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Thromb Haemost 2000; 84(06): 937-941
DOI: 10.1055/s-0037-1614152
Rapid Communication
Schattauer GmbH

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

J. Oldenburg
1   From the Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany
2   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
B. von Brederlow
1   From the Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany
2   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
A. Fregin
1   From the Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany
,
S. Rost
1   From the Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany
,
W. Wolz
1   From the Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany
,
W. Eberl
3   Städtisches Klinikum Braunschweig, Klinik für Kinderund Jugendmedizin, Braunschweig, Germany
,
S. Eber
4   Universitäts-Kinderklinik, Göttingen, Germany
,
E. Lenz
4   Universitäts-Kinderklinik, Göttingen, Germany
,
R. Schwaab
2   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
H. H. Brackmann
2   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
W. Effenberger
2   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
U. Harbrecht
2   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
L. J. Schurgers
5   Department of Biochemistry, University of Maastricht, MD Maastricht, The Netherlands
,
C. Vermeer
5   Department of Biochemistry, University of Maastricht, MD Maastricht, The Netherlands
,
C. R. Müller
1   From the Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany
› Author AffiliationsThis study was supported by grants of the Stiftung Hämotherapie-Forschung, the Gesellschaft für Thrombose und Hämostaseforschung and the DFG (Ol 100/3-1) to J.O. and C.R.M.
Further Information

Publication History

Received 23 March 2000

Accepted after resubmission 03 August 2000

Publication Date:
13 December 2017 (online)

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Summary

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 γ-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 γ-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.

Keywords

Hereditary bleeding disorder - γ-carboxylation - vitamin K epoxidase-reductase
 

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