Hyperphosphatemic tumoral calcinosis caused by FGF23 compound heterozygous mutations: what are the therapeutic options for a better control of phosphatemia?

  • Debora Claramunt-Taberner
  • Aurélia Bertholet-Thomas
  • Marie-Christine Carlier
  • Frédérique Dijoud
  • Franck Chotel
  • Caroline Silve
  • Justine Bacchetta
Brief Report

Abstract

Background

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disease caused by mutations in genes encoding FGF23 or its regulators, and leading to functional deficiency or resistance to fibroblast growth factor 23 (FGF23). Subsequent biochemical features include hyperphosphatemia due to increased renal phosphate reabsorption, and increased or inappropriately normal 1,25-dihydroxyvitamin D (1,25-D) levels.

Case-diagnosis/treatment

A 15-year-old girl was referred for a 1.2-kg-calcified mass of the thigh, with hyperphosphatemia (2.8 mmol/L); vascular impairment and soft tissue calcifications were already present. DNA sequencing identified compound heterozygous mutations in the FGF23 gene. Management with phosphate dietary restriction, phosphate binders (sevelamer, aluminum, nicotinamide), and acetazolamide moderately decreased serum phosphate levels; oral ketoconazole was secondary administered, leading to significantly decreased 1,25-D levels albeit only moderate additionally decreased phosphate levels. However, therapeutic compliance was questionable. Serum phosphate levels always remained far above the upper normal limit for age. The patient presented with two relapses of the thigh mass, requiring further surgery.

Conclusions

We suggest that control of phosphate metabolism is crucial to prevent recurrences and vascular complications in HFTC; however, the medical management remains challenging.

Keywords

Hyperphosphatemic tumoral calcinosis Fibroblast growth factor 23 Phosphate Ectopic calcifications Ketoconazole 

Notes

Compliance with ethical standards

The local ethical committee approved this retrospective case description (Comité de Protection Lyon Sud Est II, IRB approval 00009118, session 20/04/2016).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© IPNA 2018

Authors and Affiliations

  • Debora Claramunt-Taberner
    • 1
    • 2
  • Aurélia Bertholet-Thomas
    • 1
  • Marie-Christine Carlier
    • 3
  • Frédérique Dijoud
    • 4
    • 5
  • Franck Chotel
    • 5
    • 6
  • Caroline Silve
    • 7
    • 8
  • Justine Bacchetta
    • 1
    • 2
    • 5
  1. 1.Centre de Référence des Maladies Rénales Rares, Centre de Référence des Maladies Rares du Calcium et du Phosphate, Hospices Civils de LyonHôpital Femme Mère EnfantBron cedexFrance
  2. 2.INSERM, UMR 1033Faculté de Médecine Lyon EstLyonFrance
  3. 3.Département de BiologieCentre Hospitalier Lyon SudPierre-BéniteFrance
  4. 4.Département d’Anatomopathologie, Groupe Hospitalier EstHospices Civils de LyonBronFrance
  5. 5.Université de LyonLyonFrance
  6. 6.Service de Chirurgie Orthopédique Pédiatrique, Hôpital Femme Mère EnfantHospices Civils de LyonBronFrance
  7. 7.Service de Génétique et Biologie Moléculaires, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Filière OSCARHôpital CochinParisFrance
  8. 8.INSERM U1169Hôpital BicêtreLe Kremlin-BicêtreFrance

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