Hypophosphatemic Rickets, X-Linked Recessive

A number sign (#) is used with this entry because X-linked recessive hypophosphatemic rickets is caused by mutation in the CLCN5 gene (300008) on chromosome Xp11.22.

For a general phenotypic description and a discussion of genetic heterogeneity of hypophosphatemic rickets, see 193100.

Description

X-linked recessive hypophosphatemic rickets is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.

Clinical Features

Bolino et al. (1993) reported an Italian family with X-linked recessive hypophosphatemic rickets. Five males presented with rickets or osteomalacia, hypophosphatemia, hypercalciuria, and proteinuria. The patients developed nephrocalcinosis with progressive renal failure in adulthood.

Oudet et al. (1997) reported a French family with X-linked recessive hypophosphatemic rickets.

Mapping

In an Italian family with X-linked recessive hypophosphatemic rickets, Bolino et al. (1993) identified a putative disease locus on chromosome Xp11.2 at 0% recombination with DXS1039.

Molecular Genetics

In affected members of an Italian family with X-linked recessive hypophosphatemic rickets reported by Bolino et al. (1993), Lloyd et al. (1996) identified a mutation in the CLCN5 gene (S244L; 300008.0007).

Oudet et al. (1997) reported a second family with the S244L mutation but with a milder phenotype than that in the family reported by Lloyd et al. (1996). The family reported by Oudet et al. (1997) had neither nephrocalcinosis nor nephrolithiasis. The affected individuals were, however, significantly younger than those of the family reported by Lloyd et al. (1996).