Haemophilia B Leyden in Greece

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Hemophilia B is a rare inherited bleeding disorder caused by deficiency of coagulation Factor IX.
• The cross-reacting material (CRM)-negative form of hemophilia B is characterized by reduced Factor IX activity and antigen levels.
• Phenotypic variability in hemophilia B can be influenced by genetic and environmental factors.

Purpose of the Study:

• To describe a five-generation Greek family with a unique presentation of hemophilia B.
• To investigate the genetic basis and clinical characteristics of this distinct hemophilia B variant.
• To compare the findings with previously described forms of hemophilia B, such as hemophilia B Leyden.

Main Methods:

• Clinical evaluation of affected family members across five generations.
• Coagulation assays including ox-brain prothrombin time.
• Measurement of Factor IX activity and antigen levels.
• Assessment of bleeding symptoms and their correlation with Factor IX levels.

Main Results:

• The family exhibits CRM-negative hemophilia B with significantly lower Factor IX levels in younger generations (Generation V) compared to older generations (Generation III).
• A notable age-dependent increase in Factor IX levels was observed in one patient, from 1 U/dL at age 13 to 10 U/dL at age 14.
• Younger patients present with severe to moderate bleeding symptoms (spontaneous muscle and joint hemorrhages), while older patients have mild or no bleeding symptoms.

Conclusions:

• This Greek family presents a phenotype consistent with hemophilia B Leyden, characterized by age-dependent increases in Factor IX levels and clinical severity.
• The findings highlight the genetic heterogeneity of hemophilia B and the potential for age-related recovery of Factor IX function.
• Further research is warranted to elucidate the specific genetic mutations and molecular mechanisms underlying this distinct hemophilia B variant.