Rare Rheumatology News

Disease Profile

Hypophosphatemic rickets

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

ageofonset-all.svg

ICD-10

E83.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

rnn-xlinkeddominant.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Kidney and Urinary Diseases;

Summary

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]

Symptoms

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]

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.

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

Cause

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]

Organizations

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

    Learn more

    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

    • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
    • Genetics Home Reference (GHR) contains information on Hypophosphatemic rickets. This website is maintained by the National Library of Medicine.
    • 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.

        References

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

        Rare Rheumatology News