Overview
Bartter's and Gitelman's Syndromes
1. Clinical Overview
Summary
Bartter's and Gitelman's syndromes are Autosomal Recessive renal tubular disorders defined by the triad of: Hypokalaemia, Metabolic Alkalosis, and Normal/Low Blood Pressure. They represent biochemical "mimics" of diuretics:
- Bartter's affects the Loop of Henle (mimics Furosemide). It presents in childhood with polyuria, growth failure, and Hypercalciuria.
- Gitelman's affects the Distal Convoluted Tubule (mimics Thiazides). It presents in adolescence/adulthood with fatigue, cramps, Hypocalciuria, and severe Hypomagnesaemia. [1,2]
Clinical Pearls
The "Normotensive" Rule: If a patient has Hypokalaemic Metabolic Alkalosis, check the Blood Pressure first.
- High BP = Mineralocorticoid Excess (Conn's, Cushing's, Liddle's, Licorice).
- Normal/Low BP = Salt Wasting (Bartter's, Gitelman's) or GI Loss (Vomiting).
The Calcium Discriminator: How to tell them apart? Check Urine Calcium.
- Bartter's blocks Ca²⁺ reabsorption -> High Urine Ca²⁺ (Stones).
- Gitelman's enhances Ca²⁺ reabsorption -> Low Urine Ca²⁺ (No stones).
Magnesium Magic: If the Magnesium is profoundly low (less than 0.5 mmol/L) in an adult with 'fatigue', assume Gitelman's until proven otherwise.
2. Epidemiology
Demographics
- Gitelman's: 1 in 40,000 (The most common hereditary tubulopathy).
- Bartter's: 1 in 1,000,000 (Very rare).
Genetics
- Inheritance: Both Autosomal Recessive.
- Bartter's: NKCC2 or ROMK genes.
- Gitelman's: SLC12A3 (encodes the NCC transporter).
3. Pathophysiology
Bartter's Syndrome (The Loop Defect)
- Site: Thick Ascending Limb (TAL) of Loop of Henle.
- Defect: Dysfunction of the NKCC2 transporter (Na-K-2Cl).
- Effect: Inability to reabsorb Na/Cl. This abolishes the lumen-positive potential that drives Calcium and Magnesium reabsorption.
- Result: Massive Na/Cl loss, K loss, Ca loss (High urine Ca).
Gitelman's Syndrome (The DCT Defect)
- Site: Distal Convoluted Tubule (DCT).
- Defect: Dysfunction of the NCC transporter (Na-Cl).
- Effect: Inability to reabsorb Na/Cl. However, the DCT usually reabsorbs Calcium inversions to Sodium. When NCC is blocked, Calcium reabsorption is increased.
- Result: Mild Na loss, K loss, Mg loss (mechanism of Mg loss unclear, involves TRPM6 down-regulation), Ca retention (Low urine Ca).
Why Hypokalaemic Alkalosis?
Salt wasting -> Volume depletion -> RAAS activation -> High Aldosterone -> Aldosterone reabsorbs Na in exchange for secreting K+ and H+ in the collecting duct.
4. Differential Diagnosis
| Condition | BP | Urine Cl | Urine Ca | Serum Mg | Features |
|---|---|---|---|---|---|
| Bartter's | Low | High | High | Mild Low | Polyhydramnios, Stones. |
| Gitelman's | Low | High | Low | Very Low | Cramps, Fatigue, Chondrocalcinosis. |
| Pyloric Stenosis / Vomiting | Low | Low | Variable | Normal | Hx of vomiting. |
| Diuretic Abuse | Low | High | Variable | Variable | Screen urine for drugs. |
| Conn's Syndrome | High | - | - | Normal | Aldosterone:Renin Ratio High. |
5. Clinical Presentation
Bartter's (Severe / Infantile)
Gitelman's (Mild / Adult)
Antenatal
Polyhydramnios (fetal polyuria). Prematurity.
Infancy
Failure to thrive, Dehydration episodes, Polyuria.
Complications
Nephrocalcinosis (kidney stones) -> CKD.
6. Investigations
Biochemistry
- Serum:
- Low K+.
- High Bicarbonate (Metabolic Alkalosis).
- Mg: Normal (Bartter) / Low (Gitelman).
- Renin/Aldosterone: Both High (Secondary Hyperaldosteronism).
- Urine:
- Chloride: >20 mmol/L (Rule out vomiting).
- Calcium:Creatinine Ratio: High (Bartter) vs Low (Gitelman).
