Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases...Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases,recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition.Although they share some characteristic metabolic abnormalities such as hypokalemia,metabolic alkalosis,hyperplasia of the juxtaglomerular apparatus with hyperreninemia,hyperaldosteronism,the clinical and laboratory manifestations may not always allow distinction between them.Diuretics tests,measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change(< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS,except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists.The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children.Clinical symptoms and biochemical markers of GS and classic form of BS(type III) may overlap and thus genetic analysis may specify the real cause of symptoms.However,although genetic analysis is available,its use remains limited because of limited availability,large gene dimensions,lack of hot-spot mutations,heavy workup time and costs involved.Furthermore,considerable overlap exists between the different genotypes and phenotypes.Although BS and GS usually have distinct presentations and are associated with specific gene mutations,there remains considerable overlap between their phenotypes and genotypes.Thus,they are better described as a spectrum of clinical manifestations caused by different gene mutations.展开更多
Objective： To determine the gene location of two Gitelman syndrome （GS） family SLC12A3 genes and explore treatments using Chinese medicine （CM） prescriptions. Methods： In order to locate the two GS mutations, sa...Objective： To determine the gene location of two Gitelman syndrome （GS） family SLC12A3 genes and explore treatments using Chinese medicine （CM） prescriptions. Methods： In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine （including potassium, Panangin and potassium-sparing diuretics） with CM prescription based on Buyang Huanwu Decoction （补阳还五汤） and Sijunzi Decoction （四君子汤）. The treatment included three stages, oral potassium chloride for the first 2 weeks （stage 1）, potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks （stage 2）, CM along with the medicine in stage 2 for the final 2 weeks （stage 3）. Results： The three mutations occurring in proband 1 from pedigree 1 were Thr60Met, 965-1_976de113ins12 （small indels mutation） and Ala122Ala （homozygous silent mutation）. Likewise, three mutations, Asn359Lys, Thr382Met and Arg913GIn, appeared in the proband 2 from pedigree Ⅱ. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L （baseline）, 2.5 mmol/L （stage 1）, 3.1 mmol/L （stage 2） and 3.9 mmol/L （stage 3） in the proband 1, and 2.8 mmol/L （baseline）, 3.1 mmol/L （stage 1）, 3.5 mmol/L （stage 2） and 4.3 mmol/L （stage 3） in the proband 2, respectively. The symptoms （numbness of limbs, weakness, palpitations, etc.） of both probands were all alleviated. Conclusions： The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.展开更多
目的探讨儿童Gitelman综合征(GS)的临床表现、实验室检查结果、诊断和治疗方案,进一步提高临床对该病的诊疗水平。方法选择2017年1月至2018年11月,首都儿科研究所附属儿童医院内分泌科收治的9例(No.1~9)GS患儿为研究对象。回顾性分析其...目的探讨儿童Gitelman综合征(GS)的临床表现、实验室检查结果、诊断和治疗方案,进一步提高临床对该病的诊疗水平。方法选择2017年1月至2018年11月,首都儿科研究所附属儿童医院内分泌科收治的9例(No.1~9)GS患儿为研究对象。回顾性分析其临床病例资料,对其临床表现、基因检测、治疗及转归、随访结果进行分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果①临床表现及诊断结果:6例(No.1、3、4、6、8~9)患儿表现为感染或骨骼畸形,2例(No.2、7)为身材矮小,1例(No.5)为双下肢无力。生化检查结果:所有患儿均存在血K+浓度降低,8例(No.1~8)存在血Mg 2+浓度降低,7例(No.1、3~8)存在代谢性碱中毒,尿液24 h K+浓度均增高,5例(No.2、4、6、8~9)肾小管损害标志物β2微球蛋白增高。基因检测结果:5例(No.1、6~9)患儿均存在SLC12A3基因突变。其中,No.1、8、9患儿为错义突变;No.6患儿为剪切突变与移码突变,并且其移码突变导致mRNA上终止密码子提前出现,氨基酸终止;No.7患儿为移码突变。No.6患儿的移码突变c.578_582dupCCACC及No.9患儿的错义突变c.1084G>A与c.1613G>T,均为在人类基因突变数据库(http://www.hgmd.cf.ac.uk)中尚未报道的新发突变。②治疗结果:对9例患儿采取补充钾剂、螺内酯[1~3 mg/(kg·d)]及门冬氨酸钾镁(1~2片/次,2~3次/d)治疗后,3例(No.5、7~8)患儿出院时血K+浓度尚未完全恢复正常,但是较入院时明显上升,其余6例(No.1~4、6、9)患儿血K+浓度恢复正常。所有患儿出院时,血Mg^2+浓度基本恢复正常。③随访结果:出院后3个月时,9例患儿血K+、Mg^2+浓度均接近正常值;2例(No.2、7)身材矮小患儿的生长速率较治疗前改善;5例(No.2、4、6、8~9)患儿截至随访终点时,肾小管损伤标志物β2微球蛋白升高无进行性加重,其中2例(No.4、8)患儿β2微球蛋白值已基本恢复至正常值。结论儿童GS�展开更多
