SLC12A3基因突变Gitelman综合征并身材矮小1例临床分析

Gitelman综合征（Gitelman syndrome,GS）又被称为家族性低钾低镁血症,是一种以低钾低氯性碱中毒、低镁血症、低尿钙、高肾素活性为特征的常染色体隐性遗传的失盐性肾小管疾病,血压可正常或偏低。大多数患者经过“食补+药物”替代治疗有良好的预后,早期发现并予相应治疗,可显著提高患者生活质量。现将西安市儿童医院收治的1例Gitelman综合征并身材矮小患者临床资料及诊疗过程,结合相关文献学习,做如下报道。     

青少年起病的Gitelman综合征1例并文献复习

目的探讨Gitelman综合征(Gitelman syndrome, GS)患儿的临床表现及遗传学特点, 以提高临床医师对GS的认识。方法回顾性分析河北省人民医院2022年9月收治的1例GS患儿临床表现、实验室检查、诊断和治疗等并复习相关文献。结果 12岁男孩, 以双下肢无力为主入院, 实验室检查提示存在低血钾、低血镁、低尿钙和代谢性碱中毒。基因检测发现SLC12A3基因存在2处复合杂合突变(c.1456G>A和c.634G>A), 明确诊断为GS, 予补钾等治疗好转后出院。结论 GS漏诊率高, 如临床上疑诊GS, 应及早行基因检测明确诊断。     

不同伴随症的Gitelman综合征的诊治研究

目的 报道3例特殊Gitelman综合征(GS)的临床特征及诊治情况。方法 回顾分析2019年至2022年就诊于河南科技大学第二附属医院内分泌科的3例GS患者的临床资料。结果 病例1为GS急性严重低血钾发作入院，经中心静脉补钾缓解后继续以周围静脉及口服补钾补镁治疗后好转，携带SLC12A3基因c.1925G>A、c.911C>T复合杂合突变；病例2诊断为GS伴矮身材，家属暂时拒绝使用生长激素，口服补钾治疗后身高略有增长，携带c.1963C>T、c.1964G>A复合杂合突变；病例3诊断主要为GS伴2型糖尿病，口服氯化钾缓释片、螺内酯、吲哚美辛控制血钾，降糖以达格列净、阿卡波糖、二甲双胍缓释片联用，携带c.1195C>T纯合突变。结论 对于GS患者严重急性期的补钾治疗可能需要通过中心静脉输注，此外应特别关注相关伴随症，如矮小身材、糖尿病等的治疗。     

1例Gitelman综合征病人的护理

Gitelman综合征(GS)是常染色体隐性遗传性肾小管疾病,GS的主要临床特征为低氯性低钾性碱中毒、低血镁、低尿钙、肾素-血管紧张素-醛固酮系统(RAAS)激活以及正常或偏低的血压[1].其发病基础是由于编码噻嗪类利尿剂敏感的钠氯共同转运体(NCCT) 的SLC12A3 基因突变[2].由Gitelman等在1966年首次报道,以后即以其名字来命名.本病多成年起病,临床表型变异很大,可表现肌肉乏力和抽搐,有时伴有恶心、呕吐、腹痛和发热、面部感觉异常等,部分病人也可以完全无临床症状.现将我院收治的1例Gitelman综合征病人的护理报告如下.     

SLC12A3基因突变致成人Gitelman综合征4例

Gitelman综合征(Gitelman syndrome,GS)又称家族性低钾低镁综合征,1966年由Gitelman等[1]首次报道,是由编码肾脏远曲小管钠-氯协同转运蛋白(Na-Cl cotransporter,NCCT)的SLC12A3基因突变所致的常染色体隐性遗传病,曾长期被认为是Bartter综合征(Bartter syndrome,BS)的一种特殊亚型,直至1996年Simon等[2]通过基因分析证实GS是独立于BS的不同疾病。GS以低血钾、低血镁、低尿钙、低氯性代谢性碱中毒、高肾素-血管紧张素-醛固酮(RAAS)活性及正常或偏低血压为主要表现,是目前已知的遗传性肾小管疾病中患病率最高的病种[3]。GS的临床表现缺乏特异性,且起病隐匿,易漏诊、误诊。本研究通过对4例SLC12A3基因突变致成人GS患者的临床资料进行回顾性分析,旨在提高临床医师对该病的认识及诊治水平。     

