The expanding family of hypophosphatemic syndromes
- 14 December 2011
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Bone and Mineral Metabolism
- Vol. 30 (1), 1-9
- https://doi.org/10.1007/s00774-011-0340-2
Abstract
Investigation of X-linked hypophosphatemia (XLH) has led to the identification of a novel phosphate-regulating homeostatic system. Initially considered vitamin D-refractory rickets, renal phosphate wasting was identified as the cardinal biochemical feature of XLH and several related disorders. Current therapy employs calcitriol and phosphate, which usually improves, but does not completely heal deformities and short stature. Later complications of XLH include development of osteophytes, entheses, and osteoarthritis. The mutated gene in XLH, PHEX, is expressed in osteocytes, but its role in the pathogenesis of phosphate wasting is poorly understood. Many hypophosphatemic disorders are mediated by FGF23, a unique fibroblast growth factor with endocrine properties. Renal action of FGF23 leads to reduced expression of type II sodium-phosphate co-transporters, as well as reduced expression of CYP27B1, which encodes vitamin D 1α-hydroxylase. FGF23-mediated hypophosphatemia is characterized by inappropriately normal circulating 1,25-dihydroxyvitamin D together with renal phosphate wasting. The FGF23 system serves as a novel mechanism by which the mineralizing skeleton can communicate phosphate supply to the kidney and thereby mediate excretion or conservation of this important skeletal component. Other forms of FGF23-mediated hypophosphatemia represent various aberrations in this axis. Secretion of excess FGF23 (as in tumor-induced osteomalacia), and mutations preventing proteolytic cleavage of FGF23 result in similar clinical features. Other hypophosphatemic disorders are discussed.Keywords
This publication has 67 references indexed in Scilit:
- A clinician's guide to X-linked hypophosphatemiaJournal of Bone and Mineral Research, 2011
- Calcitonin Administration in X-Linked HypophosphatemiaNew England Journal of Medicine, 2011
- Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 GeneAmerican Journal of Human Genetics, 2010
- Loss-of-Function ENPP1 Mutations Cause Both Generalized Arterial Calcification of Infancy and Autosomal-Recessive Hypophosphatemic RicketsAmerican Journal of Human Genetics, 2010
- Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formationProceedings of the National Academy of Sciences of the United States of America, 2009
- Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp MiceCalcified Tissue International, 2009
- A mouse model with postnatal endolymphatic hydrops and hearing lossHearing Research, 2008
- A translocation causing increased α-Klotho level results in hypophosphatemic rickets and hyperparathyroidismProceedings of the National Academy of Sciences of the United States of America, 2008
- Klotho converts canonical FGF receptor into a specific receptor for FGF23Nature, 2006
- Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolismNature Genetics, 2006