What is the underlying pathology of hereditary angioedema?

Hereditary angioedema (HAE) is primarily caused by a deficiency or dysfunction of the C1-inhibitor protein, which is crucial for regulating the complement and contact (or intrinsic) pathways of the coagulation system. C1-inhibitor functions to inhibit the activation of complement proteins and certain enzymes in the blood that lead to bradykinin release. In hereditary angioedema, the lack of functional C1-inhibitor results in uncontrolled production of bradykinin, a peptide that increases vascular permeability, leading to episodes of swelling in various parts of the body, including the face, extremities, gastrointestinal tract, and airway.

This dysfunction can manifest as either a quantitative deficiency (type I HAE) or a qualitative dysfunction (type II HAE) of the C1-inhibitor protein. Both types lead to similar clinical manifestations of recurrent angioedema.

Understanding this pathology is critical for recognizing the specific mechanisms of HAE and differentiating it from other conditions that may cause edema, which often involve different pathways and mediators, such as histamine (which is not elevated in HAE) or leukotrienes. Moreover, a vitamin D deficiency is not related to the mechanisms of HAE and