Pediatric Bartter Syndrome Clinical Presentation

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

History

The history of patients with Bartter syndrome may include the following:

  • Neonatal Bartter syndrome
    • Maternal polyhydramnios, secondary to fetal polyuria, is evident by 24-30 weeks' gestation. Delivery often occurs before term. The newborn has massive polyuria (rate as high as 12-50 mL/kg/h).
    • The subsequent course is characterized by life-threatening episodes of fluid loss, clinical volume depletion, and failure to thrive.
    • A subset of patients with neonatal Bartter syndrome (types IV and V) develop sensorineural deafness.
  • Classic Bartter syndrome
    • Patients have a history of maternal polyhydramnios and premature delivery.
    • Symptoms include polyuria, polydipsia, vomiting, constipation, salt craving, tendency for volume depletion, failure to thrive, and linear growth retardation.
    • Other symptoms, which appear during late childhood, include fatigue, muscle weakness, cramps, and recurrent carpopedal spasms.
    • Developmental delay and minimal brain dysfunction with nonspecific electroencephalographic changes are also present.
Next

Physical

Findings with Bartter syndrome include the following:

  • Neonatal Bartter syndrome
    • Patients are thin and have reduced muscle mass and a triangularly shaped face, which is characterized by a prominent forehead, large eyes, protruding ears, and drooping mouth.
    • Strabismus is frequently present.
    • Blood pressure is within the reference range.
    • A subset of patients with Bartter syndrome (types IV and V) develop sensorineural deafness, which is detectable with audiometry.
  • Classic Bartter syndrome: The patient's facial appearance may be similar to that encountered in the neonatal type. However, this finding is infrequent.
Previous
Next

Causes

Causes of Bartter syndrome include the following:

  • Neonatal Bartter syndrome
    • An autosomal recessive mode of inheritance is observed in some patients, although many cases are sporadic.
    • In type I Bartter syndrome, loss-of-function mutations in the sodium-chloride potassium-chloride cotransporter gene NKCC2 (locus SLC12A1 on chromosome bands 15q15-21) have been detected.
    • In type II Bartter syndrome, mutations occur in the ROMK gene (locus KCNJ1 on chromosome bands 11q24-25).
    • Newly described genetic defects include type IV (in the BSND gene) and type V (digenic, in both CLCNKB and CLCNKA genes).
  • Classic Bartter syndrome
    • Some patients have an autosomal recessive mode of inheritance, although many cases are sporadic.
    • A subset of patients display mutations in the chloride-channel gene CLCNKB (locus CLCNKB on chromosome band 1p36). These represent type III Bartter syndrome.
Previous
Proceed to Differential Diagnoses
 
 
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

  1. Lin SH, Yang SS, Chau T. A practical approach to genetic hypokalemia. Electrolyte Blood Press. Jun 2010;8(1):38-50. [Medline]. [Full Text].

  2. Deschênes G, Fila M. Primary molecular disorders and secondary biological adaptations in bartter syndrome. Int J Nephrol. 2011;2011:396209. [Medline]. [Full Text].

  3. Janssen AG, Scholl U, Domeyer C, et al. Disease-Causing Dysfunctions of Barttin in Bartter Syndrome Type IV. J Am Soc Nephrol. Sep 5 2008;[Medline].

  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].

  5. Zaffanello M, Taranta A, Palma A, et al. Type IV Bartter syndrome: report of two new cases. Pediatr Nephrol. Jun 2006;21(6):766-70. [Medline].

  6. Birkenhager R, Otto E, Schurmann MJ, et al. Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet. Nov 2001;29(3):310-4. [Medline].

  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].

  20. Shalev H, Ohali M, Kachko L, Landau D. The neonatal variant of Bartter syndrome and deafness: preservation of renal function. Pediatrics. Sep 2003;112(3 Pt 1):628-33. [Medline]. [Full Text].

  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].

 
Previous
Next
 
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
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.