What Is Hereditary Angioedema? Understanding The Inherited Disorder, Its Symptoms, Diagnosis And Treatment

Hereditary Angioedema is characterised by episodes of severe, unpredictable swelling in different parts of the body, including the face, extremities, and airways.

Hereditary angioedema s primarily an inherited disorder, caused by a deficiency or dysfunction of a protein called C1 esterase inhibitor (C1-INH). This protein plays a crucial role in regulating the production of bradykinin, a molecule responsible for blood vessel dilation.

Source : LucyHAE via Wikimedia Commons

Dr T Sathish Kumar

As a paediatric rheumatologist, I have encountered various cases of hereditary angioedema (HAE) in my practice. This rare, yet potentially life-threatening condition affects about 1 in 10,000 to 1 in 50,000 individuals. HAE is characterised by episodes of severe, unpredictable swelling in different parts of the body, including the face, extremities, and airways. To address the concerns of both medical professionals and the general public, I would like to delve into the genetics of HAE and discuss its implications for diagnosis and treatment. Understanding the genetic basis of HAE will enable us to provide better care to our patients and improve their quality of life.

The Genetics of Hereditary Angioedema

HAE is primarily an inherited disorder, caused by a deficiency or dysfunction of a protein called C1 esterase inhibitor (C1-INH). This protein plays a crucial role in regulating the production of bradykinin, a molecule responsible for blood vessel dilation and increased vascular permeability. In individuals with HAE, an increase in bradykinin levels leads to characteristic episodes of swelling.

There are three types of HAE, classified based on the levels and functionality of C1-INH:

HAE Type 1: This is the most common form, accounting for about 85% of cases. It is characterised by low levels of C1-INH in the blood.

HAE Type 2: This form affects about 15% of HAE patients and is characterised by normal or elevated levels of C1-INH, but with reduced function.

HAE Type 3: This rare form is not associated with C1-INH deficiency or dysfunction. Instead, it is linked to a mutation in the Factor XII gene, which plays a role in the blood clotting process. The exact mechanism behind HAE Type 3 is still under investigation.

Diagnosis and Genetic Testing

A detailed medical and family history, along with laboratory tests, can help in diagnosing HAE. The tests typically include measuring the levels of C1-INH and its function and assessing the levels of C4, a protein that is usually low in HAE patients.

Genetic testing can provide definitive confirmation of HAE by identifying mutations in the SERPING1 gene (responsible for HAE Type 1 and 2) or the Factor XII gene (associated with HAE Type 3). iiiGenetic testing is particularly useful for at-risk family members, as it can aid in early diagnosis and initiation of appropriate management strategies.

Treatment and Management

The management of HAE focuses on two aspects: treating acute attacks and preventing future episodes. I usually recommend the following treatment options, based on the specific needs of my patients:

For acute attacks: The use of medications like plasma-derived C1-INH concentrate, recombinant human C1-INH (now available in India), or icatibant (a bradykinin receptor antagonist) can provide rapid relief from symptoms.

For prevention: Long-term prophylaxis with plasma-derived C1-INH or a monoclonal antibody called lanadelumab can help reduce the frequency and severity of attacks in patients with frequent and severe episodes.

For short-term prevention: In situations where there is an increased risk of an attack (e.g., before dental procedures), the use of plasma-derived C1-INH or a short course of high-dose androgens can be considered.

Education and Support

As a paediatric rheumatologist, I always emphasise the importance of educating my patients and their families about the nature of HAE and its management. A comprehensive understanding of the condition will enable them to make informed decisions about their treatment and promptly recognize and respond to an acute attack.

In addition to medical treatment, I encourage my patients to seek support from patient advocacy groups and online communities. Connecting with others who are facing similar challenges can provide valuable emotional support, practical advice, and coping strategies. One such organisation is the Hereditary Angioedema Association, which offers resources, educational materials, and support networks for patients and their families.

Prophylaxis in Hereditary Angioedema

Prophylactic treatment plays a significant role in the management of hereditary angioedema by reducing the frequency and severity of acute attacks. By tailoring prophylactic strategies to each patient's unique needs, we can significantly improve their quality of life and minimise the impact of HAE on their daily activities. Prophylaxis offers numerous benefits, including increased predictability and control over the disease, reduced anxiety associated with the possibility of unexpected attacks, and enhanced overall well-being. Patients who adhere to a carefully planned prophylactic regimen are less likely to experience disruptions in their education, work, and social life, allowing them to lead more fulfilling lives despite having HAE.

The choice of prophylactic therapy should be based on individual factors such as the severity and frequency of attacks, the patient's lifestyle, and potential side effects. Close collaboration between the patient, their family, and the healthcare team is crucial to ensure the success of prophylactic treatment.

Conclusion

Understanding the genetics of hereditary angioedema is fundamental to accurate diagnosis, effective treatment, and better patient outcomes. Prophylactic treatment, tailored to individual needs, plays a vital role in managing this complex genetic disorder. By providing patients with the necessary tools and support to manage their condition, we can improve their quality of life and empower them to lead fulfilling lives. As we continue to expand our knowledge of HAE genetics and explore innovative therapeutic approaches, we hope to further enhance our ability to care for patients and their families affected by this rare but challenging condition.

(The author is a paediatric rheumatologist from Vellore)

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