Treatment of patients with hereditary angioedema with the c.988A&gt;G (p.Lys330Glu) variant in the plasminogen gene

Bork, Konrad; Wulff, K.; Witzke, Guenther; Machnig, Thomas; Hardt, Jochen

doi:10.1186/s13023-020-1334-8

Cited by 30 publications

(43 citation statements)

References 28 publications

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“…Current treatment strategies for HAEnCI rely on those already approved for HAE-C1-INH. Attempts have been made to customize treatment strategies in HAE-FXII and HAE-PLG based on the molecular pathways involved in the pathogenesis [ 36 , 52 ]. However, the exact pathogenic mechanism has yet to be elucidated, despite encouraging findings in HAE-FXII [ 57 – 59 ].…”

Section: Discussionmentioning

confidence: 99%

“…The mean duration (± SD) of icatibant treated attacks (4.3 ± 2.6 h) was significantly shorter than that of the previous 149 untreated attacks (44.7 ± 28.6 h; p < 0.0001) within the same patients. The mean duration (± SD) of attacks treated with C1-INH (31.5 ± 8.6 h) was significantly shorter than that of the previous 129 untreated attacks (48.2 ± 32.5 h; p < 0.0001) [52]. Furthermore, 2 HAE-PLG patients of French origin reported improvement in attacks upon icatibant treatment [55].…”

Section: Treatment Experiencementioning

confidence: 91%

“…Long-term prophylaxis, evaluated by attack frequency before and after treatment, appeared to be more effective in 3 patients treated with TXA (93.9% mean reduction of attack frequency) compared with 6 patients treated with progestins (46.3%), and compared with 3 patients treated with danazol (83.3%) [52].…”

Section: Treatment Experiencementioning

confidence: 91%

“…Thereby, 13 German families with the PLG mutation were identified [10]. Subsequently, more cases of HAE-PLG were identified in various European countries, the United States, and Japan [49][50][51][52][53][54][55][56]. Thus, a total of 146 patients from 33 families were reported (Table 3).…”

Section: Hereditary Angioedema With a Specific Mutation In The Plasmimentioning

confidence: 99%

“…Treatment experience with on-demand treatments was recently reported for a larger case series of 111 patients [52]. Of these, 13 patients were treated with icatibant for 201 acute swelling attacks and 12 patients were treated with plasma-derived C1-INH for 74 acute swelling attacks.…”

Section: Treatment Experiencementioning

confidence: 99%

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Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence

Bork

Machnig

Wulff

et al. 2020

Orphanet J Rare Dis

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Background Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway obstruction. Several different gene mutations linked to the HAE phenotype have been identified. Our aim was to qualitatively assess and describe the clinical differentiators of these genetically identified HAEnCI types. To achieve this, we performed a systematic literature review of patients with angioedema symptoms and a genetically confirmed diagnosis of an HAEnCI type. Results A systematic literature search, conducted in March 2020, returned 132 records, 43 of which describe patients with symptoms of angioedema and a genetically confirmed diagnosis of an HAEnCI type. Overall, this included 602 patient cases from 220 families. HAEnCI with a mutation in the coagulation factor XII gene (F12) (HAE-FXII) was diagnosed in 446 patients from 185 families (male:female ratio = 1:10). Estrogens (oral contraceptives, hormonal replacement therapy, and pregnancy) negatively impacted the course of disease in most female patients (252 of 277). Asphyxia occurred in 2 of 446 patients. On-demand and/or long-term prophylaxis treatment included C1-INH concentrates, icatibant, progestins, and tranexamic acid. HAEnCI with a specific mutation in the plasminogen gene (HAE-PLG) was diagnosed in 146 patients from 33 families (male:female ratio = 1:3). Estrogens had a negative influence on the course of disease in the minority of female patients (14 of 62). Tongue swelling was an important clinical feature. Asphyxia occurred in 3 of 146 patients. On-demand treatment with icatibant and C1-INH concentrate and long-term prophylaxis with progestins and tranexamic acid were effective. HAEnCI with a specific mutation in the angiopoietin-1 gene (HAE-ANGPT1) was diagnosed in 4 patients from 1 family and HAEnCI with a specific mutation in the kininogen-1 gene (HAE-KNG1) in 6 patients from 1 family. Conclusions A number of clinical differentiators for the different types of HAEnCI have been identified which may support clinicians to narrow down the correct diagnosis of HAEnCI prior to genetic testing and thereby guide appropriate treatment and management decisions. However, confirmation of the causative gene mutation by genetic testing will always be required.

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Section: Discussionmentioning

confidence: 99%

Section: Treatment Experiencementioning

confidence: 91%

Section: Treatment Experiencementioning

confidence: 91%

Section: Hereditary Angioedema With a Specific Mutation In The Plasmimentioning

confidence: 99%

Section: Treatment Experiencementioning

confidence: 99%

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Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence

Bork

Machnig

Wulff

et al. 2020

Orphanet J Rare Dis

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Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort

Grombirikova,

Bily,

Soucek

et al. 2023

J Clin Immunol

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Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype–phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

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Consensus on treatment goals in hereditary angioedema: A global Delphi initiative

Maurer

Aygören‐Pürsün

Banerji

et al. 2021

Journal of Allergy and Clinical Immunology

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Treatment of patients with hereditary angioedema with the c.988A>G (p.Lys330Glu) variant in the plasminogen gene

Cited by 30 publications

References 28 publications

Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence

Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence

Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort

Consensus on treatment goals in hereditary angioedema: A global Delphi initiative

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