Christmas Disease

Abstract

Hemophilia B or Christmas disease, one of two common hereditary bleeding disorders, is caused by a deficiency of factor IX in the circulation. Being an X-linked recessive disorder, it afflicts only males; females may be asymptomatic carriers or very rarely affected. Molecular mechanisms of hemophilia B are highly heterogeneous including gene deletions, insertions, complex rearrangements, and a large number of point mutations. Hot spots of mutations have been identified and are usually associated with CpG sequences. With the determination of specific mutations in hemophilia B patients, and through advances in molecular techniques, more accurate determination of carrier status and prenatal diagnosis can now be made. With a few exceptions, there are clear correlations between the mutation and the clinical features. In addition, mutations causing gross physical or functional loss of coding information appear to predispose to the development of antibodies against therapeutic factor IX. The availability of plasma-derived and recombinant factor IX concentrates has transformed the management of patients with bleeding disorders, such as Christmas disease. Gene therapy trials have several obstacles to overcome before it can be widely used as treatment for hemophilia B. Primary prophylaxis with factor IX concentrate starting in early childhood is presently the preferred mode of therapy for severe Christmas disease.