A case of hereditary angioedema with C1-inhibitor deficiency presenting predominantly with gastrointestinal symptoms was repeatedly misdiagnosed as infectious gastroenteritis, with family investigation identifying 13 clinically suspected affected individuals among 50 relatives and a heterozygous likely pathogenic nonsense variant in SERPING1 (NM_000062.3:c.1480C>T, p.Arg494Ter/R494*).
Key Findings
Background
A 26-year-old man with recurrent abdominal pain, watery diarrhea, bowel wall edema, and transient ascites was repeatedly misdiagnosed as infectious gastroenteritis before receiving a diagnosis of hereditary angioedema with C1-inhibitor deficiency.
Symptoms began in 2022 and the patient experienced recurrent episodes that were self-limited.
The patient also reported recurrent hand and foot swelling.
The misdiagnosis led to diagnostic delay and unnecessary interventions.
Complement testing showed low C4 and reduced C1-inhibitor function, with repeat testing confirming low C1-inhibitor antigen and function.
Results
Genetic testing identified a heterozygous likely pathogenic nonsense variant in SERPING1 supporting a diagnosis of type 1 HAE-C1INH.
The variant identified was NM_000062.3:c.1480C>T (p.Arg494Ter/R494*).
The variant was classified as likely pathogenic.
Low C1-inhibitor antigen and function on repeat testing was consistent with type 1 HAE-C1INH.
HAE-C1INH is described as a rare bradykinin-mediated disorder.
Results
Family investigation of 50 relatives identified 13 clinically suspected affected individuals, including three who reportedly died from laryngeal edema.
50 relatives were investigated as part of family counseling following the proband's diagnosis.
13 relatives were clinically suspected to be affected.
Three relatives reportedly died from laryngeal edema, indicating potentially fatal disease expression in this family.
Laboratory confirmation was available for the proband and two relatives only.
Conclusions
Recurrent, self-limited abdominal attacks with transient ascites should prompt C4 and C1-inhibitor testing and family counseling.
The authors emphasize this diagnostic approach to avoid misdiagnosis as infectious gastroenteritis.
Bowel wall edema and transient ascites were key imaging features in this case.
Early complement testing (C4 and C1-inhibitor antigen and function) is highlighted as the critical diagnostic step.
Family investigation is emphasized given the hereditary nature of the condition and potential for fatal outcomes.
What This Means
This research describes a case of a young man whose hereditary immune condition caused repeated episodes of severe stomach pain, diarrhea, and fluid accumulation in the abdomen. For years, doctors mistook these episodes for food poisoning or stomach infections (gastroenteritis), delaying proper diagnosis and treatment. The key to the correct diagnosis was blood tests measuring complement proteins (C4 and C1-inhibitor), which were abnormally low, and a genetic test that found a specific mutation in the SERPING1 gene. This gene normally produces a protein that controls inflammation, and when it doesn't work properly, fluid leaks into tissues causing swelling (angioedema) — in this case primarily in the gut rather than the more commonly recognized skin or throat swelling.
When the patient's 50 family members were investigated, 13 were found to likely have the same inherited condition. Tragically, three family members had already died from throat swelling (laryngeal edema), which is a life-threatening complication that can block the airway. This highlights how serious and potentially fatal this condition can be when unrecognized.
This research suggests that when patients have repeated episodes of unexplained abdominal pain and swelling that resolve on their own, doctors should consider testing for hereditary angioedema rather than assuming infectious causes. Simple blood tests measuring C4 and C1-inhibitor levels can identify the condition, and once one family member is diagnosed, relatives should also be evaluated since they may unknowingly carry the same genetic mutation and be at risk for life-threatening attacks.
Ren X, Wu J, Xu Y. (2026). Case Report: Hereditary angioedema masquerading as gastroenteritis.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1828352