Neonatal-Onset Familial Mediterranean Fever in an Infant with Human Parainfluenza Virus-4 Infection

Neonatology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Alexandre Michev ◽  
Alessandro Borghesi ◽  
Caterina Tretti ◽  
Maddalena Martella ◽  
Amelia Di Comite ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Parainfluenza Virus ◽  
Compound Heterozygous ◽  
Inborn Errors ◽  
Immunological Responses ◽  
Inflammatory Conditions ◽  
Neonatal Onset ◽  
Mediterranean Fever ◽  
Compound Heterozygous Variants ◽  
Human Parainfluenza Virus

Unusual, severe infections or inflammatory episodes in newborns and infants are largely unexplained and often attributed to immature immune responses. Inborn errors of immunity (IEI) are increasingly recognized as the etiology of life-threatening inflammatory and infectious diseases in infancy. We describe a patient with a unique neonatal-onset Familial Mediterranean Fever (FMF) due to compound heterozygous variants in <i>MEFV</i>, presenting as pleuritis following human parainfluenza virus-4 infection. Diagnostic challenges of FMF in infancy include the interpretation of the attacks as infectious episodes. Newborns and infants with acute, recurrent, or chronic, unusually severe infectious or inflammatory conditions should be screened for IEI, including both disorders with defective immunological responses and autoinflammatory disorders.

Neonatal onset familial Mediterranean fever

2018 ◽  
Vol 29 (4) ◽  
pp. 647-650 ◽  
Author(s):  
Elif Çelikel ◽  
Z. Birsin Özçakar ◽  
Semanur Özdel ◽  
Nilgün Çakar ◽  
Fatma Aydin ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Neonatal Onset ◽  
Mediterranean Fever

Intercellular adhesion molecule-1 gene polymorphisms in patients with familial mediterranean fever

Open Medicine ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. 679-682
Author(s):  
Senol Kobak ◽  
Arzu Celebi ◽  
Fahrettin Oksel ◽  
Yasemin Kabasakal ◽  
Ulus Akarca
Keyword(s):  
Familial Mediterranean Fever ◽  
Healthy Volunteers ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Unknown Etiology ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Conditions ◽  
Allele Specific ◽  
Mediterranean Fever

AbstractFamilial Mediterranean fever (FMF) is a disease of unknown etiology characterized by recurrent attacks of polyserositis and fever. Intercellular adhesion molecule-1 (ICAM-1) is known to contribute inflammatory conditions by regulating leukocyte localization at inflammatory sites. The aim of this study was to evaluate the probable association of ICAM-1 G/R 241 and ICAM-1 E/K 469 polymorphisms according to susceptibility with FMF. Sixty-seven FMF patients and 83 healthy volunteers were included in the study. Genomic DNA was extracted from EDTA-preserved whole blood of whole series of patients and controls, and genotyped by polymerase chain reaction (PCR) and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 and E/K at codon 469. The ICAM-1 241 genotype and allele frequencies of FMF patients and healthy volunteers were similar. The frequency of ICAM-1 K469 homozygosity was significantly lower in FMF patients than in the controls (32.8% vs 50.7% subsequently, p=0.03). Moreover, ICAM-1 E469 allele was more frequent in FMF patients than in controls (44.8% vs 32.3%, p:0.03). Our results showed that ICAM-1 469 gene polymorphism could contribute to the pathogenesis of FMF.

scholarly journals Molecular Patterns of MEFV Gene Mutations in Egyptian Patients with Familial Mediterranean Fever: A Retrospective Cohort Study

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Amal R. Mansour ◽  
Ayman El-Shayeb ◽  
Nihal El Habachi ◽  
Mohamad A. Khodair ◽  
Doaa Elwazzan ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Mefv Gene ◽  
Gene Mutations ◽  
Signs And Symptoms ◽  
High Serum ◽  
Compound Heterozygous ◽  
Amyloid A ◽  
Egyptian Patients ◽  
Sequencing Studies ◽  
Mediterranean Fever

