Physiological and pathological involvement of FGF-23 in mineral metabolism in human

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1) Mutation of FGF-23 gene involved in tumoral calcinosisWe identified mutation of FGF-23 gene in patients with familial tumoral calcinosis. Missense mutation was found. Expression the mutated FGF-23 gene in mammalian cells resulted in remarkable degradation of FGF-23 protein with essentially no full-length and active FGF-23 in culture media. Serum level of full-length FGF-23 was almost undetectable in patients with tumoral calcinossis we evaluated, although degradation products of FGF-23 were accumulated in circulating blood. These data indicate that loss of function of FGF-23 in human causes tumoral calcinosis that presents hyperphosphatemia and high serum level of 1,25-dihydroxyvitamin D.2) Response of circulating FGF-23 to acute increase in serum phosphate level in healthy volunteersWhen serum phosphate level was increased with intravenous infusion of dibasic potassium phosphate to 6.0 mg/dl, circulating level of FGF-23 did not change significantly within 6 hours of experiments. This result suggests that in contrast to rapid decrease in PTH secretion in response to hypercalcemia, secretion of FGF-23 cannot respond to acute changes of serum phosphate level. Physiological mechanisms for regulation of serum FGF-23 level are to be explored with further studies.3) Serum phosphate and FGF-23 levels in patients with acromegaly before and after pituitary surgerySerum phosphate level is higher in patients with acromegaly and decreases normally after successful surgery. When clinical laboratory data of consecutive 17 patients with acromegaly were analyzed, serum level of FGF-23 also concomitantly decreased with pituitary surgery. This indicates secretion of FGF-23 promptly responds to the decrease in serum phosphate level in human.