A novel CLCN5 mutation in a boy with asymptomatic proteinuria and focal global glomerulosclerosis.
Dent disease is an X-linked proximal tubulopathy that typically presents with hypercalciuria, low-molecular-weight proteinuria and slow progression to endstage renal disease. We report the case of a 5-year-old boy who presented with asymptomatic nephrotic range proteinuria and was later diagnosed with Dent disease. Absence of specific glomerular pathology in the first kidney biopsy led to erroneous treatment for presumably unsampled primary focal segmental glomerulosclerosis. Aggressive angiotensin blockade and immunosuppression resulted in significant side effects with marginal benefit. The continued nonspecific findings after a second kidney biopsy 2 years later led to the suspicion of a congenital tubulopathy. We detected a novel CLCN5 gene mutation, c.1396G > C, that creates a G466R missense change in the ClC-5 protein. Dent disease should be considered in the differential diagnosis of asymptomatic proteinuria for male patients. Profiling proteinuria in these patients by spot urine albumin/creatinine ratio may give the first clue to a tubulopathy. Determining the extent to which the clinical work-up should proceed for females with Dent phenotype or asymptomatic proteinuria remains to be a challenging clinical dilemma.
Mary Rose
MR
Valina
Christopher P
CP
Larsen
Sherry
S
Kanosky
Sharon F
SF
Suchy
Linda S
LS
Nield
Ali Mirza
AM
Onder
D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D009154:Mutation; D011507:Proteinuria / Q000235:genetics* / Q000473:pathology
C097503:CLC-5 chloride channel; D018118:Chloride Channels