Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

Abstract

BACKGROUND:

Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it.

METHODS:

Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [+/-SD] age, 48.4+/-19.6 years) and 26 healthy children (mean age, 10.9+/-5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0+/-13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9+/-17.2 years) were studied.

RESULTS:

Mean FGF-23 concentrations in the healthy adults and children were 55+/-50 and 69+/-36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481+/-528 RU per milliliter in those with suspected oncogenic osteomalacia and 353+/-510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia.

CONCLUSIONS:

FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis. FGF-23 measurements might improve the management of phosphate-wasting disorders.

• Authors: Kenneth B Jonsson, Richard Zahradnik, Tobias Larsson, Kenneth E White, Toshitsugu Sugimoto, Yasuo Imanishi, Takehisa Yamamoto, Geeta Hampson, Hiroyuki Koshiyama, Osten Ljunggren, Koichi Oba, In Myung Yang, Akimitsu Miyauchi, Michael J Econs, Jeffrey Lavigne, Harald Jüppner
• Journal: The New England journal of medicine (N Engl J Med) Vol. 348 Issue 17 Pg. 1656-63 (Apr 24 2003) ISSN: 1533-4406 [Electronic] United States
• PMID: 12711740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Massachusetts Medical Society

Chemical References

• FGF23 protein, human
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Adolescent
• Adult
• Amino Acid Sequence
• Child
• Child, Preschool
• Enzyme-Linked Immunosorbent Assay (methods)
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood, chemistry, genetics)
• Genetic Diseases, X-Linked (blood)
• Humans
• Hypophosphatemia, Familial (blood, genetics)
• Male
• Middle Aged
• Molecular Sequence Data
• Mutation
• Osteomalacia (blood)
• Paraneoplastic Syndromes (blood)
• Reference Values
• Rickets (blood, genetics)