Hemophilia is a genetic disorder in which the blood clotting process is impaired.
In healthy people, when blood clotting is needed following an injury, various proteins become activated. These proteins are called coagulation factors.
Coagulation factors are activated gradually: as soon as one protein is done with its role, the next protein comes into action, until a clot is formed. When one of these factors does not function normally, the chain of reaction is broken, and the blood clot formation is impaired.
Genetic basis
There are two main types of hemophilia: hemophilia A is caused by a deficiency in clotting factor VIII, and hemophilia B is caused by a deficiency in clotting factor IX. Type A is caused by a mutation to the gene F8C, and type B is caused by a mutation to the gene F9.
The prevalence of type A is 1 in 5,000 male births, while the prevalence of type B is 1 in 30,000 male births.
What are the symptoms?
Symptoms usually include bleeding in the joints such as the knees, ankles, hips, and elbows. However, depending on the severity of the disease, bleeding may occur in other areas of the body, such as the muscles, under the skin, and in the digestive system.
The biggest risk is posed by bleeding in the brain. Later in life, symptoms include joint damage caused by frequent bleeding in the joints that leads to destruction of the cartilage and bone.
In the past, hemophilia was considered a terminal disease and most patients died at a young age, but today patients enjoy a normal life expectancy.
How is hemophilia inherited?
The genes that produce clotting factors VIII and IX are located on the X chromosome. Since females have two X chromosomes, this disease is very rare in women and girls. However, males have a 50% risk of developing the disease when their mother is a carrier of the relevant gene mutation.
Men with hemophilia do not pass down the disease to their sons, but do pass the mutation on to their daughters, who will become carriers and will pass the mutation on to their own children.
Genetic testing – carrier screening
When several members of the family have hemophilia, one of the members undergoes genetic testing first to detect the relevant gene mutation. Next, their mother is also tested for that mutation. If the mother is found to carry the mutation, genetic screening is continued gradually in other family members.
First, the carrier mother’s daughters, sisters, and own mother are tested. According to test results, other women in the family may also be tested. Pregnant women who are found to be carriers of the relevant gene mutation can undergo amniocentesis or chorionic villus sampling to test whether the fetus is male or female, and whether they are at risk for being a carrier.
When only one family member has hemophilia, the relevant mutation should be detected and tested to see if that patient’s mother is also a carrier. If their mother is found to be a carrier, the process continues as described above.
However, if the mother is not a carrier, this is probably a new mutation (de novo). These patients will pass on the mutation to their daughters, and the disease to their sons.
Treatment
Treatment for hemophilia is based on injecting the missing clotting factor.
An early diagnosis is highly important to prevent damage to the joints and decrease the risk for fatal bleeding. When treatment is given early and regularly, people with hemophilia can lead normal lives.
