When diagnosing hereditary angioedema (HAE), a combination of factors should be considered, including symptoms, family history, and laboratory testing.1
Testing for C1-INH deficiency or dysfunction
Patients suspected of having HAE Type 1 or Type 2 should be assessed for blood levels of C1-INH function, C1-INH protein, and C4. Using complement testing, a patient’s peripheral blood test will show low C4 levels, in addition to low C1-INH activity or levels. If any of the levels are abnormally low, the tests should be repeated to confirm the diagnosis.1,3
Other forms of HAE have been described that do not involve mutations of C1-INH, and are rare. However, it is possible for patients with this type of HAE to have clinical symptoms that are indistinguishable from Types 1 and 2 and have normal plasma levels and functional C1-INH. This is called HAE with normal C1-INH (HAE nC1-INH), previously referred to as Type 3 HAE.7
delays to diagnosis of hereditary angioedema
HAE is often misdiagnosed, even among patients with a family history5:
- In a real-world registry study of patients with HAE Type 1 or Type 2, almost half of patients had initially received 1 or more misdiagnoses (185/418)
- Patients who received a misdiagnosis experienced a mean diagnostic delay of 15 years5
- In general, misdiagnosis can result in increased health resource use, including unnecessary abdominal surgeries and increased risk of death from laryngeal attacks6-8
good to know
Genetic testing increases diagnostic reliability in children. It may be helpful if the mutation of the parent is known, or if biochemical measurements are inconclusive.2,3