Hypercalciuria is regarded as a characteristic symptom of
Dent disease, an X-linked recessive tubulopathy characterized by low molecular weight (LMW)
proteinuria,
nephrocalcinosis/
nephrolithiasis, and progressive
renal failure due to mutations in the CLCN5 gene. As the presence of
hypercalciuria may affect the decision to consider a CLCN5 mutation in the differential diagnosis, the phenotypic spectrum and the relative frequency of
hypercalciuria in patients with CLCN5 mutations was determined. We assessed renal
calcium excretion in 34 male patients with proven CLCN5 mutations, who had been referred because of LMW
proteinuria and at least one additional symptom of
Dent disease.
Hypercalciuria was defined as renal
calcium excretion exceeding 0.1 mmol/kg per day. Data obtained were compared with all series of CLCN5-positive patients identified by a systematic literature survey. In 7 of our 19 families, at least 1 affected male had normal
calcium excretion.
Hypercalciuria was observed in 22 of 31 patients tested (71%) compared to 85 of 90 (94.4%) in series from Europe and North America and 74.4% from Japan. LMW
proteinuria was present in all CLCN5-positive patients; 25% of the patients in European and North American series, 45% of the Japanese, and 41% in the present series had only two of the four principal symptoms of
Dent disease. Therefore, a CLCN5 mutation should be considered irrespective of the presence of
hypercalciuria in a patient with LMW
proteinuria and one additional symptom of
Dent disease.