更新于：2024-05-01

Bartter Syndrome

巴特综合征

更新于：2024-05-01

基本信息

别名

Aldosteronism with Hyperplasia of the Adrenal Cortex、Aldosteronism with hyperplasia of the adrenal cortex、BARTTER SYNDROME

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简介

A group of disorders caused by defective salt reabsorption in the ascending LOOP OF HENLE. It is characterized by severe salt-wasting, HYPOKALEMIA; HYPERCALCIURIA; metabolic ALKALOSIS, and hyper-reninemic HYPERALDOSTERONISM without HYPERTENSION. There are several subtypes including ones due to mutations in the renal specific SODIUM-POTASSIUM-CHLORIDE SYMPORTERS.

关联

项与巴特综合征相关的临床试验

NCT05927961 / Not yet recruitingN/AIIT

Spatial Proteomics Profiles of Adrenal Adenoma/Hyperplasia Leading to Primary Aldosterone

Primary aldosteronism (PA) is a common cause of secondary hypertension, which is characterized by excessive aldosterone production by the adrenal gland. Excessive aldosterone can significantly increase the risk of cardiovascular disease and stroke. Patients with aldosterone-producing adenoma (APA) or unilateral hyperplasia (UAH) can be cured by unilateral adrenalectomy. The adrenal cortex is the outer part of the adrenal gland and is subdivided into three layers- the zona glomerulosa, the zona fasciculata, and the zona reticularis. And the outermost layer is the zona glomerulosa, and it's full of cells that make the hormone aldosterone. Although it has been investigated that the main cause of APA or UAH is the mutations of different calcium ion channels, including KCNJ5, CACNA1D, CLCN2 et al, it is still unknown whether there are any other changes of other proteins in different layers. Therefore, the investigators designed the study to characterize the proteomics profiles of adrenal adenoma/hyperplasia leading to primary aldosterone and identify biomarkers for early identification of PA by using spatial proteomics. The samples from adrenal adenoma or hyperplasia will be collected and analyzed by spatial proteomics in Hangzhou Jingjie Biotechnology Co., Ltd. The differentially expressed proteins in different layers will be screened out between APA and UAH, APA and its adjacent normal tissues, and UAH and its adjacent normal tissues, respectively. And KEGG analysis will be conducted to determine enriched pathway in these differentially expressed protein, respectively.

开始日期2023-08-01

申办/合作机构

中国人民解放军第三军医大学

NCT05186675 / Enrolling by invitationN/A

Efficacy and Safety of Percutaneous Superselective Adrenal Arterial Embolization in the Treatment of Primary Aldosteronism With Bilateral Idiopathic Hyperaldosteronism: A Prospective Cohort Study

The most common two subtypes of primary aldosteronism (PA ) are aldosterone producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA). Mineralocorticoid receptor (MR) antagonists is the main treatment for bilateral IHA, because of its side effects, the treatment compliance of those patients is poor. Hence, an alternative therapy is needed in such cases. We hypothesized that superselective adrenal artery embolization (SAAE) could be a suitable alternative approach. To our knowledge, SAAE has so far not been applied to treat bilateral IHA. This study aimed to evaluate the efficacy and safety of SAAE in the treatment of PA patients with bilateral IHA.

开始日期2022-01-01

申办/合作机构

南昌大学第二附属医院

NCT05649631 / CompletedN/AIIT

The Effect of Low Sodium Diet on Idiopathic Hyperaldosteronism

This study was a single-center randomized controlled trial which lasted 14 days and consisted of two stages (run-in period (stage I) and intervention period (stage II) each contain 7 days without potassium supplement. If participants meet the enrollment criteria at the end of stage I, they were assigned to the low sodium group (50mmol/d) or normal sodium group (100mmol/d), and then continued to finish stage II. The primary outcome was the change in serum potassium after exposure to normal sodium / low sodium diet and the secondary outcome was the assessment of BP change following a normal sodium / low sodium diet. Patients were given nifedipine controlled-release tablets 30 mg/d to lower blood pressure and were not provided any potassium supplements during the two stages. If the subject has an increase in BP (>180/110 mmHg), the dose of nifedipine controlled-release tablets will be increased to 60 mg/d. Patients will be withdrawn from the study if they cannot tolerate the diet or their serum potassium were below 2.8 mmol/L.

开始日期2021-07-01

申办/合作机构

上海交通大学

100 项与巴特综合征相关的临床结果

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100 项与巴特综合征相关的转化医学

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0 项与巴特综合征相关的专利（医药）

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2,043

项与巴特综合征相关的文献（医药）

2024-02-16·BMC medical imaging

How to identify juxtaglomerular cell tumor by ultrasound: a case series and review of the literature.

