Bartter和 Gitelman综合征

最近，众多学者应用现代分子遗传学技术对两种临床经典的肾小管疾病，即表现为遗传性低钾血症性碱中毒的Ｂａｒｔｔｅｒ综合征和Ｇｉｔｅｌｍａｎ综合征分子基础进行了详尽的描述。从分子遗传学的角度认识了四种不同的致病因子，它们均可导致低钾血症性碱中毒、失盐和低血压。这些基础研究成果极大地提高了对肾脏生理学的深层理解。     

Bartter综合征分子遗传学研究进展

Bartter综合征是一组以低钾性代谢性碱中毒为主要特征的遗传性肾小管疾病。近期的分子遗传学研究表明,六个编码肾小管离子通道或转运蛋白的基因突变可引起Bartter综合征,根据这些致病基因的不同。Banter综合征进一步分为六个亚型,即Ⅰ-Ⅴ型Bartter综合征和Gitelman综合征。该文从分子遗传学角度阐述了各种类型Bamer综合征的临床特点和可能的发病机制。     

Bartter和Gitelman综合征

最近，众多学者应用现代分子遗传学技术两种技术经典的肾小管疾病，即表现为遗传性低钾血症性碱中毒的Ｂａｒｔｔｅｒ综合征和Ｇｉｔｅｌｍａｎ综合征分子基础进行了详尽的描述。从分子遗传学的角度认识了四种不同的致病因子，它们均可导致低钾血症性碱中毒，失盐和低血压。这些基础研究成果极大地提高了对肾脏生理学的淀粉 理解。     

巴特综合征的临床分型及研究进展

巴特综合征 (Ｂａｒｔｔｅｒｓｙｎｄｒｏｍｅ ,ＢＳ)因 196 2年Ｂａｒｔｔｅｒ等[1]首先报道了 2例出现低钾性代谢性碱中毒、高醛固酮血症 ,血压正常 ,肾组织学检查显示肾小球旁器肥大的患者而得名。至 2 0世纪 90年代已报道 2 0 0余例[2 ] ,部分患者可有家族史 ,其模式为常染色体隐性遗传[3 ] 。临床资料表明 :虽然以ＢＳ命名的病例以肾脏盐的丢失 ,低钾性代谢性碱中毒及血肾素及醛固酮水平增高而血压正常为共同特点 ,但还具有其他不同的临床表现和实验室检查特征 ,故ＢＳ是指一组临床以低钾血症和代谢性碱中毒为特征的遗传性肾小管疾病[3…     

原发肾小管性低钾碱中毒的临床特点

目的 探讨原发肾小管性低钾碱中毒的临床特点.方法 收集在天津市儿童医院住院治疗的原发肾小管性低钾碱中毒患儿8例,其中Bartter综合征(BS)、Gitelman综合征(GS)各4例.回顾性分析其临床表现、实验室检查、治疗方法及转归情况.结果 4例BS均婴幼儿期起病,临床表现为间断呕吐、腹泻、脱水、生长发育迟缓.4例GS发病年龄为10～15岁,临床表现为肢体无力、四肢麻木及间断手足搐搦.8例患儿血压均正常.实验室检查均表现为低血钾、代谢性碱中毒、尿钾、尿氯排出增加;4例BS息儿血浆肾素、血管紧张素、醛固酮明显升高;4例GS患儿血管紧张素均升高,血浆肾素升高3例、醛固酮明显升高2例;BS患儿尿钙肌酐比>0.2,GS患儿伴低血镁、尿钙肌酐比<0.2.2例BS患儿B超示双肾回声均匀增强,其中1例左肾盂扩张.单纯补钾或联合补镁、吲哚美辛、螺内酯和卡托普利后症状缓解.结论 原发肾小管性低钾碱中毒主要表现为低血钾、代谢性碱中毒、血压正常.检查其血镁、尿钾、尿氯、尿钙肌酐比和血浆肾素、血管紧张素、醛固酮水平可帮助诊断.BS和GS的发病机制、临床表现、治疗及预后均有不同.     

