Analysis of clinical features, genotype, and prognosis of children with Dent disease
10.3760/cma.j.cn101070-20240827-00543
- VernacularTitle:儿童Dent病的临床表型、基因型及预后分析
- Author:
Jingyi YANG
1
;
Xiaorong LIU
1
Author Information
1. 国家儿童医学中心，首都医科大学附属北京儿童医院肾脏内科，北京 100045
- Publication Type:Journal Article
- Keywords:
Child;
Dent disease;
CLCN5 gene;
OCRL gene;
Low molecular weight proteinuria
- From:
Chinese Journal of Applied Clinical Pediatrics
2025;40(4):262-267
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize clinical and genotypic features, treatment, and prognosis of children with Dent disease.Methods:A retrospective case-series study was conducted on 15 children with Dent disease at the Nephrology Department of Beijing Children′s Hospital, Capital Medical University from January 2008 to June 2024.The patients were divided into a type Ⅰ Dent disease group and a type Ⅱ Dent disease group according to the type of mutated genes.The clinical and genotypic characteristics, treatment, and prognosis were described.Then, the treatment effect of the disease was analyzed using the t-test or Wilcoxon rank-sum test. Results:All 15 children were boys, and the average onset age was 4.45 years.The illness struck each child insidiously at first, and it was complicated by nephrolithiasis/nephrocalcinosis (66.7%), short stature (46.7%), and rickets (20.0%).There was no significant difference in urine protein or calcium levels between the 2 groups.However, the type Ⅰ Dent group had more severe clinical symptoms than the type Ⅱ Dent group.Renal biopsy results indicated that lesions affected both tubules and glomeruli.The children were diagnosed with thylakoid hyperplasia, glomerulosclerosis, and in certain cases, glomerular adhesions, pedunculated fusions, and crescents.Of the 15 children, 11 had CLCN5 gene variations, and 4 had OCRL gene variations.Five mutants found in this study were reported for the first time.Up to the end of the follow-up, 24-hour urinary calcium[0.26 (0.22, 0.36) mmol/(kg·d) vs.(0.12±0.05) mmol/(kg·d), P<0.001], Ratio of urine calcium to creatinine[(0.36±0.16) mg/mg vs.(0.26±0.13) mg/mg, P=0.043], 24-hour urinary protein[74.34 (65.63, 79.26) mg/(kg·d) vs.59.88 (56.77, 64.23) mg/(kg·d), P=0.002], and urinary β2-microglobulin/creatinine levels[33.85 (12.26, 43.37) vs.(10.47±7.55) mg/mg, P=0.001] after treatment were significantly lower than those before treatment.The differences in urinary protein/creatinine and urinary α1-microglobulin/creatinine levels were not significant before and after treatment.Two children in the type Ⅰ Dent group experienced a progressive deterioration in renal function during follow-up, and they progressed to chronic kidney disease (CKD) stages 3 and 5, respectively. Conclusions:Dent disease can affect both tubules and glomeruli.The clinical symptoms of type Ⅰ Dent disease are severer than type Ⅱ Dent disease.Dent disease, mainly brought on by mutations in the CLCN5 gene.Whole-exon gene testing is an effective method of validating a diagnosis and helps in early detection, classification, and treatment of Dent disease.There is currently no specific treatment available for this disease.Symptomatic treatment can reduce urine calcium and protein levels and rectify electrolyte imbalances, but it may not prevent further impairment of renal function.Most children have normal kidney function and a good prognosis, with a small percentage progressing to CKD.