Review

作者: Li Wang ; Meiying Li ; Siqi Jin ; Yunshu Ouyang ; Fenglan Wang ; Ke Lv ; Jianchu Li ; Yuxin Jiang ; He Liu ; Qingli Zhu

PURPOSE:

To study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT).

METHODS:

From January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively.

RESULTS:

The 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9-5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm.

CONCLUSIONS:

JGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.

2024-02-13·BMJ case reports

Bartter syndrome-like phenotype in a patient with type 2 diabetes mellitus.

Article

作者: Ravi Kumar ; Nirmal Shreshta ; Samir Samdarshi ; Parikshit Chauhan

Bartter syndrome (BS) is a rare genetic tubulopathy affecting the loop of Henle leading to salt wasting. It is commonly seen in utero or in the early neonatal period. Rare cases of acquired BS are reported in association with infections like tuberculosis, granulomatous conditions like sarcoidosis, autoimmune diseases and drugs. The mainstay of management includes potassium, calcium and magnesium supplementation. We report the case of a woman in her 50s with a history of type 2 diabetes mellitus for the last 10 years, who presented with diabetic foot ulcers and generalised weakness with ECG changes suggestive of hypokalaemia. She had severe hypokalaemia with high urine potassium excretion and hypochloraemic metabolic alkalosis. She poorly responded to intravenously administered potassium supplements and had persistent hypokalaemia. On further evaluation of the persistent hypokalaemia, a diagnosis of idiopathic Bartter-like phenotype was made. She responded well to tablet indomethacin and is presently asymptomatic and is being maintained on tablet indomethacin after 6 months of follow-up.

2024-02-02·CEN case reports

A case of pseudo-Bartter/Gitelman syndrome caused by long-term laxative abuse, leading to end-stage kidney disease.

Article

作者: Atsushi Kondo ; Kunihiko Yoshiya ; Nana Sakakibara ; China Nagano ; Tomoko Horinouchi ; Kandai Nozu

Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is a disorder that presents with hypokalemia and metabolic alkalosis resembling Gitelman syndrome (GS) due to secondary factors, such as lifestyle and /or medicines. Notably, PBS/PGS is more likely to cause renal dysfunction than GS. We report the first case of PBS/PGS due to long-term laxative abuse leading to end-stage kidney disease (ESKD). The patient was a 49-year-old woman with a history of constipation since school, who had used excessive doses of laxatives on her own judgment for nine years at least from 22 years of age. Two years later, blood tests revealed hypokalemia (serum K 3.1 mEq/L), and nine years later, the patient's renal function began to deteriorate (Cr-eGFR 48.7 mL/min/1.73 m²). Since abuse of laxatives was suspected as the cause, it was changed to the proper dosage of laxatives. At 33 years, the patient developed acute kidney injury (AKI), due to a urinary tract infection, and required intensive treatment, including hemodialysis. Although the patient was eventually weaned off dialysis, the renal function did not recover to pre-AKI levels. In suspected GS, comprehensive genetic testing for renal disease-related genes was performed; however, no obvious pathogenic variants were identified. Thereafter, despite decreasing the laxative doses and potassium supplementation, her renal function continued to decline. At 49 years, the patient developed ESKD and was started on maintenance hemodialysis. PBS/PGS is a disease that can lead to ESKD. An early diagnosis of PBS/PGS is crucial to prevent renal function deterioration, and the underlying causes should be removed immediately.