Background. Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive disease which is mainly seen in the Turks, Armenians, Arabs, and Jews. It is characterized by recurrent episodes of fever, polyserositis, and rash. MEFV gene, encoding pyrin protein, is located on the short arm of chromosome 16. FMF is associated with a broad mutational spectrum in this gene. Certain mutations are more common in particular ethnic groups. To date, different mutations of MEFV were observed in studies carried out in different regions worldwide. However, most of these studies did not extensively investigate the Egyptian population, in spite of the high prevalence of FMF in this geographical region. Aim. To identify the frequency of MEFV gene mutations among the patients who presented with FMF like symptoms and, to characterize the different genetic mutations and their association with increased Amyloid A among Egyptian patients. Methods. FMF Strip Assay (Vienna Lab Diagnostics, Vienna, Austria) was used. This test is based on reverse hybridization of biotinylated PCR products on immobilized oligonucleotides for mutations and controls in a parallel array of allele-specific oligonucleotides. Results. Among the 1387 patients presenting with signs and symptoms suggestive of FMF, 793 (57.2%) were of undefined mutations, whereas 594 had MEFV gene mutations. 363 patients (26.2%) were heterozygous mutants, 175 patients (12.6%) were compound heterozygous mutants, and 56 patients (4%) were homozygous mutants. The most commonly encountered gene mutations in heterozygous and homozygous groups were E148Q (38.6%), M694I (18.1%), and V726A (15.8%). The most commonly encountered gene mutations in the compound heterozygous groups were E148Q+M694I observed in 20.6% of the patients, followed by M694I+V726A and M6801+V726A found in 18.9% and 11.4 %, respectively. The most commonly encountered gene mutation associated with abdominal pain, fever, and high serum Amyloid A was E148Q allele (37.5%). Conclusions. Unlike all previous publications, E148Q allele was found to be the most frequent in the studied patients. Moreover, this allele was associated with increased Amyloid A. 793 patients were free of the 12 studied Mediterranean mutations, which implies the necessity to perform future sequencing studies to reveal other mutations.

Clinical significance of E148Q heterozygous variant in paediatric Familial Mediterranean Fever

Rheumatology ◽  
2021 ◽  
Author(s):  
Irit Tirosh ◽  
Yonatan Yacobi ◽  
Asaf Vivante ◽  
Ortal Barel ◽  
Yishay Ben-Moshe ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Familial Mediterranean Fever ◽  
Clinical Significance ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Leg Pain ◽  
Compound Heterozygous ◽  
Phenotype Correlation ◽  
Heterozygous Variant ◽  
Mediterranean Fever

Abstract Objectives Familial Mediterranean Fever (FMF) results from mutations in the Mediterranean fever (MEFV) gene. The p.E148Q is one of the most frequent protein alternations in the MEFV gene, yet the exact E148Q genotype–phenotype correlation remains unclear. The aim of this study was to examine clinical significance of heterozygous E148Q variant in a paediatric FMF cohort. Methods We compared the clinical manifestations and disease severity score of four genetic sub-groups: (1) patients harboring a single heterozygous p.E148Q variant (n = 6); (2) patients harboring a single p.M694V heterozygous variant (n = 88); (3) patients harboring compound heterozygous p.M694V and p.E148Q variants (n = 36) and (4) homozygotes for p.M694V variant (n = 160). Results Of 646 FMF children from our centre, only 1% (6 patients) of our genetically characterized FMF cohort had a single E148Q variant, most presenting with recurrent fevers and abdominal pain. None of the participants were found to harbor homozygous E148Q. Overall, M694V/E148Q compound heterozygosity did not exhibit a more severe phenotype compared to patients with a single M694V variant. The former group were less likely to have abdominal pain and exertional leg pain (p &lt; 0.004 and p &lt; 0.001 respectively) and more likely to have chest pain (P &lt; 0.01). Both sub-groups showed milder clinical phenotype compared to patients with M694V homozygosity. Conclusion Our findings demonstrate that a single heterozygous E148Q variant is unlikely to cause FMF in children and that E148Q/M694V is clinically indistinguishable from a single M694V variant. Thus, E148Q heterozygosity does not result in clinically meaningful phenotype in children.

scholarly journals Neonatal onset Familial Mediterranean Fever

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
ZB Özçakar ◽  
S Şahin-Kunt ◽  
S Özdel ◽  
F Yalçınkaya
Keyword(s):  
Familial Mediterranean Fever ◽  
Neonatal Onset ◽  
Mediterranean Fever

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

scholarly journals POS0073 ASSOCIATION OF SAA1 GENE POLYMORPHISM -13T/C (RS12218) WITH CRYOPYRIN ASSOCIATED PERIODIC SYNDROMES (CAPS), BUT NOT FAMILIAL MEDITERRANEAN FEVER (FMF)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 243.2-243
Author(s):  
I. Guseva ◽  
E. Fedorov ◽  
S. Salugina ◽  
M. Krylov ◽  
E. Samarkina
Keyword(s):  
Familial Mediterranean Fever ◽  
Gene Polymorphism ◽  
Protein Concentration ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Compound Heterozygous ◽  
Protein Levels ◽  
Amyloid A ◽  
Significant Difference ◽  
Mediterranean Fever

