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Hemophilia A [D66.0]

OMIM numbers: 306700, 300841 (F8)

Dipl.-Biol. Birgit Busse

Scientific Background

Hemophilia A is an X chromosomal recessive coagulation disorder, caused by a deficiency of the coagulation factor VIII. The deficiency results in a disorder in the intrinsic pathway of the coagulation cascade and leads to signs and symptoms of a hemorrhagic diathesis with prolonged aPTT time.

Hemophilia A cannot be distinguished from hemophilia B (factor IX deficiency) regarding its phenotype. The two disorders are distinguished by biochemical measurement of the respective enzyme activity.

More than 2,500 mutations leading to hemophilia A have been identified in the F8 gene. Depending on the mutation, the enzyme activity is impaired to varying degrees; therefore the disease is categorized into different degrees of severity.

  • Severe Hemophilia A: Factor VIII activity < 1%
  • Moderate Hemophilia A: factor VIII activity 1-5%
  • Mild hemophilia A: factor VIII activity 6-40%

Due to the X chromosomal inheritance pattern, mainly men are affected. The prevalence is estimated to be approx. 1 in 6,000. In rare cases, female heterozygous carriers with a skewed X inactivation may develop signs and symptoms as well. Approx. 30% of all hemophilia A cases are caused by de novo mutations. Milder forms as well as approx. 50% of the severe forms are caused by point mutations in the F8 gene. Approx. half of all severe hemophilia A cases are caused by gene inversions in intron 1 or intron 22. Treatment consists of intravenous administration of recombinant factor VIII.