Liddle Syndrome:Clinical And Genetic Profiles

Objective:Liddle syndrome is a rare autosomal dominant monogenic hypertension resulting from gain-of-function mutations of the epithelial sodium channel?ENaC?.Liddle syndrome is characterized by early-onset hypertension and hypokalemia.No more than 100 families or sporadic cases have been identified,and most of them were reported in the form of case report.Herein,we analyzed clinical and genetic features of 12 cases of Liddle syndrome.Methods:Clinical data of 12 patients were studied retrospectively.Genomic DNA was extracted from peripheral blood leukocytes in patients and part of their family members.Polymerase chain reaction was employed to amplify the exon 13 of the P and y subunits of ENaC.And then,the PCR products were bi-directionally sequenced.Results:1.Clinical and Biochemical Features:The onset age of the twelve patients?9 males,3 females?was 16±3 years old.The blood pressure of the patients was poorly controlled even they had been put on one to three anti-hypertensive drugs.The highest blood pressure in the course of disease is 196±22/121±16 mmHg.All patients had hypokalemia,and the lowest serum potassium level in the course of disease was 2.3 ± 0.5 mmol/L.Upright plasma renin activity were suppressed in all patients.The plasma aldosterone concentration of most patients were also suppressed.Five patients were given spironolactone,and showed no response.All patients were treated with triamterene,and the blood pressures were well controlled and serum potassium returned to normal.Serum creatinine level were elevated in two patients upon triamterene treatment.2.Genetic analysis:Eight mutation alleles were identified in 11 patients,which were c.1690C>T?p.Arg564Ter?,c.1696C>T?p.Arg566Ter?,c.1702C>T?p.Gln568Ter?,c.1849C>T?p.Pro617Ser?,c.1853C>T?p.Pro618Leu?,c.1806₁807insG?p.Pro603Alafs*5?,c.1848₁849insT?p.Pro617Serfs*5?and c.1854₁855insC?p.Asn619Glnfs*3?.Three of the eight mutations,i.e.,p.Gln568Ter,p.Pro603Alafs,and p.Pro617Serfs,were newly-identified ones.Conclusion:Liddle syndrome patients present with severe early-onset hypertension,hypokalemia,suppressed upright plasma renin activity,and suppressed or normal range plasma aldosterone concentration.The patients showed no response to spironolactone,and responded well to triamterene therapy,but serum creatinine level needs to be closely monitored during the therapy.Eight gene mutation sites in SCNN1B were found in our series,and three mutated sites were newly identified.