Hamostaseologie 2025; 45(S 01): S70-S71
DOI: 10.1055/s-0044-1801648
Abstracts
Topics
T-07 Hereditary bleeding disorders

Hemophilia B Leyden: Characteristics and natural history in the PedNet Registry

M Kartal-Kaess
1   Inselspital, University Hospital, University of Bern, Division of Pediatric Hematology & Oncology, Department of Pediatrics, Bern, Switzerland
,
F Pinto
2   Royal Hospital for Children, Glasgow, UK
,
V Labarque
3   University Hospitals Leuven, Department of Pediatrics, Pediatric Hemato-Oncology, Leuven, Belgium
,
M D Kovel
4   PedNet Haemophilia Research Foundation, Baarn, Netherlands
,
B Nolan
5   Children's Health Ireland at Crumlin, Children's Coagulation Centre, Dublin, Ireland
,
M Carcao
6   Haemophilia Clinic and Haemostasis Program, Hospital for Sick Children, University of Toronto, Division of Haematology/Oncology, Department of Paediatrics, Toronto, Canada
,
R d'Oiron
7   Centre de Référence de l'Hémophilie et des Maladies Hémorragiques Rares, Hôpital Bicêtre AP-HP, et INSERM Hémostase inflammation thrombose HITH U1176, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France
,
T S Mikkelsen
8   University Hospital Aarhus, Department of Pediatric Oncology and Hematology, Aarhus, Denmark
,
R Ljung
9   Lund University, Department of Clinical Sciences Lund, Lund, Sweden
,
N G Andersson
10   Skåne University Hospital, Center for Thrombosis and Hemostasis, Malmö, Sweden
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Introduction: A unique and rare form of Hemophilia B (HB) is HB Leyden. We evaluated the International PedNet Registry database to explore the natural history of HB Leyden, investigate genotype-phenotype correlations and guide clinical decision-making. The primary obejctive was to assess the association between genetic variants, endogenous factor (F) IX levels over time, treatment and bleeding phenotype in children with HB Leyden.

Method: Data on genetic variants, FIX levels at diagnosis and over time, onset and type of bleeding, and treatment modality were extracted from the PedNet Registry including children with hemophilia born since 2000.

Results: Of 457 individuals with HB, 24 showed a HB Leyden genotype. The most frequent F9 variant was c.-35G>A affecting 14 individuals, followed by c.-35G>C (n=4), c.-49T>A (n=2), and c.-52C>T, c.-34A>G and c.-22delT (n=1 each). Major clinical differences in bleeding and treatment modality were observed comparing c.-35G>A to non-c.-35G>A genotypes: For all children with a c.-35G>A genotype, FIX levels showed a rise, but not normalization over time, irrespective of initial severity, before the age of four years. In children with non-c.-35G>A genotypes, a rise in FIX was less common (4/9) and occurred later.

Conclusion: HB Leyden is caused by the variant c.-35G>A in>50% of cases, in whom a FIX increase occurs at very young ages, associated with a low bleeding rate. This contrasts to the phenotype of individuals with HB Leyden due to a non-c.-35G>A variant. Our study may thus help guide clinical decision-making in this rare HB entity.



Publication History

Article published online:
13 February 2025

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