Pei Yuxin, Jiang Mengjie, Zhilang Lin, Rong Liping, Chen Lizhi, Jiang Xiaoyun
Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Pediatr Res. 2025 Mar 24. doi: 10.1038/s41390-025-03977-3.
Nucleoporin nephropathy, a rare genetic kidney disorder, is not well-characterized despite its early onset in childhood.
We analyzed the clinical and genetic data of pediatric patients diagnosed with nucleoporin nephropathy at a southern Chinese pediatric nephrology center, and reviewed global cases reported up until July 2024.
In our center, five pediatric patients (aged 10 months to 8 years) were diagnosed with nucleoporin nephropathy. Three presented with steroid-resistant nephrotic syndrome, and one had initial extrarenal symptoms. All patients progressed to end-stage kidney disease. Global data shows 111 cases of nucleoporin nephropathy; 76.6% of patients initially presented with nephrotic syndrome, unresponsive to steroids or immunosuppressive therapy. 89.4% progressed to end-stage kidney disease in adolescence. Among the 37 transplant recipients, only 2 had proteinuria recurrence. Neurological symptoms were observed in a significant portion of patients, with variation across genotypes. East Asian patients, who account for 40.4% of the cases, often exhibit compound heterozygous missense, early renal involvement, and fewer extrarenal symptoms.
Routine nucleoporin gene testing is advised for Asian children with steroid-resistant nephrotic syndrome or end-stage kidney disease to prevent unnecessary treatments. While kidney transplantation has a favorable outlook, managing extrarenal symptoms of nucleoporin pehropathy is challenging.
Explore the link between nucleoporin gene mutations and disease phenotypes for a new understanding of NUP nephropathy. The renal phenotypes associated with NUP mutations display a remarkably consistent pattern as early-onset SRNS and progression to ESKD in adolescence. Highlight the importance in finding and managing the extrarenal symptoms associated with nucleoporin nephropathy. Regional specificities in NUP gene mutations are becoming apparent, with East Asian patients often presenting compound heterozygous mutations, early onset, rapid progression to end-stage kidney disease, and fewer extrarenal symptoms. Emphasize the necessity of nucleoporin gene testing for Asian children to prevent ineffective treatments.
核孔蛋白肾病是一种罕见的遗传性肾脏疾病，尽管在儿童期早期发病，但目前对其特征了解不足。
我们分析了中国南方一家儿科肾脏病中心诊断为核孔蛋白肾病的儿科患者的临床和基因数据，并回顾了截至2024年7月全球报道的病例。
在我们中心，5名儿科患者（年龄10个月至8岁）被诊断为核孔蛋白肾病。3例表现为激素抵抗型肾病综合征，1例最初有肾外症状。所有患者均进展为终末期肾病。全球数据显示有111例核孔蛋白肾病；76.6%的患者最初表现为肾病综合征，对激素或免疫抑制治疗无反应。89.4%的患者在青春期进展为终末期肾病。在37名移植受者中，只有2例蛋白尿复发。相当一部分患者出现神经症状，不同基因型表现各异。占病例40.4%的东亚患者常表现为复合杂合错义突变、早期肾脏受累且肾外症状较少。
建议对患有激素抵抗型肾病综合征或终末期肾病的亚洲儿童进行常规核孔蛋白基因检测，以避免不必要的治疗。虽然肾移植前景良好，但管理核孔蛋白肾病的肾外症状具有挑战性。
探索核孔蛋白基因突变与疾病表型之间的联系，以重新认识核孔蛋白肾病。与核孔蛋白突变相关的肾脏表型呈现出显著一致的模式，即早发性激素抵抗型肾病综合征并在青春期进展为终末期肾病。强调发现和管理与核孔蛋白肾病相关的肾外症状的重要性。核孔蛋白基因突变的区域特异性日益明显，东亚患者常表现为复合杂合突变、发病早、迅速进展为终末期肾病且肾外症状较少。强调对亚洲儿童进行核孔蛋白基因检测以避免无效治疗的必要性。
