Hemoglobin最新文献

We report the identification and characterization of a rare hemoglobin variant resulting from a mutation in the β-globin chain gene. The case involved a 36-year-old Han Chinese woman who was initially identified through a routine blood test that showed red blood cell microcytosis and hypochromia. Subsequent hemoglobin analysis using capillary electrophoresis revealed an unusual chromatographic pattern, characterized by a significant shoulder peak adjacent to the normal hemoglobin A (HbA), alongside the expected HbA and HbA2 peaks. To determine the genetic basis of this abnormality, HBB gene sequencing was performed. This analysis identified a heterozygous missense mutation, c.24G > C, located in exon 1. This mutation results in a GAG > GAC codon change, corresponding to a substitution of glutamic acid for aspartic acid at position 7 of the β-globin chain (Glu7Asp). This study represents the first detailed clinical and molecular description of this particular variant. The variant has been submitted to the IthaGenes global hemoglobin variant database with the submission ID 4156. In silico analysis using the PolyPhen-2 algorithm predicted this variant as 'probably damaging', with a score of 0.998. This report enriches the clinical and hematological information available for this HBB gene variant. Its accurate identification is crucial to prevent misdiagnosis and to ensure appropriate and reliable genetic counseling and prenatal diagnosis for affected individuals and their families.

Severe forms of β-thalassemia are typically autosomal recessive disorders characterized by hemolytic anemia, jaundice, and hepatosplenomegaly. More than 300 variants in the β-globin gene cluster have been reported, revealing a complex genotype-phenotype landscape. Here, we report a transfusion-dependent β-thalassemia proband carrying only one allele with the known common frameshift mutation HBB: c.84_85insC (β^{CD27/28 (+C)}), which is expected to lead to premature termination of β-globin synthesis. Whole-genome sequencing (WGS) revealed two additional intronic variants in the proband: HBB:c.315 + 16G > C (IVS-II-16 G > C) and HBB: c.316-185C > T (IVS-II-666 C > T). After excluding the occurrence of other known pathogenic mutations of β-thalassemia, we propose that the compound heterozygous mutation of HBB: c.84_85insC and these intronic mutations contributes to the severe clinical manifestations in this case. Furthermore, WGS identified several variants in the HBS1L-MYB intergenic region, which may be associated with the markedly elevated HbF level (73.6%) observed. In summary, our findings enhance the understanding of phenotypic diversity attributable to HBB intronic variants and expand the mutational spectrum relevant for prenatal diagnosis and genetic counseling of β-thalassemia.

Pain has emerged as a potential complication in thalassemia but its management has not been optimized. This study assessed the prevalence of pain and its association with QoL in adult patients with transfusion-dependent thalassemia (TDT). A prospective cross-sectional study was conducted from April to June 2023 in thalassemia clinic of Hospital Tengku Ampuan Rahimah, Klang. Adult patients who have been treated with iron chelators were recruited. Data collection was performed using the Brief Pain Inventory and tranfusion-dependent quality of life questionnaire. A total of 83 adult patients with TDT were recruited. This study found that 32% of the study participants had pain within the past 24 hours and the average pain score was moderate. The overall score for emotional health and physical health demonstrates a significant lower score compared to other QoL domains (p = 0.00). A significant association between pain and QoL was observed (p = 0.01). Non HbE β thalassemia, taking oral deferasirox and fracture history were found to be factors influencing pain. No variable was independently associated with higher QoL, regardless at the age of diagnosis, baseline ferritin, severe MRI T2* liver results, taking oral deferiprone or deferasirox. With the identification of affecting variables, appropriate treatment plan may be formulated to reduce pain and improve the QoL of thalassemia patients.

α-Thalassemia is a prevalent genetic disorder, and recent global migration has increased the need for effective screening and diagnosis, even in historically low-prevalence regions. Accurate diagnosis of symptomatic individuals and carriers is essential for appropriate management. This multi-year retrospective study presents 776 cases correlating CBC parameters, hemoglobin fractionation, α-globin gene deletion/duplication analysis, and complete α-globin sequencing. Among these cases, 174 (22%) had abnormal Hb fractionation patterns by HPLC, and 602 (78%) had normal pattern. By deletion/duplication analysis, 576 (74%) had an intact α-globin gene cluster, while deletions were detected in 24% (188/776) of cases; 103 (13%) with one-gene, 82 (11%) two-gene, 3 (0.3%) with three-gene deletions, and 12 (1.5%) had α- gene triplication. Sequencing identified variant hemoglobin in 198 (26%) samples, including 163 α-globin variants, the remaining 36 variants were either β or delta globin variants. Notably, 28 α-globin variants were undetectable by HPLC/CE, 18 of which were non-deletional or 'thalassemic' variants. A total of 72 (9.3%) samples were found to have combined α-globin gene deletion and an α-globin variant. CBC parameters showed no significant differences between normal individuals and those with one or more α-gene deletions or non-deletional α-globin variants. EMQN thresholds demonstrated 81% sensitivity and 25% specificity for detecting deletional α-thalassemia. Our findings highlight the utility of molecular analysis for carrier detection and the necessity of α-globin full gene sequencing in cases with unexplained clinical phenotypes.

