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Liddle syndrome in a Serbian family and literature review of underlying mutations

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Abstract

Severe and reproducible low-renin hypertension responsive to salt restriction and amiloride–thiazide therapy in a 13-year-old otherwise asymptomatic boy suggested Liddle syndrome. This assumption was strengthened by a positive family history of hypertension poorly responsive to conventional treatment or sudden deaths under 40 years of age in four generations. DNA analysis of the beta and gamma subunits of the epithelial sodium channel revealed a heterozygous mutation c.C1852T (p.Pro618Ser) in the SCNN1B gene in the patient and in both his hypertensive mother and uncle. A PubMed search revealed 21 different disease-causing mutations reported to date, all but two clustering in the cytoplasmic C-terminal regions of either beta (16 mutations) or gamma (5) subunit, leading to a three- to eightfold increase in the amiloride-sensitive sodium current. Inter- and intrafamilial variability in both hypertension and hypokalemia were disclosed, which may not be obligatory among the subjects carrying a Liddle mutation. Conclusion: Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension.

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Acknowledgments

Portions of this work were presented at the 1st Congress of Pediatrics of Serbia, October 17–20, 2010, Belgrade (Abstract Book, p. 210), and at the 44th Annual Scientific Meeting of the European Society for Paediatric Nephrology, 14–17 September 2011, Cavtat-Dubrovnik, Croatia (Pediatr Nephrol 2011; 26:1717). Molecular genetic analysis in proband was done at the Molecular Genetic Laboratory, Medical Genetics Service, Addenbrooke's Hospital, Cambridge, UK. The work is partially supported by the Ministry of Science of the Republic of Serbia, grant no. 145046. R.B. now receives support by the Ministry of Education and Science, grant no. OI175079.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Medical Faculty, University of Belgrade, Belgrade, Serbia

    Radovan Bogdanović

  2. Institute of Mother and Child Healthcare of Serbia “Dr Vukan Čupić”, 8 Radoja Dakica Street, 11070, Belgrade, Serbia

    Radovan Bogdanović, Vladimir Kuburović, Nataša Stajić, Sanja Ninić & Sergej Prijić

  3. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Sadaf S. Mughal & Alina Hilger

  4. Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany

    Michael Ludwig

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  1. Radovan Bogdanović
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Correspondence to Radovan Bogdanović.

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Bogdanović, R., Kuburović, V., Stajić, N. et al. Liddle syndrome in a Serbian family and literature review of underlying mutations. Eur J Pediatr 171, 471–478 (2012). https://doi.org/10.1007/s00431-011-1581-8

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