HemoglobinPub Date : 2025-07-27DOI: 10.1080/03630269.2025.2533221
Adwait Marhatta, Jui Choudhuri, Joseph J Mulvey, Sean Campbell, Yanan Fang
{"title":"When Unstable Hemoglobin Lansing Interacts with Alpha Thalassemia Along with <i>HbS</i>: An Interesting Case with Unique Clinical Presentation.","authors":"Adwait Marhatta, Jui Choudhuri, Joseph J Mulvey, Sean Campbell, Yanan Fang","doi":"10.1080/03630269.2025.2533221","DOIUrl":"https://doi.org/10.1080/03630269.2025.2533221","url":null,"abstract":"<p><p>Hemoglobin (Hb) Lansing is a rare mildly unstable variant of α globin. Here, we report the first case of compound Hb Lansing/<i>HbS</i> coinherited with a single α thalassemia deletion (-alpha<sup>3.7</sup>) in a 27-year-old woman. The patient exhibited moderate hemolytic anemia and low oxygen saturation by pulse oximetry, which failed to improve with supplemental oxygen. Notably, her oxygen saturation levels were normal by arterial blood gas. Capillary electrophoresis and high-performance liquid chromatography showed an <i>HbS</i> peak along with other abnormal peaks. Subsequent α globin gene sequencing revealed one copy of the -alpha<sup>3.7</sup> α-globin deletion and one copy of Hb Lansing variant in the alpha2-globin gene. Hemoglobin Lansing is known to cause spuriously low pulse oximetry. Additionally, the co-inheritance of the Hb Lansing and a single α thalassemia deletion may contribute to her moderate hemolytic anemia. The timely identification of hemoglobin variants is crucial for understanding the underlying cause when encountering unexpectedly low pulse oximetry, facilitating genetic counseling, and preventing unnecessary investigations and treatments. Further research is also needed to enhance our comprehension of the interactions among various hemoglobin variants; especially those associated with single a α thalassemia deletion.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemoglobinPub Date : 2025-07-27DOI: 10.1080/03630269.2025.2538623
Lucía Rodríguez-Noriega Béjar, Clara Simón Bernaldo de Quirós, Soledad González Muñíz, Ramón Gutiérrez Martínez
{"title":"Coexistence of Mycoplasma Pneumonia and Pulmonary Embolism as a Cause of Acute Chest Syndrome in a Child with Sickle Cell Disease.","authors":"Lucía Rodríguez-Noriega Béjar, Clara Simón Bernaldo de Quirós, Soledad González Muñíz, Ramón Gutiérrez Martínez","doi":"10.1080/03630269.2025.2538623","DOIUrl":"https://doi.org/10.1080/03630269.2025.2538623","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a chronic, inherited hemoglobinopathy associated with significant morbidity and mortality, particularly in pediatric patients. Among its numerous complications, acute chest syndrome (ACS) remains one of the leading causes of hospitalization and death in children with SCD. ACS is a multifactorial condition, often precipitated by infection but also involving noninfectious causes such as thromboembolism. We present an 8-year-old girl with homozygous SCD who developed a protracted, atypical ACS. Initial findings suggested lobar pneumonia with serologic evidence of <i>Mycoplasma pneumoniae</i> infection. Despite antibiotics, persistent symptoms prompted CT, revealing both pneumonia and an acute pulmonary embolism (PE). The patient received therapeutic anticoagulation and transfusion support, leading to complete resolution of PE at six-month follow-up. This case highlights the critical importance of a broad differential diagnosis in pediatric SCD-related ACS; thromboembolic complications must be actively considered, especially in atypical or refractory cases. We hypothesize that <i>Mycoplasma pneumoniae</i> infection may synergistically exacerbate the inherent hypercoagulable state in SCD, contributing to PE development. This potential link warrants further investigation. Early diagnosis, comprehensive management, and proactive measures like hydroxyurea and long-term pulmonary monitoring are crucial for improving outcomes.