高危筛查联合家系筛查法筛查成人血液透析人群中法布里病患者——附法布里病GLA IVS4+919G>A突变1例家系报道  

High-risk screening combined with family screening for Fabry disease in adult hemodialysis population—a family report of GLA IVS4+919G>A mutation in Fabry disease

作　　者：陈冰蓉 童敏青 路智红[1] 毛建华[1] Chen Bingrong;Tong Minqing;Lu Zhihong;Mao Jianhua(Department of Nephrology,Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Department of Pediatrics,Yongkang First People's Hospital of Zhejiang Province,Yongkang 321300,China)

机构地区：[1]浙江大学医学院附属儿童医院肾脏内科,国家儿童健康与疾病临床医学研究中心,杭州310052 [2]浙江省永康市第一人民医院,永康321300

出　　处：《中华肾脏病杂志》2024年第1期18-23,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金(U20A20351);国家重点研发计划项目(2022YFC2705103、2021YFC2702002);浙江省重点研发计划(2021C03079)。

摘　　要：目的采用高危筛查联合家系筛查法筛查成人血液透析人群中潜在的法布里病患者,探讨提高法布里病诊断效率的方法。方法该研究为横断面调查研究。研究对象为2022年11月至2023年2月在浙江省永康市第一人民医院接受血液透析治疗的成人终末期肾病患者。对纳入患者行法布里病高危筛查。男性患者采用干血纸片α-半乳糖苷酶A(α-galactosidase A,α-Gal A)测定行高危筛查,女性患者采用干血纸片脱乙酰基三己糖酰基鞘酯醇(glycosphingolipids,Lyso-GL-3)测定行高危筛查,对筛查结果异常者行GLA基因检测以明确法布里病诊断。对确诊者的家系成员进行GLA基因筛查,并用干血纸片法测定α-Gal A酶活性和Lyso-GL-3水平。对确诊法布里病患者行尿常规、血生化、眼部、听力、头颅磁共振成像、心电图等检查,评估相关器官损害情况。结果共244例血液透析患者入选该研究,年龄25~81岁(中位年龄61岁),男139例(56.97%),女105例(43.03%)。高危筛查发现1例女性法布里病患者,基因检测示GLA IVS4+919G>A变异,患病率为0.41%。筛查该法布里病患者的41名家族成员,最终确诊法布里病患者12例(包括先证者),女性9例,男性3例。其中酶学检查异常者9例,底物异常者10例,基因测序异常者11例。12例患者均无肢端疼痛、少汗、血管角质瘤、角膜异常、听力损害等表现。心脏损害8例,尿检查异常(白蛋白尿/血尿)9例,肾功能异常1例,头颅磁共振成像异常4例。结论通过对成人血液透析患者进行高危和家系联合筛查,成功发现1个GLA IVS4+919G>A突变家系,共确诊12例法布里病患者。高危筛查联合家系筛查可有效地发现潜在的法布里病患者,提高其筛查效率。Objective To explore the combination of high risk screening and family screening for potential patients with Fabry disease in adult hemodialysis population,and to improve the diagnostic efficiency of the disease.Methods It was a cross-sectional investigation study.High-risk screening for Fabry disease was performed on adult hemodialysis patients with end-stage kidney disease who were admitted to Yongkang First People's Hospital of Zhejiang Province between November 2022 and February 2023.Dry blood paperα-galactosidase A(α-Gal A)detection assay was performed in males,or glycosphingolipids(Lyso-GL-3)detection assay was performed in females.GLA genetic assay was performed for further diagnosis after abnormal screening results.Family screening was carried out on the family members of the confirmed Fabry disease patients,andα-Gal A activity and Lyso-GL-3 of peripheral blood were measured.Additionally,urine routine,blood biochemistry,eye examination,hearing test,cranial magnetic resonance imaging,and electrocardiogram were performed to assess organ damage.Results Among 244 hemodialysis patients,139(56.97%)were males and 105(43.03%)were females.The age ranged from 25 to 81 years(with median age of 61 years).One female patient with Fabry disease was identified GLA IVS4+919G>A mutation,resulting in a total prevalence of 0.41%.Pedigree screening was conducted on 41 family members of the patient,leading to the confirmation of 12 patients(including the proband),including 3 males and 9 females.Among them,9 patients were abnormal in enzyme examination,10 patients were abnormal in substrate,and 11 patients were abnormal in gene sequencing.None of the 12 patients exhibited limb pain,hypohidrosis,angiokeratoma,corneal opacity,and hearing impairment.Eight patients had heart abnormalities.Nine patients had abnormal urine routine(albuminuria or hematuria)and one patient had abnormal renal function.Four patients had abnormal cranial magnetic resonance imaging findings.Conclusions One GLA IVS4+919G>A mutation family is successfully

关 键 词：法布里病 肾透析 早期诊断 高危筛查 家系筛查 

分 类 号：R692.5[医药卫生—泌尿科学]