Skip to main content
ISTH 2023 Main banner
Back

    Poster Networking

    Nurses and Allied Health

    Poster Networking Session

    PB0246 - FXIII Deficiency: A genetic diagnostic dilemma

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    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 126g/L, platelet count 291 x 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.