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Diseases

Genetic and Rare Diseases Information Center (GARD)

Hypophosphatemic rickets


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Your Question

I was diagnosed with hypophosphatemic rickets 24 years ago. My brother is not affected. Are my future children at risk to have this condition?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is hypophosphatemic rickets?

Hypophosphatemic rickets (previously called vitamin D-resistant rickets) is a disorder in which the bones become painfully soft and bend easily, due to low levels of phosphate in the blood.[1] Symptoms usually begin in early childhood and can range in severity. Severe forms may cause bowing of the legs and other bone deformities; bone pain; joint pain; poor bone growth; and short stature. In some affected babies, the space between the skull bones closes too soon (craniosynostosis). This sometimes results in developmental abnormalities. Hypophosphatemic rickets is almost always inherited and may be caused by changes (mutations) in any of several genes.[1] Most commonly it is due to the PHEX gene and inherited in an X-linked dominant manner. Less commonly it is inherited in an X-linked recessive manner (often called Dent disease); autosomal dominant manner; or autosomal recessive manner.[2][3] Treatment involves taking phosphate and calcitriol in order to raise phosphate levels in the blood and promote normal bone formation.[1]
Last updated: 3/1/2016

What causes hypophosphatemic rickets?

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

How is hypophosphatemic rickets inherited?

Hypophosphatemic rickets is most often inherited in an X-linked dominant manner. This means that the gene responsible for the condition is located on the X chromosome, and having only one mutated copy of the gene is enough to cause the condition.

Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females.

If a father has the mutated X-linked gene:
  • all of his daughters will inherit the mutated gene (they will all receive his X chromosome)
  • none of his sons will inherit the mutated gene (they only inherit his Y chromosome)
If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene.

Less commonly, hypophosphatemic rickets is inherited in an X-linked recessiveautosomal dominant, or autosomal recessive manner.[2][3]
Last updated: 3/1/2016

Because I have hypophosphatemic rickets, are my children at risk to suffer the same disorder?

Hypophosphatemic rickets is a genetic condition. This puts your offspring at risk to inherit the mutation which causes the disease. It is most commonly inherited in an X-linked -dominant manner, but cases following x-linked recessive, autosomal dominant and autosomal recessive inheritance patterns have also been documented [4]. To learn more about the specific risks to your future children, we recommend that you consult with a genetics professional.
Last updated: 9/17/2009

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 6/5/2014

References
Related Diseases
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.