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

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.[1]

Hypophosphatemic rickets is almost always inherited and may be caused by changes (mutations) in any of several genes.[1] There are several forms which are distinguished by their genetic cause and pattern of inheritance. Most commonly hypophosphatemic rickets is due to changes in the PHEX gene and inherited in an X-linked dominant manner (X-linked hypophosphatemia). 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
The symptoms of hypophosphatemic rickets usually begin in infancy or early childhood. Specific symptoms and severity can vary greatly among affected children. The condition can be so mild that there are no noticeable symptoms, or so severe that it causes bowing of the legs and other bone deformities; bone pain; joint pain; and short stature. Other symptoms may include premature closure of the skull bones in babies (craniosynostosis); limited joint movement; and dental abnormalities.[1][2] If left untreated, symptoms worsen over time.[2]
Last updated: 3/1/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal calcium-phosphate regulating hormone level 0100530
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality
[ more ] 		0000682
Bowing of the long bones
Bowed long bones
Bowing of long bones
[ more ] 		0006487
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption
[ more ] 		0000684
Dolichocephaly
Long, narrow head
Tall and narrow skull
[ more ] 		0000268
Exostoses
Formation of new noncancerous bone on top of existing bone
0100777
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Pectus excavatum
Funnel chest
0000767
Short stature
Decreased body height
Small stature
[ more ] 		0004322
30%-79% of people have these symptoms
Craniosynostosis 0001363
Scoliosis 0002650
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Last updated: 7/1/2020
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
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 recessive, autosomal dominant, or autosomal recessive manner.[2][3]
Last updated: 3/1/2016
The long-term outlook (prognosis) for people with hypophosphatemic rickets is good. With appropriate management, normal health and normal lifespan are expected.[4]

If the condition is not treated (especially while children are growing), skeletal deformities may be permanent.[5]
Last updated: 3/1/2016

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Hypophosphatemic rickets. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Hypophosphatemic rickets. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Hypophosphatemic rickets:
    XLH CoRDS Registry
    X-Linked Hypophosphatemic Rickets International Registry
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Hypophosphatemic rickets. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers. 
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Hypophosphatemic rickets in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hypophosphatemic rickets. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How long is the average life expectancy for a person who has Vitamin D-resistant rickets? See answer

  • If vitamin D is increased will calcium levels raise higher than they usually are? Because I have x-linked vitamin D resistant rickets, can any of my boys who inherited this disease, pass it on to their children? I was told "no" by one doctor and "yes" by another. Thank you for checking on this for us. See answer

  • I was born with hypophosphatemic rickets. As a child I was given buffered sodium phosphate, which helped to stop my calcium levels becoming too high. This has been stopped for some time now. I am now an adult and am taking Calcitrol, but my calcium levels are still high. How are high calcium levels in adults with hypophosphatemic rickets treated? See answer

  • My nephew was diagnosed with hypophosphatemic rickets. He is on calcitriol but is not responding. What causes this, and is there any treatment? See answer

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

  • My son has hypophosphatemic rickets and frequently develops abscesses in his mouth. Our doctor believes this is due to the weakened bones caused by this condition. Can you give me more information on this? See answer


  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.
  4. James CM Chan. Hypophosphatemic Rickets. Medscape Reference. December 2, 2015; http://emedicine.medscape.com/article/922305-overview#a7.
  5. Neil K. Kaneshiro. Rickets. MedlinePlus. August 30, 2014; https://www.nlm.nih.gov/medlineplus/ency/article/000344.htm.