Porphyria seen in familial Mediterranean fever patients: Study
Doctors should watch for overlapping symptoms, researchers say
Written by |
Clinicians have identified undiagnosed cases of acute hepatic porphyria (AHP) among people with suspected Familial Mediterranean Fever (FMF), an inherited inflammatory condition with nearly identical symptoms, a study reported.
While the main manifestation of both conditions is sudden abdominal pain, symptoms exclusive to AHP were neuropathic, such as numbness, tingling, or nerve pain, alongside vomiting, urinary incontinence, and high blood pressure.
“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,” the researchers wrote.
The study, “Acute hepatic porphyria masquerading as familial Mediterranean fever: results of a cross-sectional porphobilinogen screening,” was published in the Orphanet Journal of Rare Diseases.
Masquerading symptoms
Porphyrias are caused by mutations that disrupt the production of heme, the molecule that carries oxygen in the blood. When this process breaks down, toxic intermediate substances called porphyrins accumulate in the body’s tissues, which can drive sudden, intense abdominal pain, often with vomiting, weakness, and psychiatric symptoms.
Despite the seriousness of these episodes, many people go years without a correct diagnosis, largely because the AHP symptoms closely resemble those of many other conditions.
One condition with a particularly striking overlap is FMF, an inherited inflammatory disease that causes recurring bouts of fever and, most notably, severe abdominal pain, the same hallmark symptom of an AHP attack. As the name suggests, it usually occurs in people of Mediterranean origin.
Despite this obvious similarity, researchers had never formally studied whether patients diagnosed with FMF might actually have undetected AHP, until now.
A team at the Istanbul University-Cerrahpaşa in Turkey recruited 104 people suspected of having FMF due to severe recurring episodes of abdominal pain. The researchers included 50 people with genetically confirmed FMF and 50 healthy volunteers to serve as control groups.
Most of the patients, with or without confirmed FMF, were managed with colchicine, a medication designed to reduce inflammation to prevent painful attacks.
When urine tests were used to screen for AHP, all participants in both control groups returned results well within the normal range. In the suspected FMF group, however, five out of 104 patients (4.8%) had urinary levels of porphobilinogen (a porphyrin precursor) above the AHP diagnostic threshold.
All five met the clinical criteria for an AHP diagnosis, as each had severe abdominal pain alongside at least one additional feature recognized by the European Porphyria Network.
Four of the five newly identified AHP patients were women, with a mean age of 22.8. Their symptoms first appeared at a mean age of 8.8, resulting in a mean diagnostic delay of 16.4 years.
“Most AHP patients had a history of multiple hospitalizations for abdominal pain, neuropathic symptoms, headache, and mood disturbances, which often led to misdiagnosis and treatment in different outpatient clinics,” the team noted.
Three of the five patients carried the MEFV gene mutation R202Q, associated with FMF, which may have contributed to their initial misclassification. And three patients reported partial relief of their symptoms with colchicine.
During acute attacks, all five patients experienced pain and weakness. Four reported gastrointestinal symptoms and tingling or abnormal sensations in the limbs, and four also showed psychiatric changes. Urinary incontinence and high blood pressure were each present in two patients.
Researchers also examined which symptoms were most useful for distinguishing AHP from FMF in patients with an uncertain diagnosis.
Vomiting and neuropathic symptoms, such as numbness, tingling, or nerve pain, were particular warning signs for AHP, with neuropathic symptoms appearing exclusively in AHP patients and in none of the FMF cases. Urinary incontinence and high blood pressure, though less common, were similarly associated with AHP.
On the other hand, symptoms characteristic of FMF, including fever, arthritis, rash, and chest pain, were absent in all five AHP patients, suggesting that “their presence may contribute to exclude AHP in the differential diagnosis,” the team wrote.
“This study emphasizes the importance of considering AHP in the differential diagnosis of patients with suspected FMF, especially in patients with neurological symptoms,” the researchers concluded.
