摘要目的:总结GLA基因IVS4+919G >A变异致法布雷病一家系的临床表型和遗传学特征。 方法:前瞻性筛查研究。2021年10月至2023年8月对宁海县102例法布雷病高危患儿进行筛查，采用干纸血片试验法，α-半乳糖苷酶活性<2.40 μmol/（L·h）或脱乙酰基三己糖酰基鞘脂醇浓度>1.10 μg/L的患儿接受GLA基因变异检测进一步确诊，并通过先证者进行家系筛查。以成功确诊的1例法布雷病先证者及家系作为研究对象，对GLA基因IVS4+919G>A变异致法布雷病患儿的临床表型和遗传特征进行总结。结果:102例患儿中共确诊1例罕见的以双下肢疼痛为首发症状，携带GLA基因IVS4+919G>A变异的9.8岁女性法布雷病先证者。通过家系筛查发现该家系中4例成员（先证者父亲、姐姐、姑表姐、姑表兄）可确诊为法布雷病，1例成员（五姑母）为变异基因携带者，其中先证者姑表兄13.2岁，携带GLA基因IVS4+919G>A变异，以间歇性双下肢疼痛为首发症状；先证者父亲有膝关节疼痛；先证者姐姐及五姑母有视力下降；先证者姑表姐无明显症状。结论:儿童高危筛查及家系筛查对法布雷病的早诊早治有重要意义，GLA基因IVS4+919G>A变异致法布雷病早期可出现周围神经性疼痛。

abstractsObjective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.