Dent's disease manifesting as focal glomerulosclerosis: Is it the tip of the iceberg?

Yaacov Frishberg*, Dganit Dinour, Ruth Belostotsky, Rachel Becker-Cohen, Choni Rinat, Sofia Feinstein, Paulina Navon-Elkan, Efrat Ben-Shalom

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Dent's disease is an X-linked proximal tubulopathy. It often manifests in childhood with symptoms of Fanconi syndrome and low-molecular-weight proteinuria. We describe four boys from three unrelated families whose only presenting symptoms of Dent's disease were nephrotic-range proteinuria and histological findings of focal segmental and/or global glomerulosclerosis. In all families, a causal mutation in the CLCN5 gene, encoding a voltage-gated chloride transporter and chloride-proton exchanger, was identified. All three mutations are pathogenic: two are novel (p.Asp727fs and p.Trp122X), and one is a recurrent mutation, p.R648X. Given the atypical phenotype of these patients with Dent's disease, it is possible that this clinical entity is markedly underdiagnosed and that our report represents only the tip of the iceberg. The diagnosis of Dent's disease should be considered in all patients with nephrotic-range proteinuria without hypoalbuminemia or edema. Establishing the diagnosis of Dent's disease will prevent the administration of unnecessary immunosuppressive medications with their undesirable side effects.

Original languageEnglish
Pages (from-to)2369-2373
Number of pages5
JournalPediatric Nephrology
Issue number12
StatePublished - 2009


  • CLCN5 mutations
  • Children
  • Dent's
  • Focal glomerulosclerosis
  • Nephrotic proteinuria


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