Bartter综合征和Gitelman综合征的临床研究及基因诊断

发布时间：2018-08-14 15:42

【摘要】：背景Bartter综合征(Bartter syndrome,BS)和Gitelman综合征(Gitelman syndrome,GS)均属于常染色体遗传性肾小管疾病,临床共同特征为低钾血症、低氯性代谢性碱中毒、高肾素-血管紧张素-醛固酮但血压正常范围。肾组织病理学提示肾小球旁器增生和肥大为特征。低尿钙、低镁血症是临床上GS区别于BS的主要特点。基因测定为诊断BS及GS的金标准。本研究分析比较BS和GS患者的临床特征、实验室结果、基因诊断及治疗和预后等,为临床诊治提供有益信息。目的总结BS和GS综合征患者的临床表现、基因测定、诊治经过,探讨两者的病因、发病机制、治疗及预后。为正确鉴别两者提供依据。方法1.研究对象:回顾性分析2015.1-2016.9月在河南省人民医院及郑州颐和医院收治的成人Bartter综合征和Gitelman综合征患者7例的临床资料。2.实验室检查:收集入院后所测定的血、尿电解质、血气分析、立、卧位肾素、血管紧张素II(AT-II)、醛固酮(ALD)水平等相关检查指标及双肾彩超、CT的检查结果。3.基因检测:7例患者均做CLCNKB基因测序,明确可能存在的基因突变位点,1例患者复诊对其进行了SLC12A1、KCNJ1、CLCNKB、BSND及SLC12A3等基因测序。4.治疗:7例均给予补钾及吲哚美辛治疗,观察治疗后各项指标的变化。5.统计分析:采用SPSS22.0软件进行统计分析,P0.05差异有统计学意义。结果1.一般资料分析:7例患者均为成年起病,其中7例均有不同程度的乏力,2例合并心悸、胸闷,1例合并抽搐,1例四肢肌痛、麻木伴低血镁、低尿钙。临床实验室检查均有不同程度的低血钾、低血镁、代谢性碱中毒、RASS检测均增高,而血压在正常范围。2.基因测定:其中7例BS的CLCNKB基因未发现病理变异,1例测SLC12A3基因发现2个错义突变,其中一个错义突变是位于12号外显子上的c.1456GA,碱基由G突变为A,编码的氨基酸(p.Asp486Asn;Het)由天冬氨酸替换为天冬酰胺。另一个错义突变是位于7号外显子上的c.907GT,碱基由G突变为T,编码的氨基酸(p.Gly303Trp;Het)由甘氨酸替换为色氨酸。后者为本研究新发现的一个突变位点。本例更正诊断为:Gitelman综合征。3.患者用药前后实验室结果对比:7例患者经给予补钾和吲哚美辛治疗后的血钾、血钙、血氯均有升高,24h尿钾和HCO3下降,差异均有统计学意义(P0.05)。治疗后患者的PH有一定下降,血钠和24h尿钙升高,但经比较差异均无统计学意义(P0.05)。对于立、卧位的肾素活性-血管紧张素II-醛固酮水平治疗后均降低,差异有统计学意义(P0.05)。结论1.成人出现乏力、顽固性低血钾、代谢性碱中毒、立、卧位醛固酮检测水平增高而血压正常或偏低、发育迟滞时需警惕BS的可能,低血镁、低尿钙是临床上GS不同于BS的主要特点。2.两者临床表现及实验室检查极为相似,很难明确鉴别诊断,基因诊断是金标准,有利于早期确诊后进行针对性的治疗。3.BS主要以补钾纠正电解质紊乱、联合保钾利尿剂药物及前列腺素抑制剂等综合治疗为主;GS在此基础上补镁,应用前列腺素抑制剂后有效降低肾素及醛固酮水平,血钾明显升高,纠正碱中毒。
[Abstract]:Background Both Bartter syndrome (BS) and Gitelman syndrome (GS) are autosomal hereditary tubular diseases. The common clinical features are hypokalemia, hypochlorite metabolic alkalosis, hyperrenin-angiotensin-aldosterone but normal blood pressure. Hypertrophy is characterized by hypocalcemia and hypomagnesemia. Gene analysis is the gold standard for the diagnosis of BS and GS. The clinical features, laboratory results, gene diagnosis, treatment and prognosis of BS and GS were analyzed and compared in order to provide useful information for clinical diagnosis and treatment. Methods 1. The clinical data of 7 adult patients with Bartter syndrome and Gitelman syndrome admitted to Henan People's Hospital and Zhengzhou Yihe Hospital from January 2015 to September 2016 were analyzed retrospectively. Laboratory examination: collection of blood, urine electrolyte, blood gas analysis, standing, lying renin, angiotensin II (AT-II), aldosterone (ALD) levels and other related examination indicators and double kidney color Doppler ultrasound, CT examination results. 3. Gene detection: 7 patients were done CLCNKB gene sequencing, identify possible gene mutation sites, one patient re-visit its. Sequencing of SLC12A1, KCNJ1, CLCNKB, BSND and SLC12A3 were performed. 4. Treatment: Seven patients were treated with potassium supplementation and indomethacin, and the changes of indexes were observed after treatment. 5. Statistical analysis: SPSS22.0 software was used for statistical analysis, P 0.05 difference was statistically significant. Results 1. General data analysis: 7 patients were adult onset, of which 7 cases were treated with potassium and indomethacin. There were different degrees of fatigue, 2 cases with palpitations, chest tightness, 1 case with convulsions, 1 case with limb myalgia, numbness with hypomagnesia, hypocalcemia. Clinical laboratory tests showed different degrees of hypokalemia, hypomagnesemia, metabolic alkalosis, RASS detection were increased, and blood pressure in the normal range. 2. Gene determination: 7 cases of BS LCNKB gene did not find pathology. One patient detected two missense mutations in the SLC12A3 gene. One missense mutation was c.1456G A located at exon 12, the base was changed from G to A, and the encoded amino acid (p.Asp486Asn; Het) was replaced by asparagine. Gly303Trp (Het) was replaced by glycine for tryptophan. The latter was a new mutation found in this study. The correct diagnosis was Gitelman's syndrome. 3. Comparison of laboratory results before and after treatment with potassium and indomethacin in 7 patients showed elevated serum potassium, calcium and chlorine levels, decreased urinary potassium and HCO3 levels at 24 hours after treatment. There was statistical significance (P 0.05). After treatment, PH of the patients decreased, blood sodium and urinary calcium increased, but there was no significant difference between the two groups (P 0.05). Hypomagnesemia and hypocalcemia are the main characteristics of GS which are different from BS. 2. The clinical manifestations and laboratory tests are very similar. It is difficult to make a definite differential diagnosis. Genetic diagnosis is the gold standard for early diagnosis. 3. BS mainly take potassium supplement to correct electrolyte disorders, combined with potassium-preserving diuretics and prostaglandin inhibitors and other comprehensive treatment; GS on this basis, magnesium supplement, prostaglandin inhibitors can effectively reduce renin and aldosterone levels, blood potassium significantly increased, correct alkalosis.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

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