Hemoglobin最新文献

Hereditary spherocytosis (HS) is an inherited disease characterized by the presence of spherical erythrocytes in the peripheral blood. Beta-spectrin (SPTB) encodes a cytoskeletal protein previously associated with spherocytosis. Mutations in SPTB are one of the most common causes of HS. We have reported here the case of a 2-year-old boy who presented with severe anemia, jaundice, and hyperbilirubinemia at Kunming Children's Hospital. His osmotic fragility tests (OFT) and eosin maleimide (EMA) tests were positive. Genetic molecular analysis was performed to identify the underlying cause of the disease in the patient and his parents via whole-exome sequencing (WES), and revealed a heterozygous nonsense variant (c.1920G > A: p.W640*) in exon 14 of SPTB. This mutation induced a change from tryptophan to a stop codon at position 640. Sanger sequencing further confirmed that the variant was inherited from the patient's mother. The patient was diagnosed with HS based on the combined analyses of the clinical phenotype and genotype. The cumulative findings enrich the spectrum of SPTB variants, provide valuable clinical molecular insights, and lay the foundation for genetic counseling and diagnosis.

Double heterozygotes of HbE and α-Thalassemia-1 (Southeast Asian type) ((β^A/β^E, - -SEA/αα) can result in severe thalassemia conditions, such as HbE/β-thalassemia (β^E/β^T)) and Hb Bart's hydrops fetalis syndrome (- -^SEA/- -^SEA). Identification of these double heterozygotes is crucial for preventing births affected by Hb Bart's hydrops fetalis syndrome. The most accurate method for detecting HbE/SEA-α-Thalassemia-1 double heterozygotes is PCR-based analysis, which is complex and costly. This study aimed to develop a hematologic algorithm for predicting double heterozygotes of HbE/SEA-α-Thalassemia-1. A retrospective analysis was conducted on 471 datasets of red blood cell indices and HbE levels collected from hospitals in Northern Thailand. Data analysis and algorithm development were performed using statistical tools and RapidMiner software. The prevalence of HbE/SEA-α-Thalassemia-1 double heterozygotes was 12.1%. Significant differences were found in HbE levels, MCV, MCH, and RBC count between single HbE heterozygotes and HbE/SEA-α-Thalassemia-1 double heterozygotes. The predictive algorithm, named the 'Nation SEAE Algorithm,' was established as follows: HbE ≤ 20.5%; RBC > 4.55 × 10⁶/µL; and MCV ≤ 70.5 fL. This algorithm demonstrated 40% sensitivity (95% CI: 30.3-50.3), 100% specificity (95% CI: 96.4-100), 100% positive predictive value (95% CI: 96.4-100), 95.6% negative predictive value (95% CI: 90.0-98.9), a negative likelihood ratio of 0.6 (95% CI: 0.3-1.2), an infinite positive likelihood ratio, 95.7% accuracy (95% CI: 90.1-98.9), and an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) for identifying HbE/SEA-α-Thalassemia-1 double heterozygotes. Therefore, the 'Nation SEAE Algorithm' is a valuable clinical tool to support accurate identification of the double heterozygotes of HbE and SEA-α thalassemia 1.

Thalassemia is associated with high morbidity and mortality. The purpose of this study was to delineate the genetic mutation spectrum of thalassemia in Huadu District, Guangzhou, to provide a basis for prenatal diagnosis and genetic counseling. Between January 2020 and December 2024, 2,428 blood samples from individuals with suspected thalassemia were collected at Huadu District People's Hospital. α- and β-Thalassemia genotypes were identified using gap-polymerase chain reaction (Gap-PCR) and PCR-reverse dot blot (PCR-RDB). Overall, 1,774 (73.06%) patients tested positive for thalassemia. Of these, 52.37% (929/1,774) had α-thalassemia, 42.00% (745/1,774) had β-thalassemia, and 5.64% (100/1,774) had co-inheritance of α/β-thalassemia. The most frequent α-thalassemia genotype was (--^SEA/αα) seen in 62%. β-Thalassemia was dominated by high-frequency mutations, including β^CD41-42/β^N (270 cases, 36.91%) and β^IVS-II-654/β^N (26.98%). The most typical combined genotype was --^SEA/αα with β^CD41-42/β^N (18%). The mutation profile in Huadu District aligns with the Southern Chinese thalassemia spectrum but exhibits regional specificity, mirroring the overall epidemiological pattern of Southern China while demonstrating distinct regional mutation clusters. Greater emphasis should be placed on thalassemia screening, genetic counseling, and prenatal diagnosis to improve birth outcomes.

We describe the identification of an intronic variant in the β-globin gene (HBB: c0.92 + 9C > T) in a 41-year-old Spanish male presenting with microcytosis and hypochromia in the absence of iron deficiency. This variant, located in intron 1 of the HBB gene, was identified using the Devyser Thalassemia NGS kit and confirmed by Sanger sequencing. In silico predictions suggest potential splicing disruption. The hematological profile was consistent with β-thalassemia trait, although Hb A2 values were within normal ranges. This variant is not reported in public databases and is currently classified as of uncertain significance with moderate pathogenic potential according to ACMG criteria. This discrepancy between bioinformatic predictions and clinical classification is discussed. The variant has been submitted to both HbVar and IthaGenes databases (submission ID pending). This report contributes to the expanding catalog of HBB variants and underscores the diagnostic relevance of intronic regions.

