During the past ten years there has been an explosion of understanding of the metabolism of phosphate which centres around fibroblast growth factor 23 which is now thought to be the phosphotonin that had long been suspected.
Discovery of this hormone, which is synthesised by osteocytes, is secreted and circulates in plasma, therefore qualifying it as a true hormone, has led to an understanding of the mechanisms of the various forms of hypophosphataemic rickets. Its principal action is to increase urinary phosphate excretion by counteracting the tubular reabsorptive actions of the sodium/phosphate cotransporter in renal tubules. It is under the control of several other factors including PHEX, DMP1 and ENPP1 all of which combine to deactivate it and of GALNT3, FGFR1 and Klotho, which either activate it or contribute to its action in renal tubules.
Inactivating mutations in PHEX, DMP1, ENPP1 or activating mutations in FGF23 itself lead to excess phosphate loss and hypophosphataemic rickets whilst inactivating mutations of GALNT3, Klotho or FGF23 cause hyperphosphataemic tumoral calcinosis.
The relationships and interactions between these different components of the phosphate metabolic pathway will be described.
03 - 05 Nov 2010
British Society for Paediatric Endocrinology and Diabetes