Complement Study Versus CINH Gene Testing for the Diagnosis of Type I Hereditary Angioedema in Children

Pedrosa, María; Phillips-Anglés, Elsa; López‐Lera, Alberto; López-Trascasa, Margarita; Caballero, Teresa

doi:10.1007/s10875-015-0222-9

Cited by 32 publications

(56 citation statements)

References 5 publications

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“…In our cohort, equivocal or incomplete complement results occurred in several cases. This differs from a Spanish HAE study demonstrating a very good agreement between complement values and genetic testing in children [28]. However, only 9 children under the age of 1 year were included.…”

Section: Discussionmentioning

confidence: 60%

Clinical characteristics and real-life diagnostic approaches in all Danish children with hereditary angioedema

Aabom

Andersen

Fagerberg

et al. 2017

Orphanet J Rare Dis

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BackgroundWith a potentially early onset, hereditary angioedema (HAE) requires special knowledge also in infancy and early childhood. In children from families with HAE, the diagnosis should be confirmed or refuted early, which can be difficult. Studies of childhood HAE and the diagnostic approaches are limited. Our aim was to investigate the entire Danish cohort of children with HAE and non-HAE children of HAE patients for diagnostic approaches and clinical characteristics.ResultsWe included 41 children: 22 with HAE and 19 non-HAE. Of the HAE children, 14 were symptomatic—median age at onset was 4 [1–11] years. The first attack was peripheral in 8/14 children and abdominal in 6/14 children, i.e. no one had their first attacks in the upper airways. Most children had less than one attack per month. All of the symptomatic children had been treated with tranexamic acid and/or C1 inhibitor concentrate. Unlike in other countries, androgens were not used in our pediatric cohort. Home therapy with C1 inhibitor concentrate was established in 9 cases: 6 children were trained in self-administration and 3 children were treated by parents. Of the children, 10 had been diagnosed by symptoms, including 3 without family history—median age of diagnosis among these children was 5.35 [2–13.2] years. In 31 children, HAE was diagnosed or refuted before symptoms by blood samples. In 23 of these children, complement values were investigated, and in 9 cases genetic testing was added to the complement measurements. In 8 children recently investigated, genetic testing was first choice. Cord blood was used for complement measurements in 9 children and for genetic testing in 4 children. Results of complement measurements were equivocal in several cases, especially in the cord blood samples, and the sensitivity of low complement C4 for the diagnosis of HAE was 75%.ConclusionsWe investigated clinical characteristics in all Danish children with HAE. The rate of home therapy was high and androgens had been avoided. Complement values were often equivocal, especially in cord blood samples. Consequently, we have changed diagnostic practice to early genetic testing in children where the family mutation is known.

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Section: Discussionmentioning

confidence: 60%

Clinical characteristics and real-life diagnostic approaches in all Danish children with hereditary angioedema

Aabom

Andersen

Fagerberg

et al. 2017

Orphanet J Rare Dis

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“…If low C4 and low functional C1‐INH are associated with normal or elevated antigenic C1‐INH levels, then C1‐INH‐HAE type II is likely. These testings should be repeated to confirm the diagnosis of C1‐INH‐HAE 68.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, neonatal serum complement levels are influenced by birth weight and gestational age 71, 73, 74. In newborns and infants aged less than 1 year, both C1‐INH antigenic level and functional activity are low in the patients with C1‐INH‐HAE type I and are within normal range in non‐C1‐INH‐HAE patients 68, 72. However, under one year of age, C4 levels are frequently low in non‐C1‐INH‐HAE patients as well.…”

Section: Resultsmentioning

confidence: 99%

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International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

Farkas

Martinez‐Saguer²,

Bork

et al. 2016

Allergy

172

308

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BackgroundThe consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1‐INH‐HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1‐INH‐HAE.MethodsDuring an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), pediatric data were presented and discussed and a consensus was developed by voting.ResultsThe symptoms of C1‐INH‐HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1‐INH‐HAE, but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1‐INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1‐INH‐HAE family member should be screened for C1‐INH deficiency. Pediatric patients should always carry a C1‐INH‐HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma‐derived C1‐INH, recombinant C1‐INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow up patients in an HAE comprehensive care center.ConclusionsThe pediatric‐focused international consensus for the diagnosis and management of C1‐INH‐HAE patients was created.

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“…C1-INH gene testing should be performed to confirm the diagnosis of C1-INH-HAE in case of uncertainty, although mutations can be identified in approximately 95% of cases [51]. A recently published study reported that C1-INH plasma levels have a very good correlation with genetic analysis, also in children below 1 year of age, so it is not necessary to look for SERPING1 mutations to diagnose C1-INH-HAE in newborns [52]. Genotyping of F12 is, indeed, mandatory in the suspicion of HAE with normal C1-INH [37].…”

Section: Diagnosismentioning

confidence: 99%

Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes

Bova

Feo

Parente

et al. 2018

Int Arch Allergy Immunol

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Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system. Thus, recurrent AE can be determined by multiple and concurrent mechanisms that may generate distinct clinical phenotypes of the disease. Frequency, severity, and the location of attacks are quite different from patient to patient and, even in the same patient, they may change throughout the course of life. The severity of the clinical phenotype strongly influences the burden of the disease and patients’ quality of life. Despite major advances in our understanding of recurrent AE, many unsolved questions remain, leaving several unmet needs for patients and caregivers. This review is focused on a description of different AE phenotypes and the concurrent mechanisms leading to their pathogenesis. A better definition of cellular and molecular pathways responsible for the distinct AE phenotypes may help to improve diagnosis and may lead to a personalized approach to prophylaxis and treatment of the disease.

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Complement Study Versus CINH Gene Testing for the Diagnosis of Type I Hereditary Angioedema in Children

Cited by 32 publications

References 5 publications

Clinical characteristics and real-life diagnostic approaches in all Danish children with hereditary angioedema

Clinical characteristics and real-life diagnostic approaches in all Danish children with hereditary angioedema

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes

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