Diagnosis: Bartter Syndrome
The clinical triad of episodic weakness with paresthesia and polyuria strongly suggests Bartter syndrome, a rare salt-losing tubulopathy characterized by renal potassium and chloride wasting leading to hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism. 1
Key Diagnostic Features
The presentation points to Bartter syndrome based on:
- Episodic weakness and paresthesia: These symptoms result from hypokalemia and hypomagnesemia, which are hallmark electrolyte disturbances in Bartter syndrome 1
- Polyuria: A cardinal feature of Bartter syndrome due to impaired renal concentrating ability and secondary nephrogenic diabetes insipidus 1, 2
- Metabolic alkalosis with chloride wasting: Bartter syndrome presents with chloride-resistant metabolic alkalosis (urinary Cl >20 mEq/L) 3
Essential Diagnostic Workup
To confirm Bartter syndrome, obtain:
- Serum electrolytes: Look for hypokalemia, hypomagnesemia, and metabolic alkalosis (elevated pH and bicarbonate) 1, 3
- Renin and aldosterone levels: Both will be markedly elevated despite normotension, distinguishing this from primary aldosteronism 2, 4
- Urinary chloride: Will be >20 mEq/L despite metabolic alkalosis 3
- Urinary calcium excretion: Hypercalciuria is present in most Bartter syndrome subtypes (except BS3), helping differentiate from Gitelman syndrome 1, 2
- Renal ultrasound: Assess for nephrocalcinosis, which is common in Bartter syndrome 1, 2
- Electrocardiography: Check for QT interval prolongation due to hypokalemia and hypomagnesemia, which increases arrhythmia risk 1, 5
- Genetic testing: Consider for definitive diagnosis, particularly to identify specific Bartter syndrome subtypes (BS1-4) 1, 5
Critical Differential Diagnoses to Exclude
While Bartter syndrome is most likely, rule out:
- Gitelman syndrome: Excluded by presence of hypercalciuria and nephrocalcinosis (Gitelman has hypocalciuria) 2
- Primary hyperaldosteronism (Conn's syndrome): Would present with hypertension, not normotension 4
- Diuretic abuse: Check urine diuretic screen if history is unclear 3
- Diabetic ketoacidosis/HHS: The polyuria could suggest hyperglycemic crisis, but weakness with paresthesia plus metabolic alkalosis (not acidosis) points away from this 1
Important Clinical Pitfalls
Do not overlook cardiac complications: Hypokalemia and hypomagnesemia prolong the QT interval and can cause life-threatening ventricular arrhythmias or sudden death in Bartter syndrome patients 1, 5. Perform ECG immediately and consider Holter monitoring if palpitations or syncope are reported 1.
Avoid potassium citrate or other alkalinizing potassium salts: These will worsen the metabolic alkalosis. Use potassium chloride exclusively for supplementation 3, 5.
Consider secondary nephrogenic diabetes insipidus: The polyuria in Bartter syndrome can be severe due to impaired urinary concentrating ability, and may require assessment of urine osmolality 1, 2.
Initial Management Approach
Once Bartter syndrome is confirmed:
- Sodium chloride supplementation: 5-10 mmol/kg/day 3
- Potassium chloride supplementation: Not potassium citrate, to avoid worsening alkalosis 3, 5
- NSAIDs: Indomethacin or other NSAIDs reduce prostaglandin-mediated salt wasting and are first-line symptomatic treatment 1, 3, 2
- Gastric acid inhibitors: Use with NSAIDs to prevent gastrointestinal complications 3, 6
- Potassium-sparing diuretics: Amiloride or spironolactone can be added if needed 3, 2
Patients should be followed in specialized centers with experience in renal tubular disorders every 6-12 months for adults, with monitoring of acid-base status, electrolytes, renal function, and repeat renal ultrasound every 12-24 months. 1, 5, 6