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Etiology and Clinical FeaturesTop
Bartter and Gitelman syndromes result from loss-of-function mutations in 2 membrane transport proteins in the thick ascending limb of the loop of Henle and the distal convoluted tubule, respectively. Bartter syndrome is caused by mutations in the sodium-potassium-chloride cotransporter (NKCC) channel in the ascending loop of Henle, whereas Gitelman syndrome is a result of the sodium-chloride cotransporter (NCC) mutations in the distal convoluted tubule.
There are 5 subtypes of Bartter syndrome. Type 1 Bartter syndrome, described above, is caused by the loss-of-function mutation in the NKCC channel, which is sensitive to loop diuretics. The other subtypes develop due to mutations in various other proteins in the same loop of Henle cells involved in sodium and potassium trafficking, which maintains tubular and cellular electrical charge.
Bartter syndrome may present in various ways. Some patients are asymptomatic and are diagnosed with milder forms of the disease on the basis of hypokalemia, metabolic alkalosis, and mild hypotension. Subtypes of Bartter syndrome can also be associated with excessive thirst, polydipsia, and polyuria. More severe forms lead to neonatal death.
Both Bartter syndrome and Gitelman syndrome are quite rare and inherited in an autosomal recessive fashion.
Diagnosis in Bartter syndrome and Gitelman syndrome is one of exclusion. Patients usually present with unexplained hypokalemia and metabolic alkalosis with a low-to-normal blood pressure. Other causes of such manifestations, including surreptitious vomiting and diuretic use, must be excluded.
A tentative diagnosis is usually made on the basis of detailed history, physical examination, and assessment of other serum and urinary studies (Table 9.8-1). Although not needed for diagnosis, serum renin and aldosterone levels are elevated.
The goal of therapy in Bartter and Gitelman syndromes involves management of hypokalemia, which can be done both by oral potassium supplementation and by the use of potassium-sparing diuretics, particularly spironolactone. Because of the rise in prostaglandin levels related to the loop of Henle dysfunction in Bartter syndrome, nonsteroidal anti-inflammatory drugs can also be used and have been shown to be effective in reducing polyuria and hypokalemia.
Bartter syndrome Gitelman syndrome Age of onset Neonatal to childhood Late childhood to adulthood Serum magnesium Low to normal Low Urinary calcium High Low Urinary concentration ability Reduced Normal
Age of onset
Neonatal to childhood
Late childhood to adulthood
Low to normal
Urinary concentration ability