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THU0518 Fabry's Mutation Screening in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients
  1. M.J. Gonçalves1,2,
  2. A.F. Mourão2,3,
  3. J. Melo-Gomes4,
  4. M. Salgado5,
  5. C. Ribeiro6,
  6. I. Brito7,
  7. J.E. Fonseca1,2,
  8. H. Canhão1,2
  1. 1Rheumatology, Hospital Santa Maria, Lisbon Academic Medical Centre
  2. 2Rheumatology Research Unit, Instituto de Medicina Molecular
  3. 3Rheumatology, Hospital Egas Moniz
  4. 4Instituto Portugues de Reumatologia, Lisbon
  5. 5Rheumatology Unit, Hospital Pediatrico de Coimbra, Coimbra
  6. 6Rheumatology, Hospital de Faro, Faro
  7. 7Rheumatology, Centro Hospitalar S. João, Porto, Portugal


Background Fabry's disease (FD) is a lysosomal storage disorder initiated by sphingolipid accumulation owing to a deficiency of the enzyme a-galactosidase A (a-Gal A). Classically affected males present with pain (more frequently, acroparestesias in the extremities, but also episodes of joint pain associated with fever and high erythrocyte sedimentation rate), cutaneous lesions and gastrointestinal symptoms. During the course of the disease, renal, cardiac and cerebrovascular complications often develop, causing high morbidity and premature death. Clinical picture in females is more heterogeneous, with some patients having a milder phenotype.

The prevalence of FD among patients diagnosed as juvenile idiopathic arthritis (JIA) is unknown, but as musculoskeletal pain may be a chief complaint at presentation, the presence of misdiagnosed cases is probable. Biochemical analysis (such as measurement of α-Gal enzyme activity in plasma) is frequently used for diagnosis purposes. However, molecular analysis is a more sensitive method, allowing the diagnosis in the subset of patients who have normal enzymatic levels. The correct diagnosis can prevent the progression of FD and avoid the exposure to immunosuppressant treatments used in JIA children that are useless for this condition.

Objectives With this study, we aim to calculate the frequency of FD in a population of JIA patients.

Methods Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded at regular time points, according to clinical practice in the Portuguese nationwide register

Molecular genetic testing to detect GLA mutations was performed. After the multiplex PCR technique for amplification of DNA fragments to optimize reactions, direct sequencing of the complete sequence of GLA gene (7 exons) was performed to identify mutations.

Results From a cohort of 292 patients with JIA (188 female, 104 male), mutations were identified in 5 patients (all female). 4 patients had the alpha-Gal A gene mutation D313Y, a rare variant, that 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 patient is a girl that presented with a persistent oligoarticular form of JIA at the age of 3 years old, now being treated with steroid intra-articular injections and conventional DMARDs.

Conclusions Excluding the D313Y alteration, which is thought not to be clinically relevant, FD mutation (R118C) presented in a frequency of 1 in 292 individuals within this nationwide JIA cohort. As our patient is a heterozygotic female, we cannot ascertain a final diagnosis of FD. The patient and her family are under further clinical investigation.

A low threshold for FD screening in JIA patients should be warranted. An early diagnosis of FD in those patients can lead to implementation of a specific therapy and allow the study of their families.


  1. Niemann M, et al. Lyso-Gb3 Indicates that the Alpha-Galactosidase A Mutation D313Y is not Clinically Relevant for Fabry Disease, JIMD Rep. 2013;7:99-102

Disclosure of Interest None declared

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