Frequency of Fabry Disease in a Juvenile Idiopathic Arthritis Cohort
Background: Fabry disease (FD) is a rare, X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (⍺-GalA). In childhood, classic FD symptomatology is rare. Majority of children present with mild non-specific symptoms, including the musculoskeletal system. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients is unknown. Objective: The aim was to identify the frequency of FD in a JIA cohort, characterizing
... arly clinical symptoms, enzyme titers and GLA genotyping. Methods: Children with JIA followed in tertiary Children Hospital cohort were selected. Clinical, laboratorial, and familiar information was recorded. Molecular genetic testing to detect GLA gene mutations was performed in the girls and enzymatic analysis in the boys. Results: In 89 patients (56.2% female, age at disease onset: 8.93 ± 4.35 years), one male (1.12%) patient presented pathogenic mutation in GLA gene, c.1244T>C p.L415P, one female patient had a variant of uncertain significance c.38C>T (p.Ala13Val). The enzymatic activity of alpha galactosidase was slightly decreased in 3 additional (3.4%) patients. We observed the presence of intronic variants in 44.44% of our cohort: c.1000-22C> T; c.370-81_-77del; c.640-16A> G; c.10C>T; c.548-125C> G and c.-12G> A. These variants and their combination were associated with clinical symptoms in our cohort. Conclusions: The incidence of FD in our cohort was 1.12%. Intronic variants were associated with symptomatology described in the literature. Screening for FD in JIA may be a reasonable strategy for those with atypical pattern pain.