Hemophilia B Leyden: Characteristics and natural history in the PedNet Registry
Bibliographic record
Abstract
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 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".