Background: The inborn absence of fibrinogen protein in plasma is an uncommon hereditary disorder with low prevalence of approximately one in a million. The clinical symptoms ranges from mild to moderate bleeding with umbilical stump bleeding as a first sign to appear at birth. Severe clinical presentation may vary from bleeding diathesis including intracranial Hemorrhage and splenic ruptures to musculoskeletal deformities.

Aims: The study aimed the exploration of gene variants in an infrequently affected fibrinogen encoding gamma gene.

Methods: The observational study was carried with approval of Institutional Ethical Board. The fibrinogen quantitative assay (Clauss Assay: Diagnostic Stago) was performed for the confirmation of diagnosis. Gene sequencing was performed on ABI PRISM® 3100 (Applied Biosystems). The results were sought on HGMD (Human Gene Mutation Database) http://www.hgmd.cf.ac.uk/ac/index.php & www.geht.org ) and Seattle SNPs (http://pga.gs.washington.edu/). ISTH-BAT was utilized for the assessment of bleeding symptoms in scores.

Results: The prolonged prothrombin Time (PT) and Activated Partial Thromboplastin time (APTT) along with negligible levels of fibrinogen. The bleeding scores were shown to have higher values. The novel gene variant identified as nonsense change, produced a truncated nonfunctional protein most likely due to skipping of NMD pathway.

Conclusions: Inherited Afibrinogenemia; a long remained unheard disease, now surfacing with an increasing incidence especially in high blood kinship regions. The Diversified pattern of symptoms in patients makes this disease more challenging with necessitation of large data contribution to design a standardized document of clinical pattern in correlation with genetic modifications.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-new-genetic-alteration-in-fibrinogen-gene-with-a-direful-phenotype-a-tie-in-in-a-newborn/