Antenatal Bartter Syndrome, Information for Medical Personnel
In contrast to Classic Bartter Syndrome and Gitelman Syndrome, the Antenatal variant of Bartter Syndrome has both the features of renal tubular hypokalemic alkalosis as well as profound systemic manifestations. Antenatal Bartter Syndrome is characterized by polyhydraminos due to intrauterine polyuria, and premature delivery is common. After birth, life-threatening episodes of fever and dehydration occur secondary to profound polyuria, vomiting, and diarrhea.
Severe electrolyte imbalances and marked growth retardation are typical. The majority of these infants also have severe hypercalciuria with associated nephrocalcinosis and osteopenia. Biochemically, these patients are distinguished by marked stimulation of renal and systemic prostaglandin E2 production. Cyclooxygenase inhibitors,eg, Indomethacin, have been shown to reverse all the clinical and laboratory derangements, save for those related to calcium homeostasis.
- Delayed Growth
- Increased prostaglandin excretion
- Severe Electrolyte Imbalances
- Growth Retardation
- Severe Hypercalciuria
As with Classic Bartter Syndrome, the weight of recent clinical evidence indicates that the primary pathogenic mechanism in Antenatal Bartter Syndrome involves defective transepithelial Cl reabsorption in the TAL.
Despite the recent sucesses in elucidating the molecular pathogenesis of the Bartter-like syndromes, therapies designed to arrest or correct the primary defects are not yet available. Therefore, the main therapeutic objective is to ameliorate the hypokalemic, hypochloremic, metabolic alkalosis. Potassium chloride supplementation is the mainstay of therapy. Oral supplementation alone is usually ineffective, however, in normalizing serum potassium concentrations, probably because large amounts of exogenous K further stimulates aldosterone synthesis with resultant increases in hyperkaliuria. The addition of K-sparing diuretics, eg, spironolactone, amilioride, or triamterene, may help to correct the total body K balance. In fact, the therapeutic combination of the K supplementation and K-sparing diuretics has been associated with increased growth rates in affected children. In young infants, marked urinary salt wasting may also occur and necessitate NaCl supplementation. Indomethacin therapy ameliorates many of the clinical and biochemical abnormalities in Antenatal Bartter Syndrome. In fact, indomethacin therapy has been shown to attenuate the systemic symptoms, eg, fever, vomiting, diarrhea; improve growth; and ameliorate the aldosterone-induced salt wasting and hypokalemia. Given that activation of the renin-angiotensin-aldosterone axis drives both urinary potassium wasting and stimulation of prostaglandin production, numerous investigators have used angiotensin-converting enzyme inhibitors in treating Bartter syndrome patients. While variable success has been noted, some patients have had significant biochemical improvement and symptomatic relief with Captopril. The major limitation of this therapy is the development of symptomatic hypotension, because blood pressure maintenance in this population is largely dependent on angiotensin II.
The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with Classic Bartter Syndrome and the Antenatal variant may improve growth and development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage renal disease.Print This Post