SAT0522 COMPARISON OF CHILDREN CARRYING E148Q VARIANT WITH CHILDREN CARRYING HOMOZYGOUS PATHOGENIC VARIANTS
Authors: Ayşe Tanatar, Şerife Gül Karadağ, Hafize Emine Sonmez, Mustafa Çakan, Nuray Aktay Ayaz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Familial Mediterranean fever (FMF) is the most frequent autoinflammatory disease. Nearly 300 <i>MEFV</i> variants had been reported and recorded in INFEVERS database. The most common disease-associated variants are mapped on exon 2 and 10 of chromosome 16. Although <i>E148Q</i> variant is the most common one among carriers, its role as a disease causing mutation is still debate (1). <h3>Objectives:</h3> The aim of our study was to evaluate and compare the demographic data, clinical features and severity scores of patients carrying only <i>E148Q</i> variant with the patients homozygous for pathogenic MEFV mutations (<i>M694V, M694I, M680I, V726A</i>). One of our objective was to test and compare these two groups for the diagnostic utility of 2 adults and 1 pediatric FMF diagnostic criteria (Tel Hashomer, Livneh and Pediatric) (2-4). <h3>Methods:</h3> The medical records of 1685 children diagnosed and followed up as FMF were reviewed retrospectively. The demographic, clinical and genetic data of children carrying only <i>E148Q</i> variant (either heterozygous or homozygous carriers) (group 1) and children with pathogenic homozygous mutations (<i>M694V, M694I, M680I, V726A</i>) (group 2) were collected. All patients were evaluated for three diagnostic criteria. <h3>Results:</h3> Children with <i>E148Q</i> variant were 128 and children with pathogenic homozygous variants were 429. Male to female ratio was 1.13 in group 1 and 1.15 in group 2 (p&gt;0.05). The mean age of patients in group 1 was 12.1±4.7, in group was 2 14±5.9 (p&lt;0.001). The mean age of symptom onset was 5.4±4.1 in group 1, 4.3±3.6 in group 2 (p=0.01. Consanguinity was significantly higher in group 2 (29% <i>vs</i> 53%, p&lt;0.01). In group 1 17.9% had a sibling with FMF, while in group 2 27% had a sibling with FMF (p=0.03). Clinical features like pleuritis, synovitis, recurrent fever, erysipelas-like erythema and monoarthrtis were significantly more common in group 2 than group 1(31.7% <i>vs</i> 9.3%; p&lt;0.001, 55.9% <i>vs</i> 32%; p&lt;0.001, 86.9% <i>vs</i> 78.9%; p&lt;0.03, 31.2% <i>vs</i> 7%; p&lt;0.001, 51.7% <i>vs</i> 28.1%; p&lt;0.001, respectively). Incomplete attacks were significantly more common in group 1 than group 2 (16.4% <i>vs</i> 7.4%; p&lt;0.005). Moderate and severe PRAS scores were significantly higher in group 2 (93.9% <i>vs</i> 71.9%; p&lt;0.001). Laboratory values like C-reactive protein, erythrocyte sedimentation rate, serum amyloid A were found significantly higher in group 2 than group 1. (3.6±6.3 <i>vs</i> 0.8±1.2; p&lt;0.001, 13±10<i> vs</i> 7.3±6; p&lt;0.001, 6.9±22.5 <i>vs</i> 2.9±2.2; p=0.007, respectively). The percentage of children diagnosed according two Tel Hashomer and pediatric criteria was significantly higher in group 2 than group 1 (88.5% <i>vs</i> 77.3%; p=0.002, 95.3% <i>vs</i> 84.3%; p&lt;0.001, respectively). But both groups show similar diagnostic utility according to Livneh criteria. <h3>Conclusion:</h3> Although children carrying <i>E148Q</i> variants meet the three validated diagnostic criteria of FMF. They had milder course of disease than children homozygous for pathogenic <i>MEFV</i> variants both clinically and in laboratory means. <h3>References</h3> [1] Touitou I (2001) The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet9, 473–83 [2] Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean fever. A survey of 470 cases and review of the literature. The American journal of medicine43:227-253 [3] Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis and rheumatism40:1879-1885. [4] Yalcinkaya F, Ozen S, Ozcakar ZB, Aktay N, Cakar N, Duzova A, Kasapcopur O, Elhan AH, Doganay B, Ekim M, Kara N, Uncu N, Bakkaloglu A (2009) A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford, England) 48:395-398. <h3>Disclosure of Interests:</h3> None declared