Hereditary Angioedema Type 3

1. Disease Summary:

Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe swelling (angioedema) affecting various parts of the body, including the face, extremities, gastrointestinal tract, and airway. HAE is classified into three types based on the underlying cause:

Type I: Caused by a deficiency of C1 inhibitor (C1-INH).
Type II: Caused by dysfunctional C1-INH.
Type III: Characterized by normal levels of C1-INH but still results in angioedema attacks. This type is often associated with mutations in genes such as F12, PLG, and ANGPT1.

HAE type 3 is particularly challenging due to its rarity and the lack of understanding regarding its pathophysiology compared to types 1 and 2.

2. Global Prevalence and Disease Burden:

The global prevalence of HAE is estimated to be approximately 1 in 50,000 individuals, although this can vary by population. For HAE type 3, specific prevalence data is scarce, with some studies indicating it may account for about 8% of all HAE cases (Guan et al., 2024, PMID: 38978028).

The disease burden is significant, as patients experience unpredictable and painful attacks that can lead to severe complications, including asphyxiation. The economic impact includes direct costs such as hospitalizations, medications, and indirect costs related to lost productivity. A systematic review indicated that the economic burden of HAE can be substantial, with annual costs for patients reaching thousands of dollars due to frequent medical visits and treatments (Guan et al., 2024, PMID: 38978028).

3. Unmet Medical Need:

The unmet medical needs for patients with HAE type 3 include:

Limited Treatment Options: Current therapies primarily target HAE types 1 and 2, leaving patients with type 3 with few effective treatment options. Most available treatments, such as C1-INH replacement therapies, are ineffective for type 3 patients due to their normal C1-INH levels (Anderson et al., 2024, PMID: 38982603).
Diagnostic Challenges: HAE type 3 is often misdiagnosed or underdiagnosed due to a lack of awareness among healthcare providers. Patients may go years without a correct diagnosis, leading to delayed treatment and increased morbidity (Craig, 2023, URL: https://www.hcplive.com/view/hereditary-angioedema-diagnosis-challenges-timothy-craig-do).
Quality of Life Impacts: Patients with HAE type 3 report lower health status and quality of life compared to those with types 1 and 2. They experience more severe attacks and higher rates of hospitalization, which significantly impacts their daily functioning and mental health (Anderson et al., 2024, PMID: 38982603).
Lack of Research: There is a scarcity of clinical studies and guidelines specifically addressing HAE type 3, which hampers the development of targeted therapies and management strategies (Guan et al., 2024, PMID: 38978028).

4. Current Treatment Options:

Current treatment options for HAE primarily focus on types 1 and 2, with limited applicability for type 3:

On-Demand Treatments: These include C1-INH concentrates (both plasma-derived and recombinant), bradykinin receptor antagonists (e.g., icatibant), and kallikrein inhibitors (e.g., ecallantide). However, these treatments are generally ineffective for type 3 patients due to their normal C1-INH levels (Guan et al., 2024, PMID: 38978028).
Prophylactic Treatments: Long-term prophylaxis options include C1-INH replacement therapy and medications like danazol and tranexamic acid. These are primarily effective for types 1 and 2 and do not address the underlying issues in type 3 patients (Anderson et al., 2024, PMID: 38982603).
Emerging Therapies: Newer therapies targeting the bradykinin pathway are being explored, but specific studies for type 3 are lacking. The need for clinical trials focusing on type 3 patients is critical to develop effective treatment strategies (Guan et al., 2024, PMID: 38978028).

5. Current Clinical Trials:

As of now, there are limited clinical trials specifically targeting HAE type 3. Most ongoing studies focus on HAE types 1 and 2. The lack of research funding and interest in type 3 highlights the urgent need for more clinical trials to explore effective treatments and management strategies for this patient population (Guan et al., 2024, PMID: 38978028).

6. Additional Context:

The challenges faced by patients with HAE type 3 underscore the need for increased awareness and education among healthcare providers. Improved diagnostic protocols and the development of targeted therapies are essential to address the unmet medical needs of this patient population. Advocacy for research funding and clinical trials focusing on HAE type 3 is crucial to enhance treatment options and improve patient outcomes.