类Gitelman综合征发病机制的研究进展

Gitelman-like综合征与Gitelman综合征(GS)的临床表现一样,是以低钾性碱中毒和低镁血症为特征。Gitelman 综合征是一种由于编码位于肾远曲小管的噻嗪类利尿剂敏感的钠氯共转运蛋白基因突变的低钾失盐性肾小管疾病,又名家族性低钾低镁血症。但仍有10%左右的临床诊断为GS,却未能检测到致病疾病的突变。专家们对于临床表现相似的、但未检测到基因致病突变的这这些患者定义为Gitelman-like 综合征,这些患者往往存在非遗传因素或线粒体DNA的突变如异亮氨酸和苯丙氨酸的突变。     

一例维吾尔族Gitelman综合征患者的临床与基因突变分析

目的　　探讨1例维吾尔族Gitelman综合征（Gitelmans syndrome，GS）患者的临床表现及其分子生物学基础。方法　　详细收集患者的临床资料、生化检查及影像学检查结果，抽取外周静脉血，提取基因组DNA，聚合酶链反应（poly-merase chain reaction，PCR）扩增SLC12A3基因的26个外显子及其与内含子的交界区，测序确定突变情况。结果　　患者临床表现、实验室检查和影像学检查符合GS诊断。基因突变分析显示,患者SLC12A3基因cDNA序列的第1964位鸟嘌呤G纯合突变为腺嘌呤A(c.1964 G＞A），造成第655位氨基酸由精氨酸改变为组氨酸（p.Arg655His）,该突变位于SLC12A3的第16外显子。结论　　通过SLC12A3基因突变分析，从分子遗传学方面证实1例维吾尔族患者GS的诊断。临床上持续低血钾、肾脏失钾、代谢性碱中毒、血压正常或偏低、低尿钙的患者应考虑该疾病诊断，基因分析有助于确诊。     

SLC12A3基因新发现突变位点突变致儿童Gitelman综合征1例

Gitelman综合征(Gitelman syndrome,GS),是一种常染色体隐性遗传肾小管失盐性肾病,临床上表现为低血镁、低尿钙、低血钾、代谢性碱中毒、肾素-血管紧张素-醛固酮系统(RAAS)激活、血压正常或是偏低[1]。GS发病较晚,生长发育一般不受影响,多表现为四肢抽搐、肢体乏力及面部感觉异常,部分患者由于长期缺镁而出现软骨钙质沉着病[2]。     

1例误诊尿崩症的Gitelman综合征病例分析

Gitelman综合征(GS)是一种常染色体隐性遗传所致的失盐性肾小管疾病,以低钾性碱中毒、低镁血症、低钙尿症和继发性醛固酮增多症为主要表现。本研究报道了1例误诊尿崩症的GS患儿的诊治过程,同时通过文献复习的方式探讨GS的临床表现、诊断方法、治疗及随访策略,并强调基因检测在本病诊断过程中的重要性。临床医师在工作中应提高对GS的认识水平,做到早期诊断并治疗GS。     

粒细胞肉瘤25例临床分析

目的 探讨粒细胞肉瘤(GS)的临床特点、治疗方法及预后.方法 选择2005年10月1日至2012年7月31日于苏州大学附属第一医院确诊的25例GS患者为研究对象.根据患者是否进行化疗联合异基因造血干细胞移植(allo-HSCT)治疗,分为移植组(n=6)和未移植组(n=19).回顾性分析患者的临床特点、病理特征以及治疗方法,并随访至2012年7月31日,应用Kaplan-Meier生存分析法和Log-Rank检验,比较两组患者的治疗效果及预后情况(本研究遵循的程序符合本院人体实验委员会所制定的伦理学标准,得到该伦理会批准).结果 GS好发部位为乳腺、皮肤、淋巴结等.25例GS患者中,移植组与未移植组3年总生存(OS)率分别为66.7％±27.2％和15.9％±9.5％,2组OS率比较差异有统计学意义(x2 =7.188,P＜0.05),移植组3年OS率明显高于未移植组.结论 GS临床少见,预后不良,诊断主要依靠免疫病理学试验,临床上以高剂量阿糖胞苷为主的化疗是较为有效的治疗方案,allo-HSCT有望成为一种更为积极的治疗方案,但治疗的总体效果及远期预后仍有待进一步临床观察.     

