Definition and classification of hereditary angioedema

2020 ◽  
Vol 41 (6) ◽  
pp. S03-S07 ◽  
Author(s):  
Steven P. Proper ◽  
William J. Lavery ◽  
Jonathan A. Bernstein
Keyword(s):  
Hereditary Angioedema ◽  
De Novo ◽  
Clinical History ◽  
Factor Xii ◽  
Life Threatening ◽  
History Of ◽  
Underlying Causes ◽  
Serping1 Gene ◽  
And Function

Hereditary angioedema (HAE) is defined as a rare genetic disease with recurrent episodes of localized bradykinin-mediated swelling of the deep tissues of the skin, respiratory, and gastrointestinal tracts that can be life threatening. Classification of HAE has evolved over time with our further understanding of clinical phenotypes, underlying causes, and available testing. In most cases, HAE is caused by a deficiency of C1-esterase inhibitor (C1-INH) on the Serpin Family G Member 1 (SERPING1) gene, either through decreased amounts of C1-INH protein (C1-INH‐HAE, type 1) or decreased function of C1-INH (C1-INH‐HAE, type 2). HAE with normal C1-INH levels and function are divided into unknown cause or into non‐C1-INH‐HAE forms, which include known mutational defects in factor XII (called FXII-HAE in the Hereditary Angioedema International Working Group consensus), angiopoietin-1, plasminogen, and kininogen 1 genes. It is possible that, after an initial workup, a patient without a family history of HAE could be classified with an acquired form of angioedema (nonhereditary) that may later prove to be HAE due to a de-novo SERPING1 mutation. Because there are forms of nonhistaminergic (H1-antihistamine unresponsive) angioedema that appear clinically very similar to HAE, it is essential that the patient undergoes a thorough clinical history and diagnostic evaluation to ensure that he or she is properly diagnosed and classified.

scholarly journals Screening for Plasminogen Mutations in Hereditary Angioedema Patients

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 402
Author(s):  
Henriette Farkas ◽  
Anna Dóczy ◽  
Edina Szabó ◽  
Lilian Varga ◽  
Dorottya Csuka
Keyword(s):  
Gene Mutation ◽  
Hereditary Angioedema ◽  
Unknown Origin ◽  
Factor Xii ◽  
Gene Encoding ◽  
New Techniques ◽  
Ex Post ◽  
Appropriate Therapy ◽  
Exon 9 ◽  
Serping1 Gene

Hereditary angioedema (HAE) is a rare disease belonging to the group of bradykinin-mediated angioedemas, characterized by recurring edematous episodes involving the subcutaneous and/or submucosal tissues. Most cases of HAE are caused by mutations in the SERPING1 gene encoding C1-inhibitor (C1-INH-HAE); however, mutation analysis identified seven further types of HAE: HAE with Factor XII mutation (FXII-HAE), with plasminogen gene mutation (PLG-HAE), with angiopoietin-1 gene mutation (ANGPT1-HAE), with kininogen-1 gene mutation (KNG1-HAE), with a myoferlin gene mutation (MYOF-HAE), with a heparan sulfate-glucosamine 3-sulfotransferase 6 (HS3ST6) mutation, and hereditary angioedema of unknown origin (U-HAE). We sequenced DNA samples stored from 124 U-HAE patients in the biorepository for exon 9 of the PLG gene. One of the 124 subjects carried the mutation causing a lysine to glutamic acid amino acid exchange at position 330 (K330E). Later, the same PLG mutation was identified in the patient’s son. The introduction of new techniques into genetic testing has increased the number of genes identified. As shown by this study, a biorepository creates the means for the ex-post analysis of recently identified genes in stored DNA samples of the patients. This makes the diagnosis more accurate with the possibility of subsequent family screening and the introduction of appropriate therapy.

scholarly journals Anaphylactic Death: A New Forensic Workflow for Diagnosis

Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 117
Author(s):  
Massimiliano Esposito ◽  
Angelo Montana ◽  
Aldo Liberto ◽  
Veronica Filetti ◽  
Nunzio Di Nunno ◽  
...  
Keyword(s):  
Clinical History ◽  
Rapid Onset ◽  
Mean Value ◽  
Laryngeal Edema ◽  
Tryptase Level ◽  
Antibody Staining ◽  
Life Threatening ◽  
History Of ◽  
Immunohistochemical Techniques

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes.

scholarly journals The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

2021 ◽  
Author(s):  
Linet Njue ◽  
Cesare Medri ◽  
Peter Keller ◽  
Miriam Diepold ◽  
Behrouz Mansouri Taleghani ◽  
...  
Keyword(s):  
Literature Review ◽  
Hemolytic Anemia ◽  
De Novo ◽  
Clinical History ◽  
Molecular Techniques ◽  
De Novo Mutation ◽  
First Case ◽  
History Of ◽  
Transfusion Dependency ◽  
Unstable Hemoglobin

AbstractHb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

scholarly journals ICD-11 extension codes support detailed clinical abstraction and comprehensive classification

