Contributions
Abstract: EP574
Type: E-Poster Presentation
Session title: Bleeding disorders (congenital and acquired)
Background
Haemophilia B is a male-dominant human bleeding disorder that it is produced by mutations at the F9 gene located at Xq27; and it is characterised by reduced levels of factor IX. Haemophilia B Leyden is a subtype of haemophilia B with a phenotype of abnormal bleeding in the first period of life, increasing levels of factor IX during the puberty by an unknown and controversial mechanism. From previous assays it has been reported an 1.9% of patients with haemophilia B Leyden.
Aims
To visualize an unknown subtype of haemophilia B, and to underwrite the importance of the existence of the worldwide database to improve its knowledge.
Methods
We report clinical, phenotypical features of a clinical case of Haemophilia B Leyden in a newborn; and genotyping analysis of FIX performed by Sanger sequencing or Next Generation Sequencing according to local practice.
Results
At 2 days of age, the patient was referred to our centre because of an important bleeding after heel neonatal screening done in a regional hospital. There were no other localizations of bleeding at the time of the examination. During and after delivery no bleeding was observed. Laboratory assays revealed a prolonged activated partial thromboplastin time (APTT) with a reduced factor IX level of 1%. During follow-up the FIX:C has gradually increased (4% with 3 months and 6% with 8 months).
At 6 months of age, the patient suffered a mild head trauma after a fall. The patient waited for 24 hours to attend to the hospital. A brain computed tomography was performed, without any visible external bleeding. He was under active surveillance during 24 hours.
There was no history of haemophilia in his family. Genotyping analysis of FIX was performed by Next-Generation Sequencing (NGS) and a point mutation (c.-35G>A, variant NM¬_000133. ) was detected, located in the F9 promoter region. The familiar study confirmed that his mother was a carrier. She had no history of bleeding and her FIX level was 163%.
Conclusion
Haemophilia B Leyden is an illness mediated by a genetic mechanism that produces an age-related increase in FIX levels. Patients with haemophilia B Leyden present a rise in the level of FIX, being this increase more pronounced after puberty. This mechanism is associated with growth hormone secretion, that is low during infancy and increases during early childhood until puberty, going the levels of FIX from the severe range to the mild, normal range progressively. This correction in plasma FIX levels occurs as well in female carriers of haemophilia B Leyden; according to this fact, an androgenic effect is not needed.
Thirteen different point mutations concerning haemophilia B Leyden have been identified, and just 35 cases with the c.35G>A variant have been reported in Factor IX Variant Database. Haemophilia B Leyden remains as a biological challenge, with more studies needed. In this respect, it is worth noting that the existence of a worldwide database can be very useful to improve our knowledge about this curious haemophilia.
Keyword(s): Factor IX, Growth hormone
Abstract: EP574
Type: E-Poster Presentation
Session title: Bleeding disorders (congenital and acquired)
Background
Haemophilia B is a male-dominant human bleeding disorder that it is produced by mutations at the F9 gene located at Xq27; and it is characterised by reduced levels of factor IX. Haemophilia B Leyden is a subtype of haemophilia B with a phenotype of abnormal bleeding in the first period of life, increasing levels of factor IX during the puberty by an unknown and controversial mechanism. From previous assays it has been reported an 1.9% of patients with haemophilia B Leyden.
Aims
To visualize an unknown subtype of haemophilia B, and to underwrite the importance of the existence of the worldwide database to improve its knowledge.
Methods
We report clinical, phenotypical features of a clinical case of Haemophilia B Leyden in a newborn; and genotyping analysis of FIX performed by Sanger sequencing or Next Generation Sequencing according to local practice.
Results
At 2 days of age, the patient was referred to our centre because of an important bleeding after heel neonatal screening done in a regional hospital. There were no other localizations of bleeding at the time of the examination. During and after delivery no bleeding was observed. Laboratory assays revealed a prolonged activated partial thromboplastin time (APTT) with a reduced factor IX level of 1%. During follow-up the FIX:C has gradually increased (4% with 3 months and 6% with 8 months).
At 6 months of age, the patient suffered a mild head trauma after a fall. The patient waited for 24 hours to attend to the hospital. A brain computed tomography was performed, without any visible external bleeding. He was under active surveillance during 24 hours.
There was no history of haemophilia in his family. Genotyping analysis of FIX was performed by Next-Generation Sequencing (NGS) and a point mutation (c.-35G>A, variant NM¬_000133. ) was detected, located in the F9 promoter region. The familiar study confirmed that his mother was a carrier. She had no history of bleeding and her FIX level was 163%.
Conclusion
Haemophilia B Leyden is an illness mediated by a genetic mechanism that produces an age-related increase in FIX levels. Patients with haemophilia B Leyden present a rise in the level of FIX, being this increase more pronounced after puberty. This mechanism is associated with growth hormone secretion, that is low during infancy and increases during early childhood until puberty, going the levels of FIX from the severe range to the mild, normal range progressively. This correction in plasma FIX levels occurs as well in female carriers of haemophilia B Leyden; according to this fact, an androgenic effect is not needed.
Thirteen different point mutations concerning haemophilia B Leyden have been identified, and just 35 cases with the c.35G>A variant have been reported in Factor IX Variant Database. Haemophilia B Leyden remains as a biological challenge, with more studies needed. In this respect, it is worth noting that the existence of a worldwide database can be very useful to improve our knowledge about this curious haemophilia.
Keyword(s): Factor IX, Growth hormone