When should hypomagnesemia be suspected in pediatric patients with a history of gastrointestinal (GI) or renal disorders, or those taking medications such as diuretics or antibiotics?

When to Suspect Hypomagnesemia in Children

Suspect hypomagnesemia in any pediatric patient with unexplained seizures, tetany, muscle weakness, or cardiac arrhythmias—particularly when these symptoms occur alongside hypocalcemia or hypokalemia that fails to correct with standard supplementation. 1, 2

High-Risk Clinical Scenarios Requiring Magnesium Assessment

Medication-Induced Magnesium Wasting

Drug-induced renal magnesium wasting is the most common cause of symptomatic hypomagnesemia in children, particularly in older children. 1 Suspect hypomagnesemia when children are receiving:

• Aminoglycoside antibiotics (most common offending agent) 1, 3
• Loop diuretics (furosemide) causing renal magnesium wasting 1, 4
• Amphotericin-B antifungal therapy 1
• Proton-pump inhibitors causing decreased intestinal absorption 3
• Thiazide diuretics inhibiting magnesium reabsorption in the distal tubule 4

The combination of these medications with gastrointestinal losses significantly increases risk. 1

Gastrointestinal Disorders

Suspect hypomagnesemia in children with:

• Chronic diarrhea or malabsorption syndromes causing direct magnesium losses 2, 4
• Short bowel syndrome with high-output stomas 5
• Inflammatory bowel disease (13-88% prevalence of deficiency) 5
• Malnutrition from any cause, especially in oncology patients 2

Gastrointestinal causes typically contribute as a secondary factor when combined with other risk factors. 1

Renal Tubular Disorders

Measure fractional excretion of magnesium (FEMg) to distinguish renal from gastrointestinal losses. 4 Suspect renal magnesium wasting when:

• FEMg >2% in the presence of hypomagnesemia indicates inappropriate renal losses 4
• Bartter syndrome presents with hypokalemia, metabolic alkalosis, and hypercalciuria 6, 4
• Gitelman syndrome presents with hypokalemia, metabolic alkalosis, and hypocalciuria 7, 4
• Familial hypomagnesemia-hypercalciuria syndrome with nephrocalcinosis and hyperuricemia 7

Neonatal Period

Hypomagnesemia is relatively frequent in neonates due to: 7

• Maternal factors: decreased intake from vomiting, overuse of laxatives, maternal magnesium sulfate therapy 6, 7
• Intrauterine growth retardation 7
• Birth asphyxia 7
• Exchange transfusion 7
• Primary hypomagnesemia (rare congenital disorder of intestinal magnesium absorption) 1, 7

Premature infants exposed to maternal magnesium sulfate therapy may have elevated magnesium initially, but require careful monitoring as levels can drop precipitously once maternal supply is removed. 6

Cardinal Clinical Presentations

Neuromuscular Manifestations

Seizures, tetany, and muscle weakness are the most common presenting symptoms. 1 Specifically look for:

• Seizures (often refractory to standard anticonvulsants until magnesium corrected) 1, 2
• Tetany and muscle irritability 1, 7
• Clonic twitching and tremors 8, 7
• Generalized weakness 1

Symptoms typically do not develop until serum magnesium falls below 1.2 mg/dL (0.5 mmol/L), though urgent treatment is indicated at levels below 1.0 mg/dL. 2, 4

Cardiovascular Manifestations

Ventricular arrhythmias are among the most life-threatening effects of hypomagnesemia. 4 Suspect magnesium deficiency in children with:

• Torsades de pointes or polymorphic ventricular tachycardia 6
• QTc prolongation >500 ms 5
• Refractory ventricular arrhythmias 6

Magnesium should be administered for documented hypomagnesemia or torsades de pointes regardless of measured serum level. 6

Electrolyte Abnormalities as Red Flags

Hypocalcemia with hyperphosphatemia suggesting impaired parathyroid function is the most common electrolyte pattern accompanying hypomagnesemia. 1 This occurs because:

• Magnesium deficiency inhibits PTH synthesis and secretion 1
• Peripheral PTH resistance may also occur 1

Hypokalemia is frequently noted and will be refractory to potassium supplementation until magnesium is corrected. 1, 4 This occurs because magnesium deficiency causes dysfunction of multiple potassium transport systems and increases renal potassium excretion. 5, 4

Diagnostic Algorithm

Step 1: Identify High-Risk Patients

Screen for magnesium deficiency in children with: 2, 4

• Unexplained seizures, tetany, or cardiac arrhythmias
• Medications known to cause magnesium wasting (aminoglycosides, diuretics, amphotericin-B)
• Chronic diarrhea or malabsorption
• Refractory hypocalcemia or hypokalemia
• Malignancy receiving chemotherapy

Step 2: Measure Serum Magnesium

Normal serum magnesium ranges from 1.8-2.2 mg/dL (0.74-0.91 mmol/L) in children. 4 However, serum levels do not accurately reflect total body magnesium status, as less than 1% of total body magnesium is in blood. 5

In neonates, reference values are higher: 0.7-1.5 mmol/L during the first two weeks of life. 6

Step 3: Determine Etiology

Calculate fractional excretion of magnesium (FEMg) to distinguish renal from extrarenal losses: 4

• FEMg <2% indicates appropriate renal conservation, suggesting gastrointestinal losses or inadequate intake 4
• FEMg >2% indicates inappropriate renal wasting despite deficiency 4

Measure urinary calcium-creatinine ratio to differentiate tubular disorders: 4

• Hypercalciuria suggests Bartter syndrome, loop diuretics, or familial hypomagnesemia-hypercalciuria syndrome 7, 4
• Hypocalciuria suggests Gitelman syndrome or thiazide diuretics 7, 4

Step 4: Assess for Associated Electrolyte Abnormalities

Check: 1, 4

• Serum calcium and phosphate (hypocalcemia with hyperphosphatemia suggests impaired PTH function)
• Serum potassium (hypokalemia commonly coexists and requires simultaneous correction)
• Acid-base status (metabolic alkalosis suggests Bartter or Gitelman syndrome)

Critical Pitfalls to Avoid

Never assume normal serum magnesium excludes deficiency—intracellular depletion can exist with normal serum levels. 5 Consider measuring red blood cell or mononuclear cell magnesium content for better assessment of total body stores. 7

Never attempt to correct hypocalcemia or hypokalemia before normalizing magnesium—these abnormalities are refractory to supplementation until magnesium is corrected. 5, 1, 4

Always check renal function before administering magnesium supplementation—magnesium is contraindicated when creatinine clearance <20 mL/min due to risk of life-threatening hypermagnesemia. 5, 4

In children with malignancy, hypomagnesemia is especially common with certain chemotherapy agents and can be complicated by diarrhea and malnutrition. 2 Maintain high index of suspicion in this population.

For neonates born to mothers who received magnesium sulfate, monitor closely for both initial hypermagnesemia and subsequent hypomagnesemia as maternal stores are depleted. 6