What are the types of Hereditary Angioedema (HAE)?

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From the Guidelines

Hereditary Angioedema (HAE) is primarily categorized into two main types: Type I and Type II, with a third form having normal C1 inhibitor levels but lacking valid diagnostic tests. The two main types of HAE, which are indistinguishable clinically, can be diagnosed based on laboratory findings: Type I HAE presents with low C1INH antigenic and functional levels, whereas Type II HAE presents with normal C1INH antigenic levels but decreased C1INH functional levels 1.

Key Characteristics of HAE Types

  • Type I HAE: characterized by low levels of C1 inhibitor protein, resulting from mutations in the C1INH gene that lead to a functional deficiency of C1INH 1.
  • Type II HAE: involves normal or elevated levels of C1 inhibitor protein that doesn't function properly, also due to mutations in the C1INH gene but resulting in a dysfunctional protein rather than a deficiency 1.
  • A third form of HAE with normal C1INH levels has been described, but its diagnosis is based on exclusion and lacks valid diagnostic tests, making it challenging to categorize and manage 1.

Clinical Implications

Understanding the specific type of HAE is crucial for selecting the appropriate treatment, which may include C1 inhibitor replacement, kallikrein inhibitors, or bradykinin receptor antagonists, depending on the type and severity of the condition 1.

Treatment Considerations

The primary mediator of swelling in patients with HAE is bradykinin, and optimal management depends on early identification of patients and access to effective, on-demand HAE-specific agents 1. Given the potential for significant morbidity and mortality associated with HAE attacks, it is essential to prioritize treatments that have been proven efficacious and safe in clinical trials, such as C1INH concentrates, plasma kallikrein inhibitors, or bradykinin B2 receptor antagonists 1.

From the FDA Drug Label

As in the placebo-controlled study, no proven cases of infections due to HIV-1/2, HAV, HBV, HCV or Parvovirus B19 were observed during the study. 6. 2 Immunogenicity In a post-marketing study forty-six subjects with Type I or Type II HAE were monitored for inhibitory or non-inhibitory antibodies to C1-INH.

The types of Hereditary Angioedema (HAE) mentioned are:

  • Type I HAE
  • Type II HAE 2

From the Research

Types of Hereditary Angioedema (HAE)

  • There are three main types of HAE: type I, type II, and type III 3, 4, 5, 6.
  • Type I HAE is the most common, occurring in approximately 85% of patients, and is characterized by a deficiency in C1-INH 4, 6.
  • Type II HAE occurs in 15% of cases and is characterized by normal or elevated quantities of C1-INH, but with dysfunctional C1-INH 4, 6.
  • Type III HAE, also known as HAE with normal C1-INH, is rare and typically estrogen-dependent, with normal C1-INH activity 3, 4, 6.

Subtypes of HAE with Normal C1-INH

  • Current guidelines recommend subdividing HAE with normal C1-INH into subtypes based on underlying mutations, such as:
  • Kininogen-1 (HAE-KNG1) 3
  • Plasminogen gene (PLG-HAE) 3
  • Myoferlin gene mutation (MYOF-HAE) 3
  • Heparan sulfate-glucosamine 3-sulfotransferase 6 (HS3ST6) 3
  • Mutation in Hageman factor (factor XII) 3, 6
  • Angiopoietin-1 (HAE-ANGPT-1) 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hereditary and acquired angioedema.

Allergy and asthma proceedings, 2019

Research

[Hereditary angioedema. A report of a case and literature review].

Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993), 2006

Research

Chapter 22: Hereditary and acquired angioedema.

Allergy and asthma proceedings, 2012

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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