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-5"},"PeriodicalIF":1.0,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of Common α-Hemoglobin Variants in Thailand by Using Real-Time PCR with High Resolution Melting Analysis.","authors":"Siriphat Muangpa, Sawichayaporn Jermnim, Prissana Charoenporn, Pawanrat Suannum, Monthira Samaisombat, Peerapon Wong, Nonglak Yimtragool","doi":"10.1080/03630269.2025.2528728","DOIUrl":"https://doi.org/10.1080/03630269.2025.2528728","url":null,"abstract":"<p><p>α-Hemoglobin (Hb) variants are common genetic mutations worldwide. The appropriate techniques must be followed to scan and identify these variants, particularly in routine investigations for thalassemia and hemoglobinopathies in countries with high prevalence of α and β-thalassemia. High resolution melting (HRM) analysis is a popular and effective technique for identifying genetic variations with rapid output results. This study designed four newly developed primer pairs that had full coverage of the <i>HBA</i> genes for detection of α-Hb variants using real-time PCR with HRM analysis. Forty-one blood samples were collected from individuals with known or suspected α-Hb variants. The results demonstrated clearly distinguished melting patterns of nine α-Hb variants including Hb Constant Spring, Hb Q-Thailand, Hb Pakse', Hb Hekinan, Hb Nakhon Ratchasima, Hb Siam, Hb Thailand, Hb Queens, and Hb Quong Sze compared with the wild-type sample pattern. All mutations were confirmed by DNA nucleotide sequencing. This study presents the first case report of the combination of Hb Shaare Zedek co-inherited with Hb Hekinan in a Thai patient. Interactions between these two Hb variants displayed a high level of Hb F (23.5%) on an HPLC Hb chromatogram and a mild symptom phenotype with low mean corpuscular volume (71.3 fL) and mean corpuscular hemoglobin (21.8 pg) in the proband. Overall, HRM analysis is a suitable, rapid, and powerful technique for the identification of gene mutations, and for the diagnosis of common and rare α-Hb variants to prevent and control thalassemia in Thailand.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-11"},"PeriodicalIF":1.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemoglobinPub Date : 2025-07-20DOI: 10.1080/03630269.2025.2534705
Chao Ye, Jilin Qing, Yan Wei, Yilian Zhao, Xiaoxing Zhou, Mengru Xie, Zhizhong Chen
{"title":"Novel Double Heterozygosity: <i>HBA2</i>: c.70G > A (Hb Chad)/<i>HBB</i>: c.-78A > G and Novel Compound Heterozygosity: <i>HBA2</i>: c.70G > A (Hb Chad)/<i>HBA1</i>: c.84G > T (Hb Hekinan II) Hemoglobinopathy in a Chinese Family.","authors":"Chao Ye, Jilin Qing, Yan Wei, Yilian Zhao, Xiaoxing Zhou, Mengru Xie, Zhizhong Chen","doi":"10.1080/03630269.2025.2534705","DOIUrl":"https://doi.org/10.1080/03630269.2025.2534705","url":null,"abstract":"<p><p><i>HBA2</i>: c.70G > A (Hb Chad) and <i>HBA1</i>: c.84G > T (Hb Hekinan II) are extremely rare α-globin chain variants, while <i>HBB</i>: c.-78A > G is a relatively common mutation in β-thalassemia. This study aims to identify potential hemoglobin variants in a 12-year-old Chinese boy (proband) and evaluate the presence of thalassemia trait in his parents. We used an automated blood cell analyzer to obtain hematological data, capillary zone electrophoresis to analyze hemoglobin, and sequencing of α-globin and β-globin genes for molecular characterization. The proband exhibited typical thalassemia traits, with hemoglobin electrophoresis suggesting a complex α- and β-chain hemoglobinopathy. Genetic testing revealed that the proband was a double heterozygote for <i>HBA2</i>: c.70G > A (Hb Chad) and <i>HBB</i>: c.-78A > G, while the proband's mother was a compound heterozygote for <i>HBA2</i>: c.70G > A (Hb Chad) and <i>HBA1</i>: c.84G > T (Hb Hekinan II). This study reports for the first time two novel cases of hemoglobinopathy in a Chinese family, involving <i>HBA2</i>: c.70G > A (Hb Chad)/<i>HBB</i>: c.-78A > G and <i>HBA2</i>: c.70G > A (Hb Chad)/<i>HBA1</i>: c.84G > T (Hb Hekinan II).</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemoglobinPub Date : 2025-07-16DOI: 10.1080/03630269.2025.2534709
Juan Yang, Fan Jiang, Dong-Zhi Li
