Pediatric Nephrology

, Volume 27, Issue 9, pp 1477–1487 | Cite as

Genetic disorders of phosphate regulation

Educational Review

Abstract

Regulation of phosphate homeostasis is critical for many biological processes, and both hypophosphatemia and hyperphosphatemia can have adverse clinical consequences. Only a very small percentage (1%) of total body phosphate is present in the extracellular fluid, which is measured by routine laboratory assays and does not reflect total body phosphate stores. Phosphate is absorbed from the gastrointestinal tract via the transcellular route [sodium phosphate cotransporter 2b (NaPi2b)] and across the paracellular pathway. Approximately 85% of the filtered phosphate is reabsorbed from the kidney, predominantly in the proximal tubule, by NaPi2a and NaPi2c, which are present on the brush border membrane. Renal phosphate transport is tightly regulated. Dietary phosphate intake, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D3, and fibroblast growth factor 23 (FGF23) are the principal regulators of phosphate reabsorption from the kidney. Recent advances in genetic techniques and animal models have identified many genetic disorders of phosphate homeostasis. Mutations in NaPi2a and NaPi2c; and hormonal dysregulation of PTH, FGF23, and Klotho, are primarily responsible for most genetic disorders of phosphate transport. The main focus of this educational review article is to discuss the genetic and clinical features of phosphate regulation disorders and provide understanding and treatment options.

Keywords

Hypophosphatemia Hyperphosphatemia FGF23 Klotho Sodium phosphate contransporters 

Notes

Acknowledgments

This work was supported by Children’s Medical Center Research Foundation Grant (JG) and NIH grant K08DK089295-01 (JG), NIH grant DK41612 and DK078596 (MB), T32 DK07257 (Peter Igarashi and MB), O’Brien Center P30DK079328 (Peter Igarashi, PI).

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© IPNA 2012

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of Texas Southwestern Medical Center at DallasDallasUSA
  2. 2.Department of Internal MedicineUniversity of Texas Southwestern Medical Center at DallasDallasUSA
  3. 3.Department of PediatricsU.T. Southwestern Medical CenterDallasUSA

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