项与巴特综合征相关的新闻（医药）

2024-02-08

·生物探索

Nature | 钙感受器的双重游戏：揭秘其对G蛋白选择性和异构体调节的新机制

引言钙敏感受体(CaSR)是一个家族C的G蛋白偶联受体(GPCR)，在调节全身钙稳态中起核心作用。2024年2月7日，斯坦福大学Georgios Skiniotis团队（斯坦福大学Feng He、Cheng-Guo Wu、浙江大学高洋及哥本哈根大学Sabrina N. Rahman为该文章的共同第一作者）在Nature 在线发表题为“Allosteric modulation and G-protein selectivity of the Ca2+-sensing receptor”的研究论文，该研究使用冷冻电镜和功能分析来研究嵌入在脂质纳米盘中的人CaSR的激活及其在存在和不存在拟钙化药物cinacalcet的情况下与功能性Gi和Gq蛋白的偶联。高分辨率结构显示，Gi和Gq在活化的CaSR二聚体中驱动额外的构象变化，以稳定涉及关键蛋白-脂质相互作用的七跨膜结构域(7TM)的更广泛的不对称界面。受体的选择性Gi和Gq偶联是通过细胞内环2和C端的大量重排实现的，它们对两种G蛋白亚型的结合有不同的贡献，导致不同的CaSR-G蛋白界面。这些结构还揭示了天然多胺靶向CaSR上的多个位点，通过压缩两个原体之间带负电荷的区域来增强受体的激活。此外，该研究发现氨基酸l-色氨酸是一种众所周知的CaSR细胞外结构域的配体，它占据了G蛋白偶联原聚体的7TM束，与cinacalcet和其他变构调节剂位于同一位置。这些结果为CaSR对G蛋白的激活和选择性，以及内源性和外源性配体对其变构调节提供了一个框架。循环Ca2+水平的严格调节是人体生理的一个重要组成部分，它在很大程度上依赖于CaSR。该受体检测血清钙的升高并激活G蛋白信号，以限制甲状旁腺激素(PTH)的分泌并促进肾钙排泄。人类CaSR中数百种自然发生的突变导致各种疾病，包括家族性低钙血症/高钙血症1型、严重新生儿甲状旁腺功能亢进、常染色体显性低钙血症1型(ADH1)和5型巴特综合征。在影响全球近10%人口的慢性肾脏疾病患者中观察到CaSR的表达和激活降低。CaSR属于C家族GPCR，该家族还包括调节神经传递的γ-氨基丁酸B (GABAB)和代谢性谷氨酸(mGlu)受体(mGlu1-mGlu8)。家族C GPCR的功能是专性同源或异源二聚体，内源性配体参与远离膜平面的细胞外结构域(ECD)，通常包括一个配体结合的Venus flytrap结构域(VFT)，在大多数情况下，通过一个富含半胱氨酸的结构域(CRD)连接到特征7TM束。这个家族的成员表现出明显的G蛋白偶联选择性。mGlu1和mGlu5激活包括Gq/11在内的多种G蛋白，而其他mGlu受体优先激活Gi/o。另一方面，CaSR主要激活Gq/11和Gi/o亚型。早期对洗涤剂溶解mGlu2、mGlu4和GABAB的结构研究表明，C家族GPCR采用一种独特的机制与Gi偶联，涉及细胞内环的重组，而不打开7TM束。然而，目前尚不清楚这种机制是否适用于其他G蛋白亚型，以及C家族受体如何实现G蛋白的选择性。脂质纳米圆盘中活性态CaSR和CaSR -G蛋白复合物的冷冻电镜结构（Credit: Nature）CaSR的一个显著特征是它与多种天然配体结合，包括多价阳离子(如Ca2+)、阴离子(如磷酸、l -氨基酸、多肽和多胺)。这些配体在不同生理条件下相对浓度的变化可以促进或抑制受体的激活，因此CaSR似乎是一个微调的信号平台，整合各种化学输入来引发其生理作用。CaSR是由合成的阳性和阴性变构调节剂(PAM和NAMs)靶向治疗的，它们分别增强受体的激活或失活。例如，cinacalcet是FDA批准的靶向CaSR的PAM药物，用于治疗继发性甲状旁腺功能亢进和甲状旁腺癌。虽然已经报道了人类CaSR与不同配体(包括Ca2+， l -色氨酸(Trp)和PAM或NAMs)结合的冷冻电镜结构，但其他配体(如多胺)的结合模式尚未表征。该研究试图建立CaSR激活和G蛋白亚型偶联的丰富机制框架。在脂质纳米盘中重构的人类CaSR的冷冻电镜快照，以及功能数据的补充，揭示了CaSR如何利用由脂质和精胺分子稳定的不对称界面激活一个原聚体中的G蛋白；Gi和Gq如何参与采用不同构象的相同受体元件；7TM PAM细胞如何诱导侧链重排促进G蛋白偶联；天然氨基酸色氨酸可以在没有外源PAMs的情况下与7TM束结合。原文链接https://www.nature.com/articles/s41586-024-07055-2责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Science最新发布：全世界最前沿的125个科学问题热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈

