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Congenital Deficiency of Vitamin K Dependent Coagulation Factors in Two Families Presents as a Genetic Defect of the Vitamin K-Epoxide-Reductase-Complex

2000; Thieme Medical Publishers (Germany); Volume: 84; Issue: 12 Linguagem: Inglês

10.1055/s-0037-1614152

2567-689X

Johannes Oldenburg, Benigna von Brederlow, Andreas Fregin, Simone Rost, Werner Wolz, W. Eberl, Sammy L. Eber, Elizabeth K. Lenz, R Schwaab, Hans‐Hermann Brackmann, W. Effenberger, Ursula Harbrecht, Leon J. Schurgers, Cees Vermeer, C. R. Müller,

Blood Coagulation and Thrombosis Mechanisms

Hereditary combined deficiency of the vitamin K dependent coagulation factors is a rare bleeding disorder. To date, only eleven families have been reported in the literature. The phenotype varies considerably with respect to bleeding tendency, response to vitamin K substitution and the presence of skeletal abnormalities, suggesting genetic heterogeneity. In only two of the reported families the cause of the disease has been elucidated as either a defect in the gamma-carboxylase enzyme (1) or in a protein of the vitamin K 2,3-epoxide reductase (VKOR) complex (2). Here we present a detailed phenotypic description of two new families with an autosomal recessive deficiency of all vitamin K dependent coagulation factors. In both families offspring had experienced severe or even fatal perinatal intracerebral haemorrhage. The affected children exhibit a mild deficiency of the vitamin K dependent coagulation factors that could be completely corrected by oral substitution of vitamin K. Sequencing and haplotype analysis excluded a defect within the gamma-carboxylase gene. The finding of highly increased amounts of vitamin K epoxide in all affected members of both families indicated a defect in a protein of the VKOR-multienzyme-complex. Further genetic analysis of such families will provide the basis for a more detailed understanding of the structure-function relation of the enzymes involved in vitamin K metabolism.