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目的:检测和分析法布里病（Fabry disease）患者及其部分家系成员的α半乳糖苷酶A（α-galactosidase A，GLA）基因变异，观察患者临床表型和阿加糖酶α治疗效果。方法:该文为病例系列分析。收集2022年3月至2023年4月经中山大学附属第一医院确诊的5例法布里病病例及其亲属的临床资料和血标本，采用全外显子测序进行基因检测。采用液相色谱-串联质谱仪测定患者GLA活性和底物浓度。收集患者临床表现、家族史和辅助检查结果，随访观察患者阿加糖酶α治疗效果和病情转归。结果:基因测序共确定 GLA基因5个变异，其中1个为新发现变异，4个为错义变异，1个为无义突变。5例患者常见的临床表现包括水肿（4/5）和排汗减少（4/5）；4例患者肾活检显示不同程度的肾脏损伤，其中1例合并IgA肾病。辅助检查发现有患者出现眼部受累（4/5）、心脏受累（4/5）和听力受累（2/5）。5例患者均接受了阿加糖酶α治疗，4例男性患者接受阿加糖酶α治疗（16.8±5.9）次，患者的脱乙酰基三己糖酰基鞘脂醇（globotriaosylsphingosine，Lyso-GL-3）水平较基线下降45.6%±15.5%。 结论:本研究发现1个 GLA新变异，丰富了人类基因变异库。法布里病可合并IgA肾病等肾脏疾病，患者出现不明原因蛋白尿合并排汗减少等肾外表现时应考虑法布里病可能。阿加糖酶α治疗可降低Lyso-GL-3浓度，改善患者临床症状。

Objective:To detect and analyze the α-galactosidase A ( GLA) gene mutations in Fabry disease patients and their family members, observe the clinical phenotype of the patients, and assess the therapeutic effect of agalsidase alpha. Methods:It was a case series analysis. A total of 5 Fabry disease patients was diagnosed at the First Affiliated Hospital of Sun Yat-sen University from March 2022 to April 2023, and the clinical data and blood samples of the patients and their family members were collected. Genetic testing was performed using whole exome sequencing. GLA activity and substrate concentration were measured using the liquid chromatography-tandem mass spectrometry. Patients' clinical manifestations, family history, and auxiliary examination results were collected, and the therapeutic efficacy of agalsidase alpha and disease progression were followed up.Results:A total of 5 GLA gene mutations were identified by gene sequencing, including 1 novel mutation. Among them, 4 mutations were missense mutation, and the other one was nonsense mutation. Common clinical manifestations included edema (4/5) and reduced sweating (4/5). Renal pathology biopsy of 4 patients showed varying degrees of kidney damage, one of which was combined with IgA nephropathy. Auxiliary examinations revealed ocular involvement in 4 patients, cardiac involvement in 4 patients, and hearing impairment in 2 patients. All 5 patients received agalsidase alpha treatment, with 4 male patients receiving (16.8±5.9) times administrations of agalsidase alpha, and their globotriaosylsphingosine (Lyso-GL-3) levels decreased by 45.6%±15.5% from baseline. Conclusions:One novel GLA gene mutation is detected, which enriches the human gene mutation database. Fabry disease can be accompanied by kidney disease such as IgA nephropathy. When patients present with unexplained proteinuria combined with extrarenal manifestations such as reduced sweating, Fabry disease should be considered. Agalsidase alpha treatment can reduce Lyso-GL-3 concentration, and improve clinical symptoms.