Hemizygous loss of function mutations in CLCN5 causing end-stage kidney disease without Dent disease phenotype

Dent disease type 1 is suspected in the presence of a complete phenotype of low molecular weight (LMW) proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, nephrolithiasis, haematuria, hypophosphatemia or chronic kidney disease (CKD). We present two brothers who presented with CKD alone. In the absence of typical clinical features, further assessment of LMW proteinuria and hypercalciuria was not undertaken. Whole-genome sequencing revealed hemizygous loss of function mutations in chloride voltage-gated channel 5 (CLCN5) consistent with Dent disease. Dent disease should, therefore, be considered in patients with an incomplete phenotype, including unexplained CKD alone.

Automated summary

This article presents two brothers with only chronic kidney disease (CKD) as a symptom, but the presence of non-typical clinical features led to further assessment. Whole-genome sequencing revealed mutations in the CLCN5 gene, confirming the diagnosis of Dent disease. Therefore, Dent disease should be considered in patients with an incomplete phenotype, including unexplained CKD alone.