Suzuki Sayaka, Hosoda Yuzuru, Umeda Miku, Maegaki Masaya, Adachi Koji, Tajima Fumihito, Hatayama Yuki, Hosoda Rina, Hara Kentaro, Kawamura Koji, Yamashiro Yasuhiro, Hattori Yukio, Fukuda Tetsuya
Department of Hematology, Tottori University Hospital, Nishi-chou 36-1, Yonago, 683-8504, Japan.
Division of Clinical Laboratory Medicine, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, School of Medicine, Tottori University, Yonago, 683-8503, Japan.
Int J Hematol. 2025 Aug 13. doi: 10.1007/s12185-025-04052-7.
A Japanese woman presented with a history of neonatal jaundice and recurrent episodes of severe fatigue and jaundice during viral infections in her late teens. Her mother, aunt, and grandmother had similar clinical histories. During an admission for fever and fatigue, blood tests revealed acute hemolysis and an abnormal hemoglobin band on high-performance liquid chromatography. β-globin gene sequencing identified a codon 34 substitution from GTC (Val) to GAC (Asp), confirming the presence of the unstable hemoglobin variant Hb Santander. This very rare hemoglobinopathy was previously reported only in a single sporadic case involving a Spanish man; this is the first documented case in a Japanese family. Our observation of four affected individuals across three generations provided insight into the progression of Hb Santander from birth to old age. Unstable hemoglobin variants can lead to recurrent, severe episodes of acute hemolytic crisis. Chronic hemolysis in the steady state was compensated without anemia or polycythemia but was associated with an increased risk of gallstone formation. Hb Santander does not appear to be a life-shortening hemoglobinopathy; however, clinical vigilance is necessary for acute hemolysis triggered by drugs or infections and for gallstones at a younger age, particularly in patients with Gilbert syndrome.
一名日本女性有新生儿黄疸病史，在十几岁后期的病毒感染期间反复出现严重疲劳和黄疸。她的母亲、阿姨和祖母有相似的临床病史。在因发热和疲劳入院期间，血液检查显示急性溶血，高效液相色谱法检测到异常血红蛋白条带。β-珠蛋白基因测序确定第34密码子由GTC（缬氨酸）替换为GAC（天冬氨酸），证实存在不稳定血红蛋白变异体Hb桑坦德。这种非常罕见的血红蛋白病此前仅在一例涉及一名西班牙男性的散发病例中报道过；这是日本家族中的首例记录病例。我们对三代人中四名受影响个体的观察为Hb桑坦德从出生到老年的病程提供了见解。不稳定血红蛋白变异体可导致反复、严重的急性溶血危机发作。稳定状态下的慢性溶血得到代偿，无贫血或红细胞增多症，但与胆结石形成风险增加有关。Hb桑坦德似乎不是一种缩短寿命的血红蛋白病；然而，对于由药物或感染引发的急性溶血以及年轻时的胆结石，尤其是患有吉尔伯特综合征的患者，临床警惕是必要的。
