Liddle syndrome

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...

OBJECTIVES: Liddle syndrome is an autosomal dominant hereditary disease caused by a single gene mutation. Typical clinical manifestations are early-onset hypertension and hypokalemia. CASE PRESENTATION: This report describes a 17-year-old male with hypertension and hypokalemia. We performed Captopril inhibition and postural stimulation test to diagnose and type primary aldosteronism. The plasma renin activity was consistently low, and aldosterone levels were high, hence the patient was initially diagnosed with primary aldosteronism...

The objective of this study was to clinically and genetically characterize a pedigree with Liddle syndrome (LS). A LS pedigree comprising with one proband and seven family members was enrolled. The subjects' symptoms, laboratory results and genotypes were analyzed. Peripheral venous samples were collected from the subjects, and genomic DNA was extracted. DNA library construction and exome capture were performed on an Illumina HiSeq 4000 platform. The selected variant sites were validated using Sanger sequencing...

PURPOSE OF REVIEW: Worldwide, compared to other racial/ethnic groups, individuals of African ancestry have an excessively higher burden of hypertension-related morbidities, especially stroke. Identifying modifiable biological targets that contribute to these disparities could improve global stroke outcomes. In this scoping review, we discuss how pathological perturbations in the renin-angiotensin-aldosterone pathways could be harnessed via physiological profiling for the purposes of improving blood pressure control for stroke prevention among people of African ancestry...

Recent advances in the management of kidney tubular diseases have resulted in a significant cohort of adolescents and young adults transitioning from pediatric- to adult-focused care. Most of the patients under adult-focused care have glomerular diseases, whereas rarer tubular diseases form a considerable proportion of pediatric patients. The purpose of this review is to highlight the clinical signs and symptoms of tubular disorders, as well as their diagnostic workup, including laboratory findings and imaging, during young adulthood...

OBJECTIVE: Plasma renin and aldosterone assays are useful in clinical practice for the aetiological assessment of arterial hypertension (hypertension) and / or a disturbance of the electrolyte balance. The objective of our work is to describe the main indications exploration of the renin aldosterone system, its results, its diagnostic and etiological impact. DESIGN AND METHOD: We conducted a retrospective study of 40 patients who received a renin / aldosterone dosage, collected in the Nephrology department at the Hédi Chaker CHU in Sfax for a period of 6 years from January 2014 until December 2020...

OBJECTIVE: Liddle syndrome (LS) is a common monogenic hypertension with continuous activation of epithelial sodium channels (ENaCs) encoded by SCNN1A, SCNN1B, and SCNN1G. This study aimed to identify the pathogenicity of a nonsense mutation in SCNN1G in a Chinese family with LS and the outcomes of tailored treatment with amiloride. DESIGN AND METHOD: Clinical data were collected from six family members and this mutation site was reported by our team at 2015. To explore the pathogenicity of candidate variants, we constructed mutant and wild-type models in vitro and measured amiloride-sensitive current in Chinese Hamster Ovary cells using patch clamp technique...

Renal tubules play an important role in maintaining water, electrolyte, and acid-base balance. Renal tubule dysfunction can cause electrolyte disorders and acid-base imbalance. Clinically, hypokalemic renal tubular disease is the most common tubule disorder. With the development of molecular genetics and gene sequencing technology, hereditary renal tubular diseases have attracted attention, and an increasing number of pathogenic genes related to renal tubular diseases have been discovered and reported. Inherited renal tubular diseases mainly occur due to mutations in genes encoding various specific transporters or ion channels expressed on the tubular epithelial membrane, leading to dysfunctional renal tubular reabsorption, secretion, and excretion...

The kidneys, by equilibrating the outputs to the inputs, are essential for maintaining the constant volume, pH, and electrolyte composition of the internal milieu. Inability to do so, either because of internal kidney dysfunction (primary alteration) or because of some external factors (secondary alteration), leads to pathologies of varying severity, leading to modification of these parameters and affecting the functions of other organs. Alterations of the functions of the collecting duct (CD), the most distal part of the nephron, have been extensively studied and have led to a better diagnosis, better management of the related diseases, and the development of therapeutic tools...

The renin-angiotensin-aldosterone and arginine vasopressin-V2 receptor-aquaporin-2 systems converge upon the epithelial sodium channel ENaC to regulate blood pressure and plasma tonicity. While it is established that V2 receptors initiate renal water reabsorption through aquaporin-2, whether V2 receptors can also induce renal sodium retention through ENaC and raise blood pressure remains an open question. We hypothesized that a specific increase in V2 receptor mediated ENaC activity can lead to high blood pressure...

