Hemophilia B

Hemophilia B is a genetic disorder caused by missing or defective factor IX, a blood-clotting protein also known as FIX. The disorder also is known as Christmas Disease, after the first person to be diagnosed with this type: Stephen Christmas, in 1952.

It is the second most common type of hemophilia.

Estimated to occur in nearly 1 in 25,000 male births, hemophilia B is about four to five times less common than hemophilia A.  One subtype of hemophilia B, known as hemophilia B Leyden, accounts for approximately 3% of all type B cases.

The disease occurs worldwide, and can affect all ethnic groups equally.

Genetics and inheritance

Hemophilia B is caused by mutations in the F9 gene that result in the lack of functional FIX. Like type A, hemophilia B is inherited in an X-linked manner. Of note, the F9 gene is found on the X chromosome, one of two sex-determining chromosomes in humans. For this reason, males are more susceptible to developing the disease than females.

About one-third of hemophilia B cases are not inherited, but caused by a spontaneous genetic mutation.

Hemophilia B Leyden also is an X-linked disorder caused by low levels of clotting FIX early in life. However, in contrast to other forms of hemophilia, patients start producing FIX overtime. This is because mutations causing this subtype of hemophilia B occur in the promoter region of the F9 gene. The promoter region is a specific area in the DNA code that controls when a certain gene is turned off or on.

In hemophilia B Leyden, it is thought that a portion of the promoter region that responds to activation by hormones — specifically estrogen and testosterone — is unaffected by mutations. The increase in these hormones around puberty turns on gene expression, or activity, to a certain degree. By midlife, FIX levels in these patients are usually on the low end of the normal range, meaning that from that period on, patients may no longer require bleeding treatment.

Symptoms

Hemophilia B can be considered mild, moderate, or severe, depending on FIX activity levels. In mild cases, the disorder can cause prolonged bleeding after surgery or an injury.

Severe forms appear early during infancy or childhood. In these cases, spontaneous bleeding may occur in the absence of an injury or trauma. Other symptoms may include frequent and severe bruising, and muscle and joint bleeds. Less commonly, patients may experience nosebleeds and bleeds in the gastrointestinal tract.

Hemophilia B Leyden causes episodes of excessive bleeding in childhood, which gradually disappear after puberty.

Treatment

Hemophilia B is a treatable disease with replacement therapy, in which an infusion of the missing FIX protein is given to patients.

Replacement therapy can be used as an on-demand treatment on specific occasions to treat an acute bleed or on a routine basis to prevent bleeding episodes from occurring. This second form of treatment, known as prophylaxis, often is recommended to patients with more severe forms of the disorder. Some of the available therapies include BeneFIX, Rixubis, Ixinity, and Alprolix.

Some patients also may be treated with antifibrinolytics, which are medications that slow the process of breaking blood clots in the body.

 

Last updated: Dec. 3, 2021

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