AB0980 CASE-REVIEW ON FAMILIAL MEDITERRANEAN FEVER IN A SPECIALIZED CENTRE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1784.1-1784
Author(s):  
R. Dos Santos Sobrín ◽  
M. Martí Masanet ◽  
B. Lopez-Montesinos ◽  
L. Lacruz Pérez ◽  
I. Calvo
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Severe Disease ◽  
Strong Association ◽  
Mefv Gene ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Case Series ◽  
Case Review ◽  
Mediterranean Fever

Background:Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder caused mostly by mutations in MEFV gene. Its inheritance is autosomal recessive and is the most frequent periodic fever syndrome. First-line treatment is based in colchicine use, so biologics (anti-IL-1) are reserved for refractory cases1, 2.Objectives:To account for clinic and treatment features of patients with FMF in a specialized center as opposed to non-referent centers.Methods:This study was developed in the Pediatric Rheumatology Service in Hospital Universitario y Politécnico La Fe de Valencia. Demographic, clinic and treatment data were collected from patients diagnosed of FMF since January 2004 to September 2019.Results:106 patients met last FMF criteria3. 55% had a pathogenic mutation in genetic analysis. 52% were female. Before 10 years old, 71% of patients had the diagnosis (51% before 4 years old). Arthralgia/myalgia (73%), periodic fever (62%) and abdominal pain (54%) were the most common symptoms. Systemic Juvenile Idiopathic Arthritis (JIA, 6), other forms of JIA (9) and vasculitis (10) were the most prevalent comorbidities. When talking about treatment, 76,4% received Colchicine (60,5% with good response), 22,6% needed a classical disease modifying antirheumatic drug (mostly Methotrexate) and 22 patients got biologic treatment (73% anti-IL-1).Conclusion:When analyzing this case-review, JIA has a strong association with our patients, so it could explain severe disease activity and more articular involvement. This could be an illustration to the higher use of Methotrexate. Also, the most relevant symptom was arthralgia while fever is the most frequent in literature. Likewise, age of diagnosis has been earlier than other case-series (this would be more frequent in other autoinflammatory syndromes, as literature relates)1, 2, 4.References:[1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. (2019).[2]Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644-651.[3]Sag E, Demirel D, Demir S, et al. Performance of the new “Eurofever/PRINTO classification criteria” in FMF patients. Semin Arthritis Rheum. 2019;19:30369-5.[4]Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2004;22:S75-8.Disclosure of Interests:Raquel Dos Santos Sobrín: None declared, Miguel Martí Masanet: None declared, B Lopez-Montesinos: None declared, Lucía Lacruz Pérez: None declared, Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe & Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis

Genetic Screening of Familial Mediterranean Fever in Japan.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3846-3846
Author(s):  
Yasuko Miyahara ◽  
Kouhei Yamashita ◽  
Takashi Miyoshi ◽  
Akifumi Takaori ◽  
Masataka Sasada ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Genetic Screening ◽  
Large Scale ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Unknown Origin ◽  
Polymorphonuclear Cells ◽  
Exon 2 ◽  
Mediterranean Countries ◽  
Mediterranean Fever

Abstract There have been few reports of the patients with Familial Mediterranean Fever (FMF) in Japan, probably because FMF patients are preoccupied to be rare in Japan. We experienced 10 cases likely to be clinically diagnosed as FMF with periodic fever of unknown origin. FMF is an autosomal recessive disease resulting from the genetic mutations in the FMF gene (MEFV), which codes for a protein named Pyrin. Pyrin is expressed in mainly polymorphonuclear cells and monocytes and it is proposed that it regulates inflammation. The MEFV gene is located on chromosome 16p13.3 and comprises 10 exons. Several mutations in the MEFV gene have been identified, however the mutations are mostly located in exon 2 and 10. Therefore, we performed genetic screening of exon 2 and 10 in the 10 patient samples. The median age of the patients was 34 (17–49) years old. They are four males and six females. DNA was isolated from polymorphonuclear cells of the patients and PCR was performed with selective primers of exon 2 and 10 of MEFV gene, respectively. Thereafter, direct sequence of exon 2 and 10 of the PCR products was performed. As a result, the mutations of E148Q in exon 2 and M694I in exon 10, which are commonly observed in previous reports, were identified in seven and six out of 10 patients, respectively. All patients had either E148Q or M694I mutation. Three patients have both E148Q and M694I mutations. One 50-year-old female patient, who had a homozygous M694I mutation, suffered from severe renal AA amyloidosis. The mutation at M694 has been mostly reported as M694V, particularly in Mediterranean countries, however interestingly, all of the mutations of M694 were M694I, not M694V in our 10 Japanese patients. It is reported that healthy carrier frequency of the E148Q mutation was about 16% in Japan, so it is suggested that E148Q mutation may be profoundly involved in cause of disease, because E148Q mutation is observed among 70% of our patients. We herein report the unique genetic features of FMF patients in Japan. A further large scale of investigation would be necessary for confirming the significance of E148Q and M694I mutations in FMF patients in Japan.

scholarly journals Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in Familial Mediterranean Fever

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
E. Verrecchia ◽  
L. L. Sicignano ◽  
M. La Regina ◽  
G. Nucera ◽  
I. Patisso ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Bacterial Overgrowth ◽  
Colchicine Treatment ◽  
Small Intestinal Bacterial Overgrowth ◽  
Centre Database ◽  
Mediterranean Fever ◽  
Small Intestinal ◽  
Glucose Breath Test

Objective. Familial Mediterranean fever (FMF) is an autosomal recessive disease due to a MEFV gene mutation. Since Helicobacter pylori infection has been described to increase the severity and frequency of FMF attacks, we evaluate if overgrowth of small intestinal bacterial (SIBO), associated with a release of bacterial products, can affect the response to colchicine in FMF patients poorly responsive to colchicine. Methods. We revised our Periodic Fever Centre database to detect FMF patients who were poorly responsive to colchicine, without a well-defined cause of drug resistance. They were evaluated for SIBO presence, then treated with decontamination therapy. Results. Among 223 FMF patients, 49 subjects show colchicine resistance, and no other known causes of colchicine unresponsiveness has been found in 25 patients. All 25 patients underwent glucose breath test; 20 (80%) of them were positive, thus affected by SIBO. After a successful decontamination treatment, 11 patients (55%) did not show FMF attacks during the following three months (p<0.01), while 9 of them revealed a significant reduction of the number of attacks compared to three months before (p<0.01). Conclusion. The SIBO eradication improves laboratory and clinical features of FMF patients. Thus, patients with unresponsiveness to colchicine treatment should be investigated for SIBO.

scholarly journals POS1302 THE MUSCULOSKELETAL SYSTEM MANIFESTATIONS IN CHILDREN WITH FAMILIAL MEDITERRANEAN FEVER

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 933.1-933
Author(s):  
F. Demir ◽  
S. Canbek ◽  
B. Sözeri
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Musculoskeletal Symptoms ◽  
Compound Heterozygous ◽  
M694v Mutation ◽  
Musculoskeletal Manifestations ◽  
Mediterranean Fever ◽  
Calf Pain

