Molecular Diagnosis and Rare Diseases Laboratory, Hospital Universitario Virgen del Rocío, Unidad de Bioquímica Clínica, Seville, Spain.
Dysmorphology Department, Hospital Universitario Virgen del Rocío, Unidad de Pediatría, Seville, Spain.
Clin Genet. 2021 Jun;99(6):761-771. doi: 10.1111/cge.13936. Epub 2021 Feb 10.
The purpose of this study was to examine the applicability of the use of samples in dried blood spot (DBS) for the definitive diagnosis of Fabry disease (FD) in males and females and to compare the diagnostic role of α-galactosidase A activity (α-Gal A), levels of lyso-Gb3 and sequencing of the GLA gene in screening patients with suspected FD. Measurement of α-Gal A activity in suspected FD patients in DBS was made followed by lyso-Gb3 determination and GLA gene sequencing. Of the 2381 subjects analyzed, FD was confirmed in 24 patients. Thirteen different variants were considered like pathogenic, five of which had not been previously described (c.143A > G; c.455A > C; c.487G > T; c.554delA; c.1045_1046insA). None of the patients with normal enzyme activity had FD confirmation. The DBS measurement of α-Gal A was more sensitive than lyso-Gb3 levels in both men and women. Definitive diagnosis of FD from a single DBS is possible, allowing samples to be easily sent from anywhere to the reference laboratory.
本研究旨在探讨在男性和女性中使用干血斑（DBS）样本进行法布里病（FD）明确诊断的适用性，并比较α-半乳糖苷酶 A 活性（α-Gal A）、溶酶体神经酰胺三己糖苷（lyso-Gb3）水平和 GLA 基因测序在疑似 FD 患者筛查中的诊断作用。对疑似 FD 患者的 DBS 进行α-Gal A 活性测量，然后测定 lyso-Gb3 并进行 GLA 基因测序。在分析的 2381 名受试者中，24 名患者确诊为 FD。考虑了 13 种不同的变体，其中 5 种以前没有描述过（c.143A>G；c.455A>C；c.487G>T；c.554delA；c.1045_1046insA）。酶活性正常的患者均未确诊 FD。在男性和女性中，DBS 测量的 α-Gal A 比 lyso-Gb3 水平更敏感。从单个 DBS 即可明确诊断 FD，允许从任何地方轻松将样本送到参考实验室。
