Wild B J, Green B N, Stephens A D
Department of Haematological Medicine, King's College Hospital, London, UK.
Blood Cells Mol Dis. 2004 Nov-Dec;33(3):308-17. doi: 10.1016/j.bcmd.2004.07.004.
Analytical procedures have been developed for the detection and diagnosis of sickle cell disease in newborn babies by analyzing the hemoglobin extracted from dried blood spots on Guthrie cards using electrospray ionization mass spectrometry (ESI-MS). An essential requirement is the ability to reliably differentiate two globin chains whose molecular weights differ by only 1 Da such as adult hemoglobin (Hb A) and Hb C. This has been achieved by improving the accuracy and precision of the molecular weight determination to a fraction of a dalton. We report the potential of mass spectrometry for screening neonates for these debilitating diseases by presenting results from 147 blood spots that had been characterized by phenotypic methods and which include samples from 20 sickle cell disease, 1 beta-thalassemia major, 57 sickle cell trait, and 39 normal babies. In all cases, the mass spectrometric results agreed with the results obtained using conventional analytical practice with high-performance liquid chromatography (HPLC) and isoelectric focusing (IEF). We show that mass spectrometry is a viable technique for the diagnosis of newborns with sickle cell disease or homozygous beta0-thalassemia.
通过使用电喷雾电离质谱法（ESI-MS）分析从格思里卡片上的干血斑中提取的血红蛋白，已开发出用于检测和诊断新生儿镰状细胞病的分析程序。一个基本要求是能够可靠地区分分子量仅相差1道尔顿的两条珠蛋白链，如成人血红蛋白（Hb A）和Hb C。这已通过将分子量测定的准确性和精密度提高到道尔顿的几分之一来实现。我们通过展示147个血斑的结果来报告质谱法用于筛查新生儿这些致残性疾病的潜力，这些血斑已通过表型方法进行了表征，包括来自20例镰状细胞病、1例重型β地中海贫血、57例镰状细胞性状和39例正常婴儿的样本。在所有情况下，质谱分析结果与使用高效液相色谱（HPLC）和等电聚焦（IEF）的传统分析方法获得的结果一致。我们表明，质谱法是诊断患有镰状细胞病或纯合β0地中海贫血的新生儿的可行技术。
