title: Dent's disease manifesting as focal glomerulosclerosis: Is it the tip of the iceberg?
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.
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center and the Hebrew University-Hadassah School of Medicine, POBox 3235, 91031 Jerusalem, Israel. yaacovf@ekmd.huji.ac.il
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Frishberg
authors.forename: Dganit
authors.initials: D
authors.lastname: Dinour
authors.forename: Ruth
authors.initials: R
authors.lastname: Belostotsky
authors.forename: Rachel
authors.initials: R
authors.lastname: Becker-Cohen
authors.forename: Choni
authors.initials: C
authors.lastname: Rinat
authors.forename: Sofia
authors.initials: S
authors.lastname: Feinstein
authors.forename: Paulina
authors.initials: P
authors.lastname: Navon-Elkan
authors.forename: Efrat
authors.initials: E
authors.lastname: Ben-Shalom
mesh_terms: D001706:Biopsy; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D018389:Codon, Nonsense; D003404:Creatinine / Q000652:urine; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000601:surgery; D008297:Male; D008657:Metabolic Clearance Rate; D011507:Proteinuria / Q000235:genetics*
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D018389:Codon, Nonsense; D004247:DNA; D003404:Creatinine; D002118:Calcium