溶血神经酰胺三己糖苷表明α-半乳糖苷酶A突变D313Y在法布里病中与临床无关。
Lyso-Gb3 Indicates that the Alpha-Galactosidase A Mutation D313Y is not Clinically Relevant for Fabry Disease.
作者信息
Niemann Markus, Rolfs Arndt, Giese Anne, Mascher Hermann, Breunig Frank, Ertl Georg, Wanner Christoph, Weidemann Frank
机构信息
Department of Internal Medicine I, University of Würzburg, Würzburg, Germany.
出版信息
JIMD Rep. 2013;7:99-102. doi: 10.1007/8904_2012_154. Epub 2012 Jul 1.
The X-chromosomal-linked lysosomal storage disorder Fabry disease can lead to life-threatening manifestations. The pathological significance of the Fabry mutation D313Y is doubted, because, in general, D313Y patients do not present clinical manifestations conformable with Fabry disease. This is in contrast to the analysis of the alpha-galactosidase A activity, which is reduced in D313Y patients. We report a comprehensive clinical, biochemical and molecular genetic analysis of two patients with a D313Y mutation. The alpha-galactosidase A activity was reduced in both patients. No Fabry symptoms or Fabry organ involvement was detected in these patients. The new biomarker lyso-Gb3, severely increased in classical Fabry patients, was determined and in both patients lyso-Gb3 was below the average of a normal population.Our data for the first time not only clinically but also biochemically supports the hypothesis that the D313Y mutation is not a classical one, but a rare variant mutation.
X染色体连锁的溶酶体贮积症法布里病可导致危及生命的表现。法布里突变D313Y的病理意义受到质疑，因为一般来说，D313Y患者没有出现符合法布里病的临床表现。这与α-半乳糖苷酶A活性分析结果相反，D313Y患者的该活性降低。我们报告了对两名携带D313Y突变患者的全面临床、生化和分子遗传学分析。两名患者的α-半乳糖苷酶A活性均降低。在这些患者中未检测到法布里症状或法布里器官受累情况。测定了经典法布里病患者中严重升高的新型生物标志物溶酶体Gb3，两名患者的溶酶体Gb3均低于正常人群的平均值。我们的数据首次不仅在临床上而且在生化方面支持了以下假设：D313Y突变不是经典突变，而是罕见的变异突变。
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