Genetics of Haemophilia A

Haemophilia A is a genetic disorder characterised by defficiency of Factor VIII in the blood. The factor VIII gene is located on the X chromosome . Thus this disorder is a sex linked disorder.

One in 10,000 males is born with deficiency or dysfunction of the factor VIII molecule. Although normal hemostasis requires at least 25 percent factor VIII activity, symptomatic patients usually have factor VIII levels below 5 percent, Patients with <1 percent factor VIII activity have severe disease; Patients with levels between 1 and 5 percent have moderate disease with less frequent bleeding episodes. Those with levels over 5 percent have mild disease with infrequent bleeding that is usually secondary to trauma. Occasional patients with factor VIII levels as high as 25 percent are discovered when they bleed after major trauma or surgery. The majority of patients with hemophilia A have factor VIII levels below 5 percent.

• All daughters of haemophilics are carriers and sisters have a 50 % chance of being a carrier.

• If a carrier has a son he has 50 % chance of having haemophilia, and a daughter has 50 % chance of of being a carrier.

• Haemophilia 'breeds true' within a family. All members of a family will have same abnormality of factor VIII gene, i.e. if one member has severe form of the disease all other affected would have severe form of the disease.

• In carrriers of this disease, Ratio of factor VIIIC : von Willibrand factor (vWF) is reduced compared to the normal.

• Tracing of the haemophilia gene within families can be done using gene probes which detect restriction fragment length polymorphism (RFLPs).

• Antenatal diagnosis can be done in females having high degree of probability of being a carrier. This is done by doing chorion villus sampling at 8-9 weeks of gestation.