A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.

We describe two siblings from a consanguineous family with autosomal recessive Fanconi's syndrome and hypophosphatemic rickets. Genetic analysis revealed a homozygous in-frame duplication of 21 bp in SLC34A1, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, as the causative mutation. Functional studies in Xenopus laevis oocytes and in opossum kidney cells indicated complete loss of function of the mutant NaPi-IIa, resulting from failure of the transporter to reach the plasma membrane.

Detection and incidence of anomalies associated with hypospadias.

Hypospadias has been associated with synchronous congenital anomalies, especially in the urogenital system, and routine screening of patients with hypospadias has been advocated. In recent years, ultrasound (US) has replaced intravenous pyelography (IVP) as the primary screening test for urological deformities, yet there has never been a study of the relative diagnostic efficacy of the two tests in these patients. In this study, we assessed the incidence of urogenital and extraurogenital congenital anomalies in our hypospadias patients that were noted during physical examination and/or laboratory and imaging screening, and evaluated the efficacy of our changing routine screening protocols.

SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of autosomal recessive inheritance that was first described in a large consanguineous Bedouin kindred. HHRH is characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histological evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption.

Hereditary hypophosphatemic rickets with hypercalciuria is not caused by mutations in the Na/Pi cotransporter NPT2 gene.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a renal phosphate (Pi) wasting disease first described in an extended Bedouin kindred, is characterized by hypophosphatemia, elevated serum 1,25-dihydroxyvitamin D levels, hypercalciuria, rickets, and osteomalacia. Correction of all abnormalities, except for renal Pi wasting, can be achieved by oral Pi supplementation. These findings and the demonstration that mice that are homozygous for the disrupted Na/Pi cotransporter gene Npt2 exhibit many of the biochemical features of HHRH suggested that mutations in the human orthologue NPT2 might be responsible for HHRH.