遗传性低钾失盐性肾小管病临床分析

目的：分析遗传性低钾失盐性肾小管病的临床特点。方法：回顾性分析上海瑞金医院肾内科住院治疗Bartter综合征和Gitelman综合征共23例，其中经典型Bartter综合征4例，Gitelman综合征19例。结果：4例Bartter综合征发病年龄4月-33岁，临床上以多饮、多尿、乏力主要表现，2例患儿表现为脱水、呕吐、生长发育障碍；19例Gitelman综合征患者发病年龄10—52岁，临床上以双下肢无力、多饮、多尿、夜尿增加为主要表现，部分Gitelman综合征患者伴手足抽搐；实验室检查均表现为低血钾代谢性碱中毒，尿钾排出增加，血肾素活性、血管紧张素Ⅱ及醛固酮明显升高。而血压正常；经典型Bartter综合征尿钙肌酐比〉0．2，Gitelman综合征表现为低血镁、低尿钙、低尿钙肌酐比〈0．2；补钾或联合消炎痛、安体舒通和门冬氨酸钾镁等药物治疗后症状缓解。结论：低钾失盐性肾小管病主要特点包括低血钾代谢性碱中毒、高尿钾、血肾素、血管紧张素Ⅱ、醛固酮水平增高而血压正常，Bartter综合征和Gitelman综合征鉴别主要在发病年龄、血镁和尿钙水平，本病治疗应补钾、补镁、前列腺素合成酶抑制剂、醛固酮拮抗剂等多种药物联合应用。     

Gitelman综合征的临床特点分析

目的探讨Gitelman综合征的临床特点,以提高其诊治水平。方法选择Gitelman综合征患者6例,观察其临床表现及并发症,测量血压,检测血尿生化指标,并进行血气分析。结果患者均有不同程度的肢体乏力,血压正常;实验室检查表现为低血钾、低血镁、低尿钙、代谢性碱中毒;血肾素—血管紧张素Ⅱ-醛固酮系统激活;伴桥本甲状腺炎2例,胰岛素抵抗2例。给予门冬氨酸钾铁、氯化钾、醛固酮受体拮抗剂、消炎痛等治疗可缓解临床症状,但血钾、血镁未升至正常水平。结论临床上提示低血钾、低血镁、低尿钙等需考虑Gitelman综合征,治疗上给予门冬氨酸钾铁、氯化钾、醛固酮受体拮抗剂、消炎痛等联合应用,效果良好。     

以Graves病首诊发现合并Gitelman综合征一例

患者以间断四肢乏力起病,发现低钾血症,首诊考虑Graves病(Graves disease,GD),经抗甲状腺功能亢进(甲亢)及补钾治疗后,甲状腺功能基本恢复正常,但仍有反复低血钾。进一步检查发现同时合并低血镁、低血氯、高尿钾、低尿钙及肾素水平升高,SLC12A3基因检测发现复合杂合突变,诊断为Gitelman综合征(Gitelman syndrome,GS)合并Graves病。本病例提示甲亢合并低钾血症时,还应注意血镁、尿电解质、血气分析和肾素-血管紧张素-醛固酮系统(RAAS)等检查,必要时行低血钾相关基因检测,避免误诊漏诊。     

成人Bartter综合征14例临床分析

目的 分析成人Bartter综合征的临床特点。方法 回顾性分析北京协和医院近13年14例住院治疗的成人Bartter综合征病例。结果 成人Bartter综合征发病平均年龄31.8岁，男女发病比例大致相同，临床上以下肢乏力，心悸，胸闷，软瘫等为主要表现，14例均有不同程度的下肢乏力，其中软瘫4例；实验室检查均表现为低血钾，低谢性碱中毒，卧立位醛固酮试验显示，血肾素活性（12/14），血管紧张素Ⅱ（14/14）及醛固酮（11/14）明显升高，而血压正常；肾脏病理表现为肾小球旁细胞增生（8/10）；补钾治疗后症状缓解，血钾水平程升高。结论 成人出现双下肢乏力，低血钾，高尿钾而血压正常时需考虑到本病，行卧立位醛固酮试验可明确诊断，必要时行肾穿刺活检；本病治疗以补钾为主，辅助治疗包括补镁，前列腺素合成酶抑制剂，醛固酮拮抗剂。     

SLC12A3基因杂合突变致青少年Gitelman综合征

18岁男性,病程3年,以乏力症状起病,辅助检查提示低钾血症、代谢性碱中毒、低镁血症、低氯血症、低尿钙、高尿钾,高肾素、醛固酮水平,基因检测发现SLC12A3基因突变新位点,诊断为Gitelman综合征,予以补钾治疗后乏力症状缓解。     

