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

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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.

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Authors and Affiliations

  1. Centre de Référence des Maladies Rénales Rares, Centre de Référence des Maladies Rares du Calcium et du Phosphate, Hospices Civils de Lyon, Hôpital Femme Mère Enfant, 59 boulevard Pinel, 69677, Bron cedex, France

    Debora Claramunt-Taberner, Aurélia Bertholet-Thomas & Justine Bacchetta

  2. INSERM, UMR 1033, Faculté de Médecine Lyon Est, site Laennec, Lyon, France

    Debora Claramunt-Taberner & Justine Bacchetta

  3. Département de Biologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France

    Marie-Christine Carlier

  4. Département d’Anatomopathologie, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France

    Frédérique Dijoud

  5. Université de Lyon, 69008, Lyon, France

    Frédérique Dijoud, Franck Chotel & Justine Bacchetta

  6. Service de Chirurgie Orthopédique Pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France

    Franck Chotel

  7. Service de Génétique et Biologie Moléculaires, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Filière OSCAR, Hôpital Cochin, Paris, France

    Caroline Silve

  8. INSERM U1169, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

    Caroline Silve

Authors
  1. Debora Claramunt-Taberner
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  2. Aurélia Bertholet-Thomas
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  3. Marie-Christine Carlier
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  4. Frédérique Dijoud
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  5. Franck Chotel
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  6. Caroline Silve
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  7. Justine Bacchetta
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Corresponding author

Correspondence to Justine Bacchetta.

Ethics declarations

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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Claramunt-Taberner, D., Bertholet-Thomas, A., Carlier, MC. et al. Hyperphosphatemic tumoral calcinosis caused by FGF23 compound heterozygous mutations: what are the therapeutic options for a better control of phosphatemia?. Pediatr Nephrol 33, 1263–1267 (2018). https://doi.org/10.1007/s00467-018-3945-z

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  • DOI: https://doi.org/10.1007/s00467-018-3945-z

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