The reference OMIM entry for this protein is 228960

High molecular weight kininogen deficiency
Hmwk deficiency
Kininogen deficiency, high molecular weight
Fitzgerald trait kininogen deficiency, total, included
Kininogen deficiency, high molecular weight and low molecular weight, included
Fla

A number sign (#) is used with this entry because high molecular weight kininogen deficiency and total kininogen deficiency result from mutations in the kininogen-1 gene (KNG1; 612358).

DESCRIPTION

High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by a variety of names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Fitzgerald trait represents a 'true' deficiency of HMWK, whereas Flaujeac and Williams traits represent total kininogen deficiency, in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002; Takagaki et al., 1985).

CLINICAL FEATURES

Lacombe et al. (1975) described deficiency of a procoagulant they called Flaujeac factor, which, like Hageman (F12; 610619) and Fletcher (KLKB1; 229000) factors, participated in the 'contact phase' of coagulation. The deficiency was observed in an asymptomatic French woman born of a consanguineous marriage. Wuepper et al. (1975) showed that 4 children of the proposita had total kininogen antigen about half normal, consistent with autosomal recessive inheritance. Waldmann et al. (1975) and Saito et al. (1975) described a 'new' asymptomatic coagulation factor deficiency in a 71-year-old black man of surname Fitzgerald. The factor seemed to operate at an early stage in the intrinsic coagulation pathway and participated in other Hageman factor-mediated biologic reactions. No family data were presented. His plasma was apparently deficient in a hitherto unrecognized factor needed for expression of the functions of activated Hageman factor. Colman et al. (1975) studied an asymptomatic 64-year-old black woman of the surname Williams, who had severe abnormality of surface-activated intrinsic coagulation, and fibrinolytic and kinin-generating pathways. Fractionation of normal plasma showed that the factor that corrected the defect in Ms. Williams' plasma was kininogen. The proband was ascertained when a prolonged partial thromboplastin time was detected as part of a routine preoperative evaluation of her hemostatic mechanism. Members of her family were not available for study. However, Cheung et al. (1993) had 3 daughters and 1 granddaughter available for study when they reinvestigated the proband. Lefrere et al. (1986) discovered HMWK deficiency in the course of a preoperative hemostasis study of a 23-year-old Portuguese woman without personal or family history of hemorrhage or thrombosis. Family study showed heterozygous HMWK deficiency in the proposita, her father, and 3 of her sibs. Hayashi et al. (1990) studied 4 Japanese families with total kininogen deficiency and 1 with deficiency of HMWK only. Krijanovski et al. (2003) reported a 6-year-old male, born of first-cousin parents, with cerebral artery thrombosis and HMWK deficiency. The previously healthy child had headache and vomiting 10 days after moderate cerebral trauma, followed by loss of consciousness and subsequent visual impairment. CT scan and angiography showed extensive left vertebral-basilar artery thrombosis and a left vertebral artery dissection. The patient had a prolonged activated partial thromboplastin time (APTT) and received fresh frozen plasma before arteriography and then daily for 8 days, which resulted in normal ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 228960 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).