Hereditary Angioneurotic Edema: Two Genetic Variants

Rosen, Fred S.; Charache, Patricia; Pensky, Jack; Donaldson, Virginia H.

doi:10.1126/science.148.3672.957

Cited by 415 publications

(171 citation statements)

References 4 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…The critical nature of C1 inhibitor in plasma proteinase regulation is highlighted by the disorder hereditary angioedema, which is inherited in an autosomal dominant manner [9,10]. Two forms of the disease occur, type I, in which the plasma level of both functional and antigenic C1 inhibitor is low (5-30o70 of normal), and type II, where the antigenic level is normal but the functional level is greatly reduced [11]. This latter form is consequent on the synthesis and secretion of a dysfunctional C1 inhibitor protein that is catabolized more slowly than the active protein [12,13].…”

Section: Introductionmentioning

confidence: 99%

Identification of a new P1 residue mutation (444Arg→Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma

1990

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of a new P1 residue mutation (444Arg→Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma

1990

View full text Add to dashboard Cite

show abstract

“…These result in either low levels of C1 inhibitor (C1INH) (type I HAE) or normal levels with reduced C1 inhibitor function (type II HAE) [1]. A third type of HAE is now recognized (type III HAE), or HAE with normal C1INH due in some cases to mutations in Factor XII (FXII) [2,3].…”

Section: Introductionmentioning

confidence: 99%

A UK national audit of hereditary and acquired angioedema

Jolles

Williams

Carne

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryHereditary angioedema (HAE) and acquired angioedema (AAE) are rare lifethreatening conditions caused by deficiency of C1 inhibitor (C1INH). Both are characterized by recurrent unpredictable episodes of mucosal swelling involving three main areas: the skin, gastrointestinal tract and larynx. Swelling in the gastrointestinal tract results in abdominal pain and vomiting, while swelling in the larynx may be fatal. There are limited UK data on these patients to help improve practice and understand more clearly the burden of disease. An audit tool was designed, informed by the published UK consensus document and clinical practice, and sent to clinicians involved in the care of HAE patients through a number of national organizations. Data sets on 376 patients were received from 14 centres in England, Scotland and Wales. There were 55 deaths from HAE in 33 families, emphasizing the potentially lethal nature of this disease. These data also show that there is a significant diagnostic delay of on average 10 years for type I HAE, 18 years for type II HAE and 5 years for AAE. For HAE the average annual frequency of swellings per patient affecting the periphery was eight, abdomen 5 and airway 0·5, with wide individual variation. The impact on quality of life was rated as moderate or severe by 37% of adult patients. The audit has helped to define the burden of disease in the UK and has aided planning new treatments for UK patients.

show abstract

“…Patients with type I HAE were later shown to have low levels of this protein because its synthesis or secretion was prevented by mutations in one of the gene alleles; in general, patients with type II HAE have a defect in a gene allele that results in secretion of a nonfunctioning protein[13]. Infusion of the missing functional protein C1 inhibitor was an obvious approach to specific therapy.…”

Section: Development Of C1 Inhibitor Therapymentioning

confidence: 99%

Recombinant and Plasma-Purified Human C1 Inhibitor for the Treatment of Hereditary Angioedema

Frank¹

2010

World Allergy Organization Journal

View full text Add to dashboard Cite

BackgroundAgents for prophylaxis of hereditary angioedema (HAE) have been available in the United States for several decades, but their usefulness is limited by side effects and they cannot be used at all in some patients. No agents have been available in the United States to specifically treat acute attacks. HAE types I and II are associated with low functional levels of C1 inhibitor, and evidence accumulated over decades suggests that intravenous infusion of C1 inhibitor is useful for terminating angioedema attacks and for prophylaxis.Key PointsC1 inhibitor derived from pooled human plasma has been available for decades in Europe, and 2 preparations have been recently introduced into the United States. Both have been efficacious in carefully controlled double-blind studies. One preparation, Cinryze, was approved by the U.S. Food & Drug Administration (FDA) for prophylaxis of HAE attacks in October 2008, and the second, Berinert, was approved by the FDA for treatment of acute attacks in October 2009. A third preparation, the recombinant human C1 inhibitor Rhucin, is completing clinical trials. Although not yet approved by the FDA, preliminary results made available suggest that Rhucin, too, is effective in terminating attacks of HAE.ConclusionsAmericans will now have access to effective acute and prophylactic treatments with C1 inhibitor for hereditary angioedema.

show abstract

Hereditary Angioneurotic Edema: Two Genetic Variants

Cited by 415 publications

References 4 publications

Identification of a new P1 residue mutation (444Arg→Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma

Identification of a new P1 residue mutation (444Arg→Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma

A UK national audit of hereditary and acquired angioedema

Recombinant and Plasma-Purified Human C1 Inhibitor for the Treatment of Hereditary Angioedema

Contact Info

Product

Resources

About