2021 ◽  
Vol 21 (S6) ◽  
Author(s):  
Saskia E. Drösler ◽  
Stefanie Weber ◽  
Christopher G. Chute
Keyword(s):  
Clinical History ◽  
International Classification Of Diseases ◽  
Disease Stage ◽  
Clinical State ◽  
Classification Of Diseases ◽  
Icd 10 ◽  
Clinical Detail ◽  
History Of ◽  
Comprehensive Classification

Abstract Background The new International Classification of Diseases—11th revision (ICD-11) succeeds ICD-10. In the three decades since ICD-10 was released, demands for detailed information on the clinical history of a morbid patient have increased. Methods ICD-11 has now implemented an addendum chapter X called “Extension Codes”. This chapter contains numerous codes containing information on concepts including disease stage, severity, histopathology, medicaments, and anatomical details. When linked to a stem code representing a clinical state, the extension codes add significant detail and allow for multidimensional coding. Results This paper discusses the purposes and uses of extension codes and presents three examples of how extension codes can be used in coding clinical detail. Conclusion ICD-11 with its extension codes implemented has the potential to improve precision and evidence based health care worldwide.

scholarly journals Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Lundy McKibbin ◽  
Colin Barber ◽  
Chrystyna Kalicinsky ◽  
Richard Warrington
Keyword(s):  
Family History ◽  
Tranexamic Acid ◽  
Hereditary Angioedema ◽  
Acute Treatment ◽  
Chart Review ◽  
Positive Family History ◽  
Retrospective Chart Review ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
And Function

Abstract Background Hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent subcutaneous angioedema. The underlying pathophysiology and diagnostic criteria continues to evolve. There is a significant overlap between HAE-nC1 INH and idiopathic nonhistaminergic angioedema, ultimately this may be found to be the same condition. Characterization of cohorts suspected to have either of these conditions is warranted to help refine diagnosis, pathophysiology, and treatment response. Methods A retrospective chart review of 418 patients diagnosed with angioedema was conducted. The following inclusion criteria was used: lack of response to antihistamines, steroids, and epinephrine; normal C4, C1 inhibitor (C1 INH) level and function; lack of urticaria or pruritus; occurrence without offending drugs; and positive family history. Enzyme immunoassays for C1 INH function were performed at the Mayo Clinic. Charts meeting these criteria were reviewed for frequency and type of episodes as well as use and response to therapies. Results 6 patients met the above criteria. 3 of these completed genetic testing, none were found to have factor XII abnormalities. None had angiopoietin 1 or plasminogen gene sequencing. 5 of 6 patients were successfully treated with C1 INH or tranexamic acid for acute treatment of attacks (4 with C1 INH and 1 with tranexamic acid). 4 patients have used Icatibant with good response (typically under 40 min for near full recovery); of these, 3 required Icatibant as acute treatment after other therapies (C1 inhibitor and tranexamic acid) were ineffective. There were 9 patients who otherwise met criteria, but due to a lack of family history were classified as having idiopathic non-histaminergic angioedema. Conclusions This retrospective chart review found 6 HAE-nC1 INH patients in Manitoba. 1 responded to tranexamic acid and not C1 INH, 4 typically responded to C1 INH, and 1 responded exclusively to Icatibant. All patients—4 total—who used Icatibant responded; of these 4 patients, 3 required Icatibant after other therapies had failed.

scholarly journals DFNA20/26 and Other ACTG1-Associated Phenotypes: A Case Report and Review of the Literature

2021 ◽  
Vol 11 (4) ◽  
pp. 582-593
Author(s):  
Ugo Sorrentino ◽  
Chiara Piccolo ◽  
Chiara Rigon ◽  
Valeria Brasson ◽  
Eva Trevisson ◽  
...  
Keyword(s):  
Clinical History ◽  
Auditory Hair Cells ◽  
Pathogenic Variants ◽  
Normal Expression ◽  
Large Panel ◽  
History Of ◽  
Syndromic Hearing Loss ◽  
And Function ◽  
Actin Protein ◽  
Generation Sequencing

Since the early 2000s, an ever-increasing subset of missense pathogenic variants in the ACTG1 gene has been associated with an autosomal-dominant, progressive, typically post-lingual non-syndromic hearing loss (NSHL) condition designed as DFNA20/26. ACTG1 gene encodes gamma actin, the predominant actin protein in the cytoskeleton of auditory hair cells; its normal expression and function are essential for the stereocilia maintenance. Different gain-of-function pathogenic variants of ACTG1 have been associated with two major phenotypes: DFNA20/26 and Baraitser–Winter syndrome, a multiple congenital anomaly disorder. Here, we report a novel ACTG1 variant [c.625G>A (p. Val209Met)] in an adult patient with moderate-severe NSHL characterized by a downsloping audiogram. The patient, who had a clinical history of slowly progressive NSHL and tinnitus, was referred to our laboratory for the analysis of a large panel of NSHL-associated genes by next generation sequencing. An extensive review of previously reported ACTG1 variants and their associated phenotypes was also performed.

scholarly journals Evolution of a chordate-specific mechanism for myoblast fusion

