Diagnostic Challenges in Hereditary Angioedema with Normal C1-Inhibitor Levels: A Clinical Case Report

Hereditary angioedema with normal C1‑inhibitor (HAE-nC1INH) remains a diagnostic challenge due to normal complement parameters and clinical similarity to histamine-­mediated angioedema, frequently leading to misdiagnosis and delayed initiation of appropriate therapy. The aim of this report was to demonstrate diagnostic reasoning in a clinically suspected case of HAE-nC1INH. We present a clinical case of a 25‑year-old woman with recurrent, non-urticarial edema involving the face and extremities, resistant to antihistamines and systemic corticosteroids. Clinical presentation, family history, and laboratory findings were analyzed, including complement C4 level, C1‑inhibitor activity, thyroid hormone levels, and serum 25‑hydroxyvitamin D. The patient exhibited normal C4 levels and borderline C1‑inhibitor activity in combination with a typical clinical phenotype and positive family history, supporting a probable diagnosis of HAE-nC1INH. A pronounced vitamin D deficiency was also identified. An allergic mechanism of angioedema was considered unlikely. This case underscores the importance of heightened clinical awareness in patients with recurrent angioedema of unclear origin. Early recognition of HAE-nC1INH facilitates timely initiation of targeted therapy and prevents prolonged ineffective treatment.