Nowak Albina, Mechtler Thomas P, Desnick Robert J, Kasper David C
Department of Internal Medicine, University Hospital Zurich and University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland.
ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria.
Mol Genet Metab. 2017 Jan-Feb;120(1-2):57-61. doi: 10.1016/j.ymgme.2016.10.006. Epub 2016 Oct 19.
Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to mutations in the α-galactosidase A gene (GLA) that result in absent or markedly reduce α-galactosidase A (α-GalA) enzymatic activity. As a result, the major glycosphingolipid substrates, globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3) accumulate in plasma, urine and tissue lysosomes. In females, the diagnosis can be complicated by the fact that 40-50% of GLA-mutation confirmed heterozygotes have normal or only slightly decreased leukocyte α-GalA activities. Recently, LysoGb3 has been appreciated as a novel FD biomarker, especially for therapeutic monitoring.
Among our GLA-mutation proven FD patients, we screened 18 heterozygotes whose leukocyte α-GalA activity was determined at initial diagnosis. For these females, we measured their serum LysoGb3 levels using highly-sensitive electrospray ionization liquid chromatography tandem mass spectrometry.
We identified three unrelated females in whom the accumulating LysoGb3 was increased, whereas their leukocyte α-GalA activities were in the normal range.
LysoGb3 serves as an useful biomarker to improve the diagnosis of FD heterozygotes and for therapeutic evaluation and monitoring.
法布里病（FD）是一种罕见的X连锁溶酶体贮积症，由α-半乳糖苷酶A基因（GLA）突变引起，导致α-半乳糖苷酶A（α-GalA）酶活性缺失或显著降低。结果，主要糖鞘脂底物，即球三糖神经酰胺（Gb3）和球三糖鞘氨醇（LysoGb3）在血浆、尿液和组织溶酶体中蓄积。在女性中，40%-50%经证实的GLA突变杂合子白细胞α-GalA活性正常或仅略有降低，这一事实可能使诊断变得复杂。最近，LysoGb3被认为是一种新型的FD生物标志物，尤其用于治疗监测。
在我们经GLA突变证实的FD患者中，我们筛选了18名杂合子，这些患者在初次诊断时测定了白细胞α-GalA活性。对于这些女性，我们使用高灵敏度电喷雾电离液相色谱串联质谱法测量了她们的血清LysoGb3水平。
我们鉴定出三名无亲缘关系的女性，她们体内蓄积的LysoGb3增加，而她们的白细胞α-GalA活性在正常范围内。
LysoGb3作为一种有用的生物标志物，可改善FD杂合子的诊断以及用于治疗评估和监测。
