Hypophosphatemic rickets and mutations in the PHEX gene
Frédérique Faivre-Defrance, Benoit Soudan, Sophie Marcelli-Tourvieille, Jean-Louis Wémeau & Marie-Christine Vantyghem
Hypophosphatemic rickets is associated with mutations in the PHEX gene leaving phosphaturic peptides such as FGF23 uncleaved, enabling them to exert their phosphaturic potential in the kidney. Other forms are caused by mutations in the proteolytic processing site of FGF23 itself, while in tumour-induced Hp, overproduction of FGF23 causes the processing capacity to be exceeded, resulting in phosphaturic Hp. The aim of this work was to assess blood FGF23 levels in Hp patients and in normophosphatemic controls. Methods: 17 patients suffering from chronic Hp without HPT were compared to an age-matched control group of 18 patients. Blood levels of calcium, phosphate, PTH, 25-OH vitamin D (Nichols Diagnostics) and FGF 23 (ELISA Immunotopics) were determined. Results: FGF23 levels were higher in Hp: 46.3±614.9 vs. controls: 20.3±1.6 pg/ml, P<0.05, in regard of phosphate levels of 20.2±0.7 (Hp) vs 34.5±1.2 mg/l (controls). Vitamin D and calcium levels were normal and similar in both groups. PTH levels were higher in Hp: 70.5±15.5 vs. controls: 31.5±2.6 pg/l; P<0.05. FGF 23 correlated neither to phosphate nor vitamin D, nor calcium levels in the whole population and in Hp and control groups.
Conclusion: The lack of correlation between FGF23 levels and Hp suggests an heterogeneity of hypophosphatemic patients despite their higher FGF23 levels than controls. New genes regulating FGF 23 such as the recently discovered DMP1 could explain this heterogeneity (Nat Genet 2006 Nov).