X-linked hypophosphatemia

X-linked hypophosphatemia is a common cause of metabolic rickets in children in this country. The gene defect is localized to the Xp22 region in man. Research into this disorder has been enhanced by the discovery of a mutant gene named Hyp on the X chromosome of mice that produces a syndrome similar to the human disease. These mutant genes in humans and mice alike result in low renal tubular reabsorption of phosphate, rickets, and osteomalacia. The renal synthesis of 1,25-dihydroxyvitamin D is unresponsive to low phosphate stimuli in both. A second mutant gene on the X chromosome of mice, Gy, also causes low renal tubular reabsorption of phosphate. The underlying defects in both the human disease and the mouse models are unknown. The availability of these murine models should advance our understanding of this clinical disorder and provide an environment for the testing of novel therapies.