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Pediatric Nephrology

, Volume 22, Issue 8, pp 1219–1223 | Cite as

A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism

  • Kandai Nozu
  • Xue Jun Fu
  • Hiroshi Kaito
  • Kyoko Kanda
  • Naoki Yokoyama
  • Rafal Przybyslaw Krol
  • Toshihiro Nakajima
  • Mizutaka Kajiyama
  • Kazumoto Iijima
  • Masafumi Matsuo
Brief Report

Abstract

Bartter syndrome (BS) is a genetic disorder with hypokalemic metabolic alkalosis and is classified into five types. One of these, type II BS (OMIM 241200), is classified as neonatal Bartter syndrome, which is caused by mutations in the KCNJ1 gene. Transient hyperkalemia and hyponatremia are usually noted in the early postnatal period, but as type II BS is a relatively rare disease, its exact clinical course and genetic background have not yet been thoroughly characterized. This report concerns a male type II BS patient with a novel mutation in the KCNJ1 gene. The unique clinical findings of this case are that hyperkalemia (8.9 mEq/l), hyponatremia, and metabolic acidosis detected in the early postnatal period led to a diagnosis of pseudohypoaldosteronism (PHA). As an adolescent, however, the patient currently shows normal potassium levels and normal renal function, although with hypercalciuria and nephrocalcinosis, without having received any treatment. In such cases, KCNJ1 mutations should be suspected. In our case, genetic analysis of the KCNJ1 gene identified a novel homozygous 1-bp deletion mutation (c.607 del. C in exon 5).

Keywords

Bartter syndrome Pseudohypoaldosteronism (PHA) Hyperkalemia Hypokalemia ROMK KCNJ1 

Notes

Acknowledgement

We acknowledge Ms. Yoshimi Nozu for her help in genetic analysis. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

