Hereditary Angioedema (HAE) with a mutation in the plasminogen gene: a retrospective study of a cohort of 14 patients from Russia

2021 ◽  
Vol 18 (2) ◽  
pp. 5-19
Author(s):  
Irina A. Manto ◽  
Elena A. Latysheva ◽  
Elena A. Bliznetz ◽  
Daria O. Timoshenko ◽  
Liubov V. Aleshina ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Tranexamic Acid ◽  
Hereditary Angioedema ◽  
Scientific Literature ◽  
Comparison Group ◽  
Disease Onset ◽  
Type I ◽  
C1 Inhibitor Deficiency ◽  
Number Of Patients ◽  
New Research

BACKGROUND: In 2018, a new form of hereditary angioedema without C1-inhibitor deficiency hereditary angioedema with a mutation in the plasminogen gene was identified. The world scientific literature describes a small number of patients with this form of the disease and, therefore, new research is relevant. AIMS: To identify the sociodemographic and clinical features of patients with hereditary angioedema with plasminogen gene mutation; to evaluate the treatment efficacy; to conduct a comparative analysis in a group of patients with hereditary angioedema type I/II. MATERIAL AND METHODS: 14 patients (1 male and 13 females, mean age 51.6413.55 years) with hereditary angioedema with c.988AG mutation in the plasminogen gene (p.Lys330Glu; K330E) were enrolled in a retrospective study. The comparison group included 194 patients with hereditary angioedema type I/II (56 males and 138 females, mean age 37.0316.23 years). RESULTS: The average age at disease onset in patients with hereditary angioedema with a mutation in the plasminogen gene is 25.0710.46 years, which is significantly higher than in patients with hereditary angioedema type I/II 11.588.92 years (p 0.001). Peripheral angioedema was reported in 21.4% of patients with hereditary angioedema with a mutation in the plasminogen gene, abdominal attacks in 28.6%, which is less common than in patients with hereditary angioedema type I/II (peripheral edema 97.4%, p 0.001; abdominal attacks 86.6%, p 0.001). Face and neck angioedema was observed in all patients with hereditary angioedema with a mutation in the plasminogen gene (100%) and in 72.2% of patients in the group of hereditary angioedema type I/II (p=0.023). 85.7% of patients with hereditary angioedema with a mutation in the plasminogen gene had edema of the tongue. A decrease in the severity and duration of 28 out of 29 attacks by an average of 71.4% was reported by 4/5 of patients who used icatibant (Firazyr); 3/4 of patients reported a decrease in the frequency of attacks during treatment with tranexamic acid. CONCLUSIONS: The diseases manifestation in adulthood, the predominance of face and tongue angioedema are common features of hereditary angioedema with a mutation in the plasminogen gene. The efficacy of tranexamic acid and icatibant was demonstrated in the observed cohort of patients.

scholarly journals Molecular genetic diagnosis of hereditary angioedema

2021 ◽  
Vol 18 (1) ◽  
pp. 25-35
Author(s):  
I. E. Guryanova ◽  
Yu. S. Zharankova ◽  
E. A. Polyakova ◽  
V. V. Pugacheva ◽  
K. Ya. Skapavets ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Unknown Origin ◽  
Normal Activity ◽  
Type I ◽  
Factor Xii ◽  
C1 Inhibitor Deficiency ◽  
Serping1 Gene ◽  
Deficiency Type

Hereditary angioedema (HAE) is a rare genetic condition currently subdivided into two groups: HAE due to C1-inhibitor deficiency (Type I) or dysfunction (Type II) (C1-INH-HAE) and HAE with normal activity of C1‐INH (nC1- INH-HAE). C1-INH-HAE is estimated to occur in approximately 99 % of cases HAE and is caused by sequence variants in the SERPING1 gene. The prevalence of nC1-INH-HAE is extremely low and accounts for about 1 % of all cases of HAE. nC1-INH-HAE currently subdivided on HAE, due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 gene (KNG1-HAE), or angioedema of unknown origin (U-HAE).The amplicons of the entire coding regions and splice-sites of 18 genes from 24 patients (18 female) belonging to 17 families were analyzed by Next Generation Sequencing (NGS). The median age of patients was 33.5, of onset ‒ 16 years. 15 patients had a family history of edema.We identified seven C1-INH-HAE patients and variants were detected in the SERPING1 gene. For three patients (members of the same family), a heterozygous variant was found deep in the intron of the SERPING1 gene, which is likely to affect protein synthesis. We identified two patients with changes in the PLAUR gene, which may be associated with the manifestation of symptoms angioedema. Six patients showed abnormalities in the genes AGT and KNG1, which can probably explain their early hypertension, which could provoke the appearance of edema.

