Establishment of a flow cytometry screening method for patients with glucose transporter 1 deficiency syndrome
Establishment of a flow cytometry screening method for patients with glucose transporter 1 deficiency syndrome
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葡萄糖转运蛋白1缺乏综合征患者流式细胞术筛查方法的建立
DOI：
10.1016/j.ymgmr.2022.100954
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发表时间：
2023
影响因子：
1.9
通讯作者：
Osaka H.
中科院分区：
文献类型：
--
作者：
Nakamura S;Ito Y;Hayakawa H;Aoki S;Yamagata T;Osaka H.
目的探讨流式细胞术检测日本葡萄糖转运蛋白1缺乏综合征(Glut1DS)患者红细胞表面葡萄糖转运蛋白1(GLUT1)水平的价值。方法收集13例Glut1DS患者(8例错义突变，1例移码突变，2例无义突变，2例缺失)和1例临床疑似无SLC2A1突变的Glut1DS患者，在知情同意下采集全血。结果13例明确的Glut1DS患者中，11例μ的相对GLUT1水平低于正常对照组90%。在13例Glut1DS患者中，2例有错义突变且无智力残疾，1例无SLC2A1突变的类似Glut1DS患者的GLUT1相对水平没有降低。结论Glut1DS患者存在SLC2A1基因突变，且有较严重的智能障碍和痉挛，其相对GLUT1水平显著降低。结论该方法检测红细胞GLUT1水平简便，可作为慢性低血糖引起的不可逆神经损害发生前早期发现Glut1DS患者的一种合适的筛查方法。
ObjectiveWe assessed the usefulness of flow cytometry as a functional assay to measure glucose transporter 1 (GLUT1) levels on the surface of red blood cells (RBCs) from Japanese patients with glucose transporter 1 deficiency syndrome (Glut1DS).MethodsWe recruited 13 genetically confirmed Glut1DS patients with a solute carrier family 2 member 1 (SLC2A1) mutation (eight missense, one frameshift, two nonsense, and two deletion) and one clinically suspected Glut1DS-like patient without anSLC2A1mutation, and collected whole blood with informed consent. We stained pelleted RBCs (1 μL) from the patients with a Glut1.RBD ligand and anti-glycophorin A antibody, which recognizes a human RBC membrane protein, and analyzed the cells using flow cytometry.ResultsRelative GLUT1 levels quantified by flow cytometry in 11 of 13 patients with definite Glut1DS were 90% below those of healthy controls. Relative GLUT1 levels were not reduced in two of 13 Glut1DS patients who had a missense mutation and no intellectual disability and one Glut1DS-like patient without anSLC2A1mutation. Relative GLUT1 levels were significantly reduced in Glut1DS patients with anSLC2A1mutation, more severe intellectual disability, and spasticity.ConclusionsThis method to detect GLUT1 levels on RBCs is simple and appears to be an appropriate screening assay to identify severe Glut1DS patients in the early stage before the development of irreversible neurologic damage caused by chronic hypoglycorrhachia.