Clinical characteristics and genetic analyses of Korean children with Dent disease

Dent disease is a hereditary kidney tubular disorder caused by pathogenic variants in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes. As a rare genetic disorder, Dent disease often presents with variable clinical manifestations, leading to frequent misdiagnosis or underdiagnosis, especially in milder cases. Consequently, limited research has addressed the long-term clinical outcomes of Dent disease.

This retrospective multicenter cohort study was conducted at 9 hospitals in Korea. A total of 48 male patients from 44 unrelated families with genetically confirmed Dent disease were enrolled, and their clinical phenotypes, and genetic backgrounds were assessed.

The median age at diagnosis for Dent disease was 6.8 years, and 42 patients were diagnosed with Dent disease 1. At diagnosis, 17 patients (37.0%) demonstrated the classic triad of Dent disease features, whereas 12 patients (26.1%) presented solely with isolated low-molecular-weight proteinuria. During follow-up, whereas all patients maintained low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, and nephrolithiasis occurred in 82.6%, 56.5%, and 8.3% of patients, respectively. The cases with Dent disease 2 had a higher rate of hypophosphatemia and significant proteinuria compared to Dent disease 1. A negative correlation was identified between hypercalciuria and age in the overall Dent disease cohort. The decline rate of annual estimated glomerular filtration rate was 0.6 mL/min/1.73 m², without the case of kidney failure. At last follow-up, kidney dysfunction was present in 39.5% of cases.

Due to its rarity and phenotype variability, Dent disease is frequently under-recognized by clinicians. As over one-third of patients progress to chronic kidney disease by early adulthood, a high index of clinical suspicion and early genetic testing are essential, alongside rigorous monitoring of kidney function.