Chesney, in Therapy in Nephrology & Hypertension (Third Edition), 2008 Primary or X-Linked Hypophosphatemic Rickets Secondary hyperparathyroidism occurs commonly, probably due to effects of FGF-23 on 1,25(OH) 2D production and the effects of treatment with phosphate. Patients with XLH also develop calcification of entheses, which limits their range of motion at joints, causing stiffness. Odontoblast PHEX deficiency results in abnormalities in the dentin and cementum layers, making the teeth prone to infection. Additionally, dental abscesses are common. Clinical features of XLH are similar to those of nutritional rickets. In addition, in PHEX (Phex)-deficient mice, reduced chondrocyte expression of the sodium-dependent phosphate transporter 1 (PiT-1) contributes to reduced cellular phosphate uptake and reduced chondrocyte apoptosis. Hypophosphatemia itself decreases apoptosis of growth plate hypertrophic chondrocytes, resulting in the histologic and clinical phenotype of rickets. Consequently, FGF-23 excess causes the biochemical phenotype of XLH: hyperphosphaturia, hypophosphatemia, and inappropriately low or normal 1,25(OH) 2D concentrations. FGF-23 also inhibits the 1О±-hydroxylase, resulting in inappropriately low 1,25(OH) 2D concentrations. As phosphate is freely filtered at the glomerulus, reabsorption is critical to maintain normal phosphate homeostasis. FGF-23 interaction with the FGF receptor (FGFR) and Klotho in the kidney decreases the surface expression of sodium phosphate cotransporters NPT2a (encoded by SLC34A1) and NPT2c (encoded by SLC34A3), resulting in impaired phosphate reabsorption. Patients with PHEX deficiency have increased expression and secretion of the FGF-23 peptide hormone, which has a clear role in renal phosphate metabolism.

PHEX is expressed in osteocytes/osteoblasts and odontoblasts. PHEX overexpression does not result in a phosphate disorder, although deficiency does. However, it is still unclear whether this gene normally has a role in phosphate metabolism. Disease severity is highly variable, in terms of severity of the biochemical skeletal phenotypes. Patients with XLH have inactivating mutations in the PHEX gene, with many different mutations of different types reported. The X-linked dominant disorder, X-linked hypophosphatemia (XLH), is the most common form of inherited hypophosphatemia. Burr, in Basic and Applied Bone Biology, 2014 X-Linked Hypophosphatemia

List of dominant traits