Gitelman综合征伴胰岛素抵抗1例

本文对1例Gitelman综合征（GS）伴IR患者进行报道。患者女,27岁,以低血钾（2.62 mml/L）、低血镁（0.33 mmol/L）、代谢性碱中毒（HCO3—27.7 mmol/L）、低尿钙（1.25 mmol/24 h）、肾素及醛固酮增高、血压正常为主要特点。血糖正常,存在IR、Ins高峰后移、胰岛素曲线下面积（AUCI）388.6,经补钾、补镁治疗效果好。故临床低血钾、低血镁患者,应注意排除GS。     

Gitelman综合征--附二例报道

目的 探讨Gitelman综合征的临床特点及其与Bartter综合征的鉴别诊断。方法 回顾性分析2例Gitelman综合征的临床资料。结果 2例患者均在成年起病，主要表现为低血钾性碱中毒，血浆肾素活性增高而血压正常，肾脏穿刺活检为肾小球旁器细胞增生，并根据尿钙明显减少及低血镁，诊断Gitelman综合征。1例经补钾与补镁，症状改善；另1例经口服吲哚美辛后低血钾纠正。结论 Gitelman综合征与Bartter综合征在发病机制、临床表现及预后等方面虽相似但也有不同，应重视两者的鉴别。     

Gitelman综合征伴胰岛素抵抗1例

本文对1例Gitelman综合征(GS)伴IR患者进行报道。患者女,27岁,以低血钾(2.62mmol/L)、低血镁(0.33mmol/L)、代谢性碱中毒(HCO-327.7mmol/L)、低尿钙(1.25mmol/24h)、肾素及醛固酮增高、BP正常为主要特点。血糖正常,存在IR、Ins高峰后移、胰岛素曲线下面积(AUCi)为388.6,经补钾、补镁治疗效果好。故临床低血钾、低血镁患者,应注意鉴别排除GS。     

以顽固性低血钾为表现的糖尿病酮症酸中毒合并Gitelman综合征一例

笔者报道1例以酮症酸中毒起病,治疗过程中出现顽固性低血钾的糖尿病患者,同时伴有高尿钾、低尿钙、肾素-血管紧张素-醛固酮系统活性升高和代谢性碱中毒等特点,并最终经基因检测发现1个新的突变c.635G>T(p.G212V),从而确诊为Gitelman综合征。该病例提示在糖尿病酮症酸中毒治疗过程中如出现常规治疗无法纠正的低钾血症,同时合并低血镁、低尿钙、低血氯的患者需考虑合并Gitelman综合征的可能。     

Gitelman综合征肾脏损害

青年女性,临床表现反复四肢无力,血压偏低,伴低血钾、代谢性碱中毒,血镁正常、肾素-血管紧张素-醛固酮系统(RAAS)激活,血清肌酐升高,低尿钙,24h尿蛋白定量及尿沉渣红细胞计数均在正常范围。肾活检示肾小球球旁器肥大,肾小管间质重度慢性病变合并轻度急性病变。最终诊断Gitelman综合征相关肾损害。     

The challenges of diagnosis and management of Gitelman syndrome

Gitelman syndrome is an inherited tubulopathy characterized by renal salt wasting from the distal convoluted tubule. Defects in the sodium chloride cotransporter (encoded by SLC12A3) underlie this autosomal recessive condition. This article focuses on the specific challenges of diagnosing and treating Gitelman syndrome, with use of an illustrative case report. Symptoms relate to decreased serum potassium and magnesium levels, which include muscle weakness, tetany, fatigue and palpitations. Sudden cardiac deaths have been reported. Making a diagnosis may be difficult given its rarity but is important. A knowledge of the serum and urine biochemical picture is vital to distinguish it from a broad differential diagnosis, and application of genetic testing can resolve difficult cases. There is a group of Gitelman syndrome heterozygous carriers that experience symptoms and electrolyte disturbance and these patients should be managed in a similar way, though here genetic investigations become key in securing a difficult diagnosis. Potassium and magnesium replacement is the cornerstone of treatment, though practically this can be hard for patients to manage and often does not fully relieve symptoms even when serum levels are normalized. Challenges arise due to the lack of randomized controlled trials focussing on treatment of this rare disease; hence, clinicians endorse strategies in line with correction of the underlying pathophysiology such as sodium loading or pharmacological treatments, which seem to help some patients. Focussed dietary advice and knowing the best tolerated preparations of potassium and magnesium medications are useful tools for the physician, as well as an awareness of the specific burdens that this patient group face in order to signpost appropriate support.     