托拉塞米与呋塞米对急性心力衰竭患者尿量及电解质影响比较

目的比较托拉塞米与呋塞米对急性心力衰竭患者尿量及电解质的影响。方法将149例急性心力衰竭患者随机分为4组：托拉塞米组（n=32）,呋塞米组（n=41）,托拉塞米＋螺内酯组（n=30）,呋塞米＋螺内酯组（n=46）,用药24小时,统计出入量,测定用药前后血钾和血钠浓度,对比分析各组患者尿量及血钠和血钾变化。结果①托拉塞米组和呋塞米组24小时尿量差异无统计学意义,（3591．34±835．15）ml vs（3525．22±842．51）ml（P〉0．05）;②托拉塞米组与呋塞米组对血钠影响差异无统计学意义,（2．24±0．97）mmol／L VS（2．29±1．05）mmol／L（P〉0．05）,托拉塞米＋螺内酯组利钠作用最强（3．11±1．72）mmol／L,与托拉塞米组和呋塞米组比较差异均有统计学意义（P〈0．01）;③在排钾作用方面,托拉塞米＋螺内酯组最小（0．09±0．05）mmol／L,而呋塞米组最大（0．25±0．32）mmol／L（P〈O．01）,托拉塞米组排钾小于呋塞米组（0．12±0．06）mmol／L（P〈0．01）。结论托拉塞米与呋塞米利尿、排钠作用相近,而托拉塞米排钾作用明显弱于呋塞米,两者交替使用,有助于增加疗效,减少利尿剂抵抗的发生。     

Ionized magnesium supplementation in critically ill patients: comparing ionized and total magnesium

PURPOSE: The purpose of this study was to assess the effect of magnesium supplementation on total magnesium, ionized magnesium, ionized calcium, potassium, and pH in critically ill cancer patients and to compare the validity of the measurements. MATERIALS AND METHODS: Thirty-three consecutive critically ill patients receiving magnesium supplementation were placed in this prospective observational study at the Comprehensive Cancer Center, University Hospital. One gram (4.1 mmol) magnesium in 50 mL D5W was administered to critically ill patients, and the following were measured: total magnesium, ionized magnesium, ionized calcium, potassium, albumin, pH, BUN, creatinine, creatinine. RESULTS: Total magnesium and ionized magnesium increased by a mean of .11 +/- .02 and .05 +/- .01 mmol/L, respectively, after supplementation with 4.1 mmol of magnesium sulfate (P = .0001).Total magnesium, ionized magnesium, albumin, ionized calcium, potassium, and pH did not change significantly by the administration of 1 g of magnesium sulfate. CONCLUSION: The mean ionized magnesium (IMg+2) relationship to total magnesium (TMg) cannot be predicted before the supplementation with the available technology. After supplementation of 4.1 mmol/L the ionized magnesium level increased by .05 +/- .01 mmol/L. Magnesium supplementation had no significant effect on ionized calcium, potassium, and pH. TMg and IMg+2 should be followed independently.     

两种口服补钾方案快速改善轻度低血钾患者血钾水平的效果

目的比较两种口服补钾方案对轻度低血钾患者的效果。方法回顾性分析2009年3月至2011年3月116例口服补钾患者的临床资料,其中58例患者口服氯化钾缓释片,58例患者口服改良配制的补钾液,治疗2d后,复查血钾水平。结果116例口服补钾治疗低血钾患者的低血钾情况均有所好转,其中口服补钾液患者的低血钾改善程度明显优于口服氯化钾缓释片患者[（0．492±0．242）mmol/L比（0．219±0．131）mmol／L],差异具有统计学意义（t=2．543,P〈0．05）。结论对于轻度低血钾患者,口服补钾液效果优于口服氯化钾缓释片。     

Liquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: A case report

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.     

暴发性1型糖尿病7例并文献复习

目的 探讨中国暴发性1型糖尿病的临床特点,并与日、韩两国进行比较。方法 纳入我国暴发性1型糖尿病患者52例,日本患者161例,韩国患者29例,总结其临床特点。结果 ①我国暴发性1型糖尿病患者平均发病年龄为(32.4±12.6)岁,18岁以上患者约占总数的96%,而且18～30岁的病例数最多,约占总数的52%。②与日本相比,我国暴发性1型糖尿病患者发病年龄更低[(32.4±12.6)岁 vs (39.14±15.7)岁,P<0.05]、病程更短(3.4±2.3天 vs 4.44±3.1天,P<0.05)、发病时血糖较低[(38.5±15.3) mmol/L vs (44.2±20.0) mmol/L,P<0.05];电解质代谢紊乱更严重,表现为高血钾[(6.3±1.2) mmol/L vs (5.5±1.2) mmol/L,P<0.05],低血钠[(128.9±6.2) mmol/L vs (131.0±9.0) mmol/L,P<0.05]。③与韩国相比,我国暴发性1型糖尿病患者发病年龄更低[(32.4±12.6)岁 vs (37.4±12.4)岁,P＜0.05],起病时血钾高于韩国[(6.3±1.2 mmol/L vs (5.6±1.5) mmol/L,P＜0.05]。结论 ①暴发性1型糖尿病在我国并非罕见,且患者多以成年起病。②中国暴发性1型糖尿病患者较日本、韩国发病年龄小,发病时血钾更高。     

Serum concentration of potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate, losartan potassium or candesartan cilexetil

OBJECTIVE: To retrospectively investigate elevation of serum potassium when spironolactone (25 or 50 mg/day) and furosemide were administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) to patients with chronic heart failure for 12 months and occurrence of hyperkalemia and hypokalemia because of concomitant administration of spironolactone plus an ACE-I or ARB and furosemide. METHODS: Patients with chronic heart failure, who visited departments of cardiovascular internal medicine and cardiovascular surgery at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine, uric acid, and serum sodium were determined in every patient at the time of start of treatment and at 3 and 12 months of treatment. Data from patients in Groups A (25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) and B (50 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) were analysed for differences with respect to the ACE-I and ARB used. RESULTS: When 50 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril) or 50 mg/day losartan potassium (losartan) or 8 mg/day candesartan cilexetil (candesartan) plus 40 mg/day furosemide were concomitantly used, the mean value of serum potassium was significantly elevated only in the group treated with 50 mg/day spironolactone regardless of the concomitant drug. The number of patients with hyperkalemia (>5.5 mEq/L) at 12 months of treatment was 12 (8.8%), while the number of patients with hypokalemia (相似文献   

Relationship of potassium and magnesium concentrations in serum to cardiac arrhythmias

Low concentrations of potassium and magnesium in serum have been implicated in cardiac arrhythmias; the importance of mild hypokalemia or hypomagnesemia is uncertain. To investigate possible associations among use of diuretics, the concentration of these ions in serum, and the onset of clinically important arrhythmias, we reviewed records of 103 patients admitted to our Coronary Care Unit during three months and found mild to moderate hypokalemia and hypo- magnesemia in 18 and 24%, respectively. The significant correlation between the concentrations of magnesium and potassium in serum at admission (r = 0.27, p less than 0.007) remained constant in patients, whether they were receiving diuretics or not. Potassium concentrations were significantly lower (p less than 0.05) in patients receiving diuretics (3.93 mmol/L) than in those who were not (4.21 mmol/L), but the mean concentrations of magnesium did not differ significantly. Except for myocardial infarction, no single variable or combination of variables was highly predictive of cardiac arrhythmias in these patients. We conclude that there is no strong predictive relationship between mildly decreased concentrations of magnesium or potassium in serum and onset of cardiac arrhythmias.     

