BACKGROUND: Dysfibrinogenemia is a rare group of qualitative fibrinogen disorders caused by structural abnormalities in the fibrinogen molecule. The laboratory diagnosis of dysfibrinogenemia is controversial. Fibrinogen Paris V, clinically termed Dusart Syndrome, is a dysfibrinogenemia caused by a single base substitution in the gene coding for the Aα-chain of the fibrinogen molecule. OBJECTIVES: To diagnose the first Scandinavian family with Fibrinogen Paris V affecting several family members; the proband, a seven-year-old boy with cerebral vein thrombosis. METHODS: The diagnosis was established following the ISTH guideline for laboratory testing supplemented with fibrin structure analysis and fibrinogen gene analysis. RESULTS: Prolonged thrombin time and reduced ratio between the functional and the protein concentration of fibrinogen were observed in four family members who also were characterized by significantly reduced fibrin polymerization (p < 0.001), reduced fibrin fibre diameter (p < 0.001), reduced fibrin mass-length ratio (p < 0.001) and significantly reduced t-PA-induced fibrinolysis of the fibrin clots (p < 0.001) when compared to controls. Fibrinogen gene analysis demonstrated that five of the family members carried the Fibrinogen Paris V mutation. All laboratory tests were normal in the family members carrying the wild type of the fibrinogen gene. Four of the affected patients had suffered from thrombotic episodes. A noticeable feature in the present family was the presence of both venous and arterial thrombosis. CONCLUSIONS: Excellent concordance was observed between the screening and confirmatory tests, fibrin structure analysis and fibrinogen gene analysis. Fibrin structure analysis should be considered in the laboratory algorithm for diagnosis of dysfibrinogenemia.
Scandinavian Journal of Clinical and Laboratory Investigation, 2013, Vol 73, Issue 7, p. 585-90
Adolescent; Adult; Case-Control Studies; Child; Coagulation Protein Disorders; DNA Mutational Analysis; Female; Fibrin; Fibrinogens, Abnormal; Humans; Male; Middle Aged; Pedigree; Protein Multimerization; Scandinavia; Syndrome; Thrombin Time; Thrombosis; Young Adult; gamma-Glutamyltransferase