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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.1244 T > 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.
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.1244 T > 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.
摘要：
背景：法布里病（FD）是一种罕见的疾病，X-linked,多系统溶酶体贮积症（LSD），由水解酶α-半乳糖苷酶A（ω-GalA）缺乏引起。在童年时期,典型的FD症状很少见。大多数儿童可能表现出非特异性症状，包括肌肉骨骼系统。幼年特发性关节炎（JIA）患者中FD的患病率未知。
目的：本研究旨在确定JIA队列中FD的频率，表征早期临床症状，酶滴度，和GLA基因分型。
方法：选择在三级儿童医院队列中随访的JIA儿童。临床,记录实验室和熟悉的信息。在女孩中进行了分子遗传学检测以检测GLA基因突变，在男孩中进行了酶促分析。
结果：在89例患者中（56.2％为女性，发病年龄：8.93±4.35岁），1例男性(1.12%)患者出现GLA基因致病突变,c.1244T>Cp.L415P，一名女性患者具有不确定意义的变异c.38C>T（p。Ala13Val）。另外三名（3.4％）患者的α-半乳糖苷酶的酶活性略有下降。我们观察到我们队列中44.44%的患者存在内含子变异：c.1000-22C>T;c.370-81__77del;c.640-16A>G;c.10C>T;c.548-125C>G和c-12G>A。这些变异及其组合与我们队列中的临床症状相关。
结论：我们队列中FD的发生率为1.12%。内含子变异与文献中先前描述的症状相关。在JIA中筛查FD可能是那些患有非典型疼痛模式的人的合理策略。
目的：本研究旨在确定JIA队列中FD的频率，表征早期临床症状，酶滴度，和GLA基因分型。
方法：选择在三级儿童医院队列中随访的JIA儿童。临床,记录实验室和熟悉的信息。在女孩中进行了分子遗传学检测以检测GLA基因突变，在男孩中进行了酶促分析。
结果：在89例患者中（56.2％为女性，发病年龄：8.93±4.35岁），1例男性(1.12%)患者出现GLA基因致病突变,c.1244T>Cp.L415P，一名女性患者具有不确定意义的变异c.38C>T（p。Ala13Val）。另外三名（3.4％）患者的α-半乳糖苷酶的酶活性略有下降。我们观察到我们队列中44.44%的患者存在内含子变异：c.1000-22C>T;c.370-81__77del;c.640-16A>G;c.10C>T;c.548-125C>G和c-12G>A。这些变异及其组合与我们队列中的临床症状相关。
结论：我们队列中FD的发生率为1.12%。内含子变异与文献中先前描述的症状相关。在JIA中筛查FD可能是那些患有非典型疼痛模式的人的合理策略。