Background:Familial Mediterranean fever (FMF) is a monogenic inherited periodic fever syndrome presenting with episodes of self-limiting fever and inflammation of serosal membranes. The attacks emerge with arthritis were defined as one of the major diagnostic criteria besides involvement of serosal membranes. Non-specific musculoskeletal findings such as myalgia, arthralgia, transient synovitis, and more rare manifestations like protracted febrile myalgia can also be seen in FMF patients attacksObjectives:We aim to reveal the frequency and genotype association of musculoskeletal manifestations in children with FMF.Methods:The patients diagnosed with FMF between January 1, 2017 and June 1, 2019, and followed for at least 6 months in our pediatric rheumatology clinic were included in the study. Musculoskeletal manifestations of patients were enrolled. The patients were grouped according to the “Mediterranean Fever” (MEFV) gene variants. Musculoskeletal manifestations of the patients were compared between the groupsResults:The study group included 634 children with FMF (336 female and 298 male, F/M: 1.13/1). The clinical manifestations of patients in attack period were as follows: 99% of the patients had fever, 87.3% had abdominal pain, 20.7% had chest pain, 11.3% had vomiting, 10.7% had erysipelas like erythema, and 9.3% had headache. The musculoskeletal symptoms were accompanied by 58.6% (n: 372) of the patients during the attack period. The most common musculoskeletal manifestation was found as arthralgia (32.6%, n: 206). Also, the other musculosceletal manifestations were found as follows during attacks; arthritis in 23.7% (n: 150), myalgia in 20.5% (n: 130), exertional calf pain in 6.5% (n: 41), and protracted febrile myalgia in 1% (n: 7) of the patients. It was observed that the musculoskeletal manifestations were significantly higher in patients with homozygous M694V variant in exon-10 (p=0.017). Also, it was found that the musculoskeletal manifestations are more common in the attack periods of patients carrying the M694V variant in at least one allele (p = 0.019).Conclusion:It was determined that the musculoskeletal manifestations were seen as an attack symptom in more than half of FMF patients. Also, homozygous and compound heterozygous MEFV mutations including M694V variant found as a risk factor for emerge of musculoskeletal manifestations. In children with unexplained and recurrent musculoskeletal symptoms, especially in ethnicities with the high frequency of FMF, analysis of MEFV gene can help reveal the underlying cause.References:[1]Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R. The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum 2001;44:1416-9.[2]Jarjour RA, Dodaki R. Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep 2011;38:2033-6.Disclosure of Interests:None declared

Clinical and molecular analysis of common MEFV gene mutations in familial Mediterranean fever in Sivas population

Biologia ◽  
2009 ◽  
Vol 64 (2) ◽  
Author(s):  
Binnur Koksal ◽  
Naim Nur ◽  
Musa Sari ◽  
Ferhan Candan ◽  
Mursit Acemoglu ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Severe Disease ◽  
Mefv Gene ◽  
Point Mutations ◽  
Gene Mutations ◽  
Homozygous Mutation ◽  
Frequent Mutation ◽  
Mefv Mutations ◽  
Wide Range ◽  
Mediterranean Fever

AbstractFamilial Mediterranean fever (FMF) is the most frequent hereditary inflammatory disease characterized by self-limited recurrent attacks of fever and serositis. The aim of the current study is to determine the frequency of the mutations in 365 suspected FMF patients and to reveal whether there is a correlation between genotype and phenotype of these patients. All patients were clinically examined according to Tell-Hashomer FMF criteria and were screened genetically in terms of common 12 Mediterranean fever gene (MEFV) mutations. Various point mutations were detected in 270 (74%) patients. The most frequent mutation was M694V (26.85% of the alleles) and was followed by E148Q (15.55%), M680I (G/C) (9.62%) and V726A (7.96%). Patients who bear M694V homozygous mutation had most severe disease phenotype and high risk for amyloidosis (P = 0.04). Our results indicate that Sivas population has a wide range of heterozygous mutated carriers of MEFV gene and there is a high frequency of E148Q allele when compared to the other Mediterranean groups.

scholarly journals Atypical Familial Mediterranean Fever in a Japanese Boy with Heterozygous MEFV p.Ser503Cys Exon 5 Variant

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Tomonobu Sato ◽  
Shunichiro Takezaki ◽  
Takeru Goto ◽  
Shinichi Ishikawa ◽  
Kazumi Oura ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Colchicine Treatment ◽  
Clinical Findings ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes ◽  
Mediterranean Fever ◽  
Accompanying Symptoms

Periodic fever syndromes are heterogeneous diseases. Familial Mediterranean fever (FMF) is one of the hereditary periodic fever diseases caused by a Mediterranean fever (MEFV) gene abnormality. FMF can be categorized as typical or atypical, based on clinical findings and genetic screening. Atypical FMF has a wide variation of clinical findings and disease-causing mutations of MEFV. Therefore, it is sometimes difficult to diagnose an unknown fever as FMF. To date, a large number of various typical and atypical FMF cases have been reported in Japan. Here, we describe a Japanese boy with heterozygous MEFV p.Ser503Cys exon 5 variant who developed periodic fever. He was treated with colchicine; a complete eradication of his fever and various accompanying symptoms have been subsequently achieved for more than a year. Given that there have been a few reports about patients with this variant, little is known about the genetic and phenotypic role of heterozygous MEFV p.Ser503Cys exon 5 variant. It is therefore imperative to consider atypical FMF as a differential diagnosis when a periodic fever is encountered. Furthermore, we suggest that it is worthwhile to integrate MEFV gene analysis with the potential effects of colchicine treatment in patients with periodic fever.