scholarly journals Hereditary Angioedema due to C1 Inhibitor Deficiency: C1-INH Replacement Therapy

2014 ◽  
Vol 5 (2) ◽  
pp. 55-66
Author(s):  
Mauro Cancian
Keyword(s):  
Replacement Therapy ◽  
Hereditary Angioedema ◽  
Rare Condition ◽  
Type I ◽  
Therapeutic Approaches ◽  
C1 Inhibitor Deficiency ◽  
Deep Tissue ◽  
Gene Encoding ◽  
The Face

Hereditary angioedema (HAE) is a rare condition affecting about 1 in 50.000 individuals and caused by a mutation in the gene encoding the C1-esterase inhibitor (C1-INH), which is involved in the control of complement, clotting, fibrinolytic and kinin pathways. HAE is characterized by plasma outflow from blood vessels, leading to fluid collecting (edema) in the deep tissue layers of the face, larynx, abdomen, and extremities. Three different types of HAE have been identified: in type I the mutation leads to the lack of production of C1-INH, in type II the mutation leads to the production of dysfunctional C1-INH, while type III is extremely rare and still not fully understood. Therapeutic approaches for HAE include on-demand treatments to stop angioedema attacks and prophylactic treatment to prevent attacks both by pre-procedural (short-term) and routine (long-term) prophylaxis. Aim of the present review is to present an overview of C1-INH replacement therapy with the plasma-derived concentrate of C1-INH Berinert® (CSL Behring GmbH) in the treatment of type I and II HAE.

scholarly journals Mutational spectrum of the SERPING1 gene in patients with hereditary angioedema

2019 ◽  
Vol 16 (3) ◽  
pp. 349-356
Author(s):  
I. E. Guryanova ◽  
K. A. Paliakova ◽  
M. V. Belevtsev ◽  
O. V. Aleynikova
Keyword(s):  
Hereditary Angioedema ◽  
De Novo ◽  
Type I ◽  
C1 Inhibitor ◽  
De Novo Mutations ◽  
Genetic Condition ◽  
C1 Inhibitor Deficiency ◽  
Serping1 Gene ◽  
Deficiency Type ◽  
Global Population

Hereditary angioedema due to the C1-inhibitor deficiency (Type I) or the dysfunction (Type II) is a rare genetic condition characterized by recurrent episodes of edema with an estimated frequency of 1:10 000 and 1:50 000 in the global population without racial or gender differences. HAE Type III is even less common, and unlike Types I and II, it does not appear to be connected with the levels of the C1-inhibitor. For 45 patients (64.44% female; 35.56% male) from 19 unrelated families C1-INH-HAE was confirmed. A series of 19 different mutations in the SERPING1 gene was identified: 17 splicing (37.7%), 15 missense (33.3%), 8 frameshift (17.8%), 3 large del (6.7%), 2 nonsense (4.5%) mutations were found. De novo mutations were detected in 8 patients (17.78%). For 6 patients, the HAE diagnosis was determined at the pre-symptom stage. 9 C1NH mutations had not been previously described. The number of different mutations identified highlights the heterogeneity of the C1 inhibitor deficiency.

scholarly journals A danazolkezelés hatása C1-inhibitor-hiány okozta hereditaer angiooedemás gyermekek növekedésére

2017 ◽  
Vol 158 (32) ◽  
pp. 1269-1276 ◽  
Author(s):  
Kinga Viktória Kőhalmi ◽  
Nóra Veszeli ◽  
Andrea Luczay ◽  
Lilian Varga ◽  
Henriette Farkas
Keyword(s):  
Retrospective Study ◽  
Growth Retardation ◽  
Hereditary Angioedema ◽  
Pediatric Patients ◽  
C1 Inhibitor ◽  
Target Height ◽  
C1 Inhibitor Deficiency ◽  
Significant Difference ◽  
Effective Doses

