Hemophilia B Leyden
Fact-checked by Hemophilia B Leyden (HBL) is a rare subtype of hemophilia B, a genetic bleeding disorder characterized by the lack of a blood clotting protein called factor IX (FIX).
For most people with hemophilia B, genetic mutations in the F9 gene cause a sustained deficiency in FIX, leaving patients susceptible to prolonged and excessive bleeding episodes for their entire lives. HBL is distinct because it leads to low levels of FIX early in life, but over time, the body begins to produce more of the clotting factor and a person’s bleed risk declines.
Accounting for approximately 3% of all hemophilia B cases, HBL was named after the city in the Netherlands where it was discovered.
Understanding HBL
While both classic hemophilia B and HBL are caused by mutations in F9, the difference comes down to where the variations are located within the gene. The mutations that cause classic hemophilia B are found throughout F9, and lead to a persistent deficiency in FIX.
Mutations causing HBL occur specifically in F9‘s promoter region, an area of DNA that controls when a gene is turned off or on. In HBL, a regulatory region is disrupted by mutations, causing low gene activity early in life that leads to FIX deficiency.
Other parts of the promoter that allow the gene to be activated in response to hormones, such as testosterone, may remain unaffected, however. Research suggests that an increase in hormone levels around puberty could help increase F9 activity, allowing more FIX to be produced thereafter. While sex hormones such as testosterone have long been implicated, scientists also think growth hormone or other factors could be involved in activating the gene.
Symptoms
Similar to most other types of hemophilia, the main symptoms of HBL are easy bleeding and bruising. This could manifest as prolonged or excessive bleeding after a medical procedure, or in more severe cases, spontaneous bleeding without a clear cause. Bleeding into the joints may cause joint pain.
In contrast to other forms of hemophilia, however, HBL symptoms may not be lifelong. Bleeding in this subtype tends to be the worst in childhood, easing in adolescence and adulthood as FIX levels rise. For some, bleeding symptoms may resolve entirely in adulthood.
How HBL is inherited
The HBL inheritance pattern is similar to that of classic hemophilia B. It is an X-linked disorder, meaning that the genetic mutation causing the disease is located on the X chromosome. Because of its X-linked recessive inheritance pattern, HBL is more common in men than in women.
Women have two X chromosomes, while men only have one. If men inherit the disease-causing mutation on their only X chromosome, they will definitely develop HBL. A woman who inherits the mutation on both of her X chromosomes will typically also develop HBL.
However, women may also inherit the mutation on only one X chromosome and have a healthy version of F9Â on the other X chromosome that can produce FIX. These women, traditionally referred to as carriers, may or may not have bleeding problems.
Diagnosing HBL
In general, diagnosing HBL is similar to the process used for other types of hemophilia. Reaching a diagnosis may involve:
- collecting a family and symptom history
- blood tests to evaluate clotting abilities and activity of clotting factors, such as FIX
- genetic testing to identify disease-causing mutations, particularly if there is a family history of a bleeding disorder
Distinguishing HBL from classic hemophilia B
During the diagnostic process, it can be difficult to distinguish HBL from classic hemophilia B. That’s because they are both characterized by a FIX deficiency.
Often, making the distinction relies on tracking FIX activity over time. If the patient begins producing more FIX once puberty hits, it’s a sign of HBL. If there is a family history of hemophilia, symptom patterns of affected family members can also be informative.
Genetic testing can also be used to identify the specific disease-causing mutation a person has. If an F9 promoter mutation is found, it’s a clue that HBL may be present.
Treatment and management options
HBL is treated similarly to classic hemophilia B. The standard treatment is factor replacement therapy, which supplies the body with a functional version of the missing FIX protein. This can be used on an on-demand basis to treat active bleeds, or given prophylactically on a regular schedule to prevent bleeds. Nonfactor therapies that work to promote clotting through other mechanisms are also available for hemophilia B.
Because FIX levels usually rise after childhood, people with HBL may not require lifelong treatment. Adjustments or discontinuations will be determined by tracking FIX and bleeding symptoms over time.
Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
