World Library  
Flag as Inappropriate
Email this Article

X-linked hypophosphatemia

Article Id: WHEBN0006480091
Reproduction Date:

Title: X-linked hypophosphatemia  
Author: World Heritage Encyclopedia
Language: English
Subject: Metabolic disorders, Vitamin D, Hypovitaminosis D, List of eponymously named diseases, Chronic granulomatous disease
Publisher: World Heritage Encyclopedia

X-linked hypophosphatemia

X-linked hypophosphatemia
Classification and external resources
ICD-10 E83.3
ICD-9-CM 275.3
OMIM 307800
DiseasesDB 6513

ped/1128 article/922305

MeshName =
MeSH D053098

X-linked hypophosphatemia (XLH), also called X-linked dominant hypophosphatemic rickets, X-linked vitamin d-resistant rickets ,[1] is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of rickets in that ingestion of vitamin D is relatively ineffective. It can cause bone deformity including short stature and genu varum (bow leggedness). It is associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent inactivity of the PHEX protein.[2] The prevalence of the disease is 1:20000.[3] The leg deformity can be treated with Ilizarov frames and CHAOS surgery.


  • Cause and Genetics 1
  • Treatment 2
  • See also 3
  • References 4
  • External links 5

Cause and Genetics

XLH is associated with a mutation in the PHEX gene sequence, located on the human X chromosome at location Xp22.2-p22.1.[1][2][4] The PHEX protein regulates another protein called fibroblast growth factor 23 (produced from the FGF23 gene). Fibroblast growth factor 23 normally inhibits the kidneys' ability to reabsorb phosphate into the bloodstream. Gene mutations in PHEX prevent it from correctly regulating fibroblast growth factor 23. The resulting overactivity of this protein reduces phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of hereditary hypophosphatemic rickets. Also, in the absence of PHEX enzymatic activity, osteopontin[5] — a mineralization-inhibiting secreted substrate protein found in the extracellular matrix of bone[6] — may accumulate in the bone to contribute to the osteomalacia as shown in the mouse homolog (Hyp) of XLH.[7] Biochemically, XLH is recognized by hypophosphatemia and inappropriately high level of calcitriol (1,25-(OH)2 vitamin D3). It also affects their equilibrium, only to the effect of their balance, which their knee/ankle joints are either farther outward or inward. A person affected by this disease usually cannot touch both knees and ankles together.

The disorder is inherited in an X-linked dominant manner.[1][2] This means the defective gene responsible for the disorder (PHEX) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity in males than females.

As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the gender of the parent carrying a specific gene and can often seem complex. This is because, typically, females have two copies of the X-chromosome and males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.


Oral phosphate,[8] 9, calcitriol,[8]9; in the event of severe bowing, an osteotomy may be performed to correct the leg shape.

See also


  1. ^ a b c Online 'Mendelian Inheritance in Man' (OMIM) 307800
  2. ^ a b c
  3. ^
  4. ^ 300550
  5. ^
  6. ^
  7. ^
  8. ^ a b

9. Glorieux FH, Marie PJ, Pettifor JM, Delvin EE. (1980). Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets.

N Engl J Med. 303(18):1023.

External links

  • Hypophosphatemic rickets; XLH; Hypophosphatemia, vitamin D-resistant rickets at NIH's Office of Rare Diseases
  • The PHEXdb - a database of nucleotide variation in the PHEX gene
  • The XLH Network Inc. - a worldwide patient support organization
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.