Abstract

The aims of this study were to investigate the main clinical and laboratory features, including pregnancy and genetic analysis, of Turkish Familial Mediterranean Fever (FMF) patients and to analyze the relationships between genotypic features, age of disease onset, clinical findings, and disease severity. A study was planned within a national network of 22 different centers. Demographics, clinical and laboratory findings, attack characteristics, drugs, pregnancy and birth history, disease severity, and gene mutation analyses were evaluated. Disease severity, assessed using a scoring system developed by Pras et al., was evaluated in relation to gene mutations and age of disease onset. A total of 979 patients (643 females and 336 males; mean age: 35.92 ± 11.97 years) with FMF were included in the study. Of a total of 585 pregnancies, 7% of them resulted in preterm birth and 18.1% resulted in abortions. During pregnancy, there was no FMF attack in 61.4% of patients. Of the MEditerranean FeVer (MEFV) mutations, 150 (24.3%) cases were homozygous, 292 (47.3%) cases were heterozygous, and 175 (28.4%) were compound heterozygous. Patients with homozygous gene mutations had more severe disease activity, earlier age of disease onset, higher rates of joint and skin involvement, sacroiliitis, and amyloidosis. Patients with compound heterozygous genotype displayed severe disease activity in close resemblance to patients with homozygous mutation. In addition, patients with compound heterozygous mutations had higher rates of protracted febrile myalgia and elevated fibrinogen levels. In 63.9% of compound heterozygous patients, age of onset was < 20 years, with greater disease severity, and high rates of attack frequency and colchicine resistance. Our results suggest that indicators for disease severity include early onset of disease and homozygous gene mutations. Furthermore, patients with compound heterozygous mutations displayed significant presentations of severe disease activity.

中文翻译：

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家族性地中海热：评估全国队列的临床表现，妊娠，遗传突变分析和疾病严重性

摘要

这项研究的目的是调查土耳其家族性地中海热病（FMF）患者的主要临床和实验室特征，包括妊娠和基因分析，并分析基因型特征，疾病发作年龄，临床发现和疾病严重程度之间的关系。 。计划在由22个不同中心组成的全国网络内进行一项研究。对人口统计学，临床和实验室检查结果，发作特征，药物，妊娠和出生史，疾病严重程度以及基因突变分析进行了评估。使用由Pras等人开发的评分系统评估的疾病严重程度，与基因突变和疾病发作年龄相关。该研究共纳入979名FMF患者（643名女性和336名男性；平均年龄：35.92±11.97岁）。在总共585次怀孕中，其中7％导致早产，18.1％导致流产。在怀孕期间，有61.4％的患者没有FMF发作。在MEditerranean FeVer（MEFV）突变中，纯合子为150（24.3％），杂合子为292（47.3％），复合杂合为175（28.4％）。具有纯合子基因突变的患者具有更严重的疾病活动，更早的疾病发作年龄，更高的关节和皮肤受累率，cro关节炎和淀粉样变性病。具有复合杂合基因型的患者表现出严重的疾病活动，与具有纯合突变的患者非常相似。此外，具有复合杂合突变的患者长期发热性肌痛的发生率较高，纤维蛋白原水平升高。在63.9％的复合杂合患者中，发病年龄<20岁，疾病严重程度更高，以及较高的发作频率和秋水仙碱抗性。我们的结果表明，疾病严重程度的指标包括疾病的早期发作和纯合基因突变。此外，具有复合杂合突变的患者表现出严重疾病活动的明显表现。