The Mortality from Hereditary Angioedema Worldwide: a Review of the Real-World Data Literature

Minafra, Fernanda Gontijo; Gonçalves, Tifany Rafaely; Alves, Thaís Martins; Pinto, Jorge

doi:10.1007/s12016-021-08897-8

Cited by 19 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6 More recently, worldwide mortality amongst HAE patients due to laryngeal edema was still estimated to be as high as 5%. 7 Various events and circumstances can trigger attacks of angioedema. Trauma caused by invasive procedures is well known to induce attacks and therefore pre-procedural prophylactic medication is recommended.…”

Section: Clinical Featuresmentioning

confidence: 99%

See 1 more Smart Citation

Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation

Petersen

Fijen

Levi

et al. 2022

Semin Thromb Hemost

View full text Add to dashboard Cite

Hereditary angioedema is a rare, genetic disorder characterized by painful, debilitating and potentially life-threatening angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by prodromal symptoms. Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of hereditary angioedema in almost all patients is a mutation in the SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and kallikrein-kinin pathway are insufficiently inhibited, resulting in excessive bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders. Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific therapies have greatly improved disease control and angioedema-related quality of life. This article reviews the clinical picture of hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options.

show abstract

Section: Clinical Featuresmentioning

confidence: 99%

“…6 More recently, worldwide mortality amongst HAE patients due to laryngeal edema was still estimated to be as high as 5%. 7…”

Section: Clinical Featuresmentioning

confidence: 99%

Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation

Petersen

Fijen

Levi

et al. 2022

Semin Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Для больных наследственным ангиоотеком (НАО) характерно отсутствие реакции на антигистаминные препараты, кортикостероиды или адреналин, при этом серьезность заболевания обусловлена изменчивой клинической картиной, сопровождающейся непредсказуемыми спорадическими отеками, наибольшую опасность из которых представляют способные привести к асфиксии, а значит к необратимым повреждениям мозга, слепоте, параличу конечностей и смерти, отеки гортани [7,8,23,26]. Частота летального исхода от отека гортани встречается в 1 случае на 20 пациентов [22]. Наследственная форма ангиоотека (НАО) в большинстве случаев связана со снижением уровней С1 (ингибитор С1-эстеразы), С4 (С4-компонент комплемента), C1q (C1qкомпонент системы комплемента), выявлением и повышением уровней антител к C1 [20].…”

Section: Introductionunclassified

Applying bioinformatic analysis for prognostic assessment of the <i>HS3ST6</i> missense mutations clinical significance in the development of hereditary angioedema

