Gonçalves Maria J, Mourão Ana F, Martinho António, Simões Olívia, Melo-Gomes José, Salgado Manuel, Estanqueiro Paula, Ribeiro Célia, Brito Iva, Fonseca João E, Canhão Helena
Rheumatology Department, Hospital Santa Maria, Lisbon Academic Medical Centre, Lisboa, Portugal; Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; Rheumatology Department, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal.
Front Med (Lausanne). 2017 Mar 1;4:12. doi: 10.3389/fmed.2017.00012. eCollection 2017.
Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).
法布里病（FD）是一种与α-半乳糖苷酶A缺乏相关的溶酶体贮积症。在已确诊的青少年特发性关节炎（JIA）患者中，FD的患病率尚不清楚，但由于肌肉骨骼疼痛可能是就诊时的重要主诉，预计会有误诊病例。通过本研究，我们旨在计算JIA患者队列中FD相关突变的频率。从全国队列中选取了JIA患儿。临床和实验室信息记录在葡萄牙风湿病登记册（http://Reuma.pt）中。进行了检测基因突变的分子遗传学检测。在采用多重聚合酶链反应技术进行DNA扩增后，完成了基因完整序列的直接测序。在292例JIA患者队列中（188例女性，104例男性），有5例患者（均为女性）检测到突变。4例患者有D313Y突变，这是一种罕见变异，与血浆中酶水平低但溶酶体水平正常有关。1例患者出现错义突变R118C，该突变先前在地中海地区的FD患者中已有描述。这是首次对JIA患者队列进行FD突变筛查。未报告“经典”致病性FD突变。发现迟发性FD相关突变R118C的频率为0.34%（1/292）。
