Hemophilia is a rare, inherited bleeding disorder where the blood lacks sufficient clotting factors. These proteins are essential for coagulation, which seals damaged blood vessels and stops bleeding. Without adequate clotting factors, bleeding can persist, even from minor injuries. This can lead to external and internal bleeding, potentially causing complications.
Hemophilia’s Chromosomal Location
Hemophilia is an X-linked genetic disorder. There are two primary types: Hemophilia A and Hemophilia B. Hemophilia A, the more prevalent form, results from a deficiency or defect in clotting Factor VIII. The gene for Factor VIII, known as F8, is located on the X chromosome.
Hemophilia B arises from insufficient levels of clotting Factor IX. The F9 gene, which provides instructions for producing Factor IX, is also found on the X chromosome.
The X-Linked Inheritance Pattern
The X-linked classification dictates how hemophilia is passed through families. Females have two X chromosomes (XX), while males have one X and one Y chromosome (XY). The genes for Factor VIII and Factor IX are present only on the X chromosome, with no corresponding genes on the Y chromosome.
This genetic arrangement explains why males are more frequently affected. A male inherits his single X chromosome from his mother and his Y chromosome from his father. If his mother passes an X chromosome with an altered F8 or F9 gene, he will develop hemophilia because he lacks another X chromosome to compensate. Conversely, a female inherits one X chromosome from each parent. Even if one X chromosome carries the altered gene, her other functional X chromosome usually allows her to produce enough clotting factor, making her a carrier. Fathers with hemophilia cannot pass the condition to their sons, as they pass only their Y chromosome.
How Hemophilia Affects Individuals
Males who inherit the altered gene on their single X chromosome experience the symptoms of hemophilia. These can range from prolonged bleeding following injuries, surgeries, or dental procedures to easy bruising and spontaneous bleeding. Internal bleeding into joints and muscles is a common concern, which can cause pain, swelling, and long-term joint damage. The severity of hemophilia in males is determined by the amount of functional clotting factor in their blood; less than 1% activity indicates severe hemophilia, while 5% to 40% suggests a mild form.
Females, having two X chromosomes, are usually carriers of the hemophilia gene, meaning they carry the gene but often do not have severe symptoms. However, some female carriers can experience bleeding tendencies, with symptoms similar to those seen in males with mild hemophilia. These can include easy bruising, prolonged nosebleeds, bleeding after minor injuries, and particularly heavy or prolonged menstrual bleeding. The variability in symptoms among carriers is due to a process where one X chromosome is randomly inactivated in cells, influencing the level of functional clotting factor produced.