Kutlar Ferdane
Titus H.J. Huisman Hemoglobinopathy Laboratory, Sickle Cell Center, Medical College of Georgia, Augusta, Georgia, USA.
Hemoglobin. 2007;31(2):243-50. doi: 10.1080/03630260701297071.
Abnormalities of hemoglobin (Hb) synthesis are among the most common inherited disorders of man and can be quantitative (thalassemia syndromes) or qualitative (variant Hbs). Definite identification of hemoglobinopathies can be achieved by a stepwise algorithmic approach, starting with a detailed clinical history, through hematologic evaluation [complete blood count (CBC)], reticulocyte count, red blood cell (RBC) morphology], protein based analytic methods [Hb electrophoresis or isoelectric focusing (IEF), cation exchange high performance liquid chromatography (HPLC), reversed phase HPLC] to nucleic acid based methods [such as polymerase chain reaction (PCR), reverse transcribed (RT)-PCR, sequencing of genomic DNA and sequencing of RT-PCR amplified globin cDNA of the gene of interest]. When an abnormality of Hb function (increased or decreased oxygen affinity) or stability (unstable Hb variants) is suspected from the phenotype, special confirmatory tests (determination of p50, Heinz body prep and isopropanol or heat stability tests) can be useful. Family studies are also helpful in certain cases. A review of the application of these methods to the diagnosis of hemoglobinopathies at the Sickle Cell Center Laboratory in Augusta, GA, USA, is presented below.
血红蛋白（Hb）合成异常是人类最常见的遗传性疾病之一，可分为数量异常（地中海贫血综合征）或质量异常（变异型Hb）。血红蛋白病的明确诊断可通过逐步的算法方法实现，首先从详细的临床病史开始，经过血液学评估[全血细胞计数（CBC）]、网织红细胞计数、红细胞（RBC）形态学检查，基于蛋白质的分析方法[Hb电泳或等电聚焦（IEF）、阳离子交换高效液相色谱（HPLC）、反相HPLC]，再到基于核酸的方法[如聚合酶链反应（PCR）、逆转录（RT）-PCR、基因组DNA测序以及感兴趣基因的RT-PCR扩增珠蛋白cDNA测序]。当从表型怀疑Hb功能异常（氧亲和力增加或降低）或稳定性异常（不稳定Hb变异体）时，特殊的确诊试验（p50测定、Heinz小体制备以及异丙醇或热稳定性试验）可能会有所帮助。家系研究在某些情况下也很有帮助。以下介绍了这些方法在美国佐治亚州奥古斯塔镰状细胞中心实验室用于血红蛋白病诊断的应用情况。
