Bartter Syndrome

• Jonathan Burns M.A., M.D.

 Basic Information

Definition

Bartter syndrome refers to a rare group of autosomal recessive disorders characterized by impaired salt reabsorption in the thick ascending limb of the loop of Henle, producing metabolic alkalosis, hypokalemia, hyperreninemia, hyperplasia of the juxtaglomerular apparatus (source of kidney renin), and hypomagnesemia in some patients.

Synonyms

1. Hypokalemic alkalosis with hypercalciuria

2. Aldosteronism with normal blood pressure

3. Hyperaldosteronism with hypokalemic alkalosis

4. Hyperaldosteronism without hypertension

ICD-10CM CODES
E26.81	Bartter syndrome

Epidemiology & Demographics

Classical Bartter syndrome can present with symptoms at 2 years of age or younger. Neonatal Bartter syndrome can be diagnosed at birth or even prenatally. The exact prevalence of Bartter syndrome in the U.S. is unknown. Prevalence studies have shown higher rates in groups with consanguinity.

Clinical Presentation

1. •

   Neonatal Bartter syndrome is mostly seen between 24 and 30 weeks of gestation with maternal polyhydramnios. Frequent preterm delivery, fetal polyuria, and failure to thrive are common.

2. •

   Classical Bartter syndrome also may include a history of maternal polyhydramnios and premature delivery. The following features are characteristic:

   1. 1.

      Polyuria and polydipsia caused by decreased urinary concentrating ability with a tendency to volume depletion

   2. 2.

      Hypokalemia

   3. 3.

      Vomiting

   4. 4.

      Metabolic alkalosis

   5. 5.

      Hypercalciuria with development of kidney stones

   6. 6.

      Plasma magnesium normal or mildly reduced

   7. 7.

      Normal to low blood pressure

   8. 8.

      Elevated renin and aldosterone levels

   9. 9.

      Elevated renal prostaglandin E₂ production

   10. 10.

       Growth and mental retardation are major complications

3. •

   Other complications may include hearing loss, renal disease, cardiac arrhythmias, and sudden death.

Etiology

1. •

   The primary defect is impaired sodium, potassium, and chloride reabsorption in the thick ascending limb of the loop of Henle

2. •

   A similar phenotype results from at least five genetic mutations (Table E1)

Diagnosis

Differential Diagnosis

1. •

   Diuretic or laxative abuse

2. •

   Surreptitious vomiting, which can be a factitious disorder or an eating disorder

3. •

   Gitelman syndrome (see Table E1)

4. •

   Autosomal dominant hypocalcemia

5. •

   Hyperprostaglandin E syndrome

Workup

1. •

   Classical Bartter syndrome is usually a diagnosis of exclusion.

2. •

   Vomiting is associated with low urine chloride concentrations, distinguishing it from Bartter syndrome, which is characterized by a high urine chloride concentration. Scarring of the dorsum of the hand and dental erosions may suggest bulimia nervosa.

3. •

   Diuretic abuse is excluded by a urine diuretic screen.

Laboratory Tests

1. •

   Serum sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus, plasma renin, and plasma aldosterone

2. •

   Urine calcium, chloride, prostaglandin E, and diuretic screen

3. •

   Serum pH can only be evaluated by performing arterial blood gas analysis

4. •

   Genetic diagnosis is possible but is not widely available

Imaging Studies

1. •

   Renal ultrasonography may show nephrocalcinosis, hydronephrosis, and hydroureter in neonatal Bartter syndrome.

2. •

   Signs of hypokalemia may be manifested on ECG or prenatal ultrasound scanning and amniocentesis.

Treatment

Acute General Rx

Neonatal Bartter syndrome requires urgent correction of electrolyte imbalances and volume deficits.

Chronic Rx

1. •

   Bartter syndrome is caused by genetic mutation(s) for which there is no cure currently.

2. •

   Tubular defects cannot be corrected, and treatment is lifelong.

3. •

   Patients are generally treated by oral potassium and magnesium supplementation, but achievement of normal serum potassium and magnesium levels is often difficult.

4. •

   Nonsteroidal antiinflammatory drugs (NSAIDs) with a potassium-sparing diuretic (e.g., spironolactone) have been used effectively as treatment. Proton pump inhibitors and H₂ antagonists are associated with less gastritis and gastrointestinal bleeding than chronic NSAID use.

5. •

   Promising new treatment approaches include aliskiren, a direct renin inhibitor, and selective COX-2 inhibitors such as rofecoxib, which may help avoid GI toxicity that develops from first-line therapy: high-dose oral potassium and indomethacin.

6. •

   Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers reduce angiotensin II and aldosterone levels and may prove salutary.

7. •

   Growth hormone may be administered for short stature.

8. •

   Calcium or magnesium supplements may be required.

9. •

   Renal transplantation corrects the transporter defect of Bartter syndrome. Disease recurrence in the transplant kidney has not been reported. This aggressive approach has been performed only in isolated cases.

Referral

Nephrology or endocrinology facilitates diagnosis and management of this condition.

Pearls & Considerations

1. •

   Gitelman syndrome is statistically more common than Bartter syndrome, and most clinically suspected cases of Bartter syndrome are Gitelman syndrome, particularly in adults.

2. •

   There are four major types of Bartter syndrome (Table E2) that are not identical in presentation and prognosis. Antenatal and neonatal Bartter syndromes are associated with a worse prognosis than other types. Adult-onset Bartter syndrome is usually not fatal.

3. •

   Serum magnesium differences between Bartter and Gitelman syndromes have been described, but hypomagnesemia cannot be used to absolutely distinguish between these two disorders.

Patient/Family Education

1. •

   Foods with high potassium content should be emphasized during dietary education.

2. •

   Patients are more vulnerable to volume depletion during exercise and exposure because of potassium derangement.

3. •

   Genetic counseling may be indicated in some cases.

Suggested Readings

• Y.R. Bhat, G. Vinayaka, K. Sreelakshmi: Antenatal Bartter syndrome: a review. Int J Pediatr. 857:136 2012

• V. Chadha, U.S. Alon: Hereditary renal tubular disorders. Semin Nephrol. 29 (4):399–411 2009 19615561