Steroid resistant nephrotic syndrome (SRNS) accounts for 30% of all cases of nephrotic syndrome (NS) in children and frequently leads to end stage kidney disease (ESKD). About 30% of children with SRNS demonstrate causative mutations in podocyte- associated genes. Early identification of genetic forms of SRNS is critical to avoid potentially harmful immunosuppressive therapy. A 2-year-old male patient with NS and no family history of renal disease did not respond to 4-week steroid treatment. Kidney biopsy demonstrated mesangial proliferative glomerulopathy with basement membrane dysmorphism. Tacrolimus and Lisinopril were added to therapy pending results of genetic testing. Kidney Gene panel showed a NPHS2 c.413G>A (p.Arg138Gln) homozygous pathogenic variant. This missense variant is considered a common pathogenic founder mutation in European populations. A diagnosis of autosomal-recessive form of nonsyndromic SRNS due to NPHS2 causative variant was made. Immunosuppresive therapy was stopped, Lizinopril dose was increased and weekly infusions of Albumin/furosemide were initiated to manage edema. This case demonstrates that early genetic testing in children with SRNS avoids prolonged potentially harmful immunosuppressive therapy, allows for timely genetic family counseling, and allows earlier consideration for future living related donor kidney transplantation.

中文翻译：

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NPHS2 突变儿童的肾病综合征

类固醇抵抗性肾病综合征 (SRNS) 占所有儿童肾病综合征 (NS) 病例的 30%，并且经常导致终末期肾病 (ESKD)。大约 30% 的 SRNS 儿童表现出足细胞相关基因的致病突变。早期识别 SRNS 的遗传形式对于避免潜在有害的免疫抑制治疗至关重要。一名患有 NS 且无肾脏疾病家族史的 2 岁男性患者对 4 周的类固醇治疗没有反应。肾活检显示系膜增生性肾小球病伴基底膜畸形。他克莫司和赖诺普利被添加到治疗中，等待基因检测结果。肾脏基因组显示 NPHS2 c.413G>A (p.Arg138Gln) 纯合致病变异。这种错义变异被认为是欧洲人群中常见的致病性创始人突变。诊断为由 NPHS2 致病变异引起的常染色体隐性非综合征型 SRNS。停止免疫抑制治疗，增加利齐诺普利剂量，并开始每周输注白蛋白/呋塞米以控制水肿。该病例表明，对 SRNS 儿童进行早期基因检测可以避免长期潜在有害的免疫抑制治疗，可以及时进行遗传家庭咨询，并可以更早地考虑未来的活体相关供体肾移植。