Correction of hypokalemia by magnesium repletion in familial hypokalemic alkalosis with tubulopathy

The effect of magnesium treatment on serum potassium and potassium balance was examined in three siblings with a recently described syndrome of hypokalemic alkalosis with renal tubulopathy. Oral magnesium supplementation for 11 days in the three siblings increased mean serum potassium from 2.7 ± 0.1 meq/liter to 3.3 ± 0.2 meq/liter (p < 0.05). In addition, urinary and fecal potassium excretion decreased by about 11 meq/day. Magnesium chloride did not affect plasma renin activity while the patients were supine or upright. In contrast, mean supine plasma aldosterone concentration increased from 5.3 ± 1.5 ng/dl to 13.2 ± 4.1 ng/dl (p > 0.1) and mean upright plasma aldosterone concentration increased from 17.4 ± 3.8 ng/dl to 66.1 ± 7.3 ng/dl (p < 0.01). These findings suggest that hypokalemia and potassium loss in this disorder may be caused by abnormal magnesium metabolism. The increase in plasma aldosterone concentration may have been caused by the positive potassium balance or a direct effect of magnesium on aldosterone secretion from the adrenal gland.     

Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome

Gitelman syndrome is a renal disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria due to the defective tubular reabsorption of magnesium and potassium. This disease is caused by mutations of thiazide-sensitive Na-Cl cotransporter (TSC) gene. Gitelman syndrome is usually distinguished from Bartter syndrome by the presence of both hypomagnesemia and hypocalciuria. However, a phenotypic overlap is sometimes observed. We encountered two sporadic Japanese patients with Gitelman syndrome and analyzed their TSC gene. These patients were diagnosed as Gitelman syndrome by the typical clinical findings and biochemical abnormalities, such as mild muscular weakness, periodic paralysis, tetany, metabolic alkalosis, hypomagnesemia and hypocalciuria. In patient 1, a novel two base deletion (del TG at nucleotide 731 and 732) in exon 5 and a two base deletion (del TT at nucleotide 2543 and 2544) in exon 21 previously reported in a Japanese patient were identified. The patient 2 had a missense mutation (L623P), that was also identified in Japanese patients, and a novel in-frame 18 base insertion in exon 6 as a heterozygous state. Family analysis of two patients confirmed an autosomal recessive inheritance. In conclusion, we add two new mutations of the TSC gene in Japanese patients with Gitelman syndrome. Because the differential diagnosis between Bartter syndrome and Gitelman syndrome is sometimes difficult, molecular analysis would be a useful diagnostic tool, particularly in unusual cases with phenotypic overlapping.     

成年III型Bartter综合征1例并文献复习华中科技大学同济医学院附属同济医院

目的：总结III型Bartter综合征的临床和生化特征以及诊断方法。方法：回顾性总结我科1例长期不明原因低钾血症患者的临床表现、生化检查和基因检测结果。结果：患者,女,41岁,低钾血症2年,无服用利尿剂和肾损害药物以及缓泻剂病史。患者主诉乏力和肢体麻木,无抽搐,血压正常。生化检查有显著低钾血症,血镁正常,尿钙正常。血气分析示代谢性碱中毒。血浆肾素活性增高。肾脏B超无钙化等异常,临床疑诊先天性失盐性肾小管病。PCR检测远曲小管上皮管腔侧钠氯离子同向转运蛋白(NCCT)基因SLC12A3全部编码区26个外显子无突变,而髓袢升支粗端和远曲小管上皮基底膜侧氯离子通道蛋白基因CLCNKB第12号外显子c.1093delC杂合突变,致编码氨基酸p.His365Thr fs 368X移码突变,这是我们发现的一个新的CLCNKB基因新的突变类型。此例最后诊断为III型Bartter综合征。结论：对于低钾血症伴代谢性碱中毒和血压正常而无特殊用药史的成年患者,诊断应考虑先天性失盐性肾小管疾病包括Gitelman和III型Bartter综合征,同时检测SLC12A3和CLCNKB基因可明确诊断。     

Gitelman syndrome: report of three cases and literature review

Gitelman syndrome (GS) is a rare autosomal recessive, inherited renal tubular disorder. Herein, we report three cases of GS, one sporadic case and two siblings. They have typical laboratory findings, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. All of them were treated with oral potassium and magnesium supplements. They received regular pediatric clinic follow-up to check electrolytes and monitor development. These three cases reminded us that doctors should be alert to unexplained hypokalemia, which is usually the initial presentation of GS.     

