title: Expanding the phenotype of proteinuria in Dent disease. A case series.
abstract: BACKGROUND
  Dent disease is an X-linked recessive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure (MIM 300009). A recent case series identified four patients with CLCN5 mutations who presented with nephrotic-range proteinuria, histologic evidence of focal segmental and/or global sclerosis, and low molecular weight proteinuria.
  
  
  METHODS
  We characterize the clinical, genetic, and histopathological features of seven unrelated adolescent males with nephrotic-range proteinuria and CLCN5 mutations. Six patients underwent renal biopsy prior to assessing tubular proteinuria. All biopsied patients had either segmental sclerosis (3/6) or segmental increase in mesangial matrix (3/6). Five patients revealed some degree of foot process effacement, but only one patient biopsy revealed >50 % foot process effacement. The attenuated foot process effacement suggests the glomerulosclerosis is not due to a primary podocytopathy.
  
  
  CONCLUSIONS
  These data suggest that clinicians should consider a diagnostic evaluation for Dent disease in young males presenting with high-grade proteinuria.
authors.affiliation: Division of Pediatric Nephrology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA, mtucci@peds.uab.edu.
authors.forename: Monica T
authors.initials: MT
authors.lastname: Cramer
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Charlton
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Sahar A
authors.initials: SA
authors.lastname: Fathallah-Shaykh
authors.forename: David J
authors.initials: DJ
authors.lastname: Askenazi
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Guay-Woodford
mesh_terms: D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics; D057973:Dent Disease / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011507:Proteinuria / Q000209:etiology*
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels