What labs should be ordered to diagnose magnesium wasting and Gitelman's (Gitelman syndrome) syndrome?

Diagnostic Laboratory Tests for Magnesium Wasting and Gitelman's Syndrome

To diagnose magnesium wasting and Gitelman's syndrome, the essential laboratory tests should include serum electrolytes, urinary electrolytes with calculated fractional excretion of magnesium, and genetic testing for definitive diagnosis.

Initial Laboratory Evaluation

Serum Tests

• Complete serum electrolyte panel including:
  • Sodium
  • Potassium (typically low in Gitelman's)
  • Chloride (typically low in Gitelman's)
  • Bicarbonate (typically elevated in Gitelman's)
  • Calcium (may be normal or low)
  • Magnesium (typically low)
• Acid-base status (metabolic alkalosis is common)
• Renin and aldosterone levels (typically elevated) 1
• Creatinine (to assess kidney function)

Urinary Tests

• Urinary electrolytes:
  • Calcium-creatinine ratio (low in Gitelman's, normal/high in Bartter's) 1, 2
  • Fractional excretion of chloride (typically >0.5% in salt-wasting tubulopathies) 1
  • Fractional excretion of magnesium (>2% indicates renal magnesium wasting) 2, 3

Distinguishing Features Between Gitelman's and Other Conditions

Parameter	Gitelman's Syndrome	Bartter's Syndrome	Other Magnesium Wasting
Urinary calcium	Low (hypocalciuria)	Normal or high	Variable
Serum magnesium	Low	Variable	Low
Nephrocalcinosis	Absent	Often present	Variable
Age at onset	Adolescence/adulthood	Often in childhood	Any age

Confirmatory Testing

Genetic Testing

• Genetic testing is the gold standard for definitive diagnosis 1
• Recommended gene panel should include:
  • SLC12A3 (primary gene for Gitelman's syndrome)
  • CLCNKB (for Bartter syndrome type 3, which can mimic Gitelman's)
  • Other genes associated with salt-wasting tubulopathies 1

Additional Tests to Consider

• Renal ultrasound to detect medullary nephrocalcinosis and/or kidney stones (typically absent in Gitelman's but present in Bartter's) 1
• Exclude secondary causes of magnesium wasting:
  • Medication review (diuretics, proton pump inhibitors, certain antibiotics)
  • Assessment for other conditions causing hypomagnesemia

Diagnostic Algorithm

1. Initial presentation: Patient with hypokalemia, metabolic alkalosis, and/or hypomagnesemia
2. First-tier testing: Complete serum electrolytes, urinary calcium-creatinine ratio, fractional excretion of magnesium
3. Interpretation:
   • If fractional excretion of magnesium >2% → renal magnesium wasting
   • If urinary calcium is low + hypomagnesemia + hypokalemia + metabolic alkalosis → suspect Gitelman's syndrome
   • If urinary calcium is normal/high + hypomagnesemia + hypokalemia + metabolic alkalosis → suspect Bartter's syndrome
4. Confirmatory testing: Genetic analysis for definitive diagnosis

Common Pitfalls to Avoid

• Failure to calculate fractional excretion of magnesium, which is essential to distinguish renal from non-renal causes of hypomagnesemia
• Not considering medication-induced causes of magnesium wasting before diagnosing genetic disorders
• Relying solely on serum magnesium levels without urinary magnesium assessment
• Confusing Gitelman's syndrome with Bartter syndrome type 3, which can have overlapping features
• Not performing genetic testing, which is crucial for definitive diagnosis and appropriate genetic counseling

By following this systematic approach to laboratory testing, clinicians can accurately diagnose magnesium wasting disorders and distinguish Gitelman's syndrome from other conditions with similar presentations.