Context: Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes GalNAc transferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes.

Objective: To identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient.

Design: Mutation detection in FGF23 and GALNT3 by DNA sequencing and measurement of serum FGF23 concentrations by ELISA.

Patients or Other Participants: A 5-year-old French boy with HHS and his family members.

Results: The patient presented with painful cortical lesions in his leg. Radiographs of the affected bones showed diaphyseal hyperostosis. The lesional tissue was comprised of trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, TmP/GFR, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC.

Conclusion: The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23 levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23.