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• Congenital Renal Transport Abnormalities
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Bartter syndrome and Gitelman's syndrome are characterized by fluid, electrolyte, and hormonal abnormalities, including renal K, Na, Cl, and H wasting; hypokalemia; hyperaldosteronism; hyperreninemia; and normal BP. Findings include electrolyte, growth, and sometimes neuromuscular abnormalities. Diagnosis is assisted by urine electrolyte measurements and hormone assays but is typically a diagnosis of exclusion. Treatment consists of NSAIDs, K-sparing diuretics, low-dose ACE inhibitors, and electrolyte replacement.

Pathophysiology

Bartter syndrome and the more common Gitelman's syndrome result from deranged NaCl transport and reabsorption. In Bartter syndrome, the defect is in the ascending thick limb of the loop of Henle. In Gitelman's syndrome, the defect is in the distal tubule. Subsequent K, Na, Cl, and H wasting leads to increased renin and aldosterone release, metabolic alkalosis, hyperuricemia, and, particularly in Bartter syndrome, increased prostaglandin secretion. Hypomagnesemia is common, particularly in Gitelman's syndrome. Urinary Ca excretion is decreased in Gitelman's syndrome and is normal or increased in Bartter syndrome. In both disorders, Na wasting results in a chronically low plasma volume reflected by a normal BP despite high renin and angiotensin levels.

The features at clinical presentation vary (see Table 1: Congenital Renal Transport Abnormalities: Some Differences Between Bartter Syndrome and Gitelman's Syndrome).

Table 1
Some Differences Between Bartter Syndrome and Gitelman's Syndrome Feature Bartter Syndrome Gitelman's Syndrome Location of kidney defect Ascending loop of Henle Distal tubule Urinary Ca excretion Normal or increased, commonly with nephrocalcinosis Decreased Serum Mg level Normal or decreased Decreased, sometimes greatly Usual age at presentation Before birth to early childhood, often with intellectual disability and growth disturbance Late childhood to adulthood Neuromuscular symptoms (eg, muscle spasms, weakness) Uncommon or mild Common

Etiology

Both syndromes are usually autosomal recessive, although sporadic cases and other types of familial patterns can occur; there are several genotypes of both syndromes.

Symptoms and Signs

Bartter syndrome tends to manifest prenatally or during infancy or early childhood. Gitelman's syndrome tends to manifest during late childhood or adulthood. Bartter syndrome can manifest prenatally with intrauterine growth restriction and polyhydramnios. After birth, affected children with Bartter syndrome and sometimes those with Gitelman's syndrome have poor growth rates and appear undernourished. Most patients have low or low-normal BP and may have signs of volume depletion. Inability to retain K, Ca, or Mg can lead to muscle weakness, spasms, tetany, or palpitations, particularly in Gitelman's syndrome. Polydipsia, polyuria, and vomiting may also be present. Intellectual disability and nephrocalcinosis sometimes result, particularly in Bartter syndrome.

Bartter syndrome may result in premature birth and severe electrolyte disorders and symptoms, but neither Bartter syndrome nor Gitelman's syndrome typically leads to chronic renal insufficiency.

Diagnosis

• Serum and urine electrolyte levels
• Exclusion of similar disorders

Bartter syndrome and Gitelman's syndrome should be suspected in children with characteristic symptoms or incidentally noted laboratory abnormalities, such as metabolic alkalosis and hypokalemia. Measurement of urine electrolytes shows high levels of Na, K, and Cl that are inappropriate for the euvolemic or hypovolemic state of the patient. Diagnosis is by exclusion of other disorders:

• Primary and secondary aldosteronism can often be distinguished by the presence of hypertension and normal or low plasma levels of renin (see Table 3: Adrenal Disorders: Differential Diagnosis of Aldosteronism).
• Bulimia nervosa and surreptitious vomiting or laxative abuse can often be distinguished by low levels of urinary Cl (usually < 20 mmol/L).
• Surreptitious diuretic abuse can often be distinguished by low levels of urinary Cl and by a urine assay for diuretics.

Definitive diagnosis is through genetic testing, which is not commercially available and thus is rarely done.

Gitelman's syndrome can usually be differentiated from Bartter syndrome by the presence of hypomagnesemia and hypocalciuria.

Treatment

• NSAIDs
• SpironolactoneSome Trade Names
  ALDACTONE
  Click for Drug Monograph
  or amilorideSome Trade Names
  MIDAMOR
  Click for Drug Monograph
  
• Low-dose ACE inhibitors
• K, Mg, and Ca supplements

The combination of NSAIDs (eg, indomethacinSome Trade Names
INDOCIN
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1 to 2 mg/kg po once/day) and a K-sparing diuretic (eg, spironolactoneSome Trade Names
ALDACTONE
Click for Drug Monograph
150 mg po bid or amilorideSome Trade Names
MIDAMOR
Click for Drug Monograph
10 to 20 mg po bid) helps correct most features. Plasma electrolyte levels can be further improved by using ACE inhibitors (at low doses to minimize further hypovolemia and hypotension). However, no therapy can completely eliminate K wasting, and K supplementation (KCl 20 to 40 mEq po once/day or bid) is often necessary. Mg and Ca supplements may also be needed.

Exogenous growth hormone is sometimes considered to treat short stature in affected children, but this treatment is not widely used.

Last full review/revision September 2009 by Peter C. Brazy, MD

Content last modified September 2009