X-Linked hypophosphatemia (XLH) is a disease of phosphorus metabolism resulting from mutations in PHEX on the X chromosome that encodes for phosphate-regulating neutral endopeptidase, X-linked (PEX), a membrane-bound metalloendopeptidase that is predominantly expressed in bone and teeth. The disease manifests in children as rickets, which progresses to osteomalacia in adults. Hypophosphatemia is the primary biochemical disturbance underlying the rickets and osteomalacia. Decreased tubular reabsorption of phosphate, the direct cause of hypophosphatemia, is due to increased plasma fibroblast growth factor 23 (FGF-23) acting on renal tubular sodium/phosphate cotransporters. Three mouse models of XLH have been developed and have greatly helped unravel the pathophysiology in humans and the exploration of new approaches to medical management. Current treatments are unsatisfactory. They do not cure the disease, but only partially relieve some of the skeletal and biochemical abnormalities, and result in several undesirable side effects. New treatments aimed at decreasing plasma FGF-23 activity show significant potential for reversing both the biochemical and rachitic/osteomalacic abnormalities.
ASJC Scopus subject areas
- Pharmacology (medical)