Surabhi Madadi
AP Biology
Period 4
Genetic Disorder: Hemophilia A Hemophilia A, or “The Royal Disease,” literally means “love of bleeding.” It is the most common type of hemophilia. People with hemophilia A bleed extensively after injuries due to a missing or defective clotting protein, factor VIII. Two-thirds of hemophiliacs inherit hemophilia from their parents, while the remaining one-third obtain it from a spontaneous mutation during embryonic development.
Hemophilia has been recognized since ancient times such as the Talmud, Jewish Rabbinical writings. In 1803, Dr. John Conrad Otto recognized that the disease was hereditary and affects mainly males. Hemophilia is called “The Royal Disease” because Queen Victoria was a carrier. Her son, …show more content…
Symptoms include excessive bleeding from injuries, many deep bruises, pain and swelling in joints, blood in urine, frequent nosebleeds, and unexplained irritability in infants. Although hemophilia can be life threatening and does not have a cure, there are treatments. The most common is replacement therapy, in which clotting factor VIII is injected into the vein. The injections can be applied on a regular basis (preventative/ prophylactic treatment) or only to stop bleeding when it occurs (demand therapy). Demand therapy is less expensive and intensive, but there is the risk that bleeding will cause damage before the treatment is applied. For the clotting factor itself, it can be harvested from human plasma, but it must must be treated to prevent the spread of diseases. Otherwise, a recombinant protein is made by inserting the factor VIII gene into bacteria to be made. As with any treatment, there are complications, including developing antibodies that attack clotting factor, HIV or hepatitis C from human clotting factors, and damage to joints/muscles resulting from treatment delays. Another treatment is desmopressin, which is a man-made hormone that stimulates the release of stored factor VIII. However, desmopressin, which is given by injection or nasal spray, only works for mild hemophilia A and wears of quickly. So, it is only given at certain times, such as before dental work. …show more content…
Hemophiliacs produce either no factor VIII or a defective one. This can be the result of an inversion (40% of the time), where an inverted stretch of DNA causes severe hemophilia, or a deletion of a stretch of DNA. A nonsense substitution, in which a point mutation codes for a stop codon, produces only a part of the factor and then cuts it off, resulting in severe hemophilia. A missense substitution, in which a point mutation causes a different amino acid to be added to the protein, produces a defective protein, causing mild to moderate hemophilia. Hemophilia is a sex-linked disorder. The hemophilia allele is recessive and rare, affecting 1/5000 live births. Since males have only one X chromosome, they only need one recessive allele to have hemophilia, whereas women need two (one from each each parent). Consequently, the disorder is more frequent in males. Females who are heterozygous at this locus, or carriers (one in 2500 females), pass on the recessive allele without being affected by it much themselves. This is one reason natural selection doesn’t remove the recessive allele from the human population. In those where the recessive alleles produce no clotting factor, heterozygotes produce only half the normal amount of the clotting factor, thus categorizing the dominant allele as incompletely dominant. In those where the recessive alleles produce defective clotting factor, heterozygotes produce both