Comparison of clinical and genetic characteristics between Dent disease 1 and Dent disease 2
Comparison of clinical and genetic characteristics between Dent disease 1 and Dent disease 2
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DOI：
10.1007/s00467-020-04701-5
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发表时间：
2020-07-18
影响因子：
3
通讯作者：
Nozu, Kandai
中科院分区：
文献类型：
--
作者：
Sakakibara, Nana;Nagano, China;Nozu, Kandai
背景Dent病与低分子蛋白尿和高钙尿相关，由两个基因中的任何一个的致病变异引起：CLCN5(Dent病1)和OCRL(Dent病2)。它一般不伴有肾外表现，如果没有基因检测，很难区分Dent病1和Dent病2。我们使用迄今为止最大的队列之一，对这两种疾病的特征进行了回顾性比较。方法对临床疑似Dent病患者进行基因检测，对85例男性患者进行基因诊断，其中Dent病1例72例，Dent病2例13例。结果Dent病2组身高标准差评分(Height SDS)、血肌酐估算GFR(Cr-EGFR)(中位数：84vs.127mL/min/1.73m(2)，p<；0.01)、血清天冬氨酸转氨酶(AST)、血清丙氨酸氨基转移酶(ALT)、血清乳酸脱氢酶(LDH)、血清肌酸磷酸激酶(CK)、血钾、血清无机磷、血尿酸、尿蛋白/肌酐比值(中位数：3.5vs.1.6 mg/mg，p<)；0.01)，尿钙/肌酐比值。两组在血钠、血钙、碱性磷酸酶(ALP)、尿β2-微球蛋白、肾钙质沉着症发生率、智力残疾或自闭症谱系障碍发生率方面无显著差异。结论本研究显示了Dent病1和Dent病2的临床和实验室特征。值得注意的是，Dent病2的患者在更年轻的时候就表现出肾功能障碍，这应该为这些疾病的鉴别诊断提供线索。
Background Dent disease is associated with low molecular weight proteinuria and hypercalciuria and caused by pathogenic variants in either of two genes:CLCN5(Dent disease 1) andOCRL(Dent disease 2). It is generally not accompanied by extrarenal manifestations and it is difficult to distinguish Dent disease 1 from Dent disease 2 without gene testing. We retrospectively compared the characteristics of these two diseases using one of the largest cohorts to date. Methods We performed gene testing for clinically suspected Dent disease, leading to the genetic diagnosis of 85 males: 72 with Dent disease 1 and 13 with Dent disease 2. A retrospective review of the clinical findings and laboratory data obtained from questionnaires submitted in association with the gene testing was conducted for these cases. Results The following variables had significantly higher levels in Dent disease 2 than in Dent disease 1: height standard deviation score (height SDS), serum creatinine-based estimated GFR (Cr-eGFR) (median: 84 vs. 127 mL/min/1.73 m(2),p< 0.01), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum lactate dehydrogenase (LDH), serum creatine phosphokinase (CK), serum potassium, serum inorganic phosphorus, serum uric acid, urine protein/creatinine ratio (median: 3.5 vs. 1.6 mg/mg,p< 0.01), and urine calcium/creatinine ratio. There were no significant differences in serum sodium, serum calcium, alkaline phosphatase (ALP), urine beta 2-microglobulin, incidence of nephrocalcinosis, and prevalence of intellectual disability or autism spectrum disorder. Conclusions The clinical and laboratory features of Dent disease 1 and Dent disease 2 were shown in this study. Notably, patients with Dent disease 2 showed kidney dysfunction at a younger age, which should provide a clue for the differential diagnosis of these diseases.