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
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
BACKGROUND To screen for possible pathogenic loci in a patient with Gitelman syndrome by high-throughput exome sequencing and to explore the relationship between genotype and phenotype. CASE SUMMARY The clinical data ...BACKGROUND To screen for possible pathogenic loci in a patient with Gitelman syndrome by high-throughput exome sequencing and to explore the relationship between genotype and phenotype. CASE SUMMARY The clinical data of the patient were collected. Peripheral blood samples were obtained to isolate white blood cells and extract genomic DNA. High-throughput whole exome sequencing for candidate pathogenic genes in the proband was completed by the Huada Gene Technology Co. Ltd (Shenzhen, China). Sequencing showed a novel heterozygous missense mutation (a G to A transition at nucleotide 2582) in exon 22 of the SLC12A3 gene, which resulted in a substitution of histidine for arginine at position 816 of the LRP1B protein and caused the occurrence of disease. CONCLUSION This is the first report of a new pathogenic mutation in SLC12A3. Further functional studies are particularly necessary to explore potential molecular mechanisms.展开更多
BACKGROUND Gitelman syndrome(GS)is an autosomal recessive renal tubular disorder characterized by renal wasting hypokalemia,metabolic alkalosis,hypomagnesemia,and hypocalciuria.It is usually caused by mutations in the...BACKGROUND Gitelman syndrome(GS)is an autosomal recessive renal tubular disorder characterized by renal wasting hypokalemia,metabolic alkalosis,hypomagnesemia,and hypocalciuria.It is usually caused by mutations in the gene SLC12A3,which encodes the thiazide-sensitive Na-Cl cotransporter.GS is not usually diagnosed until late childhood or adulthood.CASE SUMMARY Here,we report the case of a one-year-old girl who was brought to the emergency department due to persistent vomiting for two days.On admission to our hospital,generalized weakness was observed,and laboratory investigations revealed severe hypokalemia(1.9 mmol/L).However,persistent hypokalemia was observed during outpatient follow-up.Suspicion of the GS phenotype was assessed via the patient’s clinical presentation,family history,and biochemical analysis of blood and urine.Further genetic analysis was performed for her and her family by exon-wide sequencing analysis of the gene SLC12A3.The genetic diagnosis of GS was established in the Taiwan region family with three affected individuals,two of whom were children(7 years/17 years)without obvious symptoms,with the youngest being only one year old(patient in our case).CONCLUSION We successfully demonstrated the early diagnosis of GS using family genetic analysis.Any instances of hypokalemia should not be neglected,as early detection of GS with suitable treatment can prevent patients from potentially lifethreatening complications.展开更多
BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carri...BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carrier family 12 member 3(SLC12A3)gene resulting in disordered function of the thiazidesensitive NaCl co-transporter.To date,many types of mutations in the SLC12A3 gene have been discovered that trigger different clinical manifestations.Therefore,gene sequencing should be considered before determining the course of treatment for GS patients.CASE SUMMARY A 55-year-old man was admitted to our department due to hand numbness and fatigue.Laboratory tests after admission showed hypokalemia,metabolic alkalosis and renal failure,all of which suggested a diagnosis of GS.Genome sequencing of DNA extracted from the patient’s peripheral blood showed a rare homozygous mutation in the SLC12A3 gene(NM_000339.2:chr16:56903671,Exon4,c.536T>A,p.Val179Asp).This study reports a rare homozygous mutation in SLC12A3 gene of a Chinese patient with GS.CONCLUSION Genetic studies may improve the diagnostic accuracy of Gitelman syndrome and improve genetic counseling for individuals and their families with these types of genetic disorders.展开更多
BACKGROUND Gitelman syndrome(GS)is an autosomal recessive salt-losing renal tubulopathy arising from mutations in the thiazide-sensitive Na-Cl cotransporter gene.Due to its low incidence and lack of awareness,GS can b...BACKGROUND Gitelman syndrome(GS)is an autosomal recessive salt-losing renal tubulopathy arising from mutations in the thiazide-sensitive Na-Cl cotransporter gene.Due to its low incidence and lack of awareness,GS can be easily misdiagnosed or missed in diagnosis.CASE SUMMARY A 24-year-old male presented with>4 years of repeated limb weakness without any treatment.The previous day,the patient was bitten by ants and showed weakness of the lower limbs.The patient had hypokalemia(1.66-2.83 mmol/L),hypomagnesemia(0.4 mmol/L),hypocalciuria(1.51-2.46 mmol/d),metabolic alkalosis(7.47-7.54),normal blood pressure,and increased activity of aldosterone and plasma renin activity(PRA)(PRA 6.4 and 16.45 ng/mL/h and aldosterone 330.64 and 756.82 pg/mL in the supine and upright position,respectively).In addition,SLCI2A3 gene mutation with GS was diagnosed.Oral and intravenous supplementation with potassium and magnesium was initiated.Serum magnesium returned to 0.48 mmol/L and serum potassium returned to 3.08 mmol/L,alleviating the patient’s fatigue symptoms.CONCLUSION GS should be considered in patients with hypokalemia complicated with hypomagnesemia.Genetic testing is essential to confirm the diagnosis.展开更多
BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutatio...BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutation in SLC12A3.GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism.It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia,which is difficult to correct.CASE SUMMARY A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo.However,the patient’s serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism.GS was confirmed by whole exome and Sanger sequencing.Gene sequencing revealed compound heterozygous mutations of c.488C>T(p.Thr163Met),c.2612G>A(p.Arg871His),and c.1171_1178dupGCCACCAT(p.Ile393fs)in SLC12A3.Protein molecular modeling was performed to predict the effects of the identified missense mutations.All three mutations cause changes in protein structure and may result in abnormal protein function.All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.CONCLUSION We have identified a novel compound heterozygous mutation in SLC12A3.The present study provides new genetic evidence for GS.展开更多
Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a n...Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.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 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.