不同类型巴特综合征3例报告及文献复习

巴特综合征(Bartter syndrome,BS)是1962 年由Bartter等首先报道的一种少见的肾小管疾病。其主要临床特征为肾电解质丢失、低钾性碱中毒,伴高肾素、高醛固酮血症。不同类型BS具有不同的发病机理、临床表现和实验室特征。现将我院自 1998年来收治的3例BS结合文献总结如下。     

关节弯曲-肾小管功能不全-新生儿胆汁淤积综合征的临床特点及分子遗传学进展北大核心CSCD

关节弯曲-肾小管功能不全-新生儿胆汁淤积（ar／hrogryposis,renaltubulardysfunction,cholestasis,ARC）综合征是一种常染色体隐性遗传性多系统疾病（OMIM编号208085）,其临床特征除了关节弯曲、肾小管功能不全、新生儿胆汁淤积3大典型症状外,     

遗传性肾病综合征的基因诊断

近年来,遗传性肾病综合征相关基因的陆续发现或为肾脏病学领域的一个突破性进展,目前约有18个与遗传性肾病综合征有关的基因已经被克隆、定位,相信将会有更多的基因陆续被发现,这些基因是大多数遗传性肾病综合征的病因。遗传性肾病综合征的分子生物学进展有助于该病诊断和治疗。遗传性肾病综合征的治疗方案复杂,常规治疗方案无效(包括激素和免疫抑制剂),因此很有必要理解并明确该类疾病的定义、分子遗传学分类、临床特征以及肾脏病理等相关进展。该文综述了遗传性肾病综合征的常见分子生物学、临床及病理特征,以期建立遗传性肾病综合征的基因诊断思路。     

遗传性肾病综合征的遗传咨询

遗传性肾病综合征指由于肾小球滤过屏障组成蛋白的编码基因或其他相关基因突变所致的肾病综合征,临床绝大多数表现为激素耐药型肾病综合征.近年来,随着分子生物学技术的匕速发展,多个与遗传性肾病综合征有关的基因被克隆、定位,这使得对多种遗传性肾病综合征进行基因诊断成为可能.而随着对遗传性肾脏疾病认识的深入和基因诊断技术的广泛开展,对此类疾病患者及家系成员提供遗传咨询也越来越有必要性,包括产前基因诊断.     

儿童Bartter综合征合并肾小球硬化肾功能衰竭1例报告

正Bartter综合征是一种以常染色体隐性遗传为主的肾小管功能异常疾病,临床少见。主要发病机制为低钾血症、代谢性碱中毒、肾素-血管紧张素-醛固酮系统及前列腺素系统激活为主,低血压或血压正常为主要临床要点。目前认为与钾离子通道基因突变有关[1]。该病预后较差,合并肾功能改变的预后更差,现报道笔者医院收治的1例合并肾小球硬化、肾功能衰竭,并行肾活检和基因检测的Bartter综合征。     

Neonatal Bartter syndrome with cholelithiasis and hydrocephalus: Rare association

Neonatal Bartter syndrome (NBS) is a rare autosomal recessive renal tubular disorder. This disease is characterized by hypokalemia, hypochloremia, and metabolic alkalosis that is often associated with failure to thrive and recurrent episodes of dehydration. The combination of BS and cholelithiasis in an infant is very rare. Herein, we report a premature male infant with NBS who developed cholelithiasis and hydrocephalus on clinical follow up. We recommend that periodic routine hepatobiliary ultrasonograpic screening for cholelithiasis should be performed in patients with NBS.     

Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes.

Clinical or biochemical findings were reevaluated in 34 pediatric patients with primary renal tubular hypokalemic metabolic alkalosis. The patients were subdivided into two groups. Bartter syndrome (primary renal tubular hypokalemic metabolic alkalosis with normocalciuria or hypercalciuria) was diagnosed in 18 patients with molar urinary calcium/creatinine ratios greater than 0.20, and Gitelman syndrome (primary renal tubular hypokalemic metabolic alkalosis with magnesium deficiency and hypocalciuria) was diagnosed in 16 patients with molar urinary calcium/creatinine ratios less than or equal to 0.20 and plasma magnesium levels less than 0.75 mmol/L. Some clinically important differences between the groups were observed. Patients with Bartter syndrome were often born after pregnancies complicated by polyhydramnios (8/18) or premature delivery (7/18) and had short stature (11/18) or polyuria, polydipsia, and a tendency to dehydration (16/18) during infancy (12/18) or before school age (18/18). Patients with Gitelman syndrome had tetanic episodes (12/16) or short stature (3/16) at school age (14/16). We conclude that the Bartter and Gitelman syndromes represent two distinct variants of primary renal tubular hypokalemic metabolic alkalosis and are easily distinguished on the basis of urinary calcium levels.     

