Haemophilia A - Genetics

Genetics

Hemophilia A is inherited as an X-linked recessive trait, and thus occurs in males and in homozygous females. However, mild hemophilia A (and B) is known to occur heterozygous females due to X-inactivation, so it is recommended that levels of factor VIII and IX be measured in all known or potential carriers prior to surgery and in the event of clinically-significant bleeding.:1701

Hemophilia occurs in approximately 1 in 5,000 males.:1700 Of these, 85% have hemophilia A and 15% have hemophilia B.:1700

5-10% of patients with hemophilia A are affected because they make a dysfunctional version of the factor VIII protein (qualitative deficiency), while the remainder are affected because they produced factor VIII in insufficient amounts (quantitative deficiency).:1700 Of those who have severe deficiency (defined as <1% activity of factor VIII), 45-50% have the same mutation, an inversion within the factor VIII gene that results in total elimination of protein production.:1700 However, since both forms of hemophilia can be caused by a variety of different mutations, initial diagnosis and classification is done by measurement of protein activity rather than by genetic tests, though genetic tests are recommended for testing of family members once a known case of hemophilia B is identified.:1700-1701

Approximately 30% of patients have no family history; their disease is presumably caused by new mutations.