细胞疗法

2023-12-01

·生物探索

最新发现！巴氏综合征的潜在新靶点和候选药物

在发表于《自然代谢》的一篇论文中，匹兹堡大学的研究人员详细介绍了一个潜在的新靶点和一种小分子候选药物，可以用于治疗巴氏综合征。这是一种罕见的、危及生命且目前无法治愈的遗传性疾病，具有毁灭性的后果。全球每30-40万名新生儿中，就约有1人患有巴氏综合征。该疾病患者的肌肉和心脏都很虚弱，会感到疲劳和反复感染。匹兹堡大学的研究人员发现，有缺陷的线粒体是导致该疾病的部分“罪魁祸首”。他们通过研究，确定了一个有望逆转疾病进程的分子靶点。该项研究的资深作者、匹兹堡大学公共卫生学教授Valerian Kagan博士解释说，在健康人体内存在一种被称为心磷脂（CL）的脂质，会在线粒体内经历一系列转变，即重塑。然而，在患有巴氏综合征的人体内，线粒体内的一个重要基因——tafazzin（TAZ）发生了突变。没有TAZ，CL的重塑就会停止，带来有害脂质的积聚。在这项最新研究中，研究小组使用了计算机模型，并对小鼠成肌细胞和巴氏综合征患者的人类心脏组织样本进行了体外研究。 Valerian Kagan说：“我们发现，溶血心磷脂是一种在TAZ缺陷突变细胞中积累的中间体，它与线粒体细胞色素c蛋白相互作用，将其转化为一种可以氧化周围一切的酶。” 事实证明，TAZ缺陷细胞中的过度氧化是可以预防的。研究小组表明，一种咪唑类化合物（IOA，imidazole-substituted oleic acid）可以阻止这种过度氧化现象，并改善巴氏综合征果蝇模型的运动功能和耐力。未来，这一发现可能为纠正遗传性TAZ缺陷和通过小分子疗法改善线粒体功能铺平道路。参考文献：Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome, Nature Metabolism (2023). DOI: 10.1038/s42255-023-00926-4 内容来源于网络，如有侵权，请联系删除。

2023-09-25

·Science Daily

Genetic code of rare kidney cancer cracked

New study reveals drivers of rare cancer and provides a possible alternative solution to surgery. The genetic code of a rare form of kidney cancer, called reninoma, has been studied for the first time. In the new paper, published today (25th September) in Nature Communications, researchers at the Wellcome Sanger Institute, Great Ormond Street Hospital and The Royal Free Hospital also revealed a new drug target that could serve as an alternative treatment if surgery is not recommended. There are around 100 cases of reninoma reported to date worldwide (1), and it is amongst the rarest of tumours in humans. Although it can usually be cured with surgery, it can cause severe hypertension or it can spread and develop into metastases. There are no existing medical treatments for reninoma and management involves surgery alone. Until now, it had been unknown what genetic error causes reninoma. In the new study, a collaboration between the Wellcome Sanger Institute and Great Ormond Street Hospital and The Royal Free Hospital, funded by The Little Princess Trust, researchers found that there is a specific error in the genetic code of a known cancer gene, NOTCH1, that is behind the development of this rare cancer. The team examined two cancer samples -- from a young adult and a child (2) -- with advanced genomic techniques, known as whole genome and single nuclear sequencing (3). Their findings suggest that the use of existing drugs targeting this specific gene is a possible solution to treating reninoma for patients where surgery is not a viable option. Taryn Treger, first author of the study and The Little Princess Trust Fellow at the Wellcome Sanger Institute, said: "Many cancerous tumours have already been deciphered with genomic technologies, however, this is not so true in rare cancers, particularly those affecting children. Our work aims to fill that gap. This is the first time that we have identified the drivers for reninoma and we hope that our work continues to pave the way towards new therapies for childhood cancers." Dr Tanzina Chowdhury, co-lead author of the study, at Great Ormond Street Hospital, said: "Rare kidney cancers known as reninomas do not respond to conventional anti-cancer therapies. The only known treatment at the moment is surgery. Our study shows that, actually, there is a specific and well-studied gene that drives this rare cancer. If we use already known drugs that affect this gene, we might be able to treat it without the need for an invasive technique such as surgery." Dr Sam Behjati, co-lead author of the study, Wellcome Senior Research Fellow at the Wellcome Sanger Institute and Honorary Consultant Paediatric Oncologist at Addenbrooke's Hospital, said: "Rare cancers are exceedingly challenging to study, and patients with such tumours may therefore not benefit from cancer research. Here, we have a powerful example of cutting-edge science rewriting our understanding of an ultra rare tumour type, reninoma, whilst delivering a finding that potentially has immediate clinical benefits for patients." Phil Brace, Chief Executive of The Little Princess Trust, said: "We are committed to funding research searching for more effective treatments for all childhood cancers and so we are delighted to hear of the discoveries that have been made. We also want to help researchers find kinder solutions for young people and so we are very pleased to hear there may be ways to treat this rare kidney cancer without the need for surgery." Notes: 1. Inam, R., Gandhi, J., Joshi, G., Smith, N. L. & Khan, S. A. Juxtaglomerular Cell Tumor: Reviewing a Cryptic Cause of Surgically Correctable Hypertension. Curr. Urol. 13, 7-12 (2019). 2. The samples came from a young child with a localised tumour from the UMBRELLA study and a young female adult with metastatic (lung) reninoma. 3. Whole genome sequencing is a method that analyses the entire genome of an organism. Single nucleus sequencing is a method that uses isolated nuclei -- the part of the cell that contains our DNA information -- instead of whole cells to understand genes and their functions.