Misdiagnosed Hereditary Angioedema with Recurrent Abdominal Pain: A Novel SERPING1 Frameshift Variant

Hereditary angioedema (HAE) is typically autosomal dominant, though recessive cases exist. It is characterized by recurrent episodes of swelling affecting the subcutaneous tissues, oropharyngeal mucosa, and gastrointestinal tract. This report describes a misdiagnosed case with a novel "SERPING1" variant.

A 22-year-old Chinese male presented with recurrent acute abdominal pain since March 2018, initially misdiagnosed as gastroenteritis or intestinal obstruction at multiple hospitals. During current hospitalization, detailed history revealed non-pitting eyelid edema in July 2019 that progressed to facial edema within 24 hours after a cold. Over the subsequent three years, he experienced recurrent subcutaneous edema involving face and extremities, typically resolving spontaneously within one week. Family history showed his father had similar self-limiting episodes of abdominal pain and edema between ages 20-30, with no recurrence after age 40. Physical examination demonstrated upper abdominal tenderness without rebound pain. Low C4 levels prompted C1INH testing and genetic analysis, confirming HAE due to C1INH deficiency type 1 (HAE-C1INH-Type1) with a novel SERPING1 variant. Since initiating lanadelumab (300mg biweekly) on April 26, 2023, the patient has completed 11 injections and remains in good condition.

HAE is a rare disease that is often misdiagnosed. Complement C4 remains a critical screening biomarker for patients with HAE. In addition, we reported a novel frameshift variant in the coding region of the SERPING1 gene, and the specificity of the position offers a unique point of interest in the discussion of the disease's causative locus.