Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation

  • Murat Bastepe
  • Harald JüppnerEmail author


Phosphorous is essential for multiple cellular functions and constitutes an important mineral in bone. Hypophosphatemia in children leads to rickets resulting in abnormal growth and often skeletal deformities. Among various causes of low serum phosphorous are inherited disorders associated with increased urinary excretion of phosphate, including autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemia (XLH), autosomal recessive hypophosphatemia (ARHP), and hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Recent genetic analyses and subsequent biochemical and animal studies have revealed several novel molecules that appear to play key roles in the regulation of renal phosphate handling. These include a protein with abundant expression in bone, fibroblast growth factor 23 (FGF23), which has proven to be a circulating hormone that inhibits tubular reabsorption of phosphate in the kidney. Two other bone-specific proteins, PHEX and dentin matrix protein 1 (DMP1), appear to be necessary for limiting the expression of fibroblast growth factor 23, thereby allowing sufficient renal conservation of phosphate. This review focuses on the clinical, biochemical, and genetic features of inherited hypophosphatemic disorders, and presents the current understanding of hormonal and molecular mechanisms that govern phosphorous homeostasis.


Hypophosphatemic disorders Phosphorus Vitamin D PTH FGF23 PHEX DMP1 


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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Endocrine UnitMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Pediatric Nephrology UnitMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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