Congenital Deficiency of Vitamin K Dependent Coagulation Factors in Two Families: Evidence for a Defective Vitamin K-Epoxide-Reductase Complex

Hereditary combined deficiency of the vitamin K-dependent coagulation factors II, VII, IX, X, Protein C and Protein S is a rare bleeding disorder that has been reported in only few families [1–11]. The phenotypic presentation of the disorder shows great variety. Levels of vitamin K-dependent proteins ranged from less than 1% to 50%. In some of the families the phenotype could be completely corrected by oral application of vitamin K [11, 12], whereas in other families even a high intravenous vitamin K dosage showed no effect [5, 7]. Notably, three families exhibited skeletal abnormalities [1, 9, 11], suggesting the involvement of vitamin K-dependent bone related proteins, such as osteocalcin and matrix Gla protein [13].