A case of pseudo-Bartter's syndrome associated with hypokalemic myopathy

A case of pseudo-Bartter's syndrome associated with hypokalemic myopathy was presented. A 37-year-old housewife was admitted to our hospital because of muscle cramps with muscle weakness and tetany. There was a history of facial edema and constipation, which have been managed with "Kanpo medicine (Chinese medicine)" and laxatives for several years. The patient was amenorrhea 3 months before entry. She began to experience muscle weakness and muscle cramps associated with gait disturbance 2 or 3 months before admission. On physical examination, she was thin with positive Trousseau's and Chvostek's signs. Laboratory studies revealed hypokalemia, low urinary excretion of potassium, hypocalcemia, metabolic alkalosis, elevated creatine phosphokinase (CPK), increased levels of plasma renin activity and plasma aldosterone concentration, and decreased sensitivity to pressor effect of angiotensin II. Potassium supplementation resulted in restoration of her symptoms and normalization of low serum calcium and elevated CPK levels. She was diagnosed to be pseudo-Bartter's syndrome due to anorexia nervosa. The mechanism(s) of hypokalemia in our case was discussed.     

Hypokalemic metabolic alkalosis: apropos of a case of Gitelman's syndrome

We present a case of Gitelman's Syndrome in a 20 year-old woman who came to our service with weakness, asthenia, leg cramps and tetany. Laboratory studies revealed metabolic alkalosis with hypokalemia, hypomagnesemia and low calcium in a 24-hour urine test. The diagnosis of this syndrome is made in some cases during adult life because this syndrome is asymptomatic over several years. Gitelman's Syndrome is autosomal recessive as is Bartter's Syndrome. The gene is located in chromosome 16q, which encodes the cotransporter Na/Cl sensitive to thiazide in the distal convoluted tubule. The defect of cotransporter produces an alteration of sodium reabsorption that causes electrolytic disorders typical of this Syndrome and different from Bartter's Syndrome. The typical electrolytic alterations are hypocalciuria and hypomagnesemia secondary to high urinary magnesium excretion. The prognosis of this syndrome is excellent and treatment consists in correction of serum electrolytes with oral administration of magnesium and potassium. In spite of this treatment, in some cases it is very difficult to reach normal serum levels of magnesium because of the high doses of oral magnesium, which produce common crises of diarrhea that increase magnesium gastrointestinal losses.     

The Effects of Serum Potassium and Magnesium Levels in a Patient with Gitelman's Syndrome on the Timing of Ventricular Wall Motion and the Pattern of Ventricular Strain and Torsion

Gitelman's syndrome is a primary renal tubular hypokalemic metabolic alkalosis. Hypokalemia and hypomagnesemia can cause cardiac tissue excitability and conduction. Global ventricular mechanical function is directly related to the contractile properties of cardiac myocytes, which are largely dependent on the flow of ions such as potassium and magnesium. Here, we show that increased levels of potassium, in addition to magnesium, in a patient with Gitelman's syndrome significantly impacts the timing of ventricular wall motion and the pattern of ventricular strain and torsion. Two‐dimensional speckle tracking echocardiography was used for evaluation of the hypokalemic–hypomagnesemic period (first day) and third day after potassium chloride and magnesium replacement therapy. The transthoracic echocardiography showed that the percent ejection fraction was similar in hypokalemic–hypomagnesemic (63%) and normokalemic–normomagnesemic (after potassium and magnesium therapy, 67%) hearts. However, decreased left ventricular apical 4‐chamber peak systolic longitudinal strain, left ventricle global peak systolic strain, and global torsion values increased after potassium chloride and magnesium replacement therapy.     

Gitelman's syndrome: an overlooked cause of chronic hypokalemia and hypomagnesemia in adults

In 1966, Gitelman described a benign variant of classical Bartter's syndrome in adults characterized by consistent hypomagnesemia and hypocalciuria, hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism with normal blood pressure. A specific gene has been found responsible for this disorder, encoding the thiazide-sensitve Na-Cl coporter (TSC) in the distal convoluted tubule. Mutant alleles result in loss of normal TSC function and the phenotype is identical to patients with chronic use of thiazide diuretics. Gitelman's syndrome is a more common cause of chronic hypokalemia than Bartter's syndrome, with which it is often confused. The distinguishing features between both syndromes are discussed.