scholarly journals Hereditary angioedema due to C1 inhibitor deficiency in Belarus: epidemiology, access to diagnosis and seven novel mutations in SERPING1 gene

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Irina Guryanova ◽  
Chiara Suffritti ◽  
Debora Parolin ◽  
Andrea Zanichelli ◽  
Nastassia Ishchanka ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
De Novo ◽  
Diagnostic Delay ◽  
Large Deletion ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Serping1 Gene ◽  
New Diagnosis ◽  
Former Ussr ◽  
Adequate Management

Abstract Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Methods Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. Results We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. Conclusions C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.

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 Mutational spectrum and genotype-phenotype relationships in a cohort of Romanian hereditary angioedema patients caused by C1 inhibitor deficiency

2019 ◽  
Vol 27 (3) ◽  
pp. 255-267
Author(s):  
Gabriella Gábos ◽  
Dumitru Moldovan ◽  
Daniela Dobru ◽  
Enikő Mihály ◽  
Noémi Bara ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Diagnostic Delay ◽  
Clinical Manifestations ◽  
Clinical Severity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regulatory Sequence ◽  
Missense Mutations ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Genetic Characteristics

Abstract Background: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) caused by SERPING1 mutations is a rare monogenic disorder characterized by a high frequency of de novo mutations, allelic heterogeneity and populational differences. Geno- and phenotype correlation data are limited. Addressing the pathogenic complexity, we proposed to analyze the clinical and genetic characteristics in a set of Romanian patients. Material and Methods: 49 patients from 22 unrelated families with C1-INH-HAE were investigated, by calculating clinical severity score (CSS), C1-INH and C4 level assessment by nephelometric assays, C1-INH function study by functional enzyme-linked immunosorbent assay, and mutation analysis by sequencing and MLPA. Clinical manifestations by missense vs other mutation mechanisms were compared. Results: The mean age at diagnosis and onset was 28.8±14.7 and 15.1±15.2 years, while the diagnostic delay 13.1±10.1 years. CSS ranged from 2 to 9, with a mean of 5.4±1.8. The frequency of missense and nonsense mutations, splice defects, frameshift mutations and large gene rearrangements was 61.22, 6.12, 22.4, 6.12 and 4.08%; in the regulatory sequence no mutation was described. In type II, only missense mutations were noted. Lower levels of C1-INH characterized index cases caused by mechanisms other than missense mutation, with more severe consequences on protein synthesis (p=0.017). 53% of the cases were identified by familial screening. Conclusion: A later onset of disease manifestations and a higher frequency of missense mutations characterize HAE in Romanian patients with SERPING1 mutation. Genetic analysis improves the management of affected families, and may inform about disease severity.

A case of hereditary angioedema with late adulthood onset

2020 ◽  
Vol 17 (3) ◽  
pp. 93-96
Author(s):  
Julia P. Pokalyukhina ◽  
Natalia N. Abramova
Keyword(s):  
Family History ◽  
Hereditary Angioedema ◽  
De Novo ◽  
Clinical Manifestations ◽  
C1 Inhibitor ◽  
De Novo Mutations ◽  
Elderly Age ◽  
C1 Inhibitor Deficiency ◽  
Diagnostic Difficulties ◽  
Diagnosis Criteria

Over the last years, high attention is given to the hereditary angioedema (HAO). Practitioners can identify the disease by clinical manifestations and family history even before specific laboratory testing. More than 95% of HAO cases are associated with C-1inhibitor deficiency/dysfunction caused by a mutation inSERPING1gene. In 25% of patients without C1-inhibitor deficiency HAO is associated with heterozygous mutations in geneF12coding Hageman XII factor. In 20172018 years two more genes responsible for normal C1-inhibitor HAO were discovered: genesPLGandANGPT1. In clinical practice patients do not always meet typical HAO diagnosis criteria. Diagnostic difficulties appear when clinical picture is not confirmed by related genetic testing results, for example, mutations in genes not described earlier are detected. It should be noted that app. 25% of patients do not have any HAO family history, i.e. have so called de novo mutations. Normally HAO onset takes place within 2 first life decades. 40% of patients have disease progress before the age of 5, and 75% of patients before the age of 15 y.o. However, it can appear in elderly age, which means certain diagnostic difficulties. It is important to analyze thoroughly patients comorbidity and make differential diagnosis with a secondary angioedema.

