Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.
Institute of Laboratory Medicine, County Hospital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland.
J Med Case Rep. 2022 Apr 10;16(1):145. doi: 10.1186/s13256-022-03374-y.
Unstable hemoglobinopathies are rare inherited disorders of hemoglobin causing a reduction of hemoglobin molecule solubility. This results in an unstable hemoglobin tetramer/globin polypeptide, which precipitates within the red blood cell. Affected red blood cells have a reduced lifespan due to oxidative stress and cellular rigidity, and tend to be phagocytized by spleen macrophages more rapidly. Unstable hemoglobin is frequently under- or misdiagnosed, because its clinical presentation varies broadly. Therefore, testing for unstable hemoglobinopathies is indicated in cases of unexplained hemolytic anemia. However, this approach is not systematically followed in clinical practice.
A 25-year-old Caucasian man with a recent history of a presumed viral upper respiratory infection was referred to the hematology outpatient clinic because of hemolytic anemia. The patient had scleral icterus, moderate splenomegaly, and mild macrocytic anemia with high reticulocyte count. Unconjugated bilirubin and lactate dehydrogenase were elevated. Haptoglobin was undetectable. Direct antiglobulin test was negative. Blood smear examination revealed anisopoikilocytosis, polychromasia, bite cells, and basophilic stippling, but no Heinz bodies. High-performance liquid chromatography and capillary electrophoresis showed slightly increased hemoglobin A2, normal fetal hemoglobin, and a variant hemoglobin. Deoxyribonucleic Acid sequencing revealed the heterozygous mutation c430delC in the beta-globin gene hallmark of hemoglobin Montreal II and the heterozygous mutation c287C>T in the alpha-globin gene corresponding to hemoglobin G-Georgia, indicative of the not yet described combination of double-heterozygous hemoglobin Montreal II and hemoglobin G-Georgia variants. Hemoglobinopathy Montreal II was here not associated with β-thalassemia syndrome, and carriers did not show ineffective erythropoiesis. In addition to the case report, we provide information about the largest pedigree with hemoglobinopathy Montreal II identified to date.
We emphasize that a transitory acute condition may uncover an underlying inherited red blood cell disorder. In this regard, awareness should be raised among hematologists caring for adult patients that unstable hemoglobinopathies should be considered in the differential diagnosis of unexplained hemolytic anemias.
不稳定血红蛋白病是一种罕见的血红蛋白遗传性疾病，导致血红蛋白分子的溶解度降低。这会导致血红蛋白四聚体/球蛋白多肽不稳定，在红细胞内沉淀。受影响的红细胞由于氧化应激和细胞刚性而寿命缩短，并且更容易被脾脏巨噬细胞更快地吞噬。不稳定血红蛋白经常被误诊或漏诊，因为其临床表现差异很大。因此，在不明原因的溶血性贫血病例中，需要进行不稳定血红蛋白病的检测。然而，在临床实践中并没有系统地遵循这种方法。
一名 25 岁的白人男性，最近患有疑似病毒性上呼吸道感染，因溶血性贫血被转至血液科门诊。患者有巩膜黄疸、中度脾肿大、轻度大细胞性贫血伴高网织红细胞计数。未结合胆红素和乳酸脱氢酶升高。触珠蛋白不可检测。直接抗球蛋白试验阴性。血涂片检查显示异形红细胞增多症、多染性、咬细胞和嗜碱性点彩，但无海因茨小体。高效液相色谱和毛细管电泳显示血红蛋白 A2 略有增加，胎儿血红蛋白正常，以及一种变异血红蛋白。脱氧核糖核酸测序显示β-珠蛋白基因中的杂合突变 c430delC 是血红蛋白 Montreal II 的特征，以及α-珠蛋白基因中的杂合突变 c287C>T 对应血红蛋白 G-Georgia，表明尚未描述的双重杂合血红蛋白 Montreal II 和血红蛋白 G-Georgia 变异的组合。血红蛋白病 Montreal II 在此不伴有β-地中海贫血综合征，且携带者没有表现出无效红细胞生成。除了病例报告外，我们还提供了迄今为止鉴定的最大的血红蛋白病 Montreal II 家系信息。
我们强调，短暂的急性疾病可能会揭示潜在的遗传性红细胞疾病。在这方面，应提高照顾成年患者的血液科医生的认识，即不明原因溶血性贫血的鉴别诊断中应考虑不稳定血红蛋白病。