Genetic Testing
- The gold standard for confirmation. Available via NHS Genomic Medicine Service (R136/R137 panel).
7. Management
Management Algorithm
HYPOKALAEMIC ALKALOSIS
↓
CHECK BP
┌─────────┴─────────┐
HIGH NORMAL/LOW
(Conn's etc) ↓
URINE CHLORIDE
┌─────┴─────┐
LOW HIGH (>20)
(Vomiting) ↓
URINE CALCIUM
┌─────┴─────┐
HIGH LOW
(Bartter's) (Gitelman's)
↓ ↓
Rx: **NSAIDs** Rx: **Mg + K**
(Indomethacin) (Supplements)
+ K Supplements + Liberal Salt
Therapeutics
- Potassium Replacement: High doses of Sando-K or Slow-K. Hard to correct completely.
- Magnesium Replacement (Gitelman's): Mg Glycerophosphate or Aspartate (Oxide causes diarrhoea).
- Potassium Sparing Diuretics: Amiloride or Spironolactone (to block the aldosterone effect and save K+).
- NSAIDs (Bartter's): Indomethacin.
- Mechanism: Bartter's is driven by massive Renal Prostaglandin (PGE2) excretion. NSAIDs block this and dramatically reduce polyuria.
- Diet: Liberal salt intake.
8. Complications
- Cardiac: Arrhythmia (Prolonged QT / Torsades) due to K/Mg deficiency.
- Renal: Nephrocalcinosis (Bartter's) can lead to Renal Failure. Gitelman's usually preserves renal function.
- Musculoskeletal: Rhabdomyolysis / Paralysis (Severe hypokalaemia).
9. Prognosis and Outcomes
- Bartter's: Variable. Type 4 (Bartter-Deafness) proceeds to CKD.
- Gitelman's: Excellent prognosis. Normal life expectancy. But cramps/fatigue can impact QoL.
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Gitelman Syndrome | KDIGO (2017) | Consensus on diagnosis and Mg replacement strategies. |
| Tubulopathies | ERKNet | Genetic testing pathways. |
Landmark Evidence
1. Blanchard et al (Kidney Int 2017)
- The definitive consensus report on Gitelman Syndrome. Emphasized that QoL is often poor despite "normal" prognosis, and Mg replacement is notoriously difficult (diarrhoea limit).
11. Patient and Layperson Explanation
What is it?
Your kidneys contain millions of tiny filter tubes. In these conditions, a specific pump in the tube is genetically broken. This pump is meant to reclaim salt, potassium, and magnesium from your urine back into your blood.
Why do I feel tired/crampy?
because the pump is broken, these minerals are flushed down the toilet. Low potassium and magnesium cause muscle weakness, cramps, and palpitations.
Is it serious?
- Bartter's (usually in children) can be serious because it causes dehydration and kidney stones.
- Gitelman's (usually in adults) is generally safe, but the symptoms can be annoying. We treat it by giving you massive supplements of salt, potassium, and magnesium to replace what you are losing.
Can it be cured?
No, because it is in your genes. You will need supplements for life.
12. References
Primary Sources
- Blanchard A, et al. Gitelman syndrome: consensus conference on diagnosis, management, and follow-up. Kidney Int. 2017;91(1):24-33.
- Seyberth HW. Bartter's and Gitelman's like syndromes: Salt-losing tubulopathies. Pediatr Nephrol. 2017.
- Walsh SB, et al. Pathophysiology and management of the inherited tubulopathies. Clin Kidney J. 2018.
13. Examination Focus
Common Exam Questions
- Diagnosis: "Hypokalemia, Alkalosis, Low BP, High Urine Ca?"
- Answer: Bartter's Syndrome.
- Diagnosis: "Adult, Low Mg, Chondrocalcinosis?"
- Answer: Gitelman's Syndrome.
- Treatment: "Drug to reduce polyuria in Bartter's?"
- Answer: Indomethacin (NSAID).
- Mechanism: "Target of Gitelman's mutation?"
- Answer: NCC (Na-Cl Co-transporter) in DCT.
Viva Points
- Why normal BP?: Because although Renin and Aldosterone are high (which usually raise BP), the kidneys are wasting salt. The salt loss balances out the vasoconstriction, resulting in normal blood pressure.
- Chondrocalcinosis: The link between Gitelman's and CPPD (Pseudogout) is due to hypomagnesaemia affecting pyrophosphate metabolism.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.