儿童2型Dent病1例并文献复习

目的 总结1例2型Dent病患儿临床资料，提高对该病的认识。方法 报道1例2型Dent病患儿的临床发现、相关实验室检查指标和肾活检病理改变。对该家系相关成员行CLCN5和OCRL基因外显子及附近调控区域直接测序，分析突变位点，并文献复习。结果 患儿，男，6岁起病，首发症状为单纯性蛋白尿，未见先天性白内障、智力低下、认知障碍及发育迟缓。实验室检查提示低分子蛋白尿，高钙尿症，镜下血尿，血清乳酸脱氢酶和磷酸肌酸激酶增高，肾活检病理提示轻微病变。患儿CLCN5和OCRL基因测序分析发现，CLCN5基因未见致病性突变，ORCL基因c.260delA(p.Q87fs105X)纯合突变，确诊为2型Dent病。家系OCRL基因突变分析显示，患儿父亲c.260delA未检出突变，母亲携带c.260delA杂合突变。c.260delA突变为移码突变，可导致OCRL基因编码蛋白截短。结论 2型Dent病以低分子蛋白尿、高钙尿症和镜下血尿为特征，血清乳酸脱氢酶、磷酸肌酸激酶增高和OCRL基因纯合移码突变支持2型Dent病诊断。

Dent-2 disease in one child and literature review

Objective To summarize and review the clinical data of a child with Dent-2 disease so as to improve our understanding to the disease.Methods Clinical data of the case with Dent-2 disease were summarized, including clinical manifestations, laboratory findings, renal pathological changes and family investigation. Mutation analysis in CLCN5 and OCRL genes was performed by direct sequencing in his family. Mutations of CLCN5 and OCRL genes were examined in normal control and related literatures from PubMed were reviewed also.Results Age at onset was 6 years old. Proteinuria was the only symptom at onset. The patient had no extrarenal symptoms of Lowe syndrome, such as peripheral cataracts, mental impairment and stunted growth. Laboratory findings showed low-molecular weight proteinuria, hypercalciuria, microscopic hematuria and elevation of creatine kinase/lactate dehydrogenase. Renal pathological change detection showed a minute lesion under light microscope. A novel homozygous c.260delA (p.Q87fs105X) mutation was found in exon 5 of OCRL gene. No mutations of CLCN5 gene were detected. Mutation analysis showed his mother carried a c.260delA mutation, but his father did not. This deletion caused a frameshift of amino acids and resulted in a truncated protein (p.Q87fs105X), and was not identified in the 100 healthy, unrelated controls.Conclusion Dent-2 disease is an X-linked tubulopathy characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis, and the development of renal insufficiency. Dent-2 disease can be diagnosed by these characteristics. Lowe syndrome was ruled out in the patient with no peripheral cataracts, mental impairment and stunted growth. Elevation of creatine kinase/lactate dehydrogenase and carrying the homozygous frameshift mutation in OCRL gene support the diagnosis of the patient in the current study. This is the first report of Dent-2 disease caused by OCRL gene mutation in Chinese family.