Though famous as a curse of royalty due Queen Victoria’s transmission of the disease to the Russian, Spanish, and Prussian royal lines in the late 19th Century, hemophilia indiscriminately occurs in all races. Hemophilia is a genetic disease. The genetic defect resides on the X chromosome consequently the majority of individuals with hemophilia are male. There are an estimated 400,000 hemophilia patients worldwide; only 25% of whom receive any treatment. Hemophilia occurs in 1 out of 5,000-10,000 male births and is rarer in females. Approximately 20,000 people in the US have hemophilia (17,000 with Hemophilia A, 3,000 with Hemophilia B.). Of these patients, more than 11,000 have a severe form of hemophilia, meaning their bodies produce little or no blood clotting factor needed for blood to clot, putting them at risk for the worst possible outcomes for the disease.
Haplomics’ work focuses on Hemophilia A, or HA, a bleeding disorder caused by the lack of activity of a protein called Factor VIII (“factor eight”), or FVIII. HA patients’ severity of disease is determined by how much FVIII activity they have; mild HA results from 6%-9% of normal FVIII activity, moderate HA results from 1%-5% of normal FVIII activity, and severe HA is characterized by <1% of normal FVIII activity. Bleeding may be controlled in Hemophilia A patients by infusing functional, replacement FVIII. The replacement FVIII may be derived from pooled plasma or prepared recombinantly in cells that harbor and express a gene encoding human FVIII. Replacement FVIII therapy is the current preferred and most effective treatment for HA.
Changes (mutations) in the F8 Gene Cause Hemophilia A
Most people are familiar with the notion that genes carry biochemical instructions cells use to make the molecular tools (proteins) cells need to grow and to carry out required bodily functions. Any alteration in a gene is called a “mutation.” A mutation may cause a loss of function in the protein product encoded by the mutated gene.
Instructions for all the proteins involved in the blood clotting cascade are carried on genes. The genes that carry instructions for making FVIII appear on the X chromosome. Reduced function in FVIII typically is a result of a mutation in the gene coding for FVIII. Hemophilia often runs in families but a mutation in a FVIII gene can happen spontaneously. In this instance a boy with Hemophilia A may be born into a family with no prior history of Hemophilia A. In very rare instances females may experience inherited hemophilia. For additional information about Hemophilia A, please click the below video.