İnvestigation of the frequency of acute hepatic porphyria in patients diagnosed with familial mediterranean fever presenti̇ng with an acute attack

Aim: Acute Hepatic Porphyria (AHP) is a group of rare inherited metabolic disorders characterized by life-threatening acute attacks, which, if left untreated, can restrict daily physical activities and reduce the quality of life due to its chronic nature. Untreated acute and recurring attacks can lead to progressive and irreversible neuropathy, kidney failure, and hepatocellular carcinoma. Early diagnosis and treatment are crucial in preventing disease progression and potential complications. The primary factor contributing to the diagnostic difficulty is that the main clinical symptom, severe abdominal pain, can be mimicked by many other diseases. Another reason for diagnostic delays is the emergence of nervous system symptoms without the main symptom of abdominal pain in some patients. The fact that the majority of patients experience only one or a few attacks in their lifetime also complicates diagnosis. Due to the clinical features of AHPs that mimic many different diseases, studies have been conducted in the literature, and cases of porphyria have been reported that were misdiagnosed with lead poisoning, Guillain-Barré syndrome(GBS), vasculitis, and polymyositis. Given that recurrent abdominal pain attacks are an important clinical feature for both diseases, Familial Mediterranean Fever (FMF) should also be considered in the differential diagnosis of AHP. However, to date, no studies have investigated the prevalence of porphyria in FMF patients in the literature. Our study aims to investigate the prevalence of AHP in FMF patients, where severe abdominal pain is a common symptomatology. Materials and Methods: In our prospective study, patients over the age of 14 with a diagnosis of Familial Mediterranean Fever (FMF) who are being followed up by the Departments of Pediatric Rheumatology and Rheumatology at Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, and who experience severe abdominal pain during an attack and have non-exon 10 biallelic variants in the MEFV gene or have a normal MEFV gene analysis, were included in the study group. During acute abdominal pain attacks, spot urine samples were collected from the patients and control groups to measure porphobilinogen (PBG), delta-aminolevulinic acid (ALA), total porphyrins, and creatinine levels. Patients with a urine PBG/creatinine ratio >10 mg/g creatinine and ≥10 μmol/mmol creatinine were diagnosed with AHP. Results: The study included 104 FMF patients. The control group consisted of two subgroups: FMF patients with biallelic pathogenic variants in exon 10 of the MEFV gene (n=50) and healthy individuals (n=50). In both control groups, spot urine samples showed normal results for PBG, ALA, and total porphyrins. In the patient group, 5 individuals (4.8%) were diagnosed with AHP based on elevated PBG/creatinine ratios in spot urine. Upon examining the data of these five patients, the average PBG/creatinine ratio was found to be 17.71±9.6 (range: 10.37-33.51) µmol/mmol creatinine and 35.43±19.21 (range: 20.75-67.05) mg/g creatinine. The mean age of these patients was 24.8±11.67 years, the mean age of FMF diagnosis was 12.9±12.72 years, AHP diagnosis was 24.8±11.67 years, and the diagnostic delay was 19.4±9.45 years. During attacks, these patients primarily experienced abdominal pain, accompanied by symptoms such as other gastrointestinal system findings, neuropathy, headache, and mood alterations. Conclusion: Although AHPs are a rare group of diseases in the general population, the high diagnosis rate in our study indicates that they can be masked by chronic diseases sharing common symptomatology and highlights the need to increase disease awareness in the community. Symptoms such as headache, peripheral neuropathy, anxiety, and gastrointestinal system complaints are warning signs that can help prevent diagnostic delays. In conclusion, AHP should be considered in the differential diagnosis, especially in cases being investigated for abdominal pain, and clinical findings suggestive of the disease should be thoroughly examined.