TY - JOUR
T1 - Dent's disease manifesting as focal glomerulosclerosis
T2 - Is it the tip of the iceberg?
AU - Frishberg, Yaacov
AU - Dinour, Dganit
AU - Belostotsky, Ruth
AU - Becker-Cohen, Rachel
AU - Rinat, Choni
AU - Feinstein, Sofia
AU - Navon-Elkan, Paulina
AU - Ben-Shalom, Efrat
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - CLCN5 mutations
KW - Children
KW - Dent's
KW - Focal glomerulosclerosis
KW - Nephrotic proteinuria
UR - http://www.scopus.com/inward/record.url?scp=70350624692&partnerID=8YFLogxK
U2 - 10.1007/s00467-009-1299-2
DO - 10.1007/s00467-009-1299-2
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C2 - 19806368
AN - SCOPUS:70350624692
SN - 0931-041X
VL - 24
SP - 2369
EP - 2373
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 12
ER -