Liddle Syndrome

Familial pseudoaldosteronism characterized by autosomal dominant inheritance of hypertension with HYPOKALEMIA; ALKALOSIS; RENIN and ALDOSTERONE level decreases. It is caused by mutations in EPITHELIAL SODIUM CHANNELS beta and gamma subunits. Different mutations in the same EPITHELIAL SODIUM CHANNELS subunits can cause PSEUDOHYPOALDOSTERONISM, TYPE I, AUTOSOMAL DOMINANT.

Also Known As:

Networked: 183 relevant articles (2 outcomes, 11 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Essential Hypertension
2.	Gitelman Syndrome
3.	Rare Diseases (Rare Disease)
4.	Pseudohypoaldosteronism
5.	Glucocorticoid-Remediable Aldosteronism

Experts

1.	Makino, Toshiaki: 8 articles (03/2021 - 07/2008)
2.	Zhou, Xian-Liang: 7 articles (01/2022 - 04/2015)
3.	Liu, Ya-Xin: 6 articles (01/2022 - 04/2015)
4.	Yang, Kun-Qi: 6 articles (01/2022 - 04/2015)
5.	Fan, Peng: 5 articles (01/2022 - 01/2019)
6.	Homma, Masato: 5 articles (01/2021 - 10/2006)
7.	Zhang, Di: 4 articles (01/2022 - 01/2019)
8.	Watanabe, Kenji: 4 articles (01/2021 - 06/2014)
9.	Yoshino, Tetsuhiro: 4 articles (01/2021 - 06/2014)
10.	Song, Lei: 4 articles (01/2020 - 11/2015)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Liddle Syndrome:

