Original Article

Pediatric Nephrology

, Volume 24, Issue 12, pp 2369-2373

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

  • Yaacov FrishbergAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine Email author 
  • , Dganit DinourAffiliated withDepartment of Nephrology and Hypertension, Chaim Sheba Medical Center, Tel-Hashomer and Tel Aviv University
  • , Ruth BelostotskyAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine
  • , Rachel Becker-CohenAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine
  • , Choni RinatAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine
  • , Sofia FeinsteinAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine
  • , Paulina Navon-ElkanAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine
  • , Efrat Ben-ShalomAffiliated withDivision of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine

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Abstract

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.

Keywords

Dent’s Nephrotic proteinuria Children Focal glomerulosclerosis CLCN5 mutations