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Disease Profile
X-linked hypophosphatemia
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.
1-9 / 1 000 000
Age of onset
Childhood
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.
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.
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.
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.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
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.
Not applicable
Other names (AKA)
X-linked hypophosphatemic rickets; XLH; Hypophosphatemic rickets, X-linked dominant;
Categories
Congenital and Genetic Diseases; Endocrine Diseases; Kidney and Urinary Diseases;
Summary
Symptoms
- Bone pain.
- Muscle pain and weakness.
- A waddling gait (manner of walking).
- Joint pain caused by hardening (calcification) of tendons and ligaments.
- Abnormal tooth development.
- Tooth abscesses and dental pain.
- Rickets that does not improve with traditional Vitamin D therapy.
In some cases, symptoms of XLH do not begin until adulthood. Symptoms that may develop in adults with XLH include joint pain and impaired mobility from enthesopathy (calcification of the tendons, ligaments, and joint capsules), tooth abscesses, and
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 | ||
Abnormality of dental enamel |
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality
[ more ] |
0000682 |
Abnormality of the metaphysis |
Abnormality of the wide portion of a long bone
|
0000944 |
Bone pain | 0002653 | |
Genu varum |
Outward bow-leggedness
Outward bowing at knees
[ more ] |
0002970 |
Hypophosphatemia |
Low blood phosphate level
|
0002148 |
Joint dislocation |
Joint dislocations
Recurrent joint dislocations
[ more ] |
0001373 |
Osteomalacia |
Softening of the bones
|
0002749 |
Rachitic rosary | 0000897 | |
Rickets |
Weak and soft bones
|
0002748 |
Tooth abscess | 0030757 | |
30%-79% of people have these symptoms | ||
0001363 | ||
Enthesitis | 0100686 | |
Osteoarthritis |
Degenerative joint disease
|
0002758 |
Decreased body height
Small stature
[ more ] |
0004322 | |
5%-29% of people have these symptoms | ||
Hearing impairment |
Deafness
Hearing defect
[ more ] |
0000365 |
Recurrent fractures |
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ] |
0002757 |
Percent of people who have these symptoms is not available through HPO | ||
Abnormality of |
Abnormal shape of pelvic girdle bone
|
0002644 |
Arthralgia |
Joint pain
|
0002829 |
Bowing of the legs |
Bowed legs
Bowed lower limbs
[ more ] |
0002979 |
Elevated alkaline phosphatase |
Greatly elevated alkaline phosphatase
High serum alkaline phosphatase
Increased alkaline phosphatase
Increased serum alkaline phosphatase
[ more ] |
0003155 |
Elevated circulating parathyroid |
0003165 | |
Femoral bowing |
Bowed thighbone
|
0002980 |
Fibular bowing |
Bowed calf bone
|
0010502 |
Flattening of the talar dome | 0008144 | |
Frontal bossing | 0002007 | |
Hypomineralization of enamel |
Poorly mineralized tooth enamel
|
0006285 |
Hypophosphatemic rickets | 0004912 | |
Metaphyseal irregularity |
Irregular wide portion of a long bone
|
0003025 |
Renal phosphate wasting | 0000117 | |
Renal tubular dysfunction |
Abnormal function of filtrating structures in kidney
|
0000124 |
Shortening of the talar neck | 0008117 | |
Spinal canal stenosis |
Narrow spinal canal
|
0003416 |
Spinal cord compression |
Pressure on spinal cord
|
0002176 |
Tibial bowing |
Bowed shankbone
Bowed shinbone
[ more ] |
0002982 |
Trapezoidal distal femoral condyles | 0006432 | |
0001423 |
Cause
Diagnosis
- A slow growth rate and noticeable bowing of the legs or other skeletal abnormalities.
- Low levels of phosphate and high levels of FGF23 in the blood.
- Lack of response of phosphate levels to vitamin D treatment.
- Phosphate wasting in the kidneys.
Testing Resources
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment
- Growth
hormone to improve growth in children. - Corrective surgery to fix bowed or bent legs.
- Treatment to repair skull abnormalities, such as premature fusion of the skull bones (synostosis).
