X-linked hypophosphatemia (XLH), also called X-linked dominant hypophosphatemic rickets, X-linked vitamin d-resistant rickets or hypophosphatemic vitamin d-resistant rickets (HPDR),[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 [edit]
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X-linked dominant inheritance works differently depending upon whether the mother (left image) or father (right image) is the carrier of a gene that causes a disease or disorder
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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 mutation results in altered (or missing) activity of the PHEX protein, which inactivates hormone-like substances (phosphatonins) that promote phosphate excretion. The resulting excess excretion of phosphate impairs bone mineralization. Biochemically, XLH is recognized by hypophosphatemia and inappropriately low 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 unaffected 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.
Difference in male to female [edit]
An affected male males legs bow outwards (ankles touch, but not the knees), causing the identification of the disease to be at an later age than a females. Females legs bow inwards (knees touch, but not the ankles).
Treatment [edit]
Oral phosphate, calcitriol, and surgery if necessary.[citation needed]
See also [edit]
References [edit]
- ^ a b c Online 'Mendelian Inheritance in Man' (OMIM) 307800"HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT; XLHR". 23 May 2011.
- ^ a b c Saito, T.; Nishii, Y.; Yasuda, T.; Ito, N.; Suzuki, H.; Igarashi, T.; Fukumoto, S.; Fujita, T. (Oct 2009). "Familial hypophosphatemic rickets caused by a large deletion in PHEX gene". European Journal of Endocrinology 161 (4): 647–651. doi:10.1530/EJE-09-0261. PMID 19581284. edit
- ^ Carpenter TO (Apr 1997). "New perspectives on the biology and treatment of X-linked hypophosphatemic rickets". Pediatr. Clin. North Am. 44 (2): 443–466. doi:10.1016/S0031-3955(05)70485-5. PMID 9130929.
- ^ 300550"PHOSPHATE-REGULATING ENDOPEPTIDASE HOMOLOG, X-LINKED; PHEX". 18 April 2011.
External links [edit]
