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Hypophosphatemia with Elevations in Serum Fibroblast Growth Factor 23 in a Child with Jansen’s Metaphyseal Chondrodysplasia

Department of Pediatric Endocrinology (W.W.B., K.L.M.), University of Alabama School of Medicine, Birmingham, Alabama 35233; Endocrine Unit and Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Feinberg School of Medicine (C.B.L.), Northwestern University, Kidney Diseases (H.P.), Children’s Memorial Hospital, Chicago, Illinois 60614; and Department of Medical and Molecular Genetics (E.G.F., K.E.W.), Indiana University School of Medicine, Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Whitney W. Brown, M.D., University of Alabama School of Medicine, Department of Pediatric Endocrinology, Children’s Park Place Suite 230, 1600 7th Avenue South, Birmingham, Alabama 35233. E-mail: dr.whitneyw.brown{at}erlanger.org.

Context: Previous studies have suggested a regulatory relationship between serum phosphorus, vitamin D, and fibroblast growth factor 23 (FGF23), a hormone that promotes renal excretion of phosphate. Despite these associations, the identity of the primary regulator of serum FGF23 is unresolved. Jansen’s metaphyseal chondrodysplasia is a rare autosomal dominant disorder associated with short-limbed dwarfism and other characteristic skeletal abnormalities. This condition is caused by mutations in the PTH/PTHrP receptor that result in ligand-independent cAMP accumulation, thus rendering the receptor constitutively active. These patients typically exhibit asymptomatic hypercalcemia and hypophosphatemia despite low or undetectable serum levels of PTH and PTHrP.

Evidence Acquisition: A literature search revealed that serum FGF23 levels had not been studied in patients with Jansen’s syndrome, a disorder in which the biochemical features present a unique opportunity to study the possible relationship between FGF23 and calcium-phosphorus-vitamin D metabolism. A case of Jansen’s syndrome is presented in which serum FGF23 concentrations, along with serum phosphorus and 1,25(OH)₂ vitamin D levels, were measured and compared with those of age-matched controls.

Evidence Synthesis: Serum FGF23 concentrations in the patient with Jansen’s syndrome were found to be markedly and persistently elevated, compared with values in healthy, age-matched controls, despite hypophosphatemia and normal 1,25(OH)₂ vitamin D levels.

Conclusion: Together, our findings indicate that serum FGF23 could be governed by factor(s) other than serum phosphorus, potentially by activation of the PTH/PTHrP receptor in bone.

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