Vitamin D Resistant Rickets

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Vitamin D Resistant Rickets
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Specialty scores for Vitamin D Resistant Rickets

Overview

Source: In partnership with Genetic and Rare Diseases Information Center, funded by the National Center for Advancing Translational Sciences, and the National Human Genome Research Institute https://rarediseases.info.nih.gov/gard.

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X-linked hypophosphatemia

overview Question

What is X-linked hypophosphatemia?

X-linked Hypophosphatemia (XLH) is an inherited disorder characterized by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to soft, weak bones (rickets). XLH is usually diagnosed in childhood. Features include bowed or bent legs, short stature, bone pain, and severe dental pain. The condition is caused by mutations in the PHEX gene on the X chromosome, and is inherited in an X-linked dominant manner. Treatment generally involves supplements of phosphate and high-dose calcitriol (the active form of Vitamin D), and may also include growth hormones, corrective surgery, and dental treatment. With consistent treatment, the long term outlook (prognosis) is typically good, although growth rate may be slow and affected individuals are usually shorter than their peers.  

Date Modified: 2016-05-27T00:00:00

basic Questions

What are the signs and symptoms of X-linked hypophosphatemia (XLH)?

Symptoms of XLH usually begin in early childhood and can vary in severity. Early signs include skeletal abnormalities such as noticeably bowed or bent legs, short stature, and irregular growth of the skull. Overtime, symptoms may progress to include bone pain, joint pain caused hardening (calcification) of tendons and ligaments, and dental pain. Some people with XLH may also experience hearing loss, although this appears to be rare.

Date Modified: 2016-05-27T00:00:00

What causes X-linked hypophosphatemia (XLH)?

XLH is caused by mutations in the PHEX  gene on the X chromosome. Nearly 300 PHEX mutations have been associated with XLH. Mutations in this gene lead to an increased concentration of fibroblast growth factor 23 (FGF23), a growth hormone that regulates the reabsorption of phosphate in the kidneys. Too much FGF23 causes phosphate wasting in the kidneys, prevents maintenance of proper phosphate levels in the blood, which causes the symptoms of XLH.

Date Modified: 2016-05-27T00:00:00

How is X-linked hypophosphatemia inherited (XLH)?

XLH is caused by mutations in the  PHEX gene, and is 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 in both males and females. A female with XLH has a 50% chance of passing along a mutation to each of her children. Because males only have one X-chromosome, a male with XLH will pass along the condition to all of his daughters, but to none of his sons. PHEX mutations are usually inherited through families, but they can also occur in people with no family history of the disorder as a new (de novo) mutation.  

Date Modified: 2016-05-27T00:00:00

Is genetic testing available for X-linked hypophosphatemia (XLH)?

XLH is generally diagnosed on the basis of a physical exam. Genetic tests are available, but are not needed to reach a diagnosis.

Date Modified: 2016-05-27T00:00:00

How is X-linked hypophosphatemia (XLH) diagnosed?

XLH is diagnosed on the basis of a physical exam, blood tests, imaging tests such as x-rays, and family history. A slow growth rate and noticeable bowing of the legs, low levels of phosphate, and high levels of FGF23 in the blood, and phosphate wasting in the kidneys are factors used in the diagnosis of XLH.

Date Modified: 2016-05-27T00:00:00

How might X-linked hypophosphatemia (XLH) be treated?

XLH is different from other types of rickets because it cannot be treated by increasing vitamin D alone. Phosphate supplements are generally required and are typically combined with high dose calcitriol. Calcitriol increases calcium levels by increasing the amount of calcium absorbed in the intestines and the amount of calcium kept in the kidneys. In children, treatment is usually started at the time of diagnosis and continues until bones stop growing. The main treatment goal for adults is to help improve pain.

Other treatment options may include the following:

  • Growth hormone to improve growth in children
  • Corrective surgery to fix bowed or bent legs in children
  • Treatment to repair skull abnormalities, such as premature fusion of the skull bones (synostosis)
  • Dental procedures to treat pain in the teeth, gums, and mouth

Clinical trials are looking at an antibody that suppresses FGF23, which prevents phosphate wasting in the kidneys. Click on the link for information about research including how to get involved.  

Date Modified: 2016-05-27T00:00:00

What is the long-term outlook for X-linked hypophosphatemia (XLH)?

With appropriate and consistent treatment, prognosis for a healthy, normal lifespan is typically good. Apart from the short stature of most affected adults, bone abnormalities can generally be corrected with medication or surgery.

Date Modified: 2016-05-27T00:00:00

Presentation(s)

Abnormality of dental enamel

Abnormality of the metaphyses

Bone pain

Genu varum

Premature loss of teeth

Craniofacial hyperostosis

Enthesitis

Osteoarthritis

Short stature

Hearing impairment

Recurrent fractures

Abnormality of pelvic girdle bone morphology

Arthralgia

Bowing of the legs

Elevated alkaline phosphatase

Elevated circulating parathyroid hormone (PTH) level

Femoral bowing

Fibular bowing

Flattening of the talar dome

Frontal bossing

Hypomineralization of enamel

Hypophosphatemia

Hypophosphatemic rickets

Metaphyseal irregularity

Osteomalacia

Phenotypic variability

Renal phosphate wasting

Renal tubular dysfunction

Shortening of the talar neck

Spinal canal stenosis

Spinal cord compression

Tibial bowing

Trapezoidal distal femoral condyles

X-linked dominant inheritance