Liddle syndrome
Authors:
Štěpán Mareš; Jan Filipovský
Authors‘ workplace:
II. interní klinika LF UK a FN Plzeň
Published in:
Vnitř Lék 2022; 68(E-8): 8-11
Category:
Review Articles
doi:
https://doi.org/10.36290/vnl.2022.115
Overview
Liddle syndrome is an inherited form of arterial hypertension with autosomal dominant pattern of inheritance. It is caused by activating mutation of genes coding of the epithelial sodium channel in distal nephron. Mutation leads to excessive reabsorbtion of sodium ions and volume expansion resulting in arterial hypertension. Antoher typical laboratory findings are hypokalaemia, low levels of serum aldosteron and metabolic alkalosis. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, often resulting in misdiagnosis and severe complications at early age. Genetic studies should be done to confirm the diagnosis. Therapy of Liddle syndrome is based on administration of epithelial sodium channel blocker amilorid.
Keywords:
Aldosterone – arterial hypertension – hypokalaemia – amilorid – epithelial sodium channel – Liddle syndrome – NEDD4
Sources
1. Wang LP, Yang KQ, Jiang XJ, Wu HY, Zhang HM, Zou YB et al. Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population. J Clin Hypertens (Greenwich). 2015 Nov;17(11):902-7.
2. Liu K, Qin F, Sun X, Zhang Y, Wang J, Wu Y et al. Analysis of the genes involved in Mendelian forms of low‑renin hypertension in Chinese early‑onset hypertensive patients. J Hypertens. 2018 Mar;36(3):502-9.
3. Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD et al. Amiloride‑sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994 Feb 3;367(6462):463-7.
4. Hanukoglu I, Hanukoglu A. Epithelial sodium channel (ENaC) family: Phylogeny, structure‑function, tissue distribution, and associated inherited diseases. Gene. 2016 Apr 1;579(2):95-132.
5. Ceccato F, Mantero F. Monogenic Forms of Hypertension. Endocrinol Metab Clin North Am. 2019 Dec;48(4):795-810.
6. Palmer BF, Alpern RJ. Liddle’s syndrome. Am J Med. 1998 Mar;104(3):301-9.
7. Tetti M, Monticone S, Burrello J, Matarazzo P, Veglio F, Pasini B et al. Liddle Syndrome: Review of the Literature and Description of a New Case. Int J Mol Sci. 2018 Mar 11;19(3).
8. Fan P, Pan XC, Zhang D, Yang KQ, Zhang Y, Tian T et al. Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early‑onset Hypertension. Am J Hypertens. 2020 Mar 12.
9. Gong L, Chen J, Shao L, Song W, Hui R, Wang Y. Phenotype‑genotype analysis in two Chinese families with Liddle syndrome. Mol Biol Rep. 2014 Mar;41(3):1569-75.
10. Mareš Š, Filipovský J, Vlková K, Pešta M, Černá V, Hrabák J et al. A novel nonsense mutation in the β‑subunit of the epithelial sodium channel causing Liddle syndrome. Blood Press. 2021 Oct;30(5):291-9.
11. Enslow BT, Stockand JD, Berman JM. Liddle’s syndrome mechanisms, diagnosis and management. Integr Blood Press Control. 2019;12:13-22.
12. Cui Y, Tong A, Jiang J, Wang F, Li C. Liddle syndrome: clinical and genetic profiles. J Clin Hypertens (Greenwich). 2017 May;19(5):524-9.
13. Yang KQ, Xiao Y, Tian T, Gao LG, Zhou XL. Molecular genetics of Liddle’s syndrome. Clin Chim Acta. 2014 Sep 25;436:202-6.
14. Schild L, Lu Y, Gautschi I, Schneeberger E, Lifton RP, Rossier Bc. Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome. Embo j. 1996 May 15;15(10):2381-7.
15. Salih M, Gautschi I, van Bemmelen MX, Di Benedetto M, Brooks AS, Lugtenberg D, et al. A Missense Mutation in the Extracellular Domain of alphaENaC Causes Liddle Syndrome. J Am Soc Nephrol. 2017 Nov;28(11):3291-9.
16. Botero‑Velez M, Curtis JJ, Warnock DG. Brief report: Liddle’s syndrome revisited--a disorder of sodium reabsorption in the distal tubule. N Engl J Med. 1994 Jan 20;330(3):178-81.
17. Al Khaja KA, Sequeira RP, Alkhaja AK, Damanhori AH. Drug treatment of hypertension in pregnancy: a critical review of adult guideline recommendations. J Hypertens. 2014 Mar;32(3):454-63.
18. Podymow T, August P. Hypertension in pregnancy. Adv Chronic Kidney, DiS. 2007 Apr;14(2):178-90.
19. Caretto A, Primerano L, Novara F, Zuffardi O, Genovese S, Rondinell, M.A. Therapeutic Challenge: Liddle’s Syndrome Managed with Amiloride during Pregnancy. Case Rep Obstet Gynecol. 2014;2014:156250.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2022 Issue E-8
Most read in this issue
- Differential diagnosis of hyponatremia and hypernatremia
- Liddle syndrome
- How to convince a patient refusing colonoscopy – a qualitative study
- Ethanol ablation of recurrent symptomatic thyroid cystic nodules in the Czech Republic