Abstract
BACKGROUND: Acute hepatic porphyria (AHP) is a heme metabolism disorder characterized by acute abdominal pain episodes, with diagnostic delays and misdiagnosis due to heterogeneous presentations and symptom overlap with other diseases. Timely diagnosis is crucial as untreated attacks can lead to life-threatening complications such as hepatocellular carcinoma, chronic kidney disease, neuropathy and chronic pain. AHP often mimics various conditions such as lead poisoning, Guillain-Barré syndrome, vasculitis and surgical abdominal conditions, leading to diagnostic challenges and inappropriate treatment. Familial Mediterranean fever (FMF), another disease with recurrent abdominal pain as its main feature, has a similar symptomatology to AHP. The aim of this study was to investigate the prevalence of AHP in patients with clinically suspected FMF without a confirmatory genotype using cross-sectional urinary porphobilinogen (PBG) screening during abdominal pain episodes. RESULTS: This cross-sectional study included a total of 104 patients under rheumatology follow-up for suspected FMF and two control groups (genetically confirmed FMF patients and healthy controls). Patients presenting with severe abdominal pain and had a spot urinary PBG/creatinine ratio of ≥ 10 µmol/mmol were diagnosed with AHP together with at least one clinical manifestation defined by the European Porphyria Network. Among 104 suspected-FMF patients, 5 (4.8%) were diagnosed with AHP, with a diagnostic delay of 16.4 ± 10.38 years. AHP patients frequently exhibited neurological (muscle weakness, paresthesia), psychiatric, and gastrointestinal (nausea, vomiting) symptoms. In likelihood ratio analyses, urinary incontinence, hypertension and neuropathic symptoms were strong discriminative indicators of AHP, whereas fever, arthritis, rash and chest pain were more indicative of FMF, aiding differential diagnosis. CONCLUSIONS: Due to diagnostic challenges and overlapping symptoms, AHP should be considered in the differential diagnosis of FMF, particularly in patients with neurological or systemic features. Urinary PBG screening and identifying predictive markers may improve diagnostic accuracy and early management of AHP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-026-04308-3.