Merta Miroslav, Reiterova Jana, Ledvinova Jana, Poupetová Helena, Dobrovolny Robert, Rysavá Romana, Maixnerová Dita, Bultas Jan, Motán Jirí, Slivkova Jitka, Sobotova Doris, Smrzova Jana, Tesar Vladimir
Department of Nephrology, 1st Medical Faculty of Charles University and General Faculty Hospital, Prague, Czech Republic.
Nephrol Dial Transplant. 2007 Jan;22(1):179-86. doi: 10.1093/ndt/gfl528. Epub 2006 Oct 13.
Fabry disease (FD) is a genetic disorder characterized by accumulation of trihexosylceramide in lysosomes of various tissues leading to multiorgan manifestations, including progressive renal disease. Previous screening studies have shown that a non-neglectable proportion of haemodialysis(HD) patients have unsuspected FD. An extensive FD screening study, the largest to date, has been conducted in HD patients in Czech Republic. We aimed to uncover previously undiagnosed FD patients, to enable them to benefit from cause-specific therapeutic intervention with enzyme replacement therapy (ERT).
Large-scale screening was executed using a convenient automated enzymatic (alpha-galactosidose A, alpha-Gal A) dried blood spot on filter paper fluorescence method.
In total, 3370 (45.1% males, 54.9% females) out of 4058 HD patients (83%) in Czech Republic participated in this blood spot screening (BSS) study. Abnormal low fluorescence readings were obtained in 117 patients (3.5%). Subsequent determination of plasma alpha-Gal A activity identified four males and three females with deficient plasma enzyme activity. Determination of alpha-Gal A activity in peripheral blood leucocytes and confirmatory molecular analysis resulted in four newly diagnosed Fabry males and one female. Subsequent family screening identified 10 family members with genotypically proven FD. Based on these screening results, ERT could be offered to five male FD patients.
BSS represents a promising screening tool that has proven to be convenient and effective in uncovering unrecognized FD patients among the chronic HD population in Czech Republic.
法布里病（FD）是一种遗传性疾病，其特征是三己糖神经酰胺在各种组织的溶酶体中蓄积，导致多器官表现，包括进行性肾病。先前的筛查研究表明，相当一部分血液透析（HD）患者患有未被怀疑的FD。在捷克共和国，针对HD患者开展了一项广泛的FD筛查研究，这是迄今为止规模最大的此类研究。我们旨在发现先前未被诊断的FD患者，使他们能够从酶替代疗法（ERT）这种针对病因的治疗干预中获益。
采用便捷的自动化酶促（α - 半乳糖苷酶A，α - Gal A）滤纸干血斑荧光法进行大规模筛查。
捷克共和国4058名HD患者中的3370名（45.1%为男性，54.9%为女性，占83%）参与了此次血斑筛查（BSS）研究。117名患者（3.5%）获得了异常低荧光读数。随后测定血浆α - Gal A活性，确定4名男性和3名女性血浆酶活性缺乏。对外周血白细胞中的α - Gal A活性进行测定并进行确诊性分子分析，结果新诊断出4名法布里病男性患者和1名女性患者。随后的家族筛查确定了10名经基因检测证实患有FD的家庭成员。基于这些筛查结果，可为5名男性FD患者提供ERT。
血斑筛查是一种很有前景的筛查工具，已证明在捷克共和国的慢性HD人群中发现未被识别的FD患者方面既方便又有效。