文摘BACKGROUND To screen for possible pathogenic loci in a patient with Gitelman syndrome by high-throughput exome sequencing and to explore the relationship between genotype and phenotype. CASE SUMMARY The clinical data of the patient were collected. Peripheral blood samples were obtained to isolate white blood cells and extract genomic DNA. High-throughput whole exome sequencing for candidate pathogenic genes in the proband was completed by the Huada Gene Technology Co. Ltd (Shenzhen, China). Sequencing showed a novel heterozygous missense mutation (a G to A transition at nucleotide 2582) in exon 22 of the SLC12A3 gene, which resulted in a substitution of histidine for arginine at position 816 of the LRP1B protein and caused the occurrence of disease. CONCLUSION This is the first report of a new pathogenic mutation in SLC12A3. Further functional studies are particularly necessary to explore potential molecular mechanisms.
文摘BACKGROUND Gitelman syndrome(GS)is an autosomal recessive renal tubular disorder characterized by renal wasting hypokalemia,metabolic alkalosis,hypomagnesemia,and hypocalciuria.It is usually caused by mutations in the gene SLC12A3,which encodes the thiazide-sensitive Na-Cl cotransporter.GS is not usually diagnosed until late childhood or adulthood.CASE SUMMARY Here,we report the case of a one-year-old girl who was brought to the emergency department due to persistent vomiting for two days.On admission to our hospital,generalized weakness was observed,and laboratory investigations revealed severe hypokalemia(1.9 mmol/L).However,persistent hypokalemia was observed during outpatient follow-up.Suspicion of the GS phenotype was assessed via the patient’s clinical presentation,family history,and biochemical analysis of blood and urine.Further genetic analysis was performed for her and her family by exon-wide sequencing analysis of the gene SLC12A3.The genetic diagnosis of GS was established in the Taiwan region family with three affected individuals,two of whom were children(7 years/17 years)without obvious symptoms,with the youngest being only one year old(patient in our case).CONCLUSION We successfully demonstrated the early diagnosis of GS using family genetic analysis.Any instances of hypokalemia should not be neglected,as early detection of GS with suitable treatment can prevent patients from potentially lifethreatening complications.
基金Supported by the National Natural Science Foundation of China,No.81700649.
文摘BACKGROUND Gitelman syndrome(GS)is an unusual,autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.It is caused by mutations in the solute carrier family 12 member 3(SLC12A3)gene resulting in disordered function of the thiazidesensitive NaCl co-transporter.To date,many types of mutations in the SLC12A3 gene have been discovered that trigger different clinical manifestations.Therefore,gene sequencing should be considered before determining the course of treatment for GS patients.CASE SUMMARY A 55-year-old man was admitted to our department due to hand numbness and fatigue.Laboratory tests after admission showed hypokalemia,metabolic alkalosis and renal failure,all of which suggested a diagnosis of GS.Genome sequencing of DNA extracted from the patient’s peripheral blood showed a rare homozygous mutation in the SLC12A3 gene(NM_000339.2:chr16:56903671,Exon4,c.536T>A,p.Val179Asp).This study reports a rare homozygous mutation in SLC12A3 gene of a Chinese patient with GS.CONCLUSION Genetic studies may improve the diagnostic accuracy of Gitelman syndrome and improve genetic counseling for individuals and their families with these types of genetic disorders.
文摘BACKGROUND Gitelman syndrome(GS)is an autosomal recessive salt-losing renal tubulopathy arising from mutations in the thiazide-sensitive Na-Cl cotransporter gene.Due to its low incidence and lack of awareness,GS can be easily misdiagnosed or missed in diagnosis.CASE SUMMARY A 24-year-old male presented with>4 years of repeated limb weakness without any treatment.The previous day,the patient was bitten by ants and showed weakness of the lower limbs.The patient had hypokalemia(1.66-2.83 mmol/L),hypomagnesemia(0.4 mmol/L),hypocalciuria(1.51-2.46 mmol/d),metabolic alkalosis(7.47-7.54),normal blood pressure,and increased activity of aldosterone and plasma renin activity(PRA)(PRA 6.4 and 16.45 ng/mL/h and aldosterone 330.64 and 756.82 pg/mL in the supine and upright position,respectively).In addition,SLCI2A3 gene mutation with GS was diagnosed.Oral and intravenous supplementation with potassium and magnesium was initiated.Serum magnesium returned to 0.48 mmol/L and serum potassium returned to 3.08 mmol/L,alleviating the patient’s fatigue symptoms.CONCLUSION GS should be considered in patients with hypokalemia complicated with hypomagnesemia.Genetic testing is essential to confirm the diagnosis.
基金Supported by the Science and Technology Plan of Health Commission of Jiangxi Province,No.202130648the Science and Technology Research Project of Department of Education of Jiangxi Province,No.GJJ201522.
文摘BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutation in SLC12A3.GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism.It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia,which is difficult to correct.CASE SUMMARY A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo.However,the patient’s serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism.GS was confirmed by whole exome and Sanger sequencing.Gene sequencing revealed compound heterozygous mutations of c.488C>T(p.Thr163Met),c.2612G>A(p.Arg871His),and c.1171_1178dupGCCACCAT(p.Ile393fs)in SLC12A3.Protein molecular modeling was performed to predict the effects of the identified missense mutations.All three mutations cause changes in protein structure and may result in abnormal protein function.All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.CONCLUSION We have identified a novel compound heterozygous mutation in SLC12A3.The present study provides new genetic evidence for GS.
文摘Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.