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??Objective??To analyze the clinical features and the results of genetic diagnosis in children with hypokalemic renal tubular diseases. Methods??The clinical data of 38 patients with hypokalemic renal tubular diseases were analyzed retrospectively??who were treated in Children’s Hospital Affiliated to Shanghai Jiao Tong University from Jan. 2010 to Jan. 2016. Results??Totally 38 patients with hypokalemic renal tubular diseases were enrolled in this study. There were 18 cases of renal tubular acidosis??RTA?? including 17 cases of type??RTA and 1 case of type?? RTA. There were 11 cases of Bartter syndrome??5 cases of Gitelman syndrome and 4 cases of Fanconi syndrome. The common clinical manifestations of hypokalemic renal tubular diseases included myasthenia??nausea??vomiting??polydipsia??polyurine and growth retardation. One case of Fanconi syndrome progressed to chronic Kidney disease??phase ????while the other
children had normal renal function. Glomerular proteinuria was found in 1??1 and 3 children with Bartter syndrome??Gitelman syndrome and Fanconi syndrome??respectively. Additionally??1 case with Fanconi syndrome has tubular proteinuria. However??urinary trace proteins associated with glomerular and tubular injury commonly elevated in these hypokalemic renal tubular diseases. Genetic analysis showed a new potential heterozygous mutations of ATPV0A4 in type??RTA and three heterozygous mutations of SLC12A3 in Gitelman syndrome. Conclusion??The clinical symptoms vary in patients and are featured mainly by myasthenia??nausea??vomiting??polydipsia??polyurine and growth retardation. Glomerular and tubular injuries are commonly found in hypokalemic renal tubular diseases. Moreover??genetic diagnosis may be helpful in diagnosis??treatment and genetic counseling.     

A short communication. Congenital renal alkalosis

Patients with idiopathic hypokalemic metabolic alkalosis and hyperrenienmia have been lumped under the heading of Bartter's syndrome. However, the clinical picture is not totally uniform. Recently, Gullner et al. described a familial disorder with hypokalemic metabolic alkalosis, hyperreninemia, and aldosteronism, but without juxtaglomerular hyperplasia. They suggested that this family had a condition other than Bartter's syndrome. The present report details the followup from infancy to adulthood of a patient with hypokalemic metabolic alkalosis, salt wasting, and hyperreninemia, but with normal aldosterone level and without juxtaglomerular hyperplasia. The authors suggest that this new condition be termed renal alkalosis. The studies suggest that the distal tubular reabsorptive capacity was defective in this patient.     

Renal Tubular Acidosis in a Case of Shwachman's Syndrome

ABSTRACT. We describe metabolic acidosis in a 15-month-old girl with clinical features of Shwachman's syndrome. Renal function tests indicated that the patient had type 1 renal tubular acidosis. Based on our findings and other reports of renal tubular dysfunction in patients with Shwachman's syndrome, we conclude that it is important to look for a possible renal tubular defect in this syndrome.     

Simultaneous mutations in the CLCNKB and SLC12A3 genes in two siblings with phenotypic heterogeneity in classic Bartter syndrome

Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide-sensitive NaCl co-transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The children were finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.     

Bartter's syndrome and tubular functional disturbances]

A 5-year-old boy is presented who exhibited the classical symptoms of the syndrome described by BARTTER et al. in 1962: growth retardation, hypokalemic alkalosis, hyperplasia of the juxtaglomerular apparatus with normotensive hyperreninism-hyperaldosteronism, polydipsia with impaired renal concentration ability resistant to pitressin. In addition, the patient showed the typical proximal tubular defects of the Fanconi syndrome: hyperphosphaturia with hypophosphatemic ricktts, generalized hyperaminoaciduria, proteinuria and glucosuria. In the cases of Bartter's syndrome described to date, no uniform pathogenetic mechanism could be identified. Proximal tubular salt wasting generally is assumed to be the primary defect. The studies carried out in this case support this hypothesis and indicate that the complete clinical picture of Bartter's syndrome may occur within the framework of multiple proximal tubular defects.     

Syndrome of hypokalemic metabolic alkalosis and hypomagnesemia associated with gentamicin therapy: case reports

Nephrotoxicity, as evidenced by renal insufficiency is a well-known consequence of gentamicin therapy. We report two patients with gentamicin-induced syndrome of hypokalemic metabolic alkalosis and hypomagnesemia. Both had complete recovery of renal tubular function after cessation of antibiotic therapy. These cases emphasize the need to routinely monitor patients receiving gentamicin therapy for electrolyte abnormalities to avoid potential morbidity.