TABLE 2.

The pathophysiology of disorders of phosphate homeostasis associated with altered phosphatonin production/circulating concentrations (64).

Clinical Disorder	Clinical phenotype	Pathophysiology
Hypophosphatemic Disorders
Tumor-induced osteomalacia (TIO)	Hypophosphatemia, hyperphosphaturia, reduced 1α, 25(OH)2D concentrations or inappropriately normal 1α, 25(OH)2D concentrations for the level of serum phosphate, osteomalacia or mineralization defect	Excess of production of phosphatonins -- FGF-23, sFRP- 4, MEPE, FGF-7.
X-linked hypophosphatemic rickets (XLH)	As in TIO	Mutations in the endopeptidase PHEX that result in increased concentrations of FGF-23, sFRP-4 and MEPE.
Autosomal dominant hypophosphatemic rickets (ADHR)	As in TIO	Mutations in the FGF-23 gene that results in the formation of a mutant form of FGF-23 that is resistant to proteolysis.
Autosomal recessive hypophosphatemia (AR HP)	As in TIO	Mutations in the gene for DMP-1; associated with elevated concentrations of FGF-23.
Hyperphosphatemic Disorders
Tumoral calcinosis	Hyperphosphatemia, hypophosphaturia, elevated or normal 1α, 25(OH)2D concentrations, ectopic calcification	Mutations in the genes for GALNT3, FGF-23, and Klotho. Some patients with GALNT3 and FGF-23 mutations have diminished concentrations of intact FGF-23. The one patient with a Klotho mutation had very high FGF-23 concentrations.
Renal failure	Hyperphosphatemia, hypophosphaturia, reduced 1α, 25(OH)2D concentrations.	Elevated FGF-23 and FGF-7 concentrations