BACKGROUND Licorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome(GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the w...BACKGROUND Licorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome(GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the world. Recently, some studies have found that GS patients had higher diabetic morbidity. However, the coexistence of these three diseases has yet to be reported.CASE SUMMARY We report the case of a 62-year-old Chinese man who was admitted with weakness in the extremities, muscle pain, and dark-colored urine. He had consumed liquorice water daily for seven days prior to admission. The laboratory tests revealed a serum potassium level of 1.84 mmol/L, magnesium 0.68 mmol/L, creatinine phosphokinase(CK) 10117 IU/L, and marked hemoglobinuria. Fractional chloride excretion and fractional magnesium excretion were increased. Plasma renin activity and aldosterone concentration were within the normal ranges. Sequence analysis of the SLC12 A3 gene revealed that he had compound heterozygous mutations. The diagnosis of liquoriceinduced severe hypokalemic rhabdomyolysis with GS and diabetes was thus genetically confirmed. Serum potassium and CK quickly improved with potassium replacement therapy, hydration, and discontinuation of liquorice ingestion. Upon follow-up at 3 mo, the levels of CK, myoglobin, and potassium remained normal, and magnesium was above 0.6 mmol/L.CONCLUSION This case emphasizes that liquorice consumption and GS should be considered causes of hypokalemia and that the diabetic status of GS patients should be noted in the clinic.展开更多
文摘Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases,recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition.Although they share some characteristic metabolic abnormalities such as hypokalemia,metabolic alkalosis,hyperplasia of the juxtaglomerular apparatus with hyperreninemia,hyperaldosteronism,the clinical and laboratory manifestations may not always allow distinction between them.Diuretics tests,measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change(< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS,except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists.The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children.Clinical symptoms and biochemical markers of GS and classic form of BS(type III) may overlap and thus genetic analysis may specify the real cause of symptoms.However,although genetic analysis is available,its use remains limited because of limited availability,large gene dimensions,lack of hot-spot mutations,heavy workup time and costs involved.Furthermore,considerable overlap exists between the different genotypes and phenotypes.Although BS and GS usually have distinct presentations and are associated with specific gene mutations,there remains considerable overlap between their phenotypes and genotypes.Thus,they are better described as a spectrum of clinical manifestations caused by different gene mutations.
基金Supported by grants from Fujian Province Natural Science Fund Project(No.2013J01277)Financial Scheme for Young Talents Training Programme of Fujian Health Industry(No.2013-ZQN-JC-6)
文摘Objective： To determine the gene location of two Gitelman syndrome （GS） family SLC12A3 genes and explore treatments using Chinese medicine （CM） prescriptions. Methods： In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine （including potassium, Panangin and potassium-sparing diuretics） with CM prescription based on Buyang Huanwu Decoction （补阳还五汤） and Sijunzi Decoction （四君子汤）. The treatment included three stages, oral potassium chloride for the first 2 weeks （stage 1）, potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks （stage 2）, CM along with the medicine in stage 2 for the final 2 weeks （stage 3）. Results： The three mutations occurring in proband 1 from pedigree 1 were Thr60Met, 965-1_976de113ins12 （small indels mutation） and Ala122Ala （homozygous silent mutation）. Likewise, three mutations, Asn359Lys, Thr382Met and Arg913GIn, appeared in the proband 2 from pedigree Ⅱ. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L （baseline）, 2.5 mmol/L （stage 1）, 3.1 mmol/L （stage 2） and 3.9 mmol/L （stage 3） in the proband 1, and 2.8 mmol/L （baseline）, 3.1 mmol/L （stage 1）, 3.5 mmol/L （stage 2） and 4.3 mmol/L （stage 3） in the proband 2, respectively. The symptoms （numbness of limbs, weakness, palpitations, etc.） of both probands were all alleviated. Conclusions： The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.