et al. 2022

View full text Add to dashboard Cite

Hereditary angioedema (HAE) is a genetically determined disease characterized by recurrent attacks of edema affecting the subcutaneous and/or submucosal layers of tissue, face, lips, neck, extremities of the body, oral cavity, intestine and/or larynx. In the latter case, the disease becomes life-threatening. The majority of HAE cases are associated with decreased levels of C1 (C1-esterase inhibitor), there are also descriptions of HAE with dysfunctional C1 inhibitor and HAE with normal C1 inhibitor. In the first and second variants, mutations in the C1NH gene are the cause of the disease. HAE with normal quantitative and functional levels of C1-inhibitor has the same clinical manifestations but with mutations in other genes, including F12, PLG, ANGPT1, KNG1, MYOF, and HS3ST6. Currently, mutations in the HS3ST6 gene remain poorly understood; only one missense mutation (p.Thr144Ser, rs746467957) associated with the development of HAE has been described.The aim of our work was to study new mutations in the HS3ST6 gene and analyze in silico their prognostic nature and clinical significance for the development of hereditary angioedema.The material was whole blood samples obtained from 13 patients with symptoms of hereditary angioedema without reduced levels and function of C1-INH.Whole exome sequencing of patients, bioinformatic analysis of HS3ST6 gene mutations using a number of databases and Web resources to predict the effect of mutations on the protein and assess the conservatism of the positions of the mutations detected was involved in study methods.Mutations in the HS3ST6 gene were identified in four patients, including two cases with two mutations simultaneously. Application of bioinformatic analysis allowed us to obtain new data on four missense mutations in the studied gene. Potential pathogenetic significance was determined for three of them. The mutation NC_000016.9:g.1962132G>A (p.A163V) is most likely to be involved in pathogenesis of HAE by indirect disruption of heparan sulfate O-sulfation directly within the protein. The NC_000016.9:g.1962024G>A mutation (p.P199L) appears to lead to the development of the disease through disruption of docking with SDC2 heparan sulfate. In the NC_000016.9:g.1962046C>T (p.A192T) mutation, destabilization of the 192 amino acid position next to PAPS, may contribute to disruption of heparan sulfate O-sulfation through disruption of protein functional activity and, therefore, catalysis transfer of sulfo group to heparan sulfate syndecan-2. Thus, in all three cases, the formation of HAE appears to be possible due to disruption of the O-sulfation steps of heparan sulfate syndecan-2.Considering that in silico methods offer new opportunities to assess the pathogenetic significance of mutations, the application of bioinformatic analysis can contribute to a detailed investigation of the causes of hereditary angioedema. The present work convincingly demonstrates that rare mutations in the HS3ST6 gene may be involved in the pathogenesis of HAE and provoke edema due to increased bradykinin release.

show abstract

“…Laryngeal HAE attacks are a medical emergency and asphyxiation can occur, causing death in approximately 1 in 20 cases. 1 A majority of cases of HAE are caused by mutations in the SERPING1 gene that encodes the C1 esterase inhibitor (C1-INH) protein. The mutations result in an absence of C1-INH protein or abnormal functioning.…”

Section: Introductionmentioning

confidence: 99%

Establishing New Standards in Hereditary Angioedema: Improving Outcomes Through Routine Prophylaxis

Kiani¹

2022

EMJ Allergy Immunol

View full text Add to dashboard Cite

Hereditary angioedema (HAE) is a rare but debilitating and potentially fatal disease that presents in various forms, and can be difficult to manage. Its underlying cause is mutations in a gene that, through its protein product, controls production of the tissue enzyme kallikrein and a peptide mediator, bradykinin. The resulting overproduction of bradykinin leads to increased vascular permeability and oedema. Patients experience episodes of swelling that are unpredictable in their timing, location, and severity, and significantly affect quality of life (QoL), both physically and psychologically.EMJ spoke to Sorena Kiani, Consultant Immunologist at the Barts Health NHS Trust (Barts), London, UK, who manages the UK's largest HAE patient cohort, ahead of a symposium held at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2022 in Prague, Czechia. He explained how new specific medications to control and prevent HAE attacks, developed in the last decade, are giving clinicians and patients the opportunity to review treatment goals and raise expectations. Three prophylactic medications are now licenced for use and recommended in international treatment guidelines, which effectively prevent future HAE attacks.Kiani describes clinical and real-world data from UK clinics that demonstrate how berotralstat, the first orally-administered HAE prophylaxis to be licenced, can reduce the number, duration, and severity of HAE attacks, resulting in measurable improvements in patients' QoL. He also discusses the importance of shared decision-making in developing individualised treatment plans that take into account patient goals and expectations. Kiani is confident that with wider access to prophylaxis, and appropriate monitoring and support, many more HAE patients can expect to live attack-free, with a normalised QoL.

show abstract

The Mortality from Hereditary Angioedema Worldwide: a Review of the Real-World Data Literature

Cited by 19 publications

References 31 publications

Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation

Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation

Applying bioinformatic analysis for prognostic assessment of the <i>HS3ST6</i> missense mutations clinical significance in the development of hereditary angioedema

Establishing New Standards in Hereditary Angioedema: Improving Outcomes Through Routine Prophylaxis

Contact Info

Product

Resources

About