Biomarker for Hereditary AngioEdema Disease
Condition: C1 Esterase Inhibitor Deficiency; Angio Edema; C4 Deficiency; HAE; Hereditary Angioedema; Hereditary Angioedema Type II; Hereditary Angioedema Type III; Hereditary Angioedema Type I
MeSH terms: Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Hereditary Angioedema Type III
Study type: Observational

Summary: 
      International, multicenter, observational, longitudinal monitoring study to identify,
      validate and/or monitor Mass Spectrometry (MS)-based biomarker/s for Hereditary Angioedeme
      (HAE) disease and to test the clinical robustness, specificity, and predictive value of
      theese biomarker/s
    

Detailed description: 
      Hereditary Angioedema (HAE) is a rare autosomal dominant genetic disorder, characterized by
      recurrent episodes of angioedema of the face, larynx, lips, abdomen, and extremities.The most
      common types of HAE develop as result of mutations in the SERPING1 gene that encodes the C1
      inhibitor (C1-INH), a protease involved in limiting bradykinin production. Excessive
      bradykinin due to low levels of C1-INH (HAE type 1) or dysfunctional C1-INH (HAE type 2)
      leads to capillary leakage and angioedema formation. The third type of HAE is not associated
      with a C1-INH deficiency, develops as a result of mutations in the Factor 12 gene (FXII) and
      affects almost exclusively women. Rare cases of HAE have also been described resulting from
      mutations in Plasminogen (PLG), Angiopoetin 1 (ANGPT1), and Kininogen 1 (KNG1).

      The characteristic symptom of hereditary angioedema is recurrent episodes of swelling due to
      the accumulation of excessive body fluid. The most commonly affected areas of the body
      include the hands, feet, eyelids, lips, genitals, larynx and gastrointestinal tract. The most
      serious complication of HAE is laryngeal edema that can become life threatening; but it is a
      relatively rare event.

      The diagnosis of hereditary angioedema is made by a thorough clinical evaluation, a detailed
      patient history, and blood tests.Clinical diagnosis is complicated because HAE is highly
      variable in the clinical phenotype and the majority of the physicians believe that they never
      seen a patient with that disorder. Laboratory diagnosis involves measurement of the C1-INH
      function, C1-INH and C4 levels. Both C1-INH protein level and function is low in HAE-1
      patients, whereas in HAE-2 individuals the C1-INH concentrations is optimal or even elevated,
      however C1-INH function is impaired. Generally, C4 levels are low in both HAE-1/2 patients.

      CENTOGENE utilizes Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry
      (LC-MRM-MS) method to identify potential disease-specific biomarkers for HAE. Such
      biomarker/s may support the early diagnosis and treatment monitoring and personalization in
      the future.

      Therefore, it is the goal of this study is to identify new biomarkers for HAE, validate the
      identified biomarkers, and monitor these biomarkers longitudinally to determine their
      clinical robustness, specificity, and predictive value.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Participants diagnosed with Hereditary Angioedema (HAE) disease
      
Biospecimen description: 
      Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)
    
Keywords: Hereditary Angioedema; Biomarker; Hereditary Angioedema Type I; Hereditary Angioedema Type II; Hereditary Angioedema Type III