2 Dent ’ s Disease

Dent’s disease (MIM #300009) is a rare X-linked disorder characterized by various degrees of proximal tubular (PT) dysfunction, nephrocalcinosis and nephrolithiasis. The exact prevalence is unknown. The disease was first reported by Dent and Friedman, who described two males with vitamin D resistant rickets, hypercalciuria and low molecular weight proteinuria (LMWP) (Dent & Friedman, 1964). Based on these data and another 13 patients with a similar phenotype, Wrong et al. coined the term “Dent’s disease” for the combination of X-linked low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease and progressive renal failure (Wrong et al., 1994). With the advent of molecular genetics it has become clear that the phenotypically similar disorders X-linked recessive nephrolithiasis with renal failure (MIM #310468) and X-linked recessive hypophosphatemic rickets (MIM #300554) are also due to mutations in the CLCN5 gene (Lloyd et al., 1996). Familial idiopathic LMW proteinuria with hypercalciuria in Japanese patients (MIM #308990) – also referred to as Dent’s Japan disease (Igarashi et al., 1995) is a fourth clinical entity resulting from CLCN5 mutations (Nakazato et al., 1997). Therefore, Scheinman proposed to summarize CLCN5-associated renal disease under the term “X-linked hypercalciuric nephrolithiasis” (Scheinman, 1998). The same clinical phenotype has been observed with some mutations in the oculo-cerebrorenal syndrome of Lowe (OCRL) gene and is referred to as Dent-2 disease (MIM #300555) (Hoopes et al., 2005; Utsch et al., 2006).