References

  1. 1.
    Bartter FC, Pronove P, Gill JR Jr, Maccardle RC (1962) Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. Am J Med 33:811–828PubMedCrossRefGoogle Scholar
  2. 2.
    Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP (1996) Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet 13(2):183–188PubMedCrossRefGoogle Scholar
  3. 3.
    Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, Lifton RP (1996) Genetic heterogeneity of Bartter’s syndrome revealed by mutations in the K+ channel, ROMK. Nat Genet 14(2):152–156PubMedCrossRefGoogle Scholar
  4. 4.
    Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R, Schurman S, Nayir A, Alpay H, Bakkaloglu A, Rodriguez-Soriano J, Morales JM, Sanjad SA, Taylor CM, Pilz D, Brem A, Trachtman H, Griswold W, Richard GA, John E, Lifton RP (1997) Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet 17(2):171–178PubMedCrossRefGoogle Scholar
  5. 5.
    Birkenhager R, Otto E, Schurmann MJ, Vollmer M, Ruf EM, Maier-Lutz I, Beekmann F, Fekete A, Omran H, Feldmann D, Milford DV, Jeck N, Konrad M, Landau D, Knoers NV, Antignac C, Sudbrak R, Kispert A, Hildebrandt F (2001) Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet 29(3):310–314PubMedCrossRefGoogle Scholar
  6. 6.
    Vargas-Poussou R, Huang C, Hulin P, Houillier P, Jeunemaitre X, Paillard M, Planelles G, Dechaux M, Miller RT, Antignac C (2002) Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome. J Am Soc Nephrol 13(9):2259–2266PubMedCrossRefGoogle Scholar
  7. 7.
    Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R, Chikatsu N, Fujita T (2002) Association between activating mutations of calcium-sensing receptor and Bartter’s syndrome. Lancet 360(9334):692–694PubMedCrossRefGoogle Scholar
  8. 8.
    Jeck N, Derst C, Wischmeyer E, Ott H, Weber S, Rudin C, Seyberth HW, Daut J, Karschin A, Konrad M (2001) Functional heterogeneity of ROMK mutations linked to hyperprostaglandin E syndrome. Kidney Int 59(5):1803–1811PubMedCrossRefGoogle Scholar
  9. 9.
    Peters M, Jeck N, Reinalter S, Leonhardt A, Tonshoff B, Klaus GG, Konrad M, Seyberth HW (2002) Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med 112(3):183–190PubMedCrossRefGoogle Scholar
  10. 10.
    Finer G, Shalev H, Birk OS, Galron D, Jeck N, Sinai-Treiman L, Landau D (2003) Transient neonatal hyperkalemia in the antenatal (ROMK defective) Bartter syndrome. J Pediatr 142(3):318–323PubMedCrossRefGoogle Scholar
  11. 11.
    Landau D (2004) Potassium handling in health and disease: lessons from inherited tubulopathies. Pediatr Endocrinol Rev 2(2):203–208PubMedGoogle Scholar
  12. 12.
    Giebisch G (1998) Renal potassium transport: mechanisms and regulation. Am J Physiol 274(2):F817–F833PubMedGoogle Scholar
  13. 13.
    Satlin LM (1999) Regulation of potassium transport in the maturing kidney. Semin Nephrol 19(2):155–165PubMedGoogle Scholar
  14. 14.
    Satlin LM (2004) Developmental regulation of expression of renal potassium secretory channels. Curr Opin Nephrol Hypertens 13(4):445–450PubMedCrossRefGoogle Scholar
  15. 15.
    Woda CB, Miyawaki N, Ramalakshmi S, Ramkumar M, Rojas R, Zavilowitz B, Kleyman TR, Satlin LM (2003) Ontogeny of flow-stimulated potassium secretion in rabbit cortical collecting duct: functional and molecular aspects. Am J Physiol Renal Physiol 285(4):F629–F639PubMedGoogle Scholar
  16. 16.
    Bailey MA, Cantone A, Yan, Q MacGregor GG, Leng Q, Amorim JB, Wang T, Hebert SC, Giebisch G, Malnic G (2006) Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter’s syndrome and in adaptation to a high-K diet. Kidney Int 70(1):51–59PubMedCrossRefGoogle Scholar
  17. 17.
    Shuck ME, Bock JH, Benjamin CW, Tsai TD, Lee KS, Slightom JL, Bienkowski MJ (1994) Cloning and characterization of multiple forms of the human kidney ROM-K potassium channel. J Biol Chem 269(39):24261–24270PubMedGoogle Scholar
  18. 18.
    Liou HH, Zhou SS, Huang CL (1999) Regulation of ROMK1 channel by protein kinase A via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. Proc Natl Acad Sci USA 96(10):5820–5825PubMedCrossRefGoogle Scholar
  19. 19.
    MacGregor GG, Xu JZ, McNicholas CM, Giebisch G, Hebert SC (1998) Partially active channels produced by PKA site mutation of the cloned renal K+ channel, ROMK2 (kir1.2). Am J Physiol 275(2):F415–F22PubMedGoogle Scholar
  20. 20.
    Schulte U, Hahn H, Konrad M, Jeck N, Derst C, Wild K, Weidemann S, Ruppersberg JP, Fakler B, Ludwig J (1999) pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome. Proc Natl Acad Sci USA 96(26):15298–15303PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2007

Authors and Affiliations

  • Kandai Nozu
    • 1
  • Xue Jun Fu
    • 1
  • Hiroshi Kaito
    • 1
  • Kyoko Kanda
    • 1
  • Naoki Yokoyama
    • 1
  • Rafal Przybyslaw Krol
    • 1
  • Toshihiro Nakajima
    • 2
  • Mizutaka Kajiyama
    • 2
  • Kazumoto Iijima
    • 3
  • Masafumi Matsuo
    • 1
  1. 1.Department of PediatricsKobe University Graduate School of MedicineKobe, HyogoJapan
  2. 2.Department of PediatricsShinko HospitalKobeJapan
  3. 3.Department of NephrologyNational Center for Child Health and DevelopmentTokyoJapan

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