2021 ◽  
Author(s):  
Haifeng Zhang ◽  
Renjie Shang ◽  
Kwantae Kim ◽  
Wei Zheng ◽  
Christopher J. Johnson ◽  
...  
Keyword(s):  
Evolutionary History ◽  
De Novo ◽  
Myoblast Fusion ◽  
Last Common Ancestor ◽  
Functional Tests ◽  
Evolutionary Origins ◽  
New Genes ◽  
History Of ◽  
Early Vertebrates ◽  
And Function

The size of an animal is determined by the size of its musculoskeletal system. Myoblast fusion is an innovative mechanism that allows for multinucleated muscle fibers to compound the size and strength of individual mononucleated cells. However, the evolutionary history of the control mechanism underlying this important process is currently unknown. The phylum Chordata hosts closely related groups that span distinct myoblast fusion states: no fusion in cephalochordates, restricted fusion and multinucleation in tunicates, and extensive, obligatory fusion in vertebrates. To elucidate how these differences may have evolved, we studied the evolutionary origins and function of membrane-coalescing agents Myomaker and Myomixer in various groups of chordates. Here we report that Myomaker likely arose through gene duplication in the last common ancestor of tunicates and vertebrates, while Myomixer appears to have evolved de novo in early vertebrates. Functional tests revealed an unexpectedly complex evolutionary history of myoblast fusion in chordates. A pre-vertebrate phase of muscle multinucleation driven by Myomaker was followed by the later emergence of Myomixer that enables the highly efficient fusion system of vertebrates. Thus, our findings reveal the evolutionary origins of chordate-specific fusogens and illustrate how new genes can shape the emergence of novel morphogenetic traits and mechanisms.

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.

Gauzoma in A Scleroderma Patient Following Open Heart Surgery: A Case Report

2018 ◽  
Vol 15 (1) ◽  
pp. 79-81
Author(s):  
Mohammadali Nazarinia ◽  
Elmira Esmaeilzadeh
Keyword(s):  
Heart Surgery ◽  
Past History ◽  
Open Heart Surgery ◽  
Clinical History ◽  
Pathology Report ◽  
Open Heart ◽  
Posterior Aspect ◽  
Scleroderma Patient ◽  
Life Threatening ◽  
History Of

Introduction: Gauzoma is an iatrogenic complication which occurs rarely due to surgical team negligence. Depending on the sterility of the retained tissue, it can lead to life threatening surgical complications or may remain asymptomatic for many years and be detected incidentally in imaging studies. It may be mistaken as tumors or aneurysms. Thus, high clinical suspicion is needed to diagnose them in patients with past history of operation. </P><P> Reporting Case: A 35 years old woman, a known case of scleroderma underwent open-heart surgery 20 years before being diagnosed as scleroderma, presented by dyspnea especially on activity. The High Resolution CT (HRCT) for evaluating the interestial lung disease was done which detected a 7 cm (in greatest diameter) inflammatory mass in posterior aspect of left hemi thorax with a radiopaque thread in its center. True cut biopsy was done and sent for pathology, which revealed fragments of foreign body materials probably gauze pad fibers with cell debris and blood. Conclusion: Here, we highlighted the details in clinical history, CT findings, and pathology report of gauzoma in thorax of a scleroderma patient following previous open-heart surgery. It can be guidance for clinician to consider this diagnosis in patients with past history of operation.

Peran Computed Tomography (CT) Toraks dalam Diagnosis Abses yang Menyerupai Massa Mediastinum

2016 ◽  
Vol 1 (3) ◽  
pp. 178-184
Author(s):  
Krishna P. Wicaksono ◽  
Aziza G. Icksan
Keyword(s):  
Clinical History ◽  
Chest Ct ◽  
X Ray ◽  
Precise Diagnosis ◽  
Life Threatening ◽  
History Of ◽  
Facial Edema ◽  
Chest X Ray ◽  
The Right ◽  
Peripheral Enhancement

Mediastnal abscess is rare, yet it could be a life threatening infecton. A precise diagnosis followed by adequate treatments need to be quickly established. Clinical informaton is usually not diagnostc. Therefore, radiological examinatons have important role.We report a ffy-one years old female with clinical history of sore throat, cough and neck-facial edema since fve days before admission. Laboratory examinatons revealed leukocytosis and ESR elevaton. Chest x-ray depicted a homogenous consolidaton in the right paratracheal region which deviated trachea to the lef. On enhanced chest CT examinaton, we found a cystc mass in the right paratracheal region, extending to the right supero-anterior mediastnum, with peripheral enhancement, air-?uid level and minimal right pleural e?usion, suggestve for mediastnal abscess. Bronchoscopy found no abnormality.Several days later, mediastnal abscess was confrmed surgically and drained through thoracotomy. Although culture of pus failed to grow any bacteria, histopathological examinaton confrmed a non-specifc chronic in?ammaton with no sign of malignancy. The main purpose of this report is to emphasize the importance of enhanced chest CT in evaluatng patent with tumor mimicking mediastnal abscess.

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