Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
J Inherit Metab Dis. 2013 Sep;36(5):881-5. doi: 10.1007/s10545-012-9547-1. Epub 2012 Oct 30.
Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry disease later-onset phenotype, IVS4+919G>A mutation, and their family members. The lyso-Gb3 levels were below the detection limit in normal control newborns and were slightly higher in adults. In males of all ages with the IVS4+919G>A mutation, lyso-Gb3 levels were elevated and were higher than in age-matched controls. The elevation of lyso-Gb3 levels in males with the IVS4+919G>A mutation was only slightly elevated compared with patients with the classical Fabry phenotype. The measurement of lyso-Gb3 levels is useful in the diagnosis of Fabry disease, including the later-onset phenotype. The DBS lyso-Gb3 level was not elevated in IVS4+919G>A heterozygotes, and is not useful for their diagnosis. Since lyso-Gb3 levels are elevated from birth in Fabry disease males, "an elevated lyso-Gb3 level" may be of little values for deciding when to begin enzyme replacement therapy.
溶神经酰基鞘氨醇（lyso-Gb3）是诊断和监测 Fabry 病治疗的有用生物标志物。然而，尚不清楚晚发型 Fabry 病患者的 lyso-Gb3 是否升高。因此，我们测量了具有晚发型 Fabry 病表型、IVS4+919G>A 突变的男性新生儿及其家庭成员的干血斑（DBS）中的 lyso-Gb3 水平。正常对照组新生儿的 lyso-Gb3 水平低于检测限，而成年人的水平略高。在所有年龄段具有 IVS4+919G>A 突变的男性中，lyso-Gb3 水平升高，且高于年龄匹配的对照组。IVS4+919G>A 突变男性的 lyso-Gb3 水平升高与经典 Fabry 表型患者相比仅略有升高。lyso-Gb3 水平的测量对于 Fabry 病的诊断（包括晚发型表型）是有用的。IVS4+919G>A 杂合子的 DBS lyso-Gb3 水平未升高，对其诊断无帮助。由于 Fabry 病男性的 lyso-Gb3 水平从出生起就升高，“lyso-Gb3 水平升高”可能对决定何时开始酶替代治疗的价值不大。
