Hemophilia is a rare, inherited blood disorder that impairs the body’s ability to form blood clots, resulting in prolonged bleeding or excessive bruising. In individuals with hemophilia, there is a deficiency or absence of specific clotting factors, proteins necessary for normal blood clot formation.
Understanding Genetic Alterations
Genetic alterations can occur as gene mutations or as chromosome mutations. A gene is a fundamental unit of heredity, a segment of DNA that contains instructions for building a specific protein. A gene mutation involves a change in the DNA sequence within a single gene, such as a substitution, insertion, or deletion of nucleotides. These changes can alter the protein the gene produces, or prevent its production.
Chromosomes are larger structures within cells that contain many genes. Chromosome mutations involve larger-scale changes, affecting the structure or number of entire chromosomes. Examples include deletions or duplications of large chromosome segments, or aneuploidy, an abnormal number of chromosomes. While gene mutations affect specific protein instructions, chromosome mutations can impact multiple genes due to their broader structural or numerical changes.
The Genetic Root of Hemophilia
Hemophilia is caused by a gene mutation, not a chromosome mutation. Hemophilia A results from mutations in the Factor VIII (F8) gene, and hemophilia B from mutations in the Factor IX (F9) gene. These genes are located on the X chromosome. Mutations within these genes lead to the body producing insufficient or defective Factor VIII or Factor IX proteins, which are necessary for normal blood clotting.
The severity of hemophilia correlates with the specific mutation and the resulting level of clotting factor activity. Individuals with severe hemophilia typically have less than 1% of normal clotting factor activity, while those with mild hemophilia may have 5% to 49% of normal factor levels. This genetic alteration directly impacts the body’s ability to create a stable blood clot, leading to the characteristic bleeding symptoms of the disorder.
How Hemophilia is Passed Down
Hemophilia is inherited in an X-linked recessive pattern. Males have one X and one Y chromosome, while females have two X chromosomes. If a male’s single X chromosome carries the mutated gene for Factor VIII or Factor IX, he will develop hemophilia. Fathers cannot pass X-linked traits to their sons because sons inherit their X chromosome from their mother.
Females usually need a mutation on both copies of the gene to develop hemophilia, which is rare. A female with one mutated X chromosome and one normal X chromosome is considered a carrier. Carriers typically have enough normal clotting factor from their healthy X chromosome to prevent severe symptoms, though some may experience mild bleeding issues. For a carrier mother, there is a 50% chance that each son will inherit the affected X chromosome and have hemophilia, and a 50% chance that each daughter will be a carrier.
Consequences of the Mutation
The specific gene mutations in Factor VIII or Factor IX directly impair the body’s coagulation cascade, the series of reactions that lead to blood clot formation. When these clotting factors are deficient or dysfunctional, the blood cannot form a stable fibrin clot, which is necessary to seal damaged blood vessels. This inability to clot properly results in prolonged and excessive bleeding, either internally or externally.
Common manifestations include bleeding into joints, which can lead to pain, swelling, and long-term joint damage. Bleeding into muscles can also occur, causing significant discomfort and swelling. In severe cases, bleeding into vital organs, such as the brain, can be life-threatening. Even minor injuries or spontaneous bleeding episodes can cause serious health problems due to the impaired clotting mechanism.