PB0246 FXIII Deficiency: A Genetic Diagnostic Dilemma
Bibliographic record
Abstract
Background: Factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder.Plasma FXIII is a protransglutaminase which is composed of two alpha-subunits (FXIII-A), and two beta-subunits (FXIII-B).FXIII deficiency is commonly diagnosed via clot lysis or quantitative XIII activity assay, the latter of which is capable of discriminating FXIII-A deficiency, FXIII-B deficiency, or anti-FXIII antibodies.Genetic analysis can assist in confirming diagnosis.Aims: We describe a case of severe FXIII deficiency in which genetics were initially confounding.Methods: We conducted a retrospective chart review.Consent was obtained from the patient/family.Results: A male subject presented at birth with prolonged umbilical stump bleeding and multiple bleeding episodes in childhood.Laboratory evaluations revealed: hemoglobin 126 g/L, platelet count 291 × 109/L, PTT 25 sec, INR 1.1, fibrinogen activity 1.5 g/L, FVIII 1.20 IU/mL, VWF:Ag 0.87 IU/mL, VWF:Act 0.68 IU/mL, FIX 0.93 IU/mL, FXIII: Ag < 0.04 IU/mL, FXIII:Act < 0.14 IU/mL, and FXIII-A < 0.02 IU/mL.FXIII:Act were 0.85 IU/mL and 0.83 IU/mL for the mother and father respectively.Genetic analysis revealed presence of two likely pathogenic class 4 variants in his FXIII-A gene: c.57_58delCT p.Ser20X and c.2111G>A p.Arg704Gln.He also had a variant in the FXIII-B gene: c.344G>A p.Arg115His.This FXIII-B variant was also found in the father who was homozygous but unaffected.We concluded this variant did not produce a pathogenic effect.A diagnosis of severe FXIII-A deficiency was made and he was started on FXIII replacement.Conclusion(s): While genetic evaluation can elucidate a diagnosis, in this case our patient had variants in both the FXIII-A and FXIII-B subunits.Parental testing was essential for interpreting that the FXIII-B subunit variant was not clinically contributory as it was found to be homozygous in an unaffected parent.
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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 | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".