Hemoglobin最新文献

HbH disease may rarely be caused by a combination of deletional α-thalassemia and an unstable α-globin chain variant. Diagnosis is challenging and may be delayed in cases with mild symptoms. Hemoglobin Dubai is an unstable α-globin chain variant that was previously reported to be asymptomatic. We report the case of a 74-year-old man with mild HbH disease due to compound heterozygosity for Hemoglobin Dubai with deletional α-thalassemia.

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 Mycoplasma pneumoniae 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 Mycoplasma pneumoniae 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.

We report a family study wherein the index patient, a 6-year-old Mozambican female, was diagnosed with compound heterozygous HbS and Hb Maputo. She presented with acute pain, swelling and tenderness in the right fronto-temporal region of the skull, which raised suspicion of sickle cell disease (SCD). Prior to this presentation, a two-year history of vague clinical symptoms (viz., periodic fever, joint pain and abdominal pain) was obtained. Both parents were clinically asymptomatic. Hemoglobin separation studies were performed using hemoglobin electrophoresis and high performance liquid chromatography. Next generation sequencing technology was employed for gene sequencing analysis of globin genes. Both parents were also fully investigated. Hemoglobin separation studies on the index patient detected two hemoglobin variants that were identified on gene sequencing analysis as HbS and Hb Maputo. The mother and father were demonstrated to have heterozygous HbS and Hb Maputo, respectively. The α globin genes in all the family members had a normal wild type configuration. Conclusion: Hb Maputo in the heterozygous state is an uncommon β chain variant that is clinically silent whereas co-inheritance of Hb Maputo and HbS causes a sickling disorder with vaso occlusive disease.

Hemoglobin (Hb) Phnom Penh is a rare Hb variant of non-clinical significance caused by a duplication of TCA within exon 3 of the human HBA1 gene, resulting in the insertion of isoleucine [c.353_355dup (p.Phe118_Thr119insIle)]. This variant can interfere with glycated Hb analysis and has been identified in several Asian populations, including Cambodian, Chinese, northeastern Thai, and Taiwanese individuals. In this study, we identified a northern Thai man with Hb Phnom Penh. The proband was a heterozygote and asymptomatic. The inheritance of Hb Phnom Penh was suspected based on his abnormal Hb pattern observed through high-performance liquid chromatography and confirmed by Sanger sequencing. Additionally, molecular analysis revealed that Hb Phnom Penh exhibits greater instability compared to HbE. Our findings report, for the first time, the presence of Hb Phnom Penh in northern Thailand and its instability, suggesting the heterogeneity of this Hb variant in Thailand and providing further insights into its basic characteristics.

Dominant β-thalassemia is a rare form of thalassemia that is caused by a heterogenous group of molecular defects, including missense, nonsense, and frameshift mutations. Among the missense mutations involving the third exon of β-globin gene is the rare Hb Dieppe (HBB:c. 383A > G) which leads to a very unstable β-variant. In the current study we report this variant in an 8-year-old girl and her 35-year-old mother in an Iraqi Kurdish family, both presenting as β-thalassemia intermedia with moderate hypochromic anemia, increased hemoglobin F and borderline hemoglobin A2. This constitutes the first report of this variant from an Eastern Mediterranean country, and underscores the pivotal role of molecular studies to diagnose Hb Dieppe and other dominant β-thalassemias, since in most cases the resultant variants are undetectable by hemoglobin electrophoresis.

Hemoglobin (Hb) Lansing is a rare mildly unstable variant of α globin. Here, we report the first case of compound Hb Lansing/HbS coinherited with a single α thalassemia deletion (-alpha^3.7) 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 HbS peak along with other abnormal peaks. Subsequent α globin gene sequencing revealed one copy of the -alpha^3.7 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.

Misdiagnosis of α-thalassemia genotypes due to primer site mutations presents diagnostic challenges in Chinese populations where -α^3.7 deletion and HBA2:c.427T>C (Hb Constant Spring) heterozygotes are prevalent. We describe two cases where conventional diagnostic approaches erroneously identified heterozygous carriers as homozygotes. Diagnostic algorithms employing gap-PCR and PCR-RDB for common thalassemia mutations initially suggested homozygous status in both probands. Proband 1 (28-year-old male) was misclassified as -α^3.7 homozygote by gap-PCR, but MLPA analysis revealed heterozygous status, subsequently confirmed by third-generation sequencing which identified concurrent NG_000006.1:g.32793 C > T mutation validated through Sanger sequencing. Proband 2 demonstrated discordant HBA2:c.427T > C results, with MLPA detecting atypical signal intensities in HBA2 and HBA1 loci. Comprehensive TGS analysis revealed trans configuration with HBA2:c.300+55T > G and HBA2:c.301-24delGinsCTCGGCCC variants. These cases highlight the important impact of mutations in the priming region on molecular diagnosis and emphasize the need for further characterization by other methods to avoid misdiagnosis when results from traditional methods are equivocal.

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 (HBA2: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⁺-thalassemia phenotype. Pedigree analysis confirmed the mutation was inherited from the paternal lineage.

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 HBA 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.