Abstract
Dent disease is a rare X-linked renal proximal tubulopathy presenting with low-molecular-weight
proteinuria (LMWP), hypercalciuria, and nephrocalcinosis, other signs of incomplete
renal Fanconi syndrome, and renal failure. Early identification of patients who harbor
disease-associated mutations is important for effective medical care and avoidance
of unnecessary interventions. We report the case of an asymptomatic 9-year-old boy
who presented with proteinuria in routine examination. Further investigation revealed
the presence of nephrotic range proteinuria, mostly LMWP and mild hypercalciuria without
nephrocalcinosis, or other features of tubular dysfunction. Renal function, growth,
and bone mineral density were within regular limits. The male gender and the presence
of LMWP and hypercalciuria even in the absence of other findings prompted us to genetic
investigation for Dent disease. A novel splice site mutation (c.416–2A > G) of the
chloride voltage-gated channel 5 (CLCN5) gene, responsible for Dent disease type 1 was identified. In silico analysis revealed that this mutation interferes with the mating of exons 4 and 5.
Due to early molecular diagnosis, our patient did not undergo a renal biopsy, neither
required aggressive pharmacological interventions. This case underscores the diversity
and complexity of CLCN5 mutations and highlights the importance of early molecular testing in male patients
with incomplete phenotype of Dent disease.
Keywords
Dent disease -
CLCN5 mutation - proteinuria - hypercalciuria
