A case of Liddle syndrome and review of literature / 中华内分泌代谢杂志

The clinical data, laboratory test, and gene mutations were collected from a family with Liddle syndrome. Literatures on Liddle syndrome published in domestic and abroad since 1994 were reviewed and the types of gene mutations were summarized. The proband was diagnosed with hypertension at the age of 24. Laboratory test showed that serum potassium was 3.65 mmol/L, plasma renin was <0.5 mU/L, and plasma aldosterone was 1.5 ng/dL. Proband′s father was diagnosed with hypertension at the age of 34 with the serum potassium 3.34 mmol/L, plasma renin 3.72 mU/L, and plasma aldosterone 6.04 ng/dL. A nonsense mutation(1724G>A, p.Trp575*) in exon 13 of SCNN1G gene was detected in the proband and his father. In 288 cases from 107 families reported in the review of domestic and foreign literature, the incidence of hypertension, hypokalemia, and low renin/low aldosterone were 95.1%, 55.2%, and 49.6%, respectively. This case suggests that the clinical phenotype of Liddle syndrome is heterogeneous. Patients with early-onset hypertension, regardless of whether they are accompanied by hypokalemia, should be screened for renin-angiotensin-aldosterone and genetic testing related to Liddle syndrome should be further detected in patients with low plasma renin/aldosterone.

Liddle syndrome: case report and literature review / 中华全科医师杂志

The clinical data and the genetic study results of a patient with Liddle syndrome were reported.The genomic DNA of peripheral blood mononuclear cells was extracted and the mutation sites of all the exons in 36 genes related to hypokalemia were screened by high-throughput sequencing.Genetic validation of patients and their parents was performed by direct sequencing.The patient presented with severe hypokalemia,low aldosterone and hypertension.The results of gene sequencing showed that the SCNN1B gene exon 13 584 codon 1751C-T,and the corresponding encoded amino acid changed from alanine to valine (A-V).Eleven families and 33 cases of Liddle syndrome diagnosed by genetic analysis were reported in Chinese literature from 1998 to June 2018.The literature review showed that all patients had hypertension,87％ (28/32) had hypokalemia and 85％ (23/27) had low aldosterone.The onset age of 21 patients was＜20 year,among whom cerebral stroke occurred in 3 patients.The normal blood pressure can be achieved by low-salt diet and administration of amiloride or triamterene.The most common mutations were missense mutations (7/11).Liddle syndrome is a controllable and treatable disease,early detection,diagnosis and treatment can avoid serious complications.

Bartter syndrome and Liddle syndrome / 中华实用儿科临床杂志

Bartter syndrome and Liddie syndrome are genetic renal tubular disorders characterized by hypokalemic alkalosis.Bartter syndrome is mainly an autosomal recessive disease,caused by mutations of one of the five ion channel genes in renal tubular epithelial cells.Plasma renin and aldosterone levels are increased but blood pressure is normal,the main treatment is to correct hypokalemia,to prevent and cure complications.Liddle syndrome is an autosomal dominant disease,caused by epithelial Na-channel gene mutation,and presented with increased blood pressure but decreased plasma levels of renin and aldosterone.Patients with Liddle syndrome should limit the intake of sodium and supplement potassium,take Triamterene or Amiloride to control hypertension.

Clinical Study of a Newly Diagnosed Case of Gitelman Syndrome in a Patient Monitored for Liddle Syndrome

A 55-year-old man who had been monitored for Liddle syndrome in the nephrology division for 15 years visited again Inje University Sanggye Paik Hospital for a newly developed electrolyte disorder. Because his blood pressure was normal and he showed hypomagnesemia and hypokalemia, a renal clearance test and renal biopsy were conducted for suspected Gitelman syndrome. The patient was diagnosed with Gitelman syndrome, which has been previously reported 12 cases in South Korea. The renal clearance test revealed a disorder of the Na-Cl cotransporter (NCCT) in the distal tubule, while the renal biopsy revealed partial expression of NCCT, typical of Gitelman syndrome. Currently, the patient is being monitored, and is receiving oral administration of calcium and magnesium.

Hypertensive Hypokalemic Disorders

Hypokalemia is a common clinical problem. The kidney is responsible for long term potassium homoeostasis, as well as the serum potassium concentration. The main nephron site where K secretion is regulated is the cortical collecting duct, mainly via the effects of aldosterone. Aldosterone interacts with the mineralocorticoid receptor to increase sodium reabsorption and potassium secretion; the removal of cationic sodium makes the lumen relatively electronegative, thereby promoting passive potassium secretion from the tubular cell into the lumen through apical potassium channels. As a result, any condition that decreases the activity of renal potassium channels results in hyperkalemia (for example, amiloride intake or aldosterone deficiency) whereas their increased activity results in hypokalemia (for example, primary aldosteronism or Liddle's syndrome). The cause of hypokalemia can usually be determined from the history. If there is no apparent cause, the initial step is to see if hypokalemia is in associated with systemic hypertension or not. In the former group hypokalaemia is associated with a high mineralocorticoid effect or hyperactive sodium channel as in Liddle's syndrome. In hypertensive hypokalemic patients, measurement of the renin, aldosterone, and cortisol concentrations would be of help in differential diagnosis.

A Case of Adrenocortical Adenoma Causing Subclinical Cushing's Syndrome Mistaken for Liddle's Syndrome / 대한내분비학회지

Subclinical Cushing's syndrome is defined as an autonomous cortisol hyperproduction without specific clinical signs of cortisol excess, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. We report a case of a 33-year-old woman with subclinical Cushing's syndrome caused by left adrenocortical adenoma, mistaken for Liddle's syndrome. The patient complained of fatigue. Laboratory findings showed metabolic alkalosis, hypokalemia, high TTKG (transtubular K concentration gradient), low plasma renin activity, and low serum aldosterone level, that findings implied as Liddle's syndrome. So we performed further study. Hormonal and radiologic studies revealed subclinical Cushing's syndrome with a left adrenal mass. The adrenal mass was resected and pathologically diagnosed as adrenocortical adenoma. After the resection of the left adrenal mass, patient's hormonal levels showed normal range.

A Case of Liddle's Syndrome in a Seventy One-year Old Woman / 대한신장학회잡지

Liddle's syndrome is a rare inherited disease with characteristic clinical manifestations of hypertension and hypokalemic metabolic alkalosis. Markedly suppressed serum aldosterone and renin levels are important laboratory findings to differentiate this disorder from primary hyperaldosteronism. When Liddle et al. reported the disorder in 1963, they proposed aggressive Na+ absorption and increased excretion of K+ as the pathogenesis of the syndrome. Since then, specific mutation in the epithelial Na+ channel located in the collecting duct of the kidney has been elucidated as a disease mechanism. Liddle's syndrome is inherited by an autosomal dominant trait and generally the onset of the syndrome is before the age of 20 with increased risk of premature death due to stroke or heart failure. Recently, however, a few cases of late onset and genetically proven nonfamilial cases with de novo mutation of beta or gamma Na+ channel have been reported. We report a case of seventy-one year old woman who had hypertension with hypokalemic metabolic alkalosis and was diagnosed as Liddle's syndrome. Further evaluation revealed low serum renin and aldosterone levels. Primary aldosteronism, Cushing's syndrome, glucocorticoid remediable aldosteronism and deficiency of 11beta-OHase and 17alpha-OHase were ruled out based on her laboratory data and history. Her hypertension and hypokalemia responded to amiloride treatment but not to spironolactone.

Liddle's syndrome: a report in a middle-aged woman

A 54-year-old woman with diabetes mellitus was hospitalized with generalized edema and weakness. She was also found to have hypertension, hypokalemia and metabolic alkalosis. Detailed examination showed subnormal plasma renin activity and plasma aldosterone concentration. Adrenal CT scanning revealed no adrenal tumor. A successful treatment with amiloride established the diagnosis of Liddle's syndrome for the patient. Liddle's syndrome, a rare hereditary disease usually found in young patients, should be considered in the differential diagnosis of hypertension even in elderly individuals.

A Case of Liddle's Syndrome Associated with Muscle Weakness / 대한신장학회잡지

Liddle's syndrome was described in 1963 by Liddle, et al., as the disease featuring a hypertension and hypokalemia but with negligible secretion of aldosterone. This syndrome, which morphologically belongs to an abnormal intrinsic tubular disorder with normal renal function, is characterized by hypokalemia, metabolic alkalosis, and hypertension due to the abnormal increase in excretion of potassium in distal tubules or collecting duct and the increase in reabsorption of sodium in distal tubules. This syndrome, which is rare disease, is observed with the low level of plasma and urinary aldosterone and suppressed plasma renin level and is known as dominant mode of inheritance with a family background. The authors paid attention to a 79-year-old man who showed a high blood pressure of 210/130mmHg as well as musle weakness, especially lower extremities due to metabolic alkalosis featuring a hypokalemia level of 2.0mEq/L when he was admitted to our hospital, Because his serum potassium were not improved with the medication of intravenous potassium supply, and his blood pressure continued to be high without the improvement of muscle weakness, we prescribed 300mg of spironolactone for two weeks. His symptom, however, was not cured. Then, instead of spironolactone, we prescribed 150mg of triamterene and a low salt diet which finally improved his symptoms. Because there has been no reported case in the Korean medical literature, we report a case of successfully treated Liddle's syndrome due to triamterene administration.

Mutation screening of epithelial sodium channel gene in a Liddle's syndrome family / 中华肾脏病杂志

Objective To screen the mutation in P and 7 subunit of epithelial sodium channel (ENaC) gene in the relatives of a patient diagnosed as Liddle's syndrome. Methods In a family of three generations, seven family members were affected with hypertension, among them a girl aged 14 years was diagnosed as Laddie's syndrome and her mother and maternal grandsire died of stroke at thirty-eight years. Peripheral blood samples were collected from all living members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the final exon of the ? ENaC (codon 513-638) and ? ENaC (codon 524-631 )gene. PCR products were purified and subjected to direct DNA sequencing. Results Genetic analysis of the ? ENaC gene revealed a missense mutation of CCC (Pro) to TCC (Ser)at codon 616 in the index case and two other family members. In these three family members, a new variant of GAC (Asp) to CAC(His) at codon 632 was found, which was linked with 616 (Ser) . This variant was not detected by direct sequencing the final exon of ? ENaC gene in 150 unrelated subjects. Through clinical examinations and biochemical measurement, thSese two mutation carriers' biochemical characteristics were all concordant with Liddle's syndrome. Neither mutation could be detected in other members of this family. The mutation TGG(Trp)573TAG(Term) of ? ENaC gene could not be found in this family either. Conclusions (1) Screening for specific mutations of ENaC in relatives of patients affected with Liddle's syndrome can be used to identify previously unrecognized cases within families. (2) A new missense mutation in the ? ENaC gene is found in this family.