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.