Clinical Research And Gene Diagnosis Of Bartter Syndrome And Gitelman Syndrome

BackgroundBartter syndrome(BS)and Gitelman syndrome(GS)are all the autosomal hereditary renal tubular disease.They share the common clinical manifestations of hypokalemia,hypochloric metabolic alkalosis,and high reninangiotensin-aldosterone levels,while normal blood pressure.Renal histopathology suggests the features of juxtaglomerular apparatus hyperplasia and hypertrophy.Hypocalciuria and hypomagnesemia are the major features distinguishing GS from BS in clinic.Moreover,gene detection is the gold standard for the diagnosis of BS and GS.This research proposed to analyze and compare the clinical features,laboratory results,gene diagnosis,treatment and prognosis of BS and GS patients,with an aim to provide useful information for clinical diagnosis and treatment.ObjectiveTo summarize the clinical manifestations,gene detection,as well as diagnosis and treatment process in BS and GS patients,so as to explore the etiology,pathogenesis,treatment and prognosis for the two diseases and to provide foundation for identifying them.Methods1.Objects of study: Clinical data from 7 adult patients with BS and GS admitted and treated in Henan Provincial People’s Hospital and Zhengzhou Yihe Hospital from January 2015 to September 2016 were retrospectively analyzed.2.Laboratory examination: Related examination indexes,such as blood and urine electrolytes,blood gas analysis,as well as renin,angiotensin II(AT-II)and aldosterone(ALD)levels in standing and supine positions;bilateral kidney Doppler ultrasound and CT examination results detected after admission were collected.3.Gene detection: All the 7 patients were conducted CLCNKB gene sequencing,so as to determine the possible gene mutation site.1 patient was carried out sequencing on genes such as SLC12A1,KCNJ1,CLCNKB,BSND and SLC12A3 in the return visit.4.Treatment: 7 patients were given potassium-supplementing and indometacin treatment;meanwhile,the changes in all indexes after treatment were observed.5.Statistical analysis: Statistical analysis was conducted using the SPSS22.0 software,and difference of P<0.05 was deemed as statistically significant.Results1.General data analysis: All the 7 cases had the disease onset in adulthood,all of whom had various degrees of weakness.Of them,2 cases combined with palpitation and chest tightness,1 had convulsion,and 1 had myalgia and numbness in four limbs,accompanying with hypocalciuria and hypomagnesemia.Clinical laboratory examination results suggested various degrees of hypokalemia,hypomagnesemia,metabolic alkalosis,as well as elevated RASS detection results.But the blood pressure was within normal range.2.Gene detection: No pathological change was found in gene CLCNKB of the 7 BS patients.Gene SLC12A3 was detected in 1 case and 2 missense mutations were found.Of them,1 missense mutation located in c.1456G>A of exon 12,the basic group mutating from G to A,and the coded amino acid(p.Asp486Asn;Het)aspartic acid was replaced with asparagine.Another missense mutation located in c.907G>T of exon 7,the basic group mutating from G to T,and the coded amino acid(p.Gly303Trp;Het)glycine was replaced with tryptophan.The latter one was a new mutation site discovered in this research.This case was diagnosed with GS.3.Comparison of laboratory results before and after medication: Serum potassium,serum calcium,and blood chloride in 7 patients were elevated after potassium supplementation and indomethacin treatment,while the 24 h urine potassium and HCO3 levels were decreased,and differences before and after treatment were statistically significant(P<0.05).PH in patients was reduced to a certain degree after treatment,and the serum sodium and 24 h urine calcium were increased,but the differences were not statistically significant(P>0.05).Renin activity,AT-II and ALD levels in standing and supine positions were reduced after treatment,with the differences of statistical significance(P<0.05).Conclusion1.The possibility of BS should be considered in adults with symptoms such as weakness,refractory hypokalemia,metabolic alkalosis,increased ALD levels in standing and supine positions with normal or lower blood pressure,and developmental retardation.Hypocalciuria and hypomagnesemia are the major features distinguishing GS from BS in clinic.2.The two have similar clinical manifestations and laboratory examination results;therefore,a definite differential diagnosis can hardly be made.At present,gene diagnosis is the gold standard,which contributes to the early targeted therapy after diagnosis.3.BS is mainly managed with comprehensive treatment such as potassium supplementing to correct electrolyte disturbance,combined with potassium-sparing diuretic and prostaglandin inhibitor.GS is treated with magnesium supplementation on this basis;the renin and ALD levels can be effectively reduced,serum potassium can be remarkably elevated,and alkalosis can be corrected after applying prostaglandin inhibitor...