Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology

Type 2N von Willebrand disease encompasses all patients with factor VIII de ficiency caused by a markedly decreased affinity of von Willebrand factor f or factor VIII. It is recessively inherited and clinically similar to mild haemophilia. The differential biological diagnosis is of major importance f or providing the optimal treatment and relevant genetic counselling. This a ccurate diagnosis is based on an evaluation of the factor V111-binding capa city of plasma von Willebrand factor. Furthermore, molecular biology techni ques allow the identification of missense mutations in the von Willebrand f actor gene. All of these induce the substitution of amino acid residues loc ated in the N terminal part of the mature von Willebrand factor molecule, w hich contains the factor VIII binding site. Most of them induce a classical type 2N von Willebrand disease phenotype with factor VIII deficiency but a normal level and multimeric pattern of von Willebrand factor.