Premium
Familial deficiency of vitamin K‐dependent clotting factors
Author(s) -
WESTON B. W.,
MONAHAN P. E.
Publication year - 2008
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2008.01853.x
Subject(s) - vitamin k epoxide reductase , clotting factor , medicine , vitamin , point mutation , warfarin , hereditary hemochromatosis , factor ix , gene mutation , carboxylation , malabsorption , endocrinology , gene , mutation , genetics , biochemistry , biology , hemochromatosis , metabolism , cytochrome p450 , cyp2c9 , catalysis , atrial fibrillation
Summary. Combined deficiency of vitamin K‐dependent clotting factors II, VII, IX and X (and proteins C, S, and Z) is usually an acquired clinical problem, often resulting from liver disease, malabsorption, or warfarin overdose. A rare inherited form of defective γ‐carboxylation resulting in early onset of bleeding was first described by McMillan and Roberts in 1966 and subsequently has been termed ‘vitamin K‐dependent clotting factor deficiency’ (VKCFD). Biochemical and molecular studies identify two variants of this autosomal recessive disorder: VKCFD1, which is associated with point mutations in the γ‐glutamylcarboxylase gene ( GGCX ), and VKCFD2, which results from point mutations in the vitamin K epoxide reductase gene ( VKOR ). Bleeding ranges in severity from mild to severe. Therapy includes high oral doses of vitamin K for prophylaxis, usually resulting in partial correction of factor deficiency, and episodic use of plasma infusions or prothrombin complex concentrate. Recent molecular studies have the potential to further our understanding of vitamin K metabolism, γ‐carboxylation, and the functional role this post‐translational modification has for other proteins. The results may also provide potential targets for molecular therapeutics and pharmacogenetics.