Abstract: Introduction: Attenuated androgens are used for the prevention of angioedema attacks of hereditary angioedema with C1-inhibitor deficiency. After prepuberty, their use can lead to growth retardation. Aim: We assessed the effect of danazol on the growth of pediatric patients with hereditary angioedema. Method: In the retrospective study on 42 patients diagnosed with hereditary angioedema, we calculated the deviation from the mid-parental target height, and analyzed it against the gender, the dose and duration of danazol treatment administered before the age of 21 years and before the age of 16 years. Results: Regarding the deviation from the mid-parental target height, we did not find any significant difference between patients taking vs. not taking danazol, males vs. females taking danazol. The dose and the duration of danazol treatment did not influence that value neither before 21, nor before 16 years of age. Conclusions: Our findings suggest that treatment with the lowest effective doses of danazol does not influence growth. Orv Hetil. 2017; 158(32): 1269–1276.

Breech Presentation: Vaginal Delivery or Caesarean Section?

2016 ◽  
Vol 2 (1) ◽  
pp. 153
Author(s):  
Tomescu Cezar Laurentiu ◽  
Rodica Sîrbu ◽  
Emin Cadar ◽  
Brezeanu Dragos ◽  
Aneta Tomescu
Keyword(s):  
Retrospective Study ◽  
Caesarean Section ◽  
Vaginal Delivery ◽  
Total Population ◽  
Population Sample ◽  
Breech Presentation ◽  
Current Paper ◽  
Clinical Hospital ◽  
Obstetrics And Gynaecology ◽  
Number Of Patients

The incidence of breech presentation is approximately 3,97%. Breech presentation is considered as being “borderline eutocic” and it requires carefully monitoring both the foetus and the mother. The aim of the current paper is to evaluate the preffered method of delivery in case of breech presentation. The paper presents a retrospective study performed in the Obstetrics and Gynaecology Departments of the County Emergency Clinical Hospital “Sf. Apostol Andrei” in Constanta, during a period of 5 years (2010-2014). The methods of birth were analyzed for a lot of 1104 patients with breech presentation with ages ranging between 16 and 44 years old. The total number of patients who gave birth through vaginal delivery was of 139 patients, amounting to 12.59% of the total population sample. The number of patients that gave birth through C-section was 965, which amounts to 87.4% of the total population sample. Birth through C-section is preferred by both obstetricians and patients alike, due to the fact that vaginal delivery is associated with a higher foetal risk in breech presentation.

scholarly journals The Global Registry for Hereditary Angioedema due to C1-Inhibitor Deficiency

2021 ◽  
Author(s):  
Andrea Zanichelli ◽  
Henriette Farkas ◽  
Laurance Bouillet ◽  
Noemi Bara ◽  
Anastasios E. Germenis ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Rare Condition ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Therapeutic Decisions ◽  
Life Threatening ◽  
Enhance Patient Care ◽  
Electronic Support ◽  
The Impact ◽  
Global Registry

AbstractHereditary angioedema (HAE) is a rare condition, mostly due to genetic deficiency of complement C1 inhibitor (C1-INH). The rarity of HAE impedes extensive data collection and assessment of the impact of certain factors known to affect the course of this disabling and life-threatening disease. Establishing a global registry could assist to overcome such issues and provides valuable patient data from different countries. The HAE Global Registry is a disease-specific registry, with web-based electronic support, where data are provided by physicians and patients through a dedicated application. We collected data between January 1, 2018, and August 31, 2020. Data on 1297 patients from 29 centers in 5 European countries were collected. At least one attack was recorded for 497 patients during the study period. Overall, 1182 patients were diagnosed with HAE type 1 and 115 with type 2. At the time of database lock, 389 patients were taking long-term prophylactic medication, 217 of which were on danazol. Most recorded attacks affected the abdomen, were generally moderate in severity, and occurred in patients who were not on prophylactic treatment (70.6%, 6244/8848). The median duration of attacks was 780 min (IQR 290–1740) in patients on prophylactic medication and 780 min (IQR 300–1920) in patients not on continuous prophylactic medication. In conclusion, the establishment of a registry for C1-INH-HAE allowed collection of a large amount of data that may help to better understand the clinical characteristics of this disease. This information may enhance patient care and guide future therapeutic decisions.

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