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Genetic and clinical features of Familial Mediterranean Fever in a cohort of patients with kidney failure

First author: Ahmed Sheyyab

Journal: Journal of Nephrology

Author of the abstract: Rim BOURGUIBA

Graphical abstract de l'article

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In its classic form, it is mainly associated with mutations in exon 10 of the MEFV gene. AA amyloidosis is the most severe complication of FMF.


The aim of this study was to compare the frequency of MEFV variants in hemodialysis patients versus healthy controls in a Mediterranean country, Jordan.


Methods

This was a cross‑sectional study including 78 patients with end‑stage kidney disease on hemodialysis and 201 healthy controls in Jordan. All patients underwent Sanger sequencing for the main MEFV variants. The following variants were tested: p.E148Q, p.P369S, p.F479L, p.M680I (G/C), p.M680I (G/A), p.I692del, p.M694V, p.M694I, p.K695R, p.V726A, p.A744S, and p.R761H.


Patients carrying a variant were then clinically assessed according to the Tel‑Hashomer criteria. Five underwent rectal biopsy to detect amyloidosis.


Results

Among dialysis patients, 16% had at least one MEFV variant versus 12.9% in the control group (not significant). The two most frequent mutations in the hemodialysis group were M694V (p = 0.035) and V726A (p = 0.009). The variants detected in both groups are summarized in Table 1. In the control group without renal failure, 22 individuals were heterozygous for the E148Q variant. Three patients met diagnostic criteria for FMF, and one case of AA amyloidosis was confirmed by biopsy.


Conclusion

FMF is the most common autoinflammatory disease in Mediterranean countries, yet it remains underdiagnosed even in high‑risk populations. This diagnostic delay leads to complications, notably AA amyloidosis. This study shows that 4% of hemodialysis patients were diagnosed with FMF. It also confirms the non‑pathogenic nature of the E148Q variant, which was detected in 22 healthy, asymptomatic individuals.


Overall, these findings underscore the importance of testing for MEFV mutations in patients with AA amyloidosis in countries where FMF is highly prevalent, in order to offer appropriate treatment to prevent AA amyloidosis and progression to renal failure.


Résultats du dépistage génétique du gène MEFV montrant le taux de fréquence des variants détectés dans les groupes souffrant d'insuffisance rénale et dans les groupes témoins

 
 
 

Adult Familial Mediterranean Fever (FMF): is a single MEFV mutation sufficient to cause severe disease?

Article title: Clinical characteristics and outcomes of adult FMF patients: comparison between those with one versus two

pathogenic MEFV exon 10 mutations

First author: Anaël Dumont

Journal: Joint Bone Spine

Author of the abstract: Rim BOURGUIBA


FMF adulte : une seule mutation MEFV suffit‑elle à rendre la maladie sévère ?

Introduction

Familial Mediterranean Fever (FMF) is an autoinflammatory disease caused by mutations in MEFV. While two pathogenic mutations typically lead to a classic and more severe phenotype, the clinical expression in patients with only one pathogenic mutation remains debated. This study compared adult FMF patients according to whether they carried one or two pathogenic MEFV mutations.


Methods

A French single‑center retrospective cohort included 581 adult FMF patients: 178 with a single pathogenic mutation and 403 with two pathogenic mutations. Diagnosis used Eurofever/PRINTO criteria, and all patients underwent MEFV sequencing. A focused analysis compared M694V/E148Q versus M694V/WT.


Results

Compared with biallelic patients, heterozygous patients were older at diagnosis and disease onset, had more personal and family history of recurrent aphthous stomatitis, and a higher BMI. No AA amyloidosis was observed in heterozygotes, and they required lower colchicine doses. These differences remained significant after adjustment for age at onset. No clinical difference was found between M694V/E148Q and M694V/WT.


Conclusion

Adult FMF patients with a single pathogenic MEFV mutation show distinct clinical features and outcomes compared with those carrying two mutations. Findings highlight FMF phenotypic heterogeneity and support tailoring management to the patient’s genetic profile.



 
 
 

Clostridioides difficile infection as a potential trigger for Familial Mediterranean Fever attacks and fecal transplantation as a rescue

Premier auteur: Sophie Georgin-Lavialle

Revue: European Journal of Internal Medicine

Clostridioides difficile infection as a potential trigger for Familial Mediterranean Fever attacks and fecal transplantation as a rescue

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease in the world. It is associated with mutations in the MEFV gene, which encodes pyrin.


The diagnosis of Clostridium difficile infection is complex in patients with FMF, as during FMF crises, the most frequent symptoms include febrile abdominal pain accompanied by a biological inflammatory syndrome, manifestations common to both conditions.

The B toxin of Clostridium difficile is a specific activator of the pyrin inflammasome.

Clostridium difficile infection complicating FMF is a rare but serious and potentially fatal infection.


It should be suspected in FMF patients presenting with unexplained persistent inflammation and/or chronic abdominal pain and/or unusual diarrhea.


=> The B toxin of C. difficile can then be tested in stool samples to exclude a false resistance to colchicine and avoid mistakenly starting anti-interleukin 1 biotherapy.


=> C. difficile infection in an FMF patient must be actively treated, including fecal transplantation if necessary.



 
 
 
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