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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".