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Abstract：
We report a rare case of hereditary spherocytosis (HS) and hereditary persistence of fetal hemoglobin (Hb) (HPFH) complicated with a β-thalassemia (β-thal) trait and a Krüppel-like factor 1 (KLF1) gene mutation misdiagnosed as β-thal intermedia (β-TI) due to a high percentage of Hb F. The proband presented with pale skin, jaundice and splenomegaly. Analysis of the thalassemia gene indicated βcodon 17/βA (HBB: c.52A>T), while Hb analysis showed significantly increased Hb F levels. The proband was diagnosed to carry β-TI, and a blood transfusion regimen together with iron chelation treatment was recommended. Due to the difference between the phenotype and genotype, next generation sequencing (NGS) was performed and the proband was found to carry a homozygous mutation on the SPTB gene combined with a heterozygous mutation in KLF1. An eosin-5-maleimide binding test (EMA-BT) showed that the mean fluorescence intensity decreased by 47.1%. The proband was finally diagnosed with HS and HPFH complicated with a β-thal trait and the high percentage of Hb F was believed to be ascribed to the KLF1 gene mutation, which is frequent in areas where thalassemia is prevalent. For patients with a β gene mutation accompanying significantly high percentage of Hb F, the diagnosis of β-TI could be warranted, and the influence of the KLF1 gene mutation should be carefully excluded to avoid misdiagnosis of other types of hereditary hemolytic diseases.
摘要：
我们报告了一例罕见的遗传性球形红细胞增多症（HS）和胎儿血红蛋白（Hb）（HPFH）的遗传性持续存在，并伴有β-地中海贫血（β-thal）特征和Krüppel样因子1（KLF1）基因突变，误诊为β-thal中间蛋白（β-TI）。黄疸和脾肿大。地中海贫血基因分析表明β密码子17/βA（HBB：c.52A>T），而Hb分析显示HbF水平显著升高。先证者被诊断为携带β-TI，建议采用输血方案和铁螯合治疗。由于表型和基因型之间的差异，进行下一代测序(NGS),发现先证者在SPTB基因上携带纯合突变,并在KLF1中携带杂合突变.伊红-5-马来酰亚胺结合试验(EMA-BT)显示平均荧光强度降低了47.1%。先证者最终被诊断为HS和HPFH并伴有β-thal性状，HbF的高百分比被认为归因于KLF1基因突变，在地中海贫血流行的地区很常见。对于β基因突变伴随着显著高百分比的HbF的患者，β-TI的诊断可能是有保证的，应仔细排除KLF1基因突变的影响，以避免误诊其他类型的遗传性溶血性疾病。