Non-transfusion-dependent thalassemias (NTDT), including thalassemia intermedia (TI), are often perceived as less severe than their transfusion-dependent counterparts. However, they impose a significant health burden, manifesting in complications such as splenomegaly, iron overload, skeletal deformities, and cardiopulmonary diseases. This case report aims to enhance understanding of the complexities associated with NTDT, particularly regarding the rapid progression of infection and the associated challenges in management. We report the case of a 62-year-old male farmer from a high-incidence region of thalassemia in China. He was diagnosed with αNTDT during a medical evaluation. His baseline hemoglobin levels were 7 g/dL at the time of genetic testing for thalassemia and 7.2 g/dL upon hospital admission prior to infection. His clinical phenotype was classified as thalassemia intermedia. The patient presented with significant comorbidities, including chronic anemia, iron overload, and pulmonary hypertension, which contributed to his rapid clinical deterioration. Within two months of his definitive diagnosis, the patient developed sepsis that rapidly progressed to multiple organ dysfunction syndrome, leading to death 43 h after admission. Sepsis in patients with NTDT progresses rapidly and is associated with a high mortality rate, primarily due to the compounded burden of chronic anemia, iron overload, and immune dysfunction. This case highlights the need for increased clinical awareness to facilitate early diagnosis and prompt management, even in αNTDT, which is generally considered a milder disorder compared to βNTDT. Enhancing community awareness and implementing proactive healthcare strategies, particularly in high-incidence areas, may significantly reduce adverse health outcomes in patients with NTDT.

Sickle cell-β-thalassaemia (Hb S/β-thal) results from the compound heterozygosity of sickle cell and β-thalassaemia alleles. The influence of α-globin genotypes on clinico-hematological and biochemical parameters in 404 cases of Hb S/β-thal with IVS I-5 (G→C) (HBB: c.20A > T/HBB: c0.92 + 5G > C) mutation was studied. Normal α-globin genotype (αα/αα), heterozygous α-thal (-α/αα) and homozygous α-thal (-α/-α) were found in 204 (50.5%), 114 (28.22%), and 86 (21.29%) cases respectively. The overall incidence of α-thal was found to be 49.5% and allele frequencies for α^-3.7 and α^-4.2 α-thal were found to be 0.23 and 0.11 respectively. RBC count, total hemoglobin and hematocrit levels were significantly higher in homozygous α-thal, intermediate in heterozygous α-thal and lower in normal α-globin genotype. Painful events per year, requirement of blood transfusion per year and hospitalization per year did not show any significant differences across these α-globin genotypes, although, the requirement of blood transfusion per year and hospitalization per year were more in patients with normal α-globin genotypes. Asymptomatic cases were higher in prevalence among homozygous α-thal (9.3%) compared to the other two groups. The age at clinical presentation was marginally later than that among other two groups. The present study shows quite high prevalence of α-thal trait among patients with Hb S/β-thal with IVS I-5 (G→C) mutation. Although influence of homozygous α-thal was found to have some protection further follow up and studies are needed to find its significance.

Beta-thalassemia is a hereditary hemoglobinopathy characterized by significant clinical variability, largely influenced by the underlying genetic mutations. We report a 47-year-old female patient with β-thalassemia intermedia harboring a rare homozygous mutation in the β-globin gene promoter: HBB:c.-136C > G (-86 C > G). The patient showed marked clinical response to hydroxyurea therapy with a notable increase in hemoglobin levels, reduction in spleen size and improvement of fatigue and bone pain due to extramedullary hematopoiesis. This report highlights the role of genetic characterization in understanding rare forms of thalassemia and the potential of hydroxyurea as a personalized treatment strategy for patients with unique genetic determinants.

We report a novel δ-chain hemoglobin (Hb) variant, designated Hb A2-Malay [HBD:c.139G > C;316-443A > G], identified in 19 Malaysian Malay individuals. This variant was consistently observed in both Capillary Electrophoresis (CE) Zone 1 and High-Performance Liquid Chromatography (HPLC) S-window analyses. Sanger sequencing revealed a new G > C substitution at the first base of codon 46 within the HBD gene, leading to a glycine to arginine amino acid change. Additionally, a cis-acting polymorphism, an A to G substitution at intron II position 456, was genotyped in all carriers. Routine genetic testing for common α-thalassemia, using Gap-PCR and Amplification Refractory Mutation System, was also performed. Four carriers exhibiting similar hematological indices were found to have a concomitant heterozygous -α^3.7 mutation. Furthermore, three β^E carriers demonstrated higher Zone 1 and S-window percentages.

Sickle cell disease (SCD) is the most common hemoglobinopathy, affecting approximately 300,000 newborns worldwide each year. Hematopoietic stem cell transplantation (HSCT) is the only current curative option for the disease. Still, it is hindered by the availability of suitable donors, socio-economic issues, transplant failure and long-term complications of transplant, including graft-versus-host disease-acute and chronic. To date, there is no standardized protocol for conditioning regimens in SCD patients. A total of 100 pediatric patients diagnosed with sickle cell disease (SCD) underwent allogeneic hematopoietic stem cell transplantation (HSCT) between January 2015 and December 2024. Fifty-five patients (59.8%) underwent HLA-identical sibling-donor, and 37(40.2%) underwent haploidentical transplants. Eighty-three (91.2%) had stable engraftment. The median follow-up time was 31.6 months. Overall survival was 86.9%(95% CI: 79.3%-93.4%) in our cohort of 92 patients transplanted for SCD from either HLA-matched siblings or haploidentical donors, with a median follow-up of 53 months, with EFS of 77% without death or rejