Acute abdomen as the first manifestation of a rare multisystemic disorder: from emergency surgery to molecular diagnosis

Abstract

Background: Acute abdomen is one of the most frequent reasons for emergency department consultation (Perelló Carbonell et al., 2004). However, in a subset of patients—particularly young individuals without relevant surgical history—the abdominal presentation may represent the first manifestation of a rare multisystemic disease (Shrestha et al., 2024). These entities, including familial Mediterranean fever (FMF), acute intermittent porphyria (AIP), and Fabry disease (FD), are often diagnosed late or after unnecessary surgical interventions (Ferreira et al., 2011). Objective: To synthesize evidence on rare multisystemic diseases presenting with acute abdomen, analyzing the diagnostic pathway from initial clinical suspicion in the emergency department to molecular confirmation, and proposing an algorithm that integrates clinical reasoning with available genetic tools. Methods: Systematic review following PRISMA 2020 guidelines (Page et al., 2021). A systematic search was conducted in PubMed/MEDLINE, Europe PMC, and Scielo (January 2000 to October 2026). Two independent reviewers selected studies, extracted data, and assessed risk of bias using the JBI tool for case reports and case series (Vinagre et al., 2024). Results: Three main entities with abdominal presentation as the inaugural symptom were identified: FMF (MEFV mutations) (Perelló Carbonell et al., 2004), AIP (HMBS mutations) (Shrestha et al., 2024), and FD (GLA mutations) (Chinese Medical Journal, 2023). In all of them, molecular diagnosis not only confirmed clinical suspicion but transformed therapeutic management and enabled family screening (Kang et al., 2022). Conclusions: Acute abdomen as the initial manifestation of a rare multisystemic disease demands a paradigm shift: from immediate surgical logic to differential clinical reasoning that integrates extra-digestive findings, family history, and molecular studies (Shrestha et al., 2024). The implementation of multidisciplinary teams and reanalysis of genomic data emerge as key strategies to reduce diagnostic delay (Annals of Laboratory Medicine, 2025).