Geller syndrome is a rare disease and part of Mendelian forms of hypertension. This syndrome is caused by a mutation in the mineralocorticoid receptor with a resultant gain of function. It is characterized by hypertension and hypokalemia, which is exacerbated by the effect of progesterone and thereby presenting during pregnancy. Our patient is a 22-year-old female diagnosed with preeclampsia who presented with hypokalemia, refractory to treatment toward the end of her third trimester. The patient's hypokalemia resolved once she delivered her infant...

[This corrects the article DOI: 10.3389/fped.2022.887214.].

Background: Liddle syndrome is a form of monogenic hypertension caused by mutations in the three homologous subunits of the epithelial sodium channels (ENaCs), α, β, and γ. It is characterized by early-onset refractory hypertension, hypokalemia, low renin activity, and hypoaldosteronism. In this study, we report a novel frame-shift mutation in SCNN1B responsible for Liddle syndrome in a Chinese family. Methods: DNA samples were collected from all participants...

PURPOSE: Through describing the confusing misdiagnosis process of Liddle syndrome, we try to reveal the importance of accurate aldosterone-renin detection and a genetic test for Liddle syndrome. METHODS: We found a family of hypertension and hypokalaemia with the proband of a 21-year-old female who had been misdiagnosed as primary aldosteronism (PA). She presented with high aldosterone and low renin levels. Aldosterone is not suppressed in the saline infusion test and captopril challenge test...

Objective: Liddle syndrome (LS) is a monogenic hypertension consistent with autosomal dominant inheritance, often with early onset high blood pressure in childhood or adolescence. This study aimed to identify the pathogenicity of a nonsense mutation in SCNN1G in a Chinese family with LS and the long-term outcomes of tailored treatment with amiloride. Methods: To explore the pathogenicity of candidate variant reported in 2015 by our team, we constructed mutant and wild-type models in vitro and measured amiloride-sensitive current in Chinese Hamster Ovary ( CHO ) cells using patch clamp technique...

Liddle syndrome (OMIM #177200) is an autosomal dominant disorder caused by gain-of-function pathogenic variants in the genes encoding epithelial sodium channel subunits, including α (SCNN1A), β (SCNN1B), and γ (SCNN1G). The majority of the reported cases carry SCNN1B variants (∼90%), and SCNN1A/G variants are relatively infrequent. Here, we report a 24-year-old Chinese male patient diagnosed with early-onset hypertension. Laboratory tests revealed hypokalemia with a low level of plasma renin activity. Liddle syndrome was confirmed by high-throughput sequencing, which identified a novel nonsense variant Q591X in the SCNN1G gene, resulting in the PY motif's deletion...

Multiple diagnostic entities are included among the causes of secondary arterial hypertension, so an appropriate screening is essential to diagnose potentially treatable pathologies. Genetic syndromes occupy a small percentage of these causes. The latter group includes Liddle syndrome, a rare genetic disease with autosomal dominant inheritance, caused by gain-of-function mutations in the genes that code for the epithelial sodium channel (ENaC), involved in sodium reabsorption in the distal renal tubules. The presence of a family history of arterial hypertension with onset at an early age and hypokalemia in some of them should lead to the suspicion of this genetic disorder, which must be confirmed with genetic tests...

Okur-Chung Neurodevelopmental Syndrome (OCNDS) is caused by heterozygous mutations to the CSNK2A1 gene, which encodes the alpha subunit of protein kinase CK2. The most frequently occurring mutation is lysine 198 to arginine (K198R). To investigate the impact of this mutation, we first generated a high-resolution phosphorylation motif of CK2WT , including the first characterization of specificity for tyrosine phosphorylation activity. A second high resolution motif representing CK2K198R substrate specificity was also generated...

Monogenic disorders of hypertension are a distinct group of diseases causing dysregulation of the renin-angiotensin-aldosterone system and are characterized by low plasma renin activity. These can chiefly be classified as causing (i) excessive aldosterone synthesis (familial hyperaldosteronism), (ii) dysregulated adrenal steroid metabolism and action (apparent mineralocorticoid excess, congenital adrenal hyperplasia, activating mineralocorticoid receptor mutation, primary glucocorticoid resistance), and (iii) hyperactivity of sodium and chloride transporters in the distal tubule (Liddle syndrome and pseudohypoaldosteronism type 2)...

Hypertension is an important modifiable risk factor for cardiovascular disease and stroke. Most cases are diagnosed as essential hypertension however, in some patients, a secondary (and potentially curable) cause is identified. Selecting the right patient to screen for a secondary cause can be challenging and certain clinical and laboratory characteristics can guide work-up. We report a case of a 67-year-old man who presented with intracranial hemorrhage. He had a history of resistant hypertension for three decades and chronic hypokalemia while on a non-diuretic antihypertensive regimen...