Kitagawa Teruo, Ishige Nobuyuki, Suzuki Ken, Owada Misao, Ohashi Toya, Kobayashi Masahisa, Eto Yoshikatsu, Tanaka Akemi, Mills Kevin, Winchester Bryan, Keutzer Joan
Tokyo Health Service Association, Tokyo, Japan.
Mol Genet Metab. 2005 Jul;85(3):196-202. doi: 10.1016/j.ymgme.2005.01.007. Epub 2005 Apr 26.
Fabry disease is an X-linked sphingolipidosis due to a deficiency of alpha-galactosidase A, which leads to the accumulation of globotriaosylceramide (GL-3) in several organs. When recombinant human alpha-galactosidase A is intravenously administered repeatedly before the patient develops permanent tissue damage, there is evidence that the accumulation of GL-3 is decreased in some organs and that the clinical symptoms are alleviated in some patients. However, Fabry disease is rare and many patients are not diagnosed until adulthood after irreversible tissue damage has occurred. Our group has developed a simple and non-invasive screening method for Fabry disease that measures total GL-3 in whole urine samples by tandem mass spectrometry. Using this method, we found that the concentration of GL-3 in whole urine sample from hemizygous patients, including pre-symptomatic young children with classic type Fabry disease, was significantly higher than that in controls. The mean concentration of GL-3 in urine from heterozygotes with symptoms was significantly higher than control concentrations, but GL-3 levels in the urine from 2 out of 8 heterozygotes of classic type Fabry disease were within control levels. An asymptomatic 14-year old hemizygote in the family of a cardiac variant did not have elevated urinary GL-3. Therefore, screening for the classic type and probably renal variant of Fabry disease is possible by measuring urinary GL-3, using our method. The early diagnosis of cardiac variant hemizygotes and some heterozygotes with all types of Fabry disease will not be possible using our method. We propose that this procedure can be used as a reliable, non-invasive, simple method for general and high-risk population screening for hemizygotic patients with the classic type and probably renal variant of Fabry disease.
法布里病是一种X连锁鞘脂贮积症，因α-半乳糖苷酶A缺乏所致，该酶缺乏会导致多种器官中球三糖神经酰胺（GL-3）蓄积。在患者出现永久性组织损伤之前反复静脉注射重组人α-半乳糖苷酶A，有证据表明某些器官中GL-3的蓄积减少，部分患者的临床症状也有所缓解。然而，法布里病较为罕见，许多患者直到成年出现不可逆组织损伤后才被诊断出来。我们团队开发了一种用于法布里病的简单、非侵入性筛查方法，通过串联质谱法测定全尿样本中的总GL-3。使用该方法，我们发现半合子患者全尿样本中GL-3的浓度显著高于对照组，包括经典型法布里病的无症状幼儿。有症状的杂合子尿液中GL-3的平均浓度显著高于对照组，但8例经典型法布里病杂合子中有2例的尿液GL-3水平在对照范围内。一名心脏变异型家族中的无症状14岁半合子其尿GL-3未升高。因此，使用我们的方法通过测定尿GL-3来筛查经典型及可能的肾变异型法布里病是可行的。使用我们的方法无法对心脏变异型半合子及所有类型法布里病的一些杂合子进行早期诊断。我们建议该检测程序可作为一种可靠、非侵入性、简单的方法，用于对经典型及可能的肾变异型法布里病半合子患者进行普通人群和高危人群筛查。