The coexistence of β-thalassemia major and Type 3 von Willebrand Disease (VWD) is an exceptionally rare clinical phenomenon. We describe a 3-year-old female with genetically confirmed β-thalassemia major due to an HBB frameshift mutation (exons 8-9) and Type 3 VWD with von Willebrand factor (VWF) antigen at 1.8%. Clinically, she presented with recurrent epistaxis, anemia, and transfusion dependence. Serial laboratory investigations revealed persistent microcytic hypochromic anemia, iron overload (ferritin 1778 ng/mL), and markedly low VWF antigen. Management included red blood cell transfusions, chelation, hydroxyurea, vitamin supplementation, and supportive care, while balancing the bleeding risks from VWD. This report underscores the diagnostic challenge and therapeutic complexity of overlapping congenital anemia and bleeding disorder. Multidisciplinary care and genetic testing were pivotal in confirming the diagnosis and guiding management.

α-Thalassemia is a common genetic disorder marked by a reduced synthesis of α-globin chains, leading to varying degrees of anemia. In this study, we describe a novel variant, HBA1:c.305T > C (Leu > Pro), identified through next-generation sequencing (NGS) genomic screening. The proband, a 6-year-old female, presented with low hemoglobin levels (103 g/L) and microcytic anemia (MCV 58.6 fL, MCH 17.7 pg). To confirm the presence of this variant, Sanger sequencing was utilized, validating the heterozygous substitution of thymine for cytosine at nucleotide position 305 in the α-globin gene. Family studies indicated that this novel variant was inherited from the father, who also exhibited hematological indicators consistent with thalassemia (MCH 26.6 pg). Furthermore, the proband was found to carry a common β-thalassemia mutation at Codon 17 (A > T), inherited from her mother. Our findings highlight the clinical relevance of the HBA1:c.305T > C variant in the context of β-thalassemia, emphasizing the need for comprehensive phenotypic evaluations to elucidate the implications of novel mutations in thalassemia.

Thalassemia is one of the most common inherited red blood cell disorders worldwide and is regarded as a major public health concern in Thailand and many countries. Thalassemia prevention and control in Thailand will face greater challenges due to the entrance of the ASEAN Economic Community (AEC) workers migrating to the country. This study examined the prevalence of thalassemia among migrant workers from Cambodia and Myanmar. Thalassemia was identified through the analysis of hemoglobin (Hb) and DNA. Out of 532 blood samples, 60.5% were found to be thalassemia heterozygotes or affected by the disease, encompassing 21 different thalassemia genotypes. The prevalence of homozygous (7.4%) and heterozygous (29.8%) Hb E was high among workers from Cambodia. Among workers from Myanmar, the prevalence of α⁺-thalassemia is interestingly high, reaching an unprecedented 46.1% in total. The prevalence of β-thalassemia heterozygotes is 3.2%. The molecular information obtained should provide useful data for improving diagnostics, as well as for planning prevention and control programs for severe thalassemia and genetic counseling among migrant workers in Thailand.

Advances in transfusion and chelation have improved survival in transfusion-dependent thalassemia major (TDT), yet cumulative iron toxicity can impair endocrine function. We evaluated whether pituitary iron detected by MRI is associated with endocrine outcomes. Medical records of 60 pediatric TDT patients (mean age 11.5±4.4 years) were reviewed. Iron burden was estimated using serum ferritin and liver iron concentration (LIC) measured by R2 MRI. Pituitary iron was assessed on 1.5-T MRI with coronal and axial sequences using a signal intensity ratio (SIR) method, placing regions of interest in the pituitary gland and nasopharyngeal fat. Endocrine outcomes included short stature, thyroid dysfunction, and hypogonadism. Short stature was present in 25 patients (41.7%), subclinical hypothyroidism in 5 (8.3%), and hypogonadism in 9 (15%). Among 54 patients who underwent liver R2 MRI, 40 (74%) had no iron overload and 14 (26%) had mild accumulation. Neither serum ferritin nor LIC correlated with endocrine complications. Additionally, LIC did not correlate with the pituitary/fat SIR. Overall, the SIR method showed limited diagnostic utility and low specificity for assessing pituitary iron deposition. In this single-center pediatric cohort, pituitary SIR did not reflect hepatic iron load or predict endocrine morbidity. Given these limitations, quantitative T2/T2* techniques may offer greater accuracy for detecting pituitary iron overload. Larger, multicenter studies are warranted to validate the clinical relevance of pituitary MRI in the assessment of endocrine dysfunction in TDT.

The hemoglobin variant, Hb D-Iran (HBB:c.67G > C), is a rare structural hemoglobinopathy mainly reported from Iran and Pakistan, with only limited documentation in India. Although usually clinically silent in the heterozygous state, it may coexist with other variants and complicate chromatographic interpretation. A 40-year-old woman from Central India was found to have two abnormal peaks in the HbA₂ (43.5%) and HbS (43.4%) windows on CE-HPLC, prompting further investigation. ARMS-PCR verified the presence of heterozygous HbS (HBB:c.20A > T), and additional tests excluded HbE and Lepore disorders, while definitive characterization through Sanger sequencing identified both Hb D-Iran and HbS mutations. Maternal screening revealed heterozygous Hb D-Iran, and the patient herself remained clinically asymptomatic, receiving genetic counseling following diagnosis. This case represents the first known report from India documenting the coexistence of Hb D-Iran with HbS. It underscores the importance of molecular diagnostic methods in accurately differentiating uncommon hemoglobin variants that may resemble more common patterns on CE-HPLC, especially in genetically heterogeneous populations.