文摘目的探讨儿童Gitelman综合征(GS)的临床表现、实验室检查结果、诊断和治疗方案,进一步提高临床对该病的诊疗水平。方法选择2017年1月至2018年11月,首都儿科研究所附属儿童医院内分泌科收治的9例(No.1~9)GS患儿为研究对象。回顾性分析其临床病例资料,对其临床表现、基因检测、治疗及转归、随访结果进行分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果①临床表现及诊断结果:6例(No.1、3、4、6、8~9)患儿表现为感染或骨骼畸形,2例(No.2、7)为身材矮小,1例(No.5)为双下肢无力。生化检查结果:所有患儿均存在血K+浓度降低,8例(No.1~8)存在血Mg 2+浓度降低,7例(No.1、3~8)存在代谢性碱中毒,尿液24 h K+浓度均增高,5例(No.2、4、6、8~9)肾小管损害标志物β2微球蛋白增高。基因检测结果:5例(No.1、6~9)患儿均存在SLC12A3基因突变。其中,No.1、8、9患儿为错义突变;No.6患儿为剪切突变与移码突变,并且其移码突变导致mRNA上终止密码子提前出现,氨基酸终止;No.7患儿为移码突变。No.6患儿的移码突变c.578_582dupCCACC及No.9患儿的错义突变c.1084G>A与c.1613G>T,均为在人类基因突变数据库(http://www.hgmd.cf.ac.uk)中尚未报道的新发突变。②治疗结果:对9例患儿采取补充钾剂、螺内酯[1~3 mg/(kg·d)]及门冬氨酸钾镁(1~2片/次,2~3次/d)治疗后,3例(No.5、7~8)患儿出院时血K+浓度尚未完全恢复正常,但是较入院时明显上升,其余6例(No.1~4、6、9)患儿血K+浓度恢复正常。所有患儿出院时,血Mg^2+浓度基本恢复正常。③随访结果:出院后3个月时,9例患儿血K+、Mg^2+浓度均接近正常值;2例(No.2、7)身材矮小患儿的生长速率较治疗前改善;5例(No.2、4、6、8~9)患儿截至随访终点时,肾小管损伤标志物β2微球蛋白升高无进行性加重,其中2例(No.4、8)患儿β2微球蛋白值已基本恢复至正常值。结论儿童GS�
基金Supported by the Fund Program for Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province,No.2017-397
文摘BACKGROUND Licorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome(GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the world. Recently, some studies have found that GS patients had higher diabetic morbidity. However, the coexistence of these three diseases has yet to be reported.CASE SUMMARY We report the case of a 62-year-old Chinese man who was admitted with weakness in the extremities, muscle pain, and dark-colored urine. He had consumed liquorice water daily for seven days prior to admission. The laboratory tests revealed a serum potassium level of 1.84 mmol/L, magnesium 0.68 mmol/L, creatinine phosphokinase(CK) 10117 IU/L, and marked hemoglobinuria. Fractional chloride excretion and fractional magnesium excretion were increased. Plasma renin activity and aldosterone concentration were within the normal ranges. Sequence analysis of the SLC12 A3 gene revealed that he had compound heterozygous mutations. The diagnosis of liquoriceinduced severe hypokalemic rhabdomyolysis with GS and diabetes was thus genetically confirmed. Serum potassium and CK quickly improved with potassium replacement therapy, hydration, and discontinuation of liquorice ingestion. Upon follow-up at 3 mo, the levels of CK, myoglobin, and potassium remained normal, and magnesium was above 0.6 mmol/L.CONCLUSION This case emphasizes that liquorice consumption and GS should be considered causes of hypokalemia and that the diabetic status of GS patients should be noted in the clinic.
