FP10-2 Patients With Mutations In Phex Or FGF23 Share FGF23 Excess But Present Distinct BONE and Mineral Metabolism Features

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP10-Osteoporosis & Other Metabolic Bone Diseases
Bench to Bedside
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:05 AM
Room 121 (Moscone Center)

Poster Board SAT-228
Claire Theret1, Laure Esterle2, Pierre-Francois Souchon3, Gwennaelle Roussey4, Emma Allain-Launay4, Anya Rothenbuhler5, Georges Deschenes6, Catherine Chaussain7, Dominique Prie8, Peter Kamenicky9, Caroline Silve10 and Agnes Linglart*11
1H˘pital de Lons le saunier, 2Bicetre hospital, le Kremlin Bicetre, France, 3Reims hospital, Reims, France, 4Nantes hospital, Nantes, France, 5Bicetre Hospital, France, 6Robert Debre hospital, Paris, France, 7Paris descartes University, Paris, France, 8Necker hospital, Paris, France, 9Fac Med Paris-Sud, Le Kremlin Bicetre, France, 10Faculte de Med Xavier Bichat and INSERM U986, Paris, France, 11CHU de Bicetre, LE KREMLIN BICETRE, France
X-linked hypophosphatemic rickets (XLHR), due to loss of function mutations in the endopeptidase PHEX, is the most frequent form of HR with elevated FGF23. PHEX is expressed by osteoblasts, osteocytes and odontoblasts; its precise function in controlling circulating FGF23 level is still unclear. FGF23, secreted by osteoblasts and osteocytes regulates phosphate handling and vitamin D metabolism mainly through its action on kidney. Extra renal effects of FGF23, including in bone, have been very recently suspected from FGF23 overexpression or underexpression in mouse models. Specific missense mutations of FGF23 prevent FGF23 cleavage and inactivation, and thus result in the rare autosomal dominant form of HR (ADHR) with elevated circulating FGF23. Although XLHR and ADHR manifest as HR and elevated FGF23, only patients with XLHR present a specific loss in PHEX function within PHEX expressing tissues (bone and teeth).


Examine the role of PHEX on bone and mineral metabolism by comparing the phenotype of patients with high FGF23 and HR due to PHEX or FGF23 mutations.


6 patients with FGF23 mutation and ADHR (4 children and 2 untreated adults); 23 patients with PHEX mutation and XLHR (18 children and 5 untreated adults); XLHR and ADHR patients were matched for age at start of treatment


Children with FGF23 mutations were diagnosed earlier (1.5±0.0 yrs) than children with PHEX mutations (2.3±0.2 yrs, p=0.03), with similar leg bowing (intercondylardistance 7.9±2.3 and 5.0±0 .7, respectively, p>0.05). At diagnosis, ADHR patients presented with bone demineralization (semi-quantitative assessment on X-rays) and fractures in one patient, whereas none of the 18 XLHR patients had bone demineralization or fractures. In addition, ADHR patients had significantly higher alkaline phosphatases than XLHR patients (2037±439 and 649±103, p=0.01, respectively). Phosphate, PTH and urinary calcium excretion were similar in both groups. Patients follow up revealed that, in opposition to XLHR, vitamin D analogs and phosphate supplements easily restored serum phosphate levels in ADHR; final height of untreated ADHR adults appears higher (-1.2 and -1 SD) than that of untreated XLHR (-3,2±1.3 SD).


Despite the limited number of patients, we pinpointed differences in the phenotypes of ADHR and XLHR. This suggests that the phenotype associated with PHEX deficiency does not uniquely result from FGF23 excess, yet advocates for a direct role of PHEX on bone mineralization and growth.

Nothing to Disclose: CT, LE, PFS, GR, EA, AR, GD, CC, DP, PK, CS, AL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm