Skip to main content
SpringerLink
Log in

A novel epithelial sodium channel β-subunit mutation associated with hypertensive Liddle syndrome

  • Brief Report
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Low-renin hypertension responsive to amiloride-thiazide therapy in a 4-year-old Afro-Haitian girl suggested Liddle syndrome. Urine steroid profiling substantiated the diagnosis and DNA analysis of the epithelial sodium channel (ENaC) revealed a novel heterozygous βENaC mutation in the patient and in her hypertensive father. Liddle syndrome should be considered as a cause of hypertension in young children particularly with suppressed renin activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A, B

References

  1. Warnock DG (1998) Liddle syndrome: An autosomal dominant form of human hypertension. Kidney Int 53:18–24

    Article  Google Scholar 

  2. Arar MY, Hogg RJ, Arant BS, Seikaly MG (1994) Etiology of sustained hypertension in children in the southwestern United States. Pediatr Nephrol 8:186–189

    Google Scholar 

  3. Task Force on Blood Pressure Control in Children (1987) Report of the Second Task Force on Blood Pressure Control in Children—1987. National Heart, Lung and Blood Institute, Bethesda, Maryland. Pediatrics 79:1–25

    PubMed  Google Scholar 

  4. Shackleton CH (1993) Mass spectrometry in the diagnosis of steroid-related disorders and hypertension research. J Steroid Biochem Mol Biol 45:127–140

    Article  Google Scholar 

  5. Ludwig M, Beck A, Wickert L, Bolkenius U, Tittel B, Hinkel K, Bidlingmaier F (1998) Female pseudohermaphroditism associated with a homozygous G-to-A (V370-to-M) substitution in the P-450 aromatase gene. J Pediatr Endocrinol Metab 11:657–664

    Google Scholar 

  6. Dluhy RG, Anderson B, Harlin B, Ingelfinger J, Lifton R (2001) Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 138:715–720

    Google Scholar 

  7. Yiu VWY, Dluhy RP, Lifton RP, Guay-Woodford LM (1997) Low peripheral plasma renin activity as a critical marker in pediatric hypertension. Pediatr Nephrol 11:434–346

    Google Scholar 

  8. Hansson JH, Schild L, Lu Y, Wilson TA, Gautschi I, Shimkets R, Nelson-Williams C, Rossier BC, Lifton RP (1995) A de novo missense mutation of the β subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. Proc Natl Acad Sci U S A 92:11495–11499

    Google Scholar 

  9. Botero-Velez M, Curtis JJ, Warnock DG (1994) Liddle’s syndrome revisited—a disorder of sodium reabsorption in the distal tubule. N Engl J Med 330:178–181

    Article  Google Scholar 

  10. Lifton RP, Dluhy RP, Powers M, Rich GM, Gutkin M, Fallo F, Gill JR, Feld L, Ganguly A, Laidlaw JC, Murnaghan DJ, Kaufman C, Stockigt JR, Ulick S, Lalovel MA (1992) Hereditary hypertension caused by chimeric gene duplications and ectopic expression of aldosterone synthetase. Nature Genet 2:66–74

    Article  Google Scholar 

  11. Wilson RC, Krozowski ZS, Li K, Obeyesekere VR, Razzaghy-Azar M, Harbison MD, Shackleton CH, Funder JW, New MI (1995) A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab 80:2263–2266

    Article  Google Scholar 

  12. Mount DB, Zandi-Nejad K (2004) Disorders of potassium balance. In: Brenner BM (ed) Brenner and Rector’s the kidney. WB Saunders, Philadelphia, pp 997–1040

  13. Flores SY, Debonneville C, Staub O (2003) The role of Nedd4/Nedd4-like dependent ubiquitylation in epithelial transport. Pflugers Arch Eur J Physiol 446:334–338

    Google Scholar 

  14. Hiltunen TP, Hannila-Handelberg T, Petajaniemi N, Kantola I, Tikkanen I, Virtamo J, Gautschi I, Schild L, Kontula K (2002) Liddle’s syndrome associated with a point mutation in the extracellular domain of the epithelial sodium channel γ subunit. J Hypertens 20:2383–2390

    Article  Google Scholar 

  15. Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR, Ulick S, Milora RV, Findling JW, Canessa CM, Rosier BC, Lifton RP (1994) Liddle’s syndrome: heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channel. Cell 79:407–414

    Article  Google Scholar 

  16. Hanson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets RA, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP (1995) Hypertension caused by a truncated epithelial sodium channel gamma subunit; genetic heterogeneity of Liddle syndrome. Nature Genet 11:76–82

    Article  Google Scholar 

  17. Yamashita Y, Koga M, Takeda Y, Enomoto N, Uchida S, Hashimoto K, Yamano S, Do K, Marumo F, Sasaki S (2001) Two sporadic cases of Liddle’s syndrome caused by de novo EnaC mutations. Am J Kidney Dis 37:499–504

    Google Scholar 

  18. Gao PJ, Zhang KX, Zhu DL, He X, Han ZY, Zhan YM, Yang LW (2001) Diagnosis of Liddle syndrome by genetic analysis of β and γ subunits of epithelial sodium channel—a report of five affected family members. J Hypertension 19:885–889

    Article  Google Scholar 

  19. Uehara Y, Sasaguri M, Kinoshita A, Tsuji E, Kiyose H, Taniguchi H, Noda K, Ideishi J, Tomita K, Arakawa K (1998) Genetic analysis of the epithelial sodium channel in Liddle’s syndrome. J Hypertension 16:1131–1135

    Article  Google Scholar 

  20. Gadallah MF, Abreo K, Work J (1995) Liddle’s syndrome, an underrecognized entity: a report of four cases, including the first report in black individuals. Am J Kidney Dis 25:829–835

    Google Scholar 

  21. Assadi FK, Kimura RE, Subramanian U, Patel S (2002) Liddle syndrome in a newborn infant. Pediatr Nephrol 17:609–611

    Google Scholar 

  22. Lackland DT, Keil JE (1996) Epidemiology of hypertension in African Americans. Semin Nephrol 16:63–70

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Miami, Miami, Florida, USA

    Michael Freundlich

  2. Department of Clinical Biochemistry, University of Bonn, Bonn, Germany

    Michael Ludwig

  3. Pediatric Specialty Center, 3427 Johnson Street, Hollywood, FL 33021, USA

    Michael Freundlich

Authors
  1. Michael Freundlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Freundlich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Freundlich, M., Ludwig, M. A novel epithelial sodium channel β-subunit mutation associated with hypertensive Liddle syndrome. Pediatr Nephrol 20, 512–515 (2005). https://doi.org/10.1007/s00467-004-1751-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-004-1751-2

Keywords

Search

Navigation