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X-LINKED
HYPOPHOSPHATEMIA
Tom Gillespie
Rinzin Dorjee
Martin Kutti
X-LINKED DOMINANT HYPOPHOSPHATEMIC RICKETS, X -
LINKED VITAMIN D-RESISTANT RICKETS OR
HYPOPHOSPHATEMIC VITAMIN D -RESISTANT RICKETS
(HPDR)
 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).
 Marked by bone distortions, nodular enlargements on the ends and sides of the
bone, delayed closure of the fontanelles, muscle pain etc.
 associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent
inactivity of the PHEX protein.
 The prevalence of the disease is 1:20000
INFECTED CHILDREN
CAUSES 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
 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
 The disorder is inherited in an X-linked dominant manner.
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
D I S O R D E R W H E N I N H E R I T E D F R O M A PA R E N T W H O H A S T H E
DISORDER.
 Males - homozygous 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), Xlinked inheritance is determined by the gender of the parent carrying a specific gene and can often seem
complex.
 This is due to the fact that, typically, females have two copies of the X-chromosome, while 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.
X-LINKED DOMINANT INHERITANCE WORKS DIFFERENTLY
DEPENDING UPON WHETHER THE MOTHER (LEFT IMAGE) OR
FAT H E R ( R I G H T I M AG E ) I S T H E C A R R I E R O F A G E N E T H AT
CAUSES A DISEASE OR DISORDER
REFERENCES
 1. Online 'Mendelian Inheritance in Man' (OMIM) 307800
 2. "Familial hypophosphatemic rickets caused by a large deletion in
PHEX gene". European Journal of Endocrinology 161 (4): 647–651.
 3. Carpenter TO (Apr 1997). "New perspectives on the biology and
treatment of X-linked hypophosphatemic rickets".