Background:Autoinflammatory diseases (AIDs) are a group of rare, genetically determined diseases characterized by a periodic events of inflammation, fever, and clinical symptoms that mimic rheumatic pathology. Laboratory serological markers of AIDs are C reactive protein (CRP) and serum amyloid A (SAA) protein.Objectives:We investigated whether SAA1 gene polymorphism -13T/C (rs12218) may affect the susceptibility to pediatric FMF and CAPS patients (pts). We also evaluate whether this polymorphism can affect CRP and SAA protein levels.Methods:26 FMF pts - 8 boys, 18 girls; age - M(SD) 7.37(5.32) years and 24 CAPS pts - 12 girls, 12 boys; age – 4.76(5.83) years, and 95 healthy individuals (controls) were included in this study. The diagnosis of FMF was based on Turkish paediatric criteria for the diagnosis of familial Mediterranean fever [1] and was confirmed by the detection of pathogenic mutations of the MEFV gene in the homozygous or compound-heterozygous states. The diagnose of CAPS was made on the basis of characteristic clinical signs and was confirmed by the detection of a pathogenic mutation in the NLRP3 gene. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in FMF and CAPS pts.Results:Table 1 shows the genotypic and allelic frequencies of SSA1 gene in FMF, CAPS and controls. There were no significant differences between FMF pts and controls in the genotypic and allelic distributions of -13T/C gene polymorphism. The frequency of -13C allele was significantly higher in CAPS pts compared with controls (OR=2.03 [CI 1.02-4.03], p=0.03). Moreover, a statistically significant difference was revealed in the genotypic and allelic distributions between FMF and CAPS pts groups (p=0.047 and p=0.02 respectively). The CRP levels did not correlate with SAA1 - 13T/C polymorphism. The SAA protein concentration was associated with SAA1 gene polymorphism in FMF pts (p=0.036).Table 1.The distribution of genotypes and alleles of SAA1 gene polymorphism -13T/C in FMF, CAPS and control groups.Genotypes/AllelesFMFn=26 (%)CAPSn=24 (%)Controlsn=95 (%)TT12 (46,2)4 (16,7)39 (41,1)TC12 (46,2)14 (58,3)42 (44,2)CC2 (7,7)6 (25,0)14 (14,7)P (pts vs controls)>0,05>0,08T24 (63,2)21 (50,0)80 (61,5)C14 (36,8)21 (50,0)50 (38,5)P (pts vs controls)>0,050.03Conclusion:Our preliminary study in small groups of pediatric FMF and CAPS pts revealed that SAA1 gene polymorphism -13T/C (rs12218) is associated with susceptibility to CAPS, but not FMF. The influence of this polymorphism on SAA protein levels in FMF pts was also shown. Further investigations are required to clarify the role of SAA1 gene polymorphism -13T/C in susceptibility to FMF and CAPS in large studies in different ethnic and population groups.References:[1]Yalcinkaya F, Ozen S, Ozcakar ZB, et al. Rheumatology (Oxford). 2009,48(4): 395-8. doi: 10.1093/rheumatology/ken509.Disclosure of Interests:None declared.

scholarly journals Familial Mediterranean Fever with Neonatal Onset: Case Report

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Kübra Arslan ◽  
Serdar Ümit Sarici ◽  
Gonca Kolukisa ◽  
Demet Altun
Keyword(s):  
Familial Mediterranean Fever ◽  
Joint Pain ◽  
Fever Of Unknown Origin ◽  
Clinical Course ◽  
Unknown Origin ◽  
Recurrent Fever ◽  
Age Group ◽  
Neonatal Onset ◽  
Mediterranean Fever ◽  
Occult Bacteremia

Familial Mediterranean fever (FMF) is an autosomal recessively inherited disorder characterized by recurrent fever and attacks of abdominal pain, chest pain, and joint pain. Attacks of recurrent fever and serositis are encountered clinically. Attacks may present either with only one symptom or many simultaneous symptoms. Although most of the patients are diagnosed clinically above the age of 2, those cases who are diagnosed before 2 years of age and with clinical course of isolated fever are believed to have a more serious course and tend to develop amyloidosis. In this article, a case who was admitted first on the 22nd day of life and later diagnosed to have FMF with recurrent attacks of isolated fever and no other focus is presented. We emphasize that FMF may present as early as in the first month of life, and it should be considered in cases presenting with fever of unknown origin and misdiagnosed to have late neonatal sepsis or occult bacteremia at this age group.

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