1.	MineralocorticoidsIBA 01/01/2004 - "Distinction between Liddle syndrome and apparent mineralocorticoid excess." 06/01/2003 - "The distinction between Liddle syndrome and apparent mineralocorticoid excess." 08/01/2018 - "None of the patients had Liddle syndrome, apparent mineralocorticoid excess or Gordon syndrome. " 04/01/2001 - "Classic linkage analyses have located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. " 12/01/1998 - "Classic linkage analyses has located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. "
2.	Epithelial Sodium Channel BlockersIBA 01/01/2020 - "They were each subsequently found with the same genetic mutation of SCNN1B consistent with Liddle syndrome and started on epithelial sodium channel inhibitors with improvement in their blood pressure. "
3.	Glycyrrhizic Acid (Glycyrrhizin)IBA 01/01/1982 - "[A case of pseudoaldosteronism induced by glycyrrhizin and study of all cases in Japan (author's transl)]." 01/01/2021 - "Clinical Risk Factors of Licorice-Induced Pseudoaldosteronism Based on Glycyrrhizin-Metabolite Concentrations: A Narrative Review." 09/01/2019 - "Glycyrrhizin (GL), the major active ingredient of Glycyrrhizae Radix, has various pharmacological actions but causes adverse effects such as pseudoaldosteronism. " 10/22/2018 - "Isolation of a novel glycyrrhizin metabolite as a causal candidate compound for pseudoaldosteronism." 10/01/2017 - "The major active ingredient of Glycyrrhizae Radix, glycyrrhizin (GL), has been shown to possess various pharmacological actions, but is also known to cause adverse effects such as pseudoaldosteronism. "
4.	Epithelial Sodium ChannelsIBA 01/01/2023 - "Liddle 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. " 01/01/2022 - "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). " 01/01/2022 - "A Family with Liddle Syndrome Caused by a Novel Stop-Gain Mutation in the γ Subunit of Epithelial Sodium Channels." 07/01/2021 - "The cause of Liddle syndrome is missense or frame shift mutations in SCNN1A, SCNN1B, or SCNN1G genes that encode epithelial sodium channel subunits. " 01/01/2021 - "Liddle syndrome (LS) is a rare autosomal dominant condition secondary to a gain-of-function mutation affecting the epithelial sodium channels (ENaCs) in the distal nephron. "
5.	Biomarkers (Surrogate Marker)IBA 11/01/2019 - "This is the first study to identify the association between a novel metabolite, compound 3, and the incidence of pseudoaldosteronism, highlighting it as a promising biomarker." 10/22/2018 - "Compound 1, when produced in Mrp2-deficiency, represents a potential causative agent of pseudoaldosteronism, and might be used as a biomarker to prevent the adverse effect." 11/01/2019 - "Identification of glycyrrhizin metabolites in humans and of a potential biomarker of liquorice-induced pseudoaldosteronism: a multi-centre cross-sectional study." 12/01/2013 - "The aim of this study was to compare (a) the pharmacokinetics of glycyrrhizin and its metabolites in rat after the first and last intravenous doses of either α- or β-glycyrrhizin administered once a day over 6 days, (b) kidney levels of the metabolites at 24 h after the last dose and (c) the urinary cortisol:cortisone ratio (as a biomarker of pseudoaldosteronism) in total urine collected for 24 h after the last dose.After"
6.	SaltsIBA 01/01/2016 - "Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. " 01/01/2016 - "Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. " 02/01/2013 - "Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). " 09/01/2003 - "The Liddle syndrome is a dominant form of salt-sensitive hypertension resulting from mutations in the beta or gamma subunit of ENaC. " 06/01/1998 - "Liddle syndrome (pseudo-hyperaldosteronism) is one of a number of monogenic disorders of salt and water transport. "
7.	Hydrocortisone (Cortisol)FDA LinkGeneric 04/01/2009 - "In this case, the observed reduction in the urinary cortisol levels, from 600.6 to 37.8 microg/day, led to a definitive diagnosis of pseudoaldosteronism instead of the apparent mineralocorticoid excess syndrome. " 11/01/2010 - "In this patient, the increased circulating cortisol associated with the stress of inflammation caused by pneumonia triggered the development of pseudoaldosteronism." 11/01/2010 - "Pseudoaldosteronism with increased serum cortisol associated with pneumonia, hypouricemia, hypocalcemia, and hypophosphatemia." 11/01/2010 - "When he developed pseudoaldosteronism, he also contracted pneumonia, and exhibited elevated levels of serum cortisol and creatinine clearance (CCr) as well as hypouricemia, hypocalcemia, and hypophosphatemia. " 04/01/2009 - "Shakuyaku-kanzo-to induces pseudoaldosteronism characterized by hypokalemia, rhabdomyolysis, metabolic alkalosis with respiratory compensation, and increased urinary cortisol levels."
8.	Yi-Gan SanIBA 01/01/2020 - "This study aimed to identify the risk factors of pseudoaldosteronism with yokukansan use. " 01/01/2020 - "We also analyzed the risk factors for pseudoaldosteronism in patients taking yokukansan. " 01/01/2020 - "Risk Factors for Pseudoaldosteronism with Yokukansan Use: Analysis Using the Japanese Adverse Drug Report (JADER) Database." 01/01/2011 - "We diagnosed pseudoaldosteronism caused by the Chinese herbal remedy Yokukansan (which includes licorice). " 09/01/2021 - "Of course, we should pay attention to the side effects, pseudoaldosteronism, but TJ-54 may be one of the alternative treatment therapies for MOH."
9.	glycyrrhetyl 3-monoglucuronideIBA 07/01/2008 - "A previous clinical study suggested that 3-monoglucuronyl-glycyrrhetinic acid (3MGA), another metabolite of GL, might play a more important role in the pathogenesis of pseudoaldosteronism. " 06/01/1995 - "3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism." 01/01/2018 - "Furthermore, an eastern blotting method was applied to the biological metabolic study of glycyrrhizic acid (GL), the major active constituent of licorice, for investigation of metabolites of GL such as 3-monoglucuronyl-glycyrrhetinic acid (3MGA) because licorice causes pseudoaldosteronism as a side effect. " 04/03/2007 - "A possible involvement of 3-monoglucuronyl-glycyrrhetinic acid, a metabolite of glycyrrhizin (GL), in GL-induced pseudoaldosteronism." 12/01/2013 - "Glycyrrhizin, the major bioactive component in licorice root extract, exists as 2 isomers, α and β-glycyrrhizin, and is associated with causing pseudoaldosteronism due to its principal metabolites, glycyrrhetinic acid and 3-monoglucuronyl-glycyrrhetinic acid. "
10.	CortisoneFDA Link 01/01/1992 - "These results suggest that increased renal cortisol as a result of decreased conversion to cortisone might play an important role in the development of pseudoaldosteronism as well as in its own mineralocorticoid activity." 12/01/2013 - "The aim of this study was to compare (a) the pharmacokinetics of glycyrrhizin and its metabolites in rat after the first and last intravenous doses of either α- or β-glycyrrhizin administered once a day over 6 days, (b) kidney levels of the metabolites at 24 h after the last dose and (c) the urinary cortisol:cortisone ratio (as a biomarker of pseudoaldosteronism) in total urine collected for 24 h after the last dose.After" 05/01/2013 - "However, yokukansan should be used with caution because of its potential to induce pseudoaldosteronism through the inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol into cortisone. " 02/01/2011 - "Glycyrrhizin, the main component of Shakuyaku-kanzo-to, has been reported to be a cause of pseudoaldosteronism by inhibiting the enzyme converting cortisol to cortisone. "

