Purpose of review
Description of the recent advances on the regulation of phosphate metabolism, gene mutations, and new approaches to treatment in patients with hypophosphatemic rickets.
Fibroblast growth factor 23 (FGF23) overproduction may be a primary cause of hypophosphatemic rickets. Inactivating mutations of phosphate-regulating gene with homologies to endopeptidases on the X chromosome, dentin matrix acidic phosphoprotein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1 are associated with X-linked hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets 1, and autosomal recessive hypophosphatemic rickets 2, respectively. Activating mutations of FGF23 gene is the cause of autosomal dominant hypophosphatemic rickets. Iron deficiency may affect autosomal dominant hypophosphatemic rickets phenotype by regulating FGF23 production.
Current treatment with activated vitamin D metabolites and oral inorganic phosphate salts may partially correct skeletal lesions and linear growth in patients with hypophosphatemic rickets. However, some patients have poor improvement by the current treatment.
Identification of the causative mutation in patients with hypophosphatemic rickets may be useful to confirm the diagnosis and probably for prognosis. Inhibition of FGF23 overproduction by anti-FGF23 neutralizing antibodies could be a future approach for treatment of patients with FGF23-dependent hypophosphatemic rickets.