Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter
Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter
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DOI：
10.1053/j.ajkd.2003.10.018
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发表时间：
2004-02-01
影响因子：
13.2
通讯作者：
Halperin, ML
中科院分区：
文献类型：
--
作者：
Lin, SH;Cheng, NL;Halperin, ML
背景Gitelman综合征（GS）最常由噻嗪敏感性氯化钠协同转运蛋白（NCC）突变引起。虽然具有相同突变的患者的症状严重程度可能不同，但具有相同突变的家庭成员的临床表现明显不同确实罕见。方法. 5例患者（3女2男）属于2个无关的中国家庭进行了调查。所有患者均患有慢性低钾血症、肾性钾（K+）消耗、代谢性贫血和正常血压。对NCC和CLCNKB基因进行直接测序。结果：家系先证者均为男性。他们有非常严重的低钾血症，并有麻痹发作的症状。他们的血浆镁浓度正常，钙排泄率正常，最大尿浓缩能力受损。相反，女性家庭成员则无症状。他们的实验室检查结果典型的GS-不太严重的低钾血症，低镁血症，低钙尿，和完整的最大肾浓缩能力。然而，所有患者都具有相同的新的NCC突变对，并且在CLCNKB中未检测到突变。结论：性别差异可能有助于解释这2个NCC新突变家系不同的临床表现。低镁血症和低钙尿症并不总是出现在GS患者。
Background. Gitelman syndrome (GS) most often results from mutations in the thiazide-sensitive sodium chloride cotransporter (NCC). Although the severity of symptoms may vary in patients who have the same mutations, a markedly different clinical presentation in family members with identical mutations is truly rare. Methods. Five patients (3 women and 2 men) belonging to 2 unrelated Chinese families were investigated. All had chronic hypokalemia, renal potassium (K+) wasting, metabolic alkalosis, and normal blood pressure. Direct sequencing of both the NCC and CLCNKB genes were performed. Results: The probands in each family were men. They had very severe hypokalemia and were symptomatic with episodes of paralysis. They had normal plasma magnesium concentrations, normal calcium excretion rates, and impaired maximal urine concentrating ability. In contrast, female family members were asymptomatic. They had laboratory findings typical of GS-less severe hypokalemia, hypomagnesemia, hypocalciuria, and intact maximal renal concentrating ability. Nevertheless, all patients had the same novel pair of NCC mutations and no mutations detected in CLCNKB. Conclusion: Differences in sex may help explain the different clinical presentations in these 2 Chinese families with novel NCC mutations. Hypomagnesemia and hypocalciuria are not always present in patients with GS.