scholarly journals A case report of a boy suffering from type 1 diabetes mellitus and familial Mediterranean fever

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Maria Francesca Gicchino ◽  
Dario Iafusco ◽  
Angela Zanfardino ◽  
Emanuele Miraglia del Giudice ◽  
Alma Nunzia Olivieri
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Familial Mediterranean Fever ◽  
Autoimmune Diseases ◽  
Type 1 Diabetes Mellitus ◽  
Medical Literature ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Mediterranean Fever

Abstract Background Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF). Case presentation A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15–30 days with peaks that reached 40 °C and lasted 24–48 h. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response. Conclusion Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto’s Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.

scholarly journals Spectrum of Mutations of Familial Mediterranean Fever Gene by Whole Sequencing Method in Iranian Patients

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Helal Nemat Farahzadi ◽  
Mohammad Taghi Akbari ◽  
Reza Shiari ◽  
Shohre Zare Karizi ◽  
Shirin Farivar
Keyword(s):  
Familial Mediterranean Fever ◽  
Age Of Onset ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Western Mediterranean ◽  
Compound Heterozygous ◽  
Mediterranean Population ◽  
Pathogenic Mutations ◽  
Sequencing Method ◽  
Mediterranean Fever

Background: Familial Mediterranean fever (FMF) is the most common type of periodic fever syndrome. The disease is most prevalent in the western Mediterranean population, but today it is widespread in the world due to the large ethnic migrations of Turks, Jews, Arabs and Armenians. The MEFV gene is the only gene known to be associated with the disease. Objectives: The aim of this study was to characterize pathogenic mutations in patients with typical FMF symptoms by sequencing the entire MEFV gene. Methods: This is a descriptive-analytical study that was performed during ten years from 2009 to 2019. On 252 patients after clinical diagnosis based on existing criteria to determine mutations referred to Tehran Medical Genetics Laboratory and the whole sequencing method for MEFV gene was used to determine mutations. Results: Out of 252 patients, 143 (56.7%) had pathogenic variants, and 109 (43.3%) had no variants reported as pathogenic mutations. Variants were identified as fallow: (1) 8.7% as homozygous; (2) 22.2% as compound heterozygous; (3) 25.7% as heterozygous. The most common variants were M694V (c.2080A > G) and E148Q (c.442G > C). Conclusions: This study showed that the age of onset of the disease was in the first and second decades of life amongst our patients and the most common complaints of patients were periodic fever and abdominal pain. The most frequent allele was M694V (c.2080A > G) followed by E148Q (c.442G > C) allele.

scholarly journals Familial Mediterranean Gene (MEFV) Mutation in Parents of Children with Familial Mediterranean Fever: What Are the Exceptions?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Leila Shahbaznejad ◽  
Sayed-Reza Raeeskarami ◽  
Raheleh Assari ◽  
Abbas Shakoori ◽  
Hamidreza Azhideh ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Cross Sectional Study ◽  
Compound Heterozygote ◽  
Mefv Mutation ◽  
Cross Sectional ◽  
Fever Syndromes ◽  
History Of ◽  
Mediterranean Fever

Objectives. Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients. Methods. In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization. Results. Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents’ mutation, except 2 whose parents had no mutation, but a patient did. Conclusion. It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently.

A case report of a boy suffering from Type 1 Diabetes Mellitus and Familial Mediterranean Fever

2020 ◽  
Author(s):  
maria francesca gicchino ◽  
Dario Iafusco ◽  
Angela Zanfardino ◽  
Emanuele Miraglia del Giudice ◽  
Alma Nunzia Olivieri
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Familial Mediterranean Fever ◽  
Autoimmune Diseases ◽  
Type 1 Diabetes Mellitus ◽  
Medical Literature ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Mediterranean Fever

Abstract Background: Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF)Case presentation: A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15-30 days with peaks that reached 40°C and lasted 24-48 hours. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response.Conclusion. Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto’s Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.

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