propensity, to develop spontaneous bleeding episodes and excessive bleeding after even minor tissue injuries and surgeries; however, individuals with any of these disorders may also exhibit a propensity to pathological thrombosis episodes.Treatment of these disorders generally involves specialized centers and the establishment of preventive measures designed based on each individuals personal and family histories of the frequency and severity of previous bleeding and thrombosis episodes, and, in a select few cases, the predicted propensity of the genetic mutations which underlie their disorders to cause bleeding and thrombosis. Signs and symptoms
Afibrinogenemia is typically the most severe of the three disorders. Common symptoms include bleeding of the umbilical cord at birth, traumatic and surgical bleeding, GI tract, oral and mucosal bleeding, spontaneous splenic rupture, and rarely intracranial hemorrhage and articular bleeding. Symptoms of hypofibrinogenemia varies from mild to severe, but can include bleeding of the GI tract, oral and mucosal bleeding, and very rarely intracranial bleeding. More commonly it presents during traumatic bleeding or surgical procedures. Most cases (60%) of dysfibrinogenemia are asymptomatic, but 28% exhibit hemorrhaging similar to that described above while 20% exhibit thrombosis (i.e. excessive clotting). Causes
The disorders associated with Factor I deficiency are generally inherited, although certain liver diseases can also affect fibrinogen levels and function (e.g. cirrhosis). Afibrinogenemia is a recessive inherited disorder, where both parents must be carriers. Hypofibrinogenemia and dysfibrinogenemia can be dominant (i.e. only one parent needs to be a carrier) or recessive. The origin of the disorders is traced back to three possible genes: FGA, FGB, or FGG.
Due to the excess activity of FGF23, phosphate levels in the blood are abnormally low, which affects the constitution of bone. Thus, burosumab is designed to bind to the FGF23 receptor and inhibit the excess activity of the FGF23 hormone within the body.While burosumab is effective for the treatment of X-linked hypophosphatemia, the National Institute for Health and Care Excellence in England and Wales initially raised concerns regarding the incremental cost-effectiveness of the new treatment but the drug is available through a simple discount scheme. History
This drug was developed by Ultragenyx and is in a collaborative license agreement with Kyowa Hakko Kirin. References
External links
"Burosumab". Drug Information Portal. U.S. National Library of Medicine.