{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:05:59Z","timestamp":1783065959278,"version":"3.54.6"},"reference-count":14,"publisher":"AOSIS","issue":"1","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Afr. J. Lab. Med."],"abstract":"<jats:p>Introduction:\u00a0Liddle syndrome is an autosomal dominantly inherited disorder usually arising from single mutations of the genes that encode for the alpha, beta and gamma epithelial sodium channel (ENaC) subunits. This leads to refractory hypertension, hypokalaemia, metabolic alkalosis, hyporeninaemia and hypoaldosteronism, through over-activation of the ENaC.Case presentation:\u00a0We describe a 5-day old neonate who presented with severe hypernatraemic dehydration requiring admission to Steve Biko Academic Hospital in South Africa in 2012. Further evaluation revealed features in keeping with Liddle syndrome. Two compound heterozygous mutations located at different subunits encoding the ENaC were detected following genetic sequencing done in 2020. The severe clinical phenotype observed here could be attributed to the synergistic effect of these known pathological mutations, but may also indicate that one of the other variants detected has hitherto undocumented pathological effects.Management and outcome:\u00a0This child\u2019s treatment course was complicated by poor adherence to therapy, requiring numerous admissions over the years. Adequate blood pressure control was achieved only after the addition of amiloride at the end of 2018, which raised the suspicion of an ENaC abnormality.Conclusion:\u00a0To our knowledge, this is the first Liddle syndrome case where a combined effect from mutations resulted in severe disease. This highlights the importance of early recognition and management of this highly treatable genetic disease to prevent the grave sequelae associated with long-standing hypertension. Whole exome sequencing may assist in the detection of known mutations, but may also unveil new potentially pathological variants.What this study adds:\u00a0This study highlights the importance of developing a high index of suspicion of tubulopathy such as Liddle syndrome for any child presenting with persistent hypertension associated with hypokalaemic metabolic alkalosis.\u00a0<\/jats:p>","DOI":"10.4102\/ajlm.v12i1.1998","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T08:56:37Z","timestamp":1683104197000},"source":"Crossref","is-referenced-by-count":6,"title":["Neonatal presentation of a patient with Liddle syndrome, South Africa"],"prefix":"10.4102","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-2050","authenticated-orcid":false,"given":"Nicolene","family":"Steyn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3368-6398","authenticated-orcid":false,"given":"Bettina","family":"Chale-Matsau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-6642","authenticated-orcid":false,"given":"Aron B.","family":"Abera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-5073","authenticated-orcid":false,"given":"Gertruida","family":"Van Biljon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-9710","authenticated-orcid":false,"given":"Tahir S.","family":"Pillay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2580","published-online":{"date-parts":[[2023,4,14]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Buyukkaragoz B, Yilmaz AC, Karcaaltincaba D, Ozdemir O, Ludwig M. Liddle syndrome in a Turkish family with heterogeneous phenotypes. Pediatr Int. 2016;58(8):801-804. https:\/\/doi.org\/10.1111\/ped.12985","DOI":"10.1111\/ped.12985"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Bogdanovic R, Kuburovic V, Stajic N, et al. Liddle syndrome in a Serbian family and literature review of underlying mutations. Eur J Pediatr. 2012;171(3):471-478. https:\/\/doi.org\/10.1007\/s00431-011-1581-8","DOI":"10.1007\/s00431-011-1581-8"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Assadi FK, Kimura RE, Subramanian U, Patel S. Liddle syndrome in a newborn infant. Pediatr Nephrol. 2002;17(8):609-611. https:\/\/doi.org\/10.1007\/s00467-002-0897-z","DOI":"10.1007\/s00467-002-0897-z"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Enslow BT, Stockand JD, Berman JM. Liddle's syndrome mechanisms, diagnosis and management. Integr Blood Pressure Control. 2019;12:13-22. https:\/\/doi.org\/10.2147\/IBPC.S188869","DOI":"10.2147\/IBPC.S188869"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Hanukoglu I, Hanukoglu A. Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. Gene. 2016;579(2):95-132. https:\/\/doi.org\/10.1016\/j.gene.2015.12.061","DOI":"10.1016\/j.gene.2015.12.061"},{"key":"ref5","unstructured":"Rifai N. Tietz textbook of clinical chemistry and molecular diagnostics. e-book. Elsevier Health Sciences: St Louis, MO; 2017."},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Dong YB, Zhu HD, Baker EH, et al. T594M and G442V polymorphisms of the sodium channel beta subunit and hypertension in a black population. J Hum Hypertens. 2001;15(6):425-430. https:\/\/doi.org\/10.1038\/sj.jhh.1001182","DOI":"10.1038\/sj.jhh.1001182"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Baker EH, Dong YB, Sagnella GA, et al. Association of hypertension with T594M mutation in \u03b2 subunit of epithelial sodium channels in Black people resident in London. Lancet. 1998;351(9113):1388-1392. https:\/\/doi.org\/10.1016\/S0140-6736(97)07306-6","DOI":"10.1016\/S0140-6736(97)07306-6"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Ambrosius WT, Bloem LJ, Zhou L, et al. Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension. Hypertension. 1999;34(4):631-637. https:\/\/doi.org\/10.1161\/01.HYP.34.4.631","DOI":"10.1161\/01.HYP.34.4.631"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Tetti M, Monticone S, Burrello J, et al. Liddle syndrome: Review of the literature and description of a new case. Int J Mol Sci. 2018;19(3):812. https:\/\/doi.org\/10.3390\/ijms19030812","DOI":"10.3390\/ijms19030812"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Rossi E, Farnetti E, Nicoli D, et al. A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome. Am J Hypertens. 2011;24(8):930-935. https:\/\/doi.org\/10.1038\/ajh.2011.76","DOI":"10.1038\/ajh.2011.76"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Liu K, Qin F, Sun X, et al. Analysis of the genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients. J Hypertens. 2018;36(3):502-509. https:\/\/doi.org\/10.1097\/HJH.0000000000001556","DOI":"10.1097\/HJH.0000000000001556"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Jones ES, Rayner BL, Spence JD, et al. High frequency of variants of candidate genes in Black Africans with low renin-resistant hypertension. Am J Hypertens. 2017;30(5):478-483. https:\/\/doi.org\/10.1093\/ajh\/hpw167","DOI":"10.1093\/ajh\/hpw167"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Polfus LM, Boerwinkle E, Gibbs RA, et al. Whole-exome sequencing reveals an inherited R566X mutation of the epithelial sodium channel beta-subunit in a case of early-onset phenotype of Liddle syndrome. 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