Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
Mol Genet Metab. 2010 Jul;100(3):257-61. doi: 10.1016/j.ymgme.2010.03.020. Epub 2010 Apr 1.
Fabry disease is an X-linked genetic disorder caused by a deficiency of alpha-galactosidase A (GLA) activity. As enzyme replacement therapy (ERT) involving recombinant GLAs has been introduced for this disease, a useful biomarker for diagnosis and monitoring of therapy has been strongly required. We measured globotriaosylsphingosine (lyso-Gb3) and globotriaosylceramide (Gb3) in plasma samples from ten hemizygous males (six classic and four variant cases) and eight heterozygous females with Fabry disease, and investigated the responses of plasma lyso-Gb3 and Gb3 in a male Fabry patient who had undergone ERT for 4years to determine whether plasma lyso-Gb3 and Gb3 could be biomarkers of Fabry disease. The results revealed that plasma lyso-Gb3 was apparently increased in male patients and was higher in cases of the classic form than those of the variant one. In Fabry females, plasma lyso-Gb3 was moderately increased in both symptomatic and asymptomatic cases, and there was a correlation between the increase in lyso-Gb3 and the decrease in GLA activity. As to plasma Gb3, the levels in the variant Fabry hemizygotes and Fabry heterozygotes could not be distinguished from those in the controls, although those in the classic Fabry hemizygotes were increased. The plasma lyso-Gb3 level in the Fabry patient who had received ERT was elevated at the baseline and fell more dramatically on ERT than that of Gb3. Plasma lyso-Gb3 could thus be a potential biomarker of Fabry disease.
法布里病是一种 X 连锁遗传疾病，由α-半乳糖苷酶 A（GLA）活性缺乏引起。由于该疾病已经引入了重组 GLAs 的酶替代疗法（ERT），因此强烈需要一种用于诊断和监测治疗的有用生物标志物。我们测量了十个半合子男性（六名经典型和四名变异型病例）和八名杂合子女性的血浆样本中的神经酰胺三己糖苷（lyso-Gb3）和神经酰胺三糖苷（Gb3），并研究了接受 ERT 治疗 4 年的男性法布里病患者血浆 lyso-Gb3 和 Gb3 的反应，以确定血浆 lyso-Gb3 和 Gb3 是否可以作为法布里病的生物标志物。结果表明，男性患者的血浆 lyso-Gb3 明显增加，经典型病例高于变异型病例。在法布里女性中，有症状和无症状病例的血浆 lyso-Gb3 均中度增加，lyso-Gb3 的增加与 GLA 活性的降低之间存在相关性。至于血浆 Gb3，变异型法布里半合子和法布里杂合子的水平与对照组无法区分，尽管经典型法布里半合子的水平升高。接受 ERT 治疗的法布里病患者的血浆 lyso-Gb3 水平在基线时升高，在 ERT 治疗后下降幅度比 Gb3 更大。因此，血浆 lyso-Gb3 可能是法布里病的潜在生物标志物。
