Bartter and Gitelman Syndromes

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, all resulting from various mutations impacting the movement of sodium, potassium, and chloride through the tubular cell.

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.

DiagnosisTop

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 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 1). Although not needed for diagnosis, serum renin and aldosterone levels are elevated.

TreatmentTop

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. Due to renal sodium wasting, a high sodium and fluid intake is frequently required to avoid hypovolemia. 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.

TablesTop