X-linked hypophosphatemia: genetic and clinical correlates

X-linked hypophosphatemia is a genetic disorder characterized by a defects in the mechanism that reabsorbs phosphate back into the kidney tubule and the kidney enzyme 1-alpha-hydroxylase, which normally converts 25-hydroxycalciferol to 1,25-dihydroxycalciferol. The gene for this disorder is carried by the X chromosome, a thread-like structure in the cell nucleus that determines female sex characteristics. X-linked hypophosphatemia results in abnormally low blood levels of phosphate, growth delay and defects in bone shape and structure due to impaired bone formation. This genetic disorder is treated with phosphate supplements to restore blood phosphate levels. Specifically, 1,25-dihydroxyvitamin D3 is given to restore levels of 1,25 dihydroxycalciferol and diuretics are given to increase elimination of fluids and calcium and reabsorption of phosphate. Diuretics prevent or reduce the side effects of treatment with 1,25-dihydroxyvitamin D3, which include elevated blood and urine levels of calcium. Unlike other forms of hypophosphatemia, X-linked hypophosphatemia is not associated with muscle weakness. However, lower than normal levels of inorganic phosphate have been detected in the muscle cells of patients with X-linked hypophosphatemia. Recent studies using the Hyp mouse, the animal model for X-linked hypophosphatemia, suggest that a hormonal factor may be responsible for the development of this disorder. Advances in genetic studies of X-linked hypophosphatemia include the identification and localization of two genes, Hyp and Gy. Future areas of research in X-linked hypophosphatemia are presented. (Consumer Summary produced by Reliance Medical Information, Inc.)