Diagnostic Considerations

Patients with Gitelman syndrome tend to have milder symptoms than do those with Bartter syndrome and to present in adolescence and early adulthood. Often, patients have minimal symptomatology and lead relatively normal lives.^{[26, 31]}

In a study of 163 patients with type III Bartter syndrome, Gitelman syndrome, or pseudo-Bartter syndrome/Gitelman syndrome, patients with pseudo- Bartter syndrome/Gitelman syndrome were significantly older at diagnosis than those in the other two groups. Compared with the Gitelman syndrome group, the pseudo-Bartter syndrome/Gitelman syndrome group included a significantly higher percentage of women and had a lower estimated glomerular filtration rate and body mass index.^[32]

Hypomagnesemia and hypocalciuria were observed in all three groups. Chronic kidney disease was observed in 40% of patients with type III Bartter syndrome, 12% of those with Gitelman syndrome, and 63% of those with pseudo- Bartter syndrome/Gitelman syndrome.^[32]

Consider possible renal tubular disorder if patients, especially dehydrated infants and young children, are found to have hypokalemia and a high serum bicarbonate concentration that do not correct with potassium and chloride replacement treatment.

Cystic fibrosis (CF) may initially present as Pseudo-Bartter syndrome with electrolyte and acid-base abnormalities such as hypochloremia, hyponatremia, hypokalemia and metabolic alkalosis, especially in early childhood.^[33]

Conditions to consider in the differential diagnosis of Bartter syndrome include the following:

Diuretic abuse
Gitelman syndrome
Hyperprostaglandin E syndrome
Familial hypomagnesemia with hypercalciuria/nephrocalcinosis
Activating mutations of the CaSR calcium-sensing receptor
Cyclical vomiting
Congenital chloride diarrhea
Gullner syndrome - Familial hypokalemic alkalosis with proximal tubulopathy
Mineralocorticoid excess
Pyloric stenosis
Hypomagnesemia
Cystic fibrosis
Hypochloremic alkalosis
Hypokalemia

Workup

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Media Gallery

Normal transport mechanisms in the thick ascending limb of the loop of Henle. Reabsorption of sodium chloride is achieved with the sodium chloride/potassium chloride cotransporter, which is driven by the low intracellular concentrations of sodium, chloride, and potassium. Low concentrations are maintained by the basolateral sodium pump (sodium-potassium adenosine triphosphatase), the basolateral chloride channel (ClC-kb), and the apical potassium channel (ROMK).
Type I neonatal Bartter syndrome. Mutations in the sodium chloride/potassium chloride cotransporter gene result in defective reabsorption of sodium, chloride, and potassium.
Type II neonatal Bartter syndrome. Mutations in the ROMK gene result in an inability to recycle potassium from the cell back into the tubular lumen, with resultant inhibition of the sodium chloride/potassium chloride cotransporter.
Classic Bartter syndrome. Mutations in the ClC-kb chloride channel lead to an inability of chloride to exit the cell, with resultant inhibition of the sodium chloride/potassium chloride cotransporter.

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Author

Lynda A Frassetto, MD Clinical Professor, Department of Internal Medicine, University of California, San Francisco, School of Medicine

Lynda A Frassetto, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Lowell J Lo, MD Assistant Clinical Professor, Division of Nephrology, Department of Medicine, University of California, San Francisco, School of Medicine; Renal Ambulatory Service and Practice Chief, Medical Director, Mount Zion Dialysis Unit

Lowell J Lo, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgements

Uri S Alon, MD Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children's Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine

Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research