静脉滴注氯化钾与门冬氨酸钾镁对血钾浓度影响的比较

测定３组低钾低镁动物（家兔）模型分别静脉滴注含钾浓度相同的氯化钾、氯化钾加硫酸镁和门冬氨酸钾镁后６０ｍｉｎ和１２０ｍｉｎ的血钾和血镁浓度。结果：氯化钾组的血钾浓度上升最明显（静滴６０ｍｉｎ时比静滴前增加０．７ｍｍｏｌ／Ｌ，１２０ｍｉｎ又较６０ｍｉｎ时增加０．３ｍｍｏｌ／Ｌ）；门冬氨酸钾镁组的血钾浓度上升较少（静滴６０ｍｉｎ时比静滴前仅增加０．４ｍｍｏｌ／Ｌ，１２０ｍｉｎ时比６０ｍｉｎ时增加０．２ｍｍｏｌ／Ｌ）；氯化钾加硫酸镁组的血钾浓度变化介于上述两组之间。３组同期血镁浓度测定结果与血钾浓度有相反的变化趋势，血钾浓度高者血镁浓度较低，反之亦然。     

Effect of varying doses of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss.

The purpose of this study was to compare the efficacy of three dosages of potassium-magnesium citrate in overcoming thiazide-induced hypokalemia and magnesium loss and increasing urinary pH and citrate. Sixty-one normal subjects first took hydrochlorothiazide at 50 mg/d. After 3 weeks of thiazide treatment or earlier if hypokalemia developed, the subjects were randomized to take one of three dosages of potassium-magnesium citrate (K ( 4 ) MgCit ( 2 ) ) for 3 weeks while continuing on the thiazide: 4 tablets per day (24 mEq potassium, 12 mEq magnesium, and 36 mEq citrate per day), 7 tablets per day (49 mEq potassium, 24.5 mEq magnesium, and 73.5 mEq citrate per day), or 10 tablets per day (70 mEq potassium, 35 mEq magnesium, and 105 mEq citrate per day). Outcome measures were changes in serum potassium and magnesium and urinary potassium, magnesium, pH, and citrate. All three dosages of potassium-magnesium citrate significantly increased serum potassium concentration, with >80% of subjects regaining normal values despite continued thiazide therapy. The two higher dosages, but not the lowest dosage, caused a small but significant increase in serum magnesium concentration, while substantially increasing urinary magnesium. All three dosages significantly increased urinary pH and citrate in a dose-dependent manner. The lowest dosage produced increases sufficient to prevent stone recurrence. Side effects of thiazide therapy were ameliorated by the highest dosage but not by the two lower dosages. Potassium-magnesium citrate at a dosage of 4 tablets per day is adequate to correct thiazide-induced hypokalemia and to increase urinary pH and citrate sufficiently for stone prevention. Higher dosages are probably required for the prevention of magnesium loss and adverse symptoms of thiazide therapy.     

Hydrochlorothiazide and spironolactone in hypertension.

A double-blind study of hydrochlorothiazide and spironolactone, alone and in combination, was conducted in 49 patients with mild-to-moderate essential hypertension after a 4-wk placebo washout period. In the whole group mean arterial blood pressure fell to levels of less than or equal to 107 mm Hg or declined by more than 15 mm Hg in 78% of the patients after twelve weeks of treatment. Sixty-nine percent of patients receiving hydrochlorothiazide alone developed serum potassium levels lower than 3.5 mEq/L; serum potassium levels were above 5.5 mEq/L in 2 patients (5.5%) receiving spironolactone 400 mg/day. Uric acid levels rose in all patients, more in those on hydrochlorothiazide, but clinical gout did not develop in any subject. Hydrochlorothiazide, spironolactone, and the combination of the two are effective antihypertensives. Spironolactone in doses of 200 and 400 mg/day was associated with side effects but did not induce a greater antihypertensive effect than doses of 100 mg/day. Our data suggest that when hydrochlorothiazide is associated with potassium loss, when gout or elevated uric acid levels are of concern, or when carbohydrate tolerance is abnormal, supplementation or replacement with spironolactone (up to 100 mg/day) may be useful in controlling blood pressure while reducing side effects.