Hemoglobin最新文献

We report a novel β-globin chain variant identified in a proband who is also a carrier of β-thalassemia. Glycated hemoglobin analysis revealed an elevated Hb A_1c level of 20.34% using high-performance liquid chromatography (HPLC), while the fasting blood glucose level was 5.49 mmol/L. Subsequent testing using an alternative HPLC system showed an Hb A_1c value of 2.8%, and the immunoturbidimetric assay failed to yield a detectable result. Sanger sequencing confirmed the presence of two heterozygous point mutations in the β-globin gene: CD1 (GTG > CTG) (HBB:c.4G > C) and CD17 (AAG > TAG) (HBB:c.52A > T). Hemoglobin analysis showed the variant electrophoresing at the HbA position. The HBB:c.4G > C mutation represents a previously unreported variant, which has been designated Hb Yongning based on the proband's geographical origin.

Silent carrier or minor α-thalassemia (α-thal) is generally considered asymptomatic or associated with mild anemia in only a few cases. However, it is not uncommon for individuals with these conditions to seek outpatient care because of anemia. Which factors contribute to the development of anemia in this population? We retrospectively observed the individuals at a general hospital in central China, a non-endemic area for thalassemia. A total of 142 participants confirmed by thalassemia genetic testing were enrolled, including 54 cases of silent carrier and 88 cases of minor α-thal. Among the participants, 88 cases (62%) were diagnosed with anemia, as their hemoglobin (Hb) concentrations were below the lower limit of the reference range recommended by the World Health Organization (WHO) for their respective gender and age groups. Multivariate analysis of anemia revealed that the -^SEA/αα genotype (P = 0.014, OR = 2.503, 95%CI: 1.203-5.204) was an independent risk factor for anemia and deserves proactive anemia management. Iron deficiency (serum ferritin <30 ng/ml) has not been identified as a risk factor, but it is found to have a high incidence (18.2%) in the anemic group and requires further investigation with a larger sample size in this population.

Comprehensive strategies are crucial for alleviating the substantial burden of sickle cell disease (SCD) in sub-Saharan Africa. Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers a potentially scalable and cost-effective cure for eligible SCD patients; however, it is currently available in only seven African countries due to difficulties in implementing alloHSCT in Low- and Middle-Income Countries (LMICs). These challenges include limited and underdeveloped healthcare infrastructure, high rates of infectious diseases worsened by emerging multidrug-resistant pathogens, restricted access to effective antimicrobial agents, and the lack of advanced transplant technologies such as T-cell depletion, HLA typing laboratories, and stem cell processing facilities. The shortage of specialized supportive care and trained staff, along with inadequate access to chemotherapeutic and immunosuppressive drugs, further hampers progress. Additionally, there is no health insurance coverage for procedures like HSCT, forcing patients and their families to pay out of pocket, which makes HSCT unaffordable for many who could greatly benefit from it. Government support remains far below what is necessary to expand transplant capacity. For those who can afford it, medical tourism for HSCT outside Africa is increasing. Unfortunately, many of these patients return to environments with limited expertise and resources for post-transplant follow-up care. This article discusses the challenges faced in establishing a dedicated alloHSCT program for SCD at a tertiary hospital in Lagos, Nigeria, and explores opportunities for improvement.

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.