{"title":"β-Thalassemia Trait Caused by a <i>SUPT5H</i> Defect: First Report of an Intragenic Deletion.","authors":"Juan Yang, Fan Jiang, Dong-Zhi Li","doi":"10.1080/03630269.2025.2534709","DOIUrl":"https://doi.org/10.1080/03630269.2025.2534709","url":null,"abstract":"","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-3"},"PeriodicalIF":1.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>HBA2</i>: C.4delG: A Novel Frameshift Mutation Causing α<sup>+</sup>-Thalassemia Found in a Chinese Family.","authors":"Wei Li, Guixi Wei, Shan Ren, Zulin Xie, Xuan Luo, Lanzuo Zhang, Yuanyuan Huang, Dejian Yuan","doi":"10.1080/03630269.2025.2523030","DOIUrl":"https://doi.org/10.1080/03630269.2025.2523030","url":null,"abstract":"<p><p>We report a novel α-thalassemia (α-thal) point mutation identified in a Chinese man with mild hypochromia and microcytosis during premarital thalassemia screening. Sanger sequencing identified a frameshift variant (<i>HBA2</i>:c.4delG) at codon 1 (deletion of G) in the first exon of the α2-globin gene. This genetic alteration produces a truncated α-globin chain with a premature termination codon at position 48, leading to an α<sup>+</sup>-thalassemia phenotype. Pedigree analysis confirmed the mutation was inherited from the paternal lineage.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemoglobinPub Date : 2025-07-06DOI: 10.1080/03630269.2025.2514142
Xianjuan Huang, Lingling Shi, Yongrong Lai, Jing Li
{"title":"<i>KLF1</i> Knockdown Differentially Regulates γ-Globin Expression: Inhibition in K562 Cells but Reactivation in β-Thalassemia Major Erythrocytes with Erythropoiesis Disruption.","authors":"Xianjuan Huang, Lingling Shi, Yongrong Lai, Jing Li","doi":"10.1080/03630269.2025.2514142","DOIUrl":"https://doi.org/10.1080/03630269.2025.2514142","url":null,"abstract":"<p><strong>Backgound: </strong>Induction of fetal hemoglobin (HbF; α2γ2) production can alleviate the clinical severity of sickle cell disease (SCD) and β-thalassemia. <i>KLF1</i> SNPs (e.g. rs2072597) correlate with elevated fetal hemoglobin levels in HPFH patients. Some studies suggest that <i>KLF1</i> may indirectly suppress γ-globin expression by regulating the <i>KLF1</i>-dependent transcriptional repressor <i>BCL11A</i> or directly activate γ-globin. This study aims to investigate the effect of <i>KLF1</i> on the γ-globin gene.</p><p><strong>Material/methods: </strong><i>KLF1</i> was downregulated in K562 cells via RNAi, with optimized shRNA delivered by lentivirus. Additionally, an in vitro erythropoiesis model using β-thalassemia major-derived mononuclear cells (MNCs) assessed γ-globin expression. γ-globin levels were quantified by RT-qPCR and Western blot (K562) or RT-qPCR alone (erythroblasts).</p><p><strong>Results: </strong>Knockdown of <i>KLF1</i> in K562 cells significantly suppressed γ-globin expression and elevated the γ/α globin mRNA ratio in human erythrocytes, concurrent with disrupted erythroid maturation. <i>KLF2</i> expression was upregulated under <i>KLF1</i>-deficient conditions.</p><p><strong>Conclusions: </strong><i>KLF1</i> exhibits dual, context-dependent regulation of globin genes, acting as both activator and repressor. These findings suggest that pharmacological targeting of <i>KLF1</i> may not be an optimal therapeutic strategy for β-hemoglobinopathies.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-8"},"PeriodicalIF":1.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemoglobinPub Date : 2025-07-01DOI: 10.1080/03630269.2025.2524437
Tevfik Balcı, Beyza Ünlü, Müşerref Başdemirci, Emre Akkaya, Öznur Köylü, Said Sami Erdem
{"title":"A Rare Hemoglobin Variant Detected for the First Time in Türkiye (Hb Iraq-Halabja): Evaluation of the Effect of Variant Hemoglobins on HbA1c Methods.","authors":"Tevfik Balcı, Beyza Ünlü, Müşerref Başdemirci, Emre Akkaya, Öznur Köylü, Said Sami Erdem","doi":"10.1080/03630269.2025.2524437","DOIUrl":"https://doi.org/10.1080/03630269.2025.2524437","url":null,"abstract":"<p><p>The commonly used methods for HbA1c measurement are cation-exchange high performance chromatography (CE-HPLC), immunologic method, capillary electrophoresis and boronate affinity HPLC. Hb-variants can reduce the reliability of HbA1c measurements. We aimed to emphasize the importance of step-by-step