scholarly journals Genetic variants of SERPING1 gene in Polish patients with hereditary angioedema due to C1 inhibitor deficiency

2020 ◽  
Vol 45 (3) ◽  
pp. 301-309
Author(s):  
Krystyna Obtułowicz ◽  
Teofila Książek ◽  
Anna Bogdali ◽  
Wojciech Dyga ◽  
Ewa Czarnobilska ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Genetic Variants ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Serping1 Gene

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.

scholarly journals Pathways of Neutrophil Granulocyte Activation in Hereditary Angioedema with C1 Inhibitor Deficiency

2021 ◽  
Author(s):  
Erika Kajdácsi ◽  
Nóra Veszeli ◽  
Blanka Mező ◽  
Zsófia Jandrasics ◽  
Kinga Viktória Kőhalmi ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Blood Cells ◽  
White Blood Cells ◽  
Neutrophil Granulocytes ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Prodromal Phase ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

AbstractHereditary angioedema (HAE) with C1-inhibitor deficiency belongs to bradykinin-mediated angioedemas. It is characterized by recurrent subcutaneous and/or submucosal swelling episodes (HAE attacks) and erythema marginatum skin rash as a pre-attack (prodromal) phase. HAE attacks were shown to be accompanied by peripheral blood neutrophilia. We aimed to find molecular mechanisms that may explain the distinct role of neutrophil granulocytes in HAE. Plasma levels of blood cells and factors related to neutrophil activation (cytokines, chemokines, chemotactic factors, enzymes, and neutrophil extracellular trap) were measured in plasma samples obtained from patients during symptom-free periods (n = 77), during prodromal phase (n = 8) and attacks (n = 14), during a spontaneously resolved attack (n = 1), and in healthy controls (n = 79). Higher counts of white blood cells, lymphocytes, and neutrophil granulocytes were found in symptom-free patients compared with controls; these cell counts were elevated further during HAE attacks. The level of chemokine (C–C motif) ligand 5, monocyte chemoattractant protein-1, and myeloperoxidase were also higher in the symptom-free patients than in the controls. Levels of monocyte chemoattractant protein-1, leukotriene B4, neutrophil elastase, and myeloperoxidase were elevated during attacks. During erythema marginatum, white blood cells and monocyte count and levels of interleukin 8 were elevated compared with symptom-free period. Similar changes were detected during the attack follow-up. We conclude that the activation of NGs in symptom-free periods and a further increase observed during attacks suggests that NGs may be involved in the pathomechanism of HAE with C1-INH deficiency.

scholarly journals A case of hereditary angioedema due to C1-inhibitor deficiency with recurrent abdominal pain diagnosed 40 years after the occurrence of the initial symptom

2021 ◽  
Author(s):  
Daisuke Honda ◽  
Isao Ohsawa ◽  
Keiichi Iwanami ◽  
Hisaki Rinno ◽  
Yasuhiko Tomino ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Hereditary Angioedema ◽  
Recurrent Abdominal Pain ◽  
Acute Attack ◽  
Severe Abdominal Pain ◽  
Initial Symptom ◽  
C1 Inhibitor ◽  
Self Administration ◽  
C1 Inhibitor Deficiency ◽  
Appropriate Treatment

AbstractHereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare disease, which induces an acute attack of angioedema mediated by bradykinin. HAE-C1-INH can cause serious abdominal pain when severe edema develops in the gastrointestinal tract. However, because it takes a long time, 13.8 years on average in Japan, from the occurrence of the initial symptom to the diagnosis due to low awareness of the disease, undiagnosed HAE-C1-INH patients sometimes undergo unnecessary surgical procedures for severe abdominal pain. We herein present a 56-year-old patient with HAE-C1-INH, who underwent numerous abdominal operations. He frequently needed hospitalization with the administration of opioid due to severe abdominal pain. However, after he was accurately diagnosed with HAE-C1-INH at 55 years of age, he could start self-administration for an acute attack with icatibant, a selective bradykinin B2 receptor antagonist. Consequently, he did not need hospitalizing for ten months after the beginning of the treatment. A series of an accurate diagnosis and appropriate treatment for HAE-C1-INH improved his quality of life. Thus, HAE-C1-INH should be considered, when we meet patients with unidentified recurrent abdominal pain. This case highlights significance of an early diagnosis and appropriate treatment for HAE-C1-INH.

Sign in / Sign up

Export Citation Format

Share Document