The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Hematology Advisor’s conference coverage.

 

Increasing factor IX (FIX) levels in early childhood were found to be independent of puberty in a case series of male children with hemophilia B Leyden, according to findings presented at the European Hematology Association (EHA) Annual Congress.1 The results of the study were presented by Saad Ahmed,  MBBS, MRCPI, FRCPath, HSE, of Children’s Health Ireland and also published in the British Journal of Haematology.2

Hemophilia B is twice as common in Ireland compared to the rest of the world,” explained Dr Ahmed. The disorder affects 1 in 12,500 males in Ireland and 1 in 30,000 males globally.


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Recent studies in symptomatic female carriers and mouse models have brought into question a longstanding belief that FIX levels are regulated by androgens. Thus, the aim of this study was to define the exact timing of the increase in FIX levels in children with hemophilia B Leyden and whether these levels are associated with puberty.

The investigators studied hemophilia B Leyden in 13 male children from 7 unrelated families at the National Irish Hemophilia Centre at Our Lady’s Children Hospital. The team sequenced commonly mutated regions of the FIX gene and promotor regions to identify causative genetic variants. They also took serial measurements of the FIX level with advancing age.

All children in the study had the same mutation (hemizygous c.-35G>A) in the promotor region of the F9 gene. The patients were divided into 2 groups based on age at diagnosis: diagnosis during the first year of life and diagnosis after the first year of life.

Five children diagnosed with hemophilia B Leyden in the first year of life were found to have moderate to severe FIX deficiency. All 5 children had progressively increasing FIX levels (range, <0.01-0.03 IU/mL) with advancing age, and they had achieved mild FIX deficiency levels (range, 0.07-0.21 IU/mL) and normal prothrombin time for their age.

The other 8 children were diagnosed after the first year of life. Similarly, their FIX levels were assessed over time (at diagnosis, at 5-15 years, and >15 years). Nearly all of these children (7/8) showed increasing FIX levels with advancing age and puberty; 1 child had his last measurement at age 5 years.

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“In line with animal studies, [growth hormone] is the likely driver for surges in the [factor IX level] in patients with haemophilia B Leyden resulting from c.35G>A mutation,” concluded Dr Ahmed.

Major limitations of the study included the small sample size and lack of growth hormone and androgen measurements.

References

  1. Ahmed SZ, O’Rourke M, Regan I, Jenkins V, Nolan B. New insights into hemophilia B Leyden. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S322.
  2. Ahmed SZ, O’Rourke M, Jenkins V, Regan I, Nolan B. Progressive increase in FIX level in males with haemophilia B Leyden and c.35G > A mutation in early childhood not related to androgen effect. Br J Haematol. 2020;189(6):e262-e265.