due to reduced dietary intake may occur in starvation, alcohol use disorder,
feeding disorder, or in those who receive total parenteral nutrition.
Reduced intestinal absorption is typically caused by mutations in an ion channel responsible for
magnesium transport in the small intestine. Increased gastrointestinal loss of magnesium
may happen in acute or chronic diarrhea. Increased renal loss may be caused by genetic
disorders, renal diseases, or diuretics that reduce magnesium reabsorption in the kidney.
Symptoms vary greatly from patient to patient. Because hypomagnesemia often leads to
hypokalemia and/or hypocalcemia, patients may also experience problems related to these conditions.
Early signs include nausea, vomiting, loss of appetite, and muscle weakness.
Neuromuscular symptoms range from hyper-excitability, tremors, muscle cramps and
spasms, to tetany, seizures, delirium, and coma. Cardiovascular symptoms may include premature
beats, arrhythmias, and ischemia. ECG changes are non-specific as these
may also result from hypokalemia or hypocalcemia. Diagnostic tests typically include blood work
for serum magnesium and other electrolytes, kidney function tests, and electrocardiogram.
Urine magnesium over 24 hours can be measured to differentiate between gastrointestinal and
renal causes. A high urinary magnesium excretion in patients with normal renal
functions may signify a drug cause. Genetic testing may be done if inherited
disorders are suspected. Prophylaxis and treatment
for hypomagnesemia typically involve magnesium supplement, oral or parenteral,
depending on the severity of the condition. During treatment, serum magnesium, potassium and calcium
must be monitored, especially in patient with renal problems, to avoid magnesium toxicity.