Therapies and Procedures

1.	Therapeutics 02/01/2006 - "[Liddle syndrome: Pathogenesis, pathophysiology, and therapy]." 01/01/2022 - "Therapy of Liddle syndrome is based on administration of epithelial sodium channel blocker amilorid." 09/01/2021 - "Of course, we should pay attention to the side effects, pseudoaldosteronism, but TJ-54 may be one of the alternative treatment therapies for MOH." 01/01/2022 - "Amiloride therapy combined with a low sodium diet is effective to alleviate the symptoms of patients with Liddle syndrome. " 05/04/2017 - "Liddle syndrome is a rare form of autosomal dominant monogenic hypertension manifested as an early onset of resistant hypertension with either no response or suboptimal response to conventional antihypertensive therapy. "
2.	Kampo Medicine (Kampo) 03/01/2021 - "I investigated the causative agents of licorice-induced pseudoaldosteronism, which is a frequent side effect of Japanese traditional Kampo medicines. " 04/01/2020 - "In six women, the highest correlation coefficient was observed between BSA and the glycyrrhiza dose in Kampo extract at the onset of pseudoaldosteronism. " 01/01/2020 - "Using cases reported in the Japanese Adverse Drug Report (JADER) database, the reporting odds ratio (ROR) was calculated and compared to assess the risk of pseudoaldosteronism for each licorice-containing Kampo formula. " 10/22/2018 - "Pseudoaldosteronism is a common adverse effect associated with traditional Japanese Kampo medicines. " 01/01/2014 - "One of the most common adverse effects of traditional Japanese kampo and traditional Chinese medicine is pseudoaldosteronism caused by licorice. "
3.	Intravenous Administration 12/01/2013 - "Comparison of the exposure of glycyrrhizin and its metabolites and the pseudoaldosteronism after intravenous administration of alpha- and beta-glycyrrhizin in rat."
4.	Polypharmacy 07/01/2022 - "We report the first case of TCM associated with licorice-induced pseudoaldosteronism causing fatal arrhythmia in an older patient on polypharmacy including yokukansan (TJ-54) and galantamine. "
5.	Oral Surgery (Maxillofacial Surgery) 09/01/2023 - "Torsade de pointes during an oral surgery caused by a combination of herbal medicine-induced pseudoaldosteronism and trigeminocardiac reflex."