National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Hypophosphatemic rickets

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My nephew was diagnosed with hypophosphatemic rickets. He is on calcitriol but is not responding. What causes this, and is there any treatment?
Hypophosphatemic rickets is almost always hereditary and may be caused by mutations in any of several genes.[1] The specific gene involved determines the way it is inherited.

Most commonly, it is caused by a mutation in the PHEX gene. Other genes that can be responsible for the condition include the CLCN5, DMP1, ENPP1, FGF23, and SLC34A3 genes.[2]

The genes associated with hereditary hypophosphatemic rickets are involved in keeping a proper balance of phosphate in the body. Many of these genes directly or indirectly regulate a protein that normally inhibits the kidneys' ability to reabsorb phosphate into the blood. Mutations affecting the function of these genes increase the production (or reduce the breakdown) of the protein, causing the protein to be overactive. The overactivity of the protein reduces phosphate reabsorption by the kidneys, leading to the features of the condition.[2]

Rarer, sporadic, acquired cases are sometimes associated with benign (non-cancerous) mesenchymal tumors that decrease resorption of phosphate.[1]
Last updated: 3/1/2016

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  1. Christopher J. LaRosa. Hypophosphatemic Rickets. Merck Manual. 2015; http://www.merckmanuals.com/home/children-s-health-issues/congenital-kidney-tubular-disorders/hypophosphatemic-rickets.
  2. Hereditary hypophosphatemic rickets. Genetics Home Reference. September, 2010; http://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets.
  3. Marla J. F. O'Neill. HYPOPHOSPHATEMIC RICKETS, AUTOSOMAL RECESSIVE, 2. OMIM. Match 19, 2010; http://omim.org/entry/613312.