#X linked dominant traits plus

No long-term studies have been reported that confirm the role of lifetime phosphorus supplementation in adults with this disorder. Hydrochlorothiazide and amiloride may be used in some cases in which there appears to be resistance to the combination of vitamin D and phosphate supplementation in terms of calcium malabsorption and hypercalciuria. Medical noncompliance is a major problem, as are excessively loose stools due to oral sodium phosphate. This form of therapy should be given during childhood.

9 The latter is commercially available and far easier to use. Oral phosphate can be administered as Joulie solution 8 or as neutral phosphate. Not only will the rachitic growth plate lesion be improved but endosteal bone trabecular lesions will also improve, a change not apparent when using vita-min D 2 or D 3 alone. Therapy is probably needed throughout the life of the patient. 1,4,8 Although this therapy has been shown to improve calcium and phosphate retention, phosphate must be administered every 4 to 5 hours because the renal phosphate leak persists (see Table 46-1).

#X linked dominant traits plus

The current recommendation regarding the most appropriate form of treatment is a combination of oral 1,25-dihydroxyvitamin D 3 in as low a dose as possible (5-50 ng/day) plus oral phosphate supplements (70 mg/kg/day). 2, 4 A defective phosphate regulatory protein (PHEX) that fails to degrade fibroblast growth factor 23 is the cause of this condition. This X-linked dominant disorder is the most common of the phosphaturic syndromes and involves a double renal tubular defect: (1) failure of Na +/PO 4 3 РІв‚¬вЂ™ cotransport across the brush border membrane of the proximal tubule and (2) reduction in the conversion of 25-hydroxyvitamin D 3 to 1,25-dihydroxyvitamin D 3 by proximal tubule cell mitochondria. 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 1РћВ±-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