solutions to the difficulties encountered in HbA1c measurement methods due to Hb-variants. We also aimed to evaluate the advantages and disadvantages of different methods used in HbA1c analysis with the example of the Hb-Iraq-Halabja variant detected for the first time in Türkiye. HbA1c level could not be measured by CE-HPLC (Adams HA-8180V analyzer, Arkray, Japan) and a peak-tailing signal was detected indicating an abnormality between stable HbA1c and HbA0 peaks (concurrent glucose level was 8.55mmol/L). In the second step, HbA1c was able to be measured by immunologic method and boronate affinity method and were found to be 5.87% and 5.90%, respectively (estimated average glucose equivalent 6.66mmol/L). In the last step, genetic analysis was performed due to suspicion of Hb variant and the very rare Hb Iraq-Halabja variant was detected. After genetic verification, HbA1c test was repeated with a different CE-HPLC (HLC-723 G11, T osoh, Tokyo, Japan) and a peak indicating variant Hb was detected between stable HbA1c and HbA0. A remarkable finding was that, unlike the previous CE-HPLC (Arkray) result, HbA1c could be measured as 3.20%. In the concurrent measurement performed on the boronate affinity HPLC (Premier Hb9210, Trinity Biotech, County Wicklow, Ireland), HbA1c result was found to be 5.40% (concurrent glucose 5.22 mmol/L). In addition, concurrent fructosamine serum value was found to be 210 μmol/L (estimated mean glucose equivalent 4.88 mmol/L). The patient's laboratory tests were generally within normal limits, and iron deficiency, hemolytic anemia, and B12-folate deficiency were excluded. The glucose bounding area of hemoglobin is generally preserved and is not affected by common Hb-variants. Boronate affinity and immunologic method (these two methods target glucose bounding areas) that give HbA1c results consistent with the patient's fasting blood glucose and fructosamine results. However, the CE-HPLC method has been observed to either fail to measure HbA1c or to measure falsely low HbA1c due to overlapping peaks of Hb variants.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemoglobinPub Date : 2025-06-10DOI: 10.1080/03630269.2025.2490291
Ping Liu, Jieyu Wang, Hongyu Luo, Xue-Wei Tang, Jianying Zhou, Fan Jiang, Jin Han
{"title":"A Novel Large Deletion Including the Major Regulatory Element Compounded with SEA Deletion Causing Hydrops-Fetalis-Syndrome.","authors":"Ping Liu, Jieyu Wang, Hongyu Luo, Xue-Wei Tang, Jianying Zhou, Fan Jiang, Jin Han","doi":"10.1080/03630269.2025.2490291","DOIUrl":"https://doi.org/10.1080/03630269.2025.2490291","url":null,"abstract":"<p><p>MCS-R regulatory elements are very important for the synthesis of α-globin. Deletion of the major α-globin regulatory elements compounded with deletion of α-globin genes can cause Hb Bart's (c4) hydrops fetalis, which is the severe form of α-thalassemia. In this report, a 19-year-old female at the 16th week of gestation came to our center due to abnormal fetal cardiothoracic ratio and thickened placental depth. The electrophoresis result of fetal umbilical cord blood revealed the level of Hb Bart's band to be 87.6%, which suggested the fetus was Hb Bart's hydrops fetalis. Next generation sequencing screen using targeted capture was used to detect the genotype of the fetus to be -SEA deletion, βA/βA. Multiplex ligation-dependent probe amplification (MLPA) is very useful to detect copy number variation (deletions/duplications), the result of which suggested the existence of -SEA deletion compounded with the novel large deletion of the major α-globin regulatory element (MCS-R2, R1, R3 and R4). Using the self-designed MLPA probe, the deletion should extend from the telomere downstream and the downstream breakpoint was between 143702 and 144291(GRch38/hg18). The novel deletion was also observed in the fetus' father and grandfather who had mild anemia. Of cases with the MCS deletion compounded with α<sup>0</sup>-thalassemia, this was the earliest time when the fetus presented fetal edema. Our study gave more evidence for genetic counseling for MCS deletion.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}