Frequency of Fabry disease in a Juvenile Idiopathic Arthritis Cohort

Abstract

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). During childhood, classic FD symptomatology is rare. The majority of children may show non-specific symptoms, including in the musculoskeletal system. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients is unknown.Objective: This study aimed to identify the frequency of FD in a JIA cohort, characterizing early clinical symptoms, enzyme titers, and GLA genotyping.Methods: Children with JIA followed in a tertiary Children Hospital cohort were selected. Clinical, laboratory and familiar information were recorded. Molecular genetic testing to detect GLA gene mutations was performed in girls and enzymatic analysis in 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). Three additional (3.4%) patients had the enzymatic activity of alpha-galactosidase slightly decreased. We observed the presence of intronic variants in 44.44% of patients in 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 symptoms previously described in the literature. Screening for FD in JIA may be a reasonable strategy for those with an atypical pattern of pain.