Pediatric Bartter Syndrome Workup

  • Author: Prasad Devarajan, MD; Chief Editor: Craig B Langman, MD   more...
 
Updated: Nov 14, 2011
 

Laboratory Studies

  • Blood and urine chemistries
    • Evaluation of hypokalemia, hypochloremia, and metabolic alkalosis is essential for diagnosis. Hypokalemia is usually severe (1.5-2.5 mEq/L).
    • Hypomagnesemia may be present and necessitates exclusion of Gitelman syndrome, in which hypomagnesemia is a cardinal finding. The differentiation is made by measuring the urinary excretion of magnesium (which is high in Gitelman syndrome and within the reference range in Bartter syndrome) and calcium (which is high in Bartter syndrome and within the referencer range in Gitelman syndrome).
    • Hyperuricemia is present in 50% of patients with Bartter syndrome, whereas in Gullner syndrome (familial hypokalemic alkalosis with proximal tubulopathy), hypouricemia, secondary to impaired proximal tubular function, is present.
    • Renin and aldosterone levels are elevated, but BP remains normal.
  • CBC count: Polycythemia may be present from hemoconcentration.
  • Renal function
    • The glomerular filtration rate (GFR)is preserved during the early stages of the disease; however, it may decrease as a result of chronic hypokalemia. One study, however, hypothesizes that GFR is affected more by secondary hyperaldosteronism than by hypokalemia.[10]
    • Increases in the fractional urinary excretion of sodium, potassium, and chloride are typical.
    • Patients with Bartter syndrome have high urinary excretion of calcium and normal urinary excretion of magnesium.
    • Patients with Gitelman syndrome have low urinary excretion of calcium and high urinary excretion of magnesium.
    • The urinary excretion of prostaglandin E2 is elevated in both neonatal and classic forms of the disease.
  • Amniotic fluid: If the diagnosis is being made prenatally, assess the amniotic fluid. The chloride content may be elevated in either Gitelman or Bartter syndrome.
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Imaging Studies

  • Renal ultrasonography may reveal nephrocalcinosis in neonatal Bartter syndrome.
  • Hydronephrosis and hydroureter secondary to chronic polyuria may also be evident.
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Other Tests

  • An ECG may reveal changes characteristic of hypokalemia such as flattened T waves and prominent U waves.
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Procedures

  • Although renal biopsy is not usually required, histologic findings may be useful in confirming the diagnosis.
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Histologic Findings

  • In both neonatal and classic Bartter syndrome, the cardinal finding is hyperplasia of the juxtaglomerular apparatus. Less frequently, hyperplasia of the medullary interstitial cells is present.
  • Glomerular hyalinization, apical vacuolization of the proximal tubular cells, tubular atrophy, and interstitial fibrosis may be present as a consequence of chronic hypokalemia.
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Contributor Information and Disclosures
Author

Prasad Devarajan, MD  Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, CEO of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Prasad Devarajan, MD is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Adrian Spitzer, MD  Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Howard Trachtman, MD  Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine

Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD  The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, Children's Memorial Hospital

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Abubakr Imam, MD, to the development and writing of the initial version of this article.

References

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  4. Kitanaka S, Sato U, Maruyama K, Igarashi T. A compound heterozygous mutation in the BSND gene detected in Bartter syndrome type IV. Pediatr Nephrol. Feb 2006;21(2):190-3. [Medline].

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  7. Garcia-Nieto V, Flores C, Luis-Yanes MI, et al. Mutation G47R in the BSND gene causes Bartter syndrome with deafness in two Spanish families. Pediatr Nephrol. May 2006;21(5):643-8. [Medline].

  8. Kramer BK, Bergler T, Stoelcker B, Waldegger S. Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance. Nat Clin Pract Nephrol. Jan 2008;4(1):38-46. [Medline].

  9. Seyberth HW. An improved terminology and classification of Bartter-like syndromes. Nat Clin Pract Nephrol. Aug 2008;[Medline].

  10. Walsh SB, Unwin E, Vargas-Poussou R, Houillier P, Unwin R. Does hypokalaemia cause nephropathy? an observational study of renal function in patients with Bartter or Gitelman syndrome. QJM. Nov 2011;104(11):939-44. [Medline].

  11. Chaudhuri A, Salvatierra O Jr, Alexander SR, Sarwal MM. Option of pre-emptive nephrectomy and renal transplantation for Bartter's syndrome. Pediatr Transplant. Mar 2006;10(2):266-70. [Medline].

  12. Bichet DG, Fujiwara TM. Reabsorption of sodium chloride--lessons from the chloride channels. N Engl J Med. Mar 25 2004;350(13):1281-3. [Medline].

  13. Estevez R, Boettger T, Stein V, et al. Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. Nature. Nov 29 2001;414(6863):558-61. [Medline].

  14. Hebert SC. Bartter syndrome. Curr Opin Nephrol Hypertens. Sep 2003;12(5):527-32. [Medline].

  15. Miyamura N, Matsumoto K, Taguchi T, et al. Atypical Bartter syndrome with sensorineural deafness with G47R mutation of the beta-subunit for ClC-Ka and ClC-Kb chloride channels, barttin. J Clin Endocrinol Metab. Feb 2003;88(2):781-6. [Medline]. [Full Text].

  16. Rodriguez-Soriano J, Vallo A, Aguirre M. Bone mineral density and bone turnover in patients with Bartter syndrome. Pediatr Nephrol. Aug 2005;20(8):1120-5. [Medline].

  17. Rodriguez-Soriano J, Vallo A, Perez de Nanclares G, et al. A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain. Pediatr Nephrol. Jul 2005;20(7):891-6. [Medline].

  18. Scheinman SJ, Guay-Woodford LM, Thakker RV, Warnock DG. Genetic disorders of renal electrolyte transport. N Engl J Med. Apr 15 1999;340(15):1177-87. [Medline].

  19. Schlingmann KP, Konrad M, Jeck N, et al. Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med. Mar 25 2004;350(13):1314-9. [Medline].

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  21. Starremans PG, Kersten FF, Knoers NV, et al. Mutations in the human Na-K-2Cl cotransporter (NKCC2) identified in Bartter syndrome type I consistently result in nonfunctional transporters. J Am Soc Nephrol. Jun 2003;14(6):1419-26. [Medline]. [Full Text].

  22. Vaisbich MH, Fujimura MD, Koch VH. Bartter syndrome: benefits and side effects of long-term treatment. Pediatr Nephrol. Aug 2004;19(8):858-63. [Medline].

 
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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), basolateral chloride channel (ClC-kb), and 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.
Table. Bartter Syndrome Genotype-Phenotype Correlations
Bartter Syndrome Genotype-Phenotype Correlations
Genetic Type Defective Gene Clinical Type
Bartter type INKCC2Neonatal
Bartter type IIROMKNeonatal
Bartter type IIICLCNKBClassic
Bartter type IVBSNDNeonatal with deafness
Bartter type VCLCNKB and CLCNKANeonatal with deafness
Gitelman syndromeNCCTGitelman syndrome
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