- Dental procedures to treat pain in the teeth and gums.
FDA-Approved Treatments
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.
- Burosumab(Brand name: Crysvita) Manufactured by Ultragenyx Pharmaceutical, Inc.
FDA-approved indication: April 2018 approved for the treatment ofX-linked hypophosphatemia (XLH) in adult and pediatric patients 1 year of age and older.
National Library of Medicine Drug Information Portal
Related diseases
Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.
Conditions with similar signs and symptoms from Orphanet
|
---|
Differential diagnosis includes autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), hereditary hypophosphatemic rickets with hypercalciuria (HHRH), fibrous dysplasia of bones, renal Fanconi syndrome (see these terms), vitamin D deficiency and tumor-induced osteomalacia.
Visit the Orphanet disease page for more information.
|
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
-
XLH Network
911 Central Ave., #161
Albany, NY 12206
Telephone: 518-350-9541
Fax: 855-318-7132
E-mail: info@xlhnetwork.org
Website: https://www.xlhnetwork.org/
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
- Genetics Home Reference (GHR) contains information on X-linked hypophosphatemia. This website is maintained by the National Library of Medicine.
- 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.
- The XLH Network, a worldwide patient support organization for people living and dealing with X-linked hypophosphatemia, provides information about XLH.
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.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has 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.
References
- XLH Network Board of Directors. What is XLH?. XLH Network. April 20, 2012; https://xlhnetwork.org/index.php/what-is-xlh/.
- Harrold Juppner. X-linked hypophosphatemia. OrphaNet. January 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=89936.
- Ruppe MD. X-Linked Hypophosphatemia. GeneReviews. April 13, 2017; https://www.ncbi.nlm.nih.gov/books/NBK83985/#rickets-xlh.
- Chesher D, Oddy M, Darbar U et al. Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis. February 19, 2018; [Epub ahead of print]:https://link.springer.com/article/10.1007%2Fs10545-018-0147-6.
- Chan JCM. Hypophosphatemic Rickets. Medscape Reference. May 1, 2017; https://emedicine.medscape.com/article/922305-overview.
- Symptoms of XLH. XLH Network. August 13, 2017; https://xlhnetwork.org/what-is-xlh/symptoms-of-xlh/.
- Melinda S Sharkey, Karl Grunseich, Thomas O Carpenter. Contemporary Medical and Surgical Management of X-linked Hypophosphatemic Rickets. The American Academy of Orthopaedic Surgeons. July 2015; https://www.ncbi.nlm.nih.gov/pubmed/26040953.
- Hereditary hypophosphatemic rickets. Genetics Home Reference. September, 2010; https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets.
- Steven J Scheinman, Marc K Drezner. Hereditary Hypophosphatemic Rickets and Tumor-Induced Osteomalacia. UpToDate. December 1, 2015; https://www.uptodate.com/contents/hereditary-hypophosphatemic-rickets-and-tumor-induced-osteomalacia?source=search_result&search=x-linked+hypophosphatemia&selectedTitle=1~10.
- Effect of Medical Treatment. XLH Network. March 28, 2016; https://www.xlhnetwork.org/what-is-xlh/treating-xlh/effect-of-medical-treatment/.
- Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A Clinician's Guide to X-Linked Hypophosphatemia. J Bone Miner Res. July, 2011; 26(7):1381-1388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157040/.
- Kawaguchi A, Miyamoto K, Wakahara K, Hosoe H, Miura A, Hanamoto T, Shimizu K. Surgical treatment of multiple spinal canal stenoses associated with vitamin D-resistant rickets. J Clin Neurosci. May, 2009; 16(5):717-719. https://www.ncbi.nlm.nih.gov/pubmed/19264492.
- Effect of Surgical Treatment. XLH Network. March 28, 2016; https://www.xlhnetwork.org/what-is-xlh/treating-xlh/effects-of-surgical-treatment/.
- James CM Chan, Karl S Roth. Hypophosphatemic Rickets: Treatment & Medication. eMedicine. December 2, 2015; https://emedicine.medscape.com/article/922305-treatment.
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