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Vnitrni Lekarstvi 2022Liddle 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...
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.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Hypertension; Hypokalemia; Mutation
PubMed: 36575060
DOI: 10.36290/vnl.2022.115 -
International Journal of Molecular... Mar 2018Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in... (Review)
Review
Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in germline mutations of the , and genes, encoding the α, β, and γ-subunits of the epithelial Na⁺ channel (ENaC), respectively. To date, 31 different causative mutations have been reported in 72 families from four continents. The majority of the substitutions cause an increased expression of the channel at the distal nephron apical membrane, with subsequent enhanced renal sodium reabsorption. The most common clinical presentation of the disease is early onset hypertension, hypokalemia, metabolic alkalosis, suppressed plasma renin activity and low plasma aldosterone. Consequently, treatment of Liddle syndrome is based on the administration of ENaC blockers, amiloride and triamterene. Herein, we discuss the genetic basis, clinical presentation, diagnosis and treatment of Liddle syndrome. Finally, we report a new case in an Italian family, caused by a p.Pro618Leu substitution.
Topics: Adolescent; Epithelial Sodium Channels; Humans; Liddle Syndrome; Male; Mutation, Missense; Phenotype
PubMed: 29534496
DOI: 10.3390/ijms19030812 -
Medicina Clinica Jun 2021Liddle syndrome is an autosomal dominant hereditary disease caused by a single gene mutation. Typical clinical manifestations are early-onset hypertension and...
INTRODUCTION
Liddle syndrome is an autosomal dominant hereditary disease caused by a single gene mutation. Typical clinical manifestations are early-onset hypertension and hypokalaemia and can be treated using ENaC blockers (amiloride and aminopterin).
PATIENTS AND METHODS
This report describes a 17-year-old male with hypertension and hypokalaemia. We performed a Captopril inhibition test and a postural stimulation test for the diagnosis and typing of primary aldosteronism.
RESULTS
The serum renin was low, and aldosterone was high, so the patient was initially misdiagnosed as primary aldosteronism. After a genetic analysis, a diagnosis of Liddle syndrome was made due to the presence of an SCNN1B p.Pro617Ser mutation. After diagnosis, the patient was administered one tablet of amiloride twice a day (each tablet contains 2.5mg of amiloride hydrochloride and 25mg of hydrochlorothiazide 25mg). The patient's blood pressure (average of 120-135/70-80mmHg) and serum potassium levels (3.6-4.0mmol/L) returned to normal and were well-controlled after treatment.
DISCUSSION
The patient is an atypical case of Liddle syndrome; genetic analysis is helpful and essential for diagnosis.
PubMed: 34147249
DOI: 10.1016/j.medcli.2021.03.035 -
The American Journal of Medicine Mar 1998
Review
Topics: Adolescent; Female; Humans; Hypertension; Syndrome
PubMed: 9552093
DOI: 10.1016/s0002-9343(98)00018-7 -
Journal of Ayub Medical College,... 2016Hypertension in paediatric age group is commonly secondary to a known cause. It is crucial to identify the cause of hypertension and treat it before development of any...
Hypertension in paediatric age group is commonly secondary to a known cause. It is crucial to identify the cause of hypertension and treat it before development of any associated complications to prevent morbidity and mortality. Paediatric Hypertension is one of the important clinical finding in a child with certain clinical syndrome. We are presenting a case of a 10 month old child presenting with hypertension and hypokalaemia, after excluding all identifiable causes and her positive response to therapy, that is amiloride, along with supportive biochemical data she was diagnosed as a case of monogenic type of hypertension known as Liddle's syndrome.
Topics: Amiloride; Epithelial Sodium Channel Blockers; Female; Humans; Infant; Liddle Syndrome
PubMed: 28586600
DOI: No ID Found -
Integrated Blood Pressure Control 2019Liddle's syndrome is a genetic disorder characterized by hypertension with hypokalemic metabolic alkalosis, hyporeninemia and suppressed aldosterone secretion that often...
