Isolated gastrointestinal hereditary angioedema associated with a pathogenic SERPING1 variant arising de novo: a case...

Hereditary angioedema (HAE) is a rare genetic disorder typically characterized by cutaneous and submucosal edema. Cases presenting exclusively with gastrointestinal symptoms, devoid of concurrent or historical cutaneous or upper airway manifestations, are uncommon. This atypical presentation poses a considerable diagnostic challenge and often leads to a marked delay in diagnosis, particularly in patients without a family history. We report the case of a 28-year-old female with an over 6-year history of recurrent, self-limiting abdominal pain. During a severe attack, abdominal computed tomography angiography (CTA) revealed jejunal wall edema and ascites, accompanied by a dramatic surge in D-dimer (>20.00 mg/L FEU) and fibrin degradation products (FDP >120.00 mg/L), closely mimicking mesenteric ischemia. However, a retrospective review of medical history identified the persistent consumption of complement C4 (0.03-0.05 g/L). Subsequent testing showed a functional C1 esterase inhibitor (fC1-INH) level of <7.0% and a C1 esterase inhibitor (C1-INH) antigen level of 6.81 μg/mL, confirming type 1 HAE. Whole-exome sequencing (WES) identified the nonsense variant NM_000062.3:c.990C>A, p.(Tyr330Ter), in SERPING1. The variant was not detected in either biological parent, supporting a de novo origin. Under the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) framework, it was classified as pathogenic on the basis of PVS1 and PS2. An abdominal attack in May 2025 resolved rapidly after icatibant administration. Long-term prophylaxis (LTP) with lanadelumab was subsequently initiated following an individualized shared decision-making process. No breakthrough attacks or treatment related adverse events occurred from June 2025 through June 2026. This report highlights that HAE should be considered in patients with recurrent, unexplained, self-limiting abdominal pain, and C4 should be included in the initial evaluation. A negative family history does not exclude HAE.