What are the diagnostic criteria for Gitelman syndrome in an adolescent or adult presenting with chronic fatigue, muscle cramps or tetany and laboratory findings of hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, elevated renin and aldosterone, and high urinary potassium loss?

Gitelman Syndrome Diagnosis

Diagnostic Criteria

Gitelman syndrome is diagnosed in an adolescent or adult presenting with the characteristic triad of hypokalemia, hypomagnesemia, and hypocalciuria, accompanied by metabolic alkalosis, elevated renin and aldosterone, and high urinary potassium loss, with definitive confirmation by genetic testing for SLC12A3 mutations. 1

Essential Laboratory Findings

The diagnosis requires documentation of the following biochemical abnormalities:

• Hypokalemia (serum potassium typically 2.4–3.0 mEq/L) with urinary potassium wasting (>20–40 mEq/L despite low serum levels) 1, 2, 3
• Hypomagnesemia (serum magnesium <1.7 mg/dL) that is persistent and often severe 1, 2, 4
• Hypocalciuria with urinary calcium-to-creatinine ratio ≤0.20, which is the critical distinguishing feature from Bartter syndrome 1, 2
• Metabolic alkalosis with serum bicarbonate >25 mEq/L and arterial pH >7.45 1, 4
• Elevated plasma renin activity and aldosterone levels indicating secondary hyperaldosteronism 1, 2, 4
• Fractional excretion of chloride >0.5% indicating renal salt wasting 1

Age of Presentation

• Gitelman syndrome typically manifests after age 6 years, most commonly during adolescence or adulthood, distinguishing it from Bartter syndrome which presents prenatally or in early infancy 1, 5, 4
• Symptoms are often mild and nonspecific, including chronic fatigue, muscle cramps, tetany, salt craving, and muscle weakness 1, 4, 3

Blood Pressure Characteristics

• Blood pressure is characteristically normal to low (e.g., 95/60–98/66 mmHg) despite the hyperreninemic hyperaldosteronism, which helps differentiate from primary aldosteronism 2, 4, 3

Critical Differential Diagnosis: Bartter Syndrome

The most important condition to distinguish from Gitelman syndrome is Bartter syndrome type 3, which shares many overlapping features:

Key Differentiating Features

Feature	Gitelman Syndrome	Bartter Syndrome
Urinary calcium	Low (hypocalciuria, ratio ≤0.20)	High (hypercalciuria, ratio >0.20)
Age of onset	After age 6, adolescence/adulthood	Prenatal or early infancy
Severity	Milder, benign course	More severe
Nephrocalcinosis	Absent	Often present
Prognosis	Better long-term	More complications

1, 5, 4

Additional Distinguishing Points

• Hypomagnesemia is universal in Gitelman syndrome but present in only 20% of Bartter syndrome cases 5, 6
• Bartter syndrome may have a history of polyhydramnios and premature birth, which is not typical of Gitelman syndrome 1

Genetic Confirmation

• Genetic testing for biallelic inactivating SLC12A3 mutations provides definitive diagnosis and is recommended for all suspected cases 1, 4
• The SLC12A3 gene encodes the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule 5, 4

Exclusions Required Before Diagnosis

Before confirming Gitelman syndrome, the following must be ruled out:

• Diuretic abuse (thiazide or loop diuretics) through careful history and, if necessary, urine screening 1, 2, 4
• Laxative abuse 2
• Persistent vomiting or diarrhea causing gastrointestinal losses 2
• Self-medication with over-the-counter preparations 2

Obsolete and Contraindicated Tests

• Thiazide or loop diuretic loading tests are obsolete and should be avoided due to risk of severe volume depletion, especially in young patients 1, 2
• These functional tests have uncertain diagnostic value and pose unnecessary risk 1

Additional Biochemical Findings

• Hypochloremia (serum chloride 85–95 mEq/L) is typically present 1
• Serum sodium may be low-normal to mildly reduced (e.g., 124 mmol/L in severe cases) 3
• Hypocalcemia can occasionally occur, though it is rare, and may present with tetany 2

Clinical Pitfalls to Avoid

• Do not assume Gitelman syndrome only presents in adulthood; rare cases present in early childhood and can lead to growth retardation and delayed puberty if undiagnosed 3
• Do not overlook the diagnosis in patients with chronic unexplained hypokalemia discovered incidentally during routine laboratory work 5, 4
• Remember that symptoms may be mild or absent despite significant biochemical abnormalities, leading to delayed diagnosis 4
• The prevalence is higher in Asian populations (estimated 1 in 4,000 to 1 in 40,000), making it one of the most common inherited renal tubulopathies 4