Genetics of Hemophilia

Hemophilia is a rare genetically inherited blood disorder. Types A and B involve specific proteins in the blood known as clotting factors. Hemophilia can be acquired without a family history. In some cases, individuals may be carriers despite not having any symptoms. They can pass on the mutation to their children, who will be carriers only if they are girls. Male children may show signs of the disease or suffer no effects at all.
 
The severity of hemophilia as a disease ranges from mild to severe. Some people experience minor symptoms. Those with significant mutations may suffer from prolonged bleeding internally for no reason at all.

The Clotting Factor

When an injury occurs in a person without a bleeding disorder, a chain reaction begins in the bloodstream. Enzymes start the process, which ends with a mesh-like blockage to prevent further blood loss. Activated platelets and proteins assist in successful clotting.
 
Genetics play a large role in providing these healthy proteins, or "factors." If one of these factors is defective, it affects the entire clotting reaction.

Hemophilia Types and Symptoms

Any of 20 clotting factors can potentially be the cause of a bleeding disorder. However, von Willebrand disease, along with Type A and Type B, are most prevalent in the general population, followed by Type C.
  • Hemophilia Type A occurs mainly in males, as does Type B. A defect in clotting factor VIII causes varying levels of abnormal bleeding. Those with Type A, or "classic" hemophilia, may experience mild, moderate or severe episodes.
  • Hemophilia Type B is affected by mutations in clotting factor IX and also occurs mainly in males. It is also known as "Christmas disease," named after Stephen Christmas, a young sufferer whose symptoms led to the discovery of Type B hemophilia in 1952. Bleeding is generally more serious in nature than Type A, but Type B is also less common.
  • Hemophilia Type C, which is caused by mutant clotting factor XI, is extremely rare and follows a different path than Types A and B. First, males and females are equally susceptible. Second, males can pass on the defective gene to sons or daughters. This condition is more prevalent among individuals of Jewish and Eastern European heritage, although in a majority of cases it produces milder bleeding levels.
Symptoms of most types of bleeding disorders are similar. In milder conditions, common occurrences include nosebleeds and easy bruising. Some women, even as carriers, experience heavier menstrual bleeding. Blood in the urine and joint pain are also common conditions.
 
Long-term effects include pain and disability from bleeding into joints and muscles. Severe complications may also arise. These include:
  • anemia from excessive or continual blood loss.
  • bleeding in the brain.
  • fatigue.
  • headaches.
  • vision impairment or loss from bleeding around the eyes.
In extreme cases, sudden joint swelling and extreme muscle pains may arise. Vomiting and double vision can also occur. Lack of treatment could lead to permanent disabilities and other chronic conditions.

Genetic Testing for Hemophilia and Risks of Disease

Genetics play a major role in determining who gets hemophilia and who does not. Both males and females can pass mutant genes to their children, but with different results.
 
The X chromosome is responsible for carrying genetic mutations for hemophilia. A female will typically be a carrier if she possesses one faulty X chromosome and one good X chromosome. Males possess one X chromosome and one Y chromosome. A hemophiliac male cannot pass the defective gene to his sons as he contributes the "Y" chromosome while the mother contributes the "X" chromosome. His daughters, on the other hand, will become carriers and, more rarely, contract the disease.
 
Heredity is not always the cause of these bleeding disorders. In Type A hemophilia, about 33 percent develop a mutant gene, known as "spontaneous mutation," with no family history of carriers. "Acquired" hemophilia can also occur when the body suddenly develops an attack on clotting factors.

Treatment and Lifestyle

No cure exists for hemophilia, but those who have the disease can live healthy lives. Patients with specific knowledge of which clotting factor is defective can receive replacement therapy. Desmopressin (DDAVP), for instance, is a synthetic drug that forces the system to produce factor VIII. It's used for pre-surgical treatment and for unexpected bleeding.
 
Human fresh frozen plasma (FFP) also provides treatment options, although laboratory-produced products are becoming widely available. Plasma treatment carries some risks for acquiring other diseases, such as hepatitis. Stringent testing, however, makes this a remote possibility.
 
Treatments have advanced significantly in the last few decades. Clotting factor replacement is safer and many of today's alternatives are seeing long-term success. Many experts also recommend prevention therapies, especially for younger children. The path to treatment includes a thorough physical evaluation and, in some cases, DNA testing. Specialists can evaluate the level of severity and make recommendations.
 
Even with a family history of carriers, many people never experience symptoms. Those with milder forms may remain unaware of their condition unless exposed to serious injuries. With the latest resources and improved genetics testing, hemophilia is becoming easier to manage.
 
Resources
 
Bloodindex (2007). Hemophilia. Retrieved December 13, 2008, from the Bloodindex Web site: http://www.bloodindex.org/hemophilia.php.
 
Genetics Home Reference (2008). Hemophilia. Retrieved December 13, 2008, from the Genetics Home Reference Web site: http://ghr.nlm.nih.gov/condition=hemophilia.
 
Mayo Foundation for Medical Education and Research (1998-2008). Hemophilia: Causes. Retrieved December 13, 2008, from the Mayo Clinic Web site: http://www.mayoclinic.com/health/hemophilia/DS00218/DSECTION=causes.
 
National Hemophilia Foundation (2006). What is a bleeding condition? Retrieved December 13, 2008, from the National Hemophilia Foundation Web site: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=26&contentid=5&rptname=bleeding.
 
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