Combined congenital deficiency of coagulation factors VII and X in two siblings with heterozygous factor V Leiden mutation (R506Q)

K. Heidinger1, R. Fischer1, M. Alrifai1, A. Pavlova2, B. Kemkes-Matthes1 (1Gie├čen, Germany, 2Bonn , Germany)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Introduction: Combined coagulation factor VII (FVII) and factor X (FX) deficiency (combined FVII/FX deficiency) is a rare bleeding disorder, in which both factors show reduced plasma activity. Estimated incidences of isolated FVII and FX deficiencies are 1: 500 000 and 1: 1 000 000. FVII and FX genes are located on the long arm of chromosome 13. Combined FVII/X deficiency can be caused by a single co-inherited clotting defect or by partial deletion within terminal end of chromosome 13. This may be associated with additional clinical features, known as 13q deletion syndrome. Factor V Leiden mutation is a known risk factor for thromboembolism and prevalent in 3 to 7 % of the population

Methods: Case report: We report about two children presented for thrombophilia screening due to positive family history of factor V Leiden mutation. The boy (12 years old) and the girl (9 years old) never had signs of thromboembolism, but both children suffered from malabsorption syndrome (abdominal distention). Diagnosis of gastrointestinal symptoms was already substantiated by prolonged prothrombin time (PT) (71 % and 61 % of normal) possibly induced by vitamin K deficiency. aPTT was in normal range. Nevertheless, vitamin K substitution showed no effect on PT and celiac disease could not be confirmed.

Results: Further investigations revealed factor VII activity of 31 % and factor X activity of 60 % in the girl. The boy showed factor VII activity of 69 % and factor X of 71 %. Genetic analysis of factor VII and factor X gene were performed. In both children identical gene mutations were found: Factor VII missense mutation F7:c.[589A>G];[=]p.(Lys197Glu) and Factor X missense mutation F10:c.[424G>A];[=]p.(Glu142Lys). Both children did not have any bleeding tendency. Additionally, both children showed heterozygous factor V Leiden mutation.

Conclusion: Conclusion: Combined factor VII and factor X deficiency is a rare coagulation disorder and often misdiagnosed. Single factor activities have to be analysed in all cases with prolonged PT even if aPTT is normal or patient is clinically asymptomatic.