Liddle's syndrome is a genetic disorder characterized by hypertension with hypokalemic metabolic alkalosis, hyporeninemia and suppressed aldosterone secretion that often appears early in life. It results from inappropriately elevated sodium reabsorption in the distal nephron. Liddle's syndrome is caused by mutations to subunits of the Epithelial Sodium Channel (ENaC). Among other mechanisms, such mutations typically prevent ubiquitination of these subunits, slowing the rate at which they are internalized from the membrane, resulting in an elevation of channel activity. A minority of Liddle's syndrome mutations, though, result in a complementary effect that also elevates activity by increasing the probability that ENaC channels within the membrane are open. Potassium-sparing diuretics such as amiloride and triamterene reduce ENaC activity, and in combination with a reduced sodium diet can restore normotension and electrolyte imbalance in Liddle's syndrome patients and animal models. Liddle's syndrome can be diagnosed clinically by phenotype and confirmed through genetic testing. This review examines the clinical features of Liddle's syndrome, the differential diagnosis of Liddle's syndrome and differentiation from other genetic diseases with similar phenotype, and what is currently known about the population-level prevalence of Liddle's syndrome. This review gives special focus to the molecular mechanisms of Liddle's syndrome.
PubMed: 31564964
DOI: 10.2147/IBPC.S188869 -
Clinica Chimica Acta; International... Sep 2014Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic... (Review)
Review
Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel (ENaC) blockers but not spironolactone therapy. Our understanding of ENaCs and Na(+) transport defects has expanded greatly over the past two decades and provides detailed insight into the molecular basis of Liddle's syndrome. In this review, we offer an overview of recent advances in understanding the molecular genetics of Liddle's syndrome, involving mutation analysis, molecular mechanisms and genetic testing. The ENaC in the distal nephron is composed of α, β and γ subunits that share similar structures. Mutations associated with Liddle's syndrome are positioned in either β or γ subunits and disturb or truncate a conserved proline-rich sequence (i.e., PY motif), leading to constitutive activation of the ENaC. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers.
Topics: Epithelial Sodium Channels; Genetic Testing; Humans; Liddle Syndrome; Molecular Biology
PubMed: 24882431
DOI: 10.1016/j.cca.2014.05.015 -
The American Journal of the Medical... Dec 2001Our current understanding of Na+ transport defects has been greatly expanded over the last several years and has provided new insights into unusual clinical syndromes... (Review)
Review
Our current understanding of Na+ transport defects has been greatly expanded over the last several years and has provided new insights into unusual clinical syndromes resulting from mutations of specific ion transporters. These genetic disorders affect Na+ balance, with both Na+ retaining and Na+ wasting conditions being the consequence. A major focus of these studies has been the epithelial sodium channel (ENaC), which can be directly affected by mutations (eg, Liddle syndrome, autosomal recessive pseudohypoaldosteronism, type I) or by changes in the response to (autosomal recessive pseudohypoaldosteronism, type I), or production of mineralocorticoids (apparent mineralocorticoid excess syndrome, glucocorticoid-remediable aldosteronism). As a result, we now have clearly defined syndromes in which ENaC activity is "dysregulated" with subsequent development of disorders of systemic blood pressure that can be attributed to a primary renal mechanisms. The focus of the current review is on Liddle syndrome ("pseudoaldosteronism").
Topics: Epithelial Sodium Channels; Genetic Linkage; Humans; Hyperaldosteronism; Hypertension; Mutation; Pseudohypoaldosteronism; Renin; Sodium Channels; Syndrome
PubMed: 11780687
DOI: 10.1097/00000441-200112000-00002 -
Nihon Jinzo Gakkai Shi 2011
Review
Topics: Epithelial Sodium Channels; Humans; Immediate-Early Proteins; Kidney Tubules, Collecting; Liddle Syndrome; Mutation; Polymorphism, Genetic; Potassium; Protein Serine-Threonine Kinases; Sodium; Sodium-Potassium-Exchanging ATPase
PubMed: 21516699
DOI: No ID Found