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目的 :对1个法布里病(Fabry病)患者及其家系进行调查,分析其临床表现、实验室检查、α-半乳糖苷酶A(alpha-galactosidase A,α-Gal A)检测和基因突变,并对照文献复习,以提高医师对法布里病的认识。方法 :对1例法布里病先证者及其家系成员共21人进行家系调查,登记基本资料,同时行血尿常规、血生化、外周血粒细胞α-Gal A活性和基因检测以及眼科、耳听力、头颅MRI、经颅多普勒超声、心电图、超声心动图、肺功能等相关系统检查,α-Gal A活性检测采用底物荧光法,基因检测采用PCR直接测序法。结果 :121例家系成员中检测出11例法布里病患者;2患者的临床表现及辅助检查结果无特异性表现;3外周血粒细胞α-Gal A活性检测结果异常者有6例,GLA基因突变11例;4不同基因突变导致的法布里病患者的临床表现不同;5首次在一个法布里病家系中发现2个不同位点的基因突变,9例突变位于7号外显子(1098del C),2例突变位于4号外显子(596T>C,p.V199A);611例法布里病患者中经典型患者生活质量受影响较大,而迟发型者生活没有任何影响。结论:1法布里病在该家系成员中发生率高(11/21),因此对于法布里病先证者一定要进行家系调查,可早期发现家族中的患者;2法布里病患者的临床和实验室检查均缺乏特异性表现,但该病可累及多个系统,故应加强对临床表现为多系统受累患者的筛查;3α-Gal A活性异常多存在于经典型的法布里病患者中,而迟发型患者该检测结果常正常,因此诊断法布里病的金标准为基因检测,尤其是对于女性杂合子更重要;4法布里病患者因基因突变位点不同而导致临床表现不同;5法布里病父不传子,发现父子同时患病的异常情况时一定要寻找可能的原因,最终明确病因;6经典型法布里病患者的生活质量受影响明显。
OBJECTIVE: To investigate the clinical manifestations, laboratory tests, detection of alpha-galactosidase A (α-Gal A) gene and its gene in one Fabry disease patient and its pedigree. Mutations, and review the literature to enhance physician awareness of Fabry disease. Methods: A total of 21 Fabri disease probands and their pedigrees were enrolled in the pedigree investigation. Basic data were collected. At the same time, hematuria, blood biochemistry, α-Gal A activity of peripheral blood neutrophils and gene detection, Ear hearing, cranial MRI, transcranial Doppler ultrasound, electrocardiogram, echocardiography, lung function and other related systems examination, α-Gal A activity detection using substrate fluorescence method, gene detection using PCR direct sequencing. Results: Of the 121 pedigree members, 11 Fabry patients were detected. The clinical manifestations and laboratory findings of 2 patients were nonspecific. 3 The abnormal results of α-Gal A activity in peripheral blood granulocytes were found in 6 patients. GLA 11 cases of mutations; 4 different mutations in Fabry disease patients with different clinical manifestations; 5 for the first time in a Fabry family found two different locus mutations, 9 mutations located in exon 7 1098del C). Two of the mutations were located on exon 4 (596T> C, p.V199A). The quality of life of the classic patients in 611 patients with Fabry disease was significantly affected, while those with late onset had no effect. CONCLUSIONS: 1 Fabry disease is a high prevalence (11/21) among members of the pedigree, and must be followed by a pedigree survey of probands and early detection of familial patients; 2 Fabry disease Of the clinical and laboratory tests are lack of specific performance, but the disease can affect multiple systems, it should be strengthened screening of patients with clinical manifestations of multiple systems involvement; 3α-Gal A abnormalities exist in the classic Faba In patients with disease, and delayed type of the test results are often normal, so the gold standard for the diagnosis of Fabry genetic testing, especially for female heterozygotes is more important; 4 Fabry disease patients due to gene mutations in different sites Leading to different clinical manifestations; 5 Fabry’s father did not pass the test, found that the father and son at the same time the anomalies must be looking for possible causes, the final clear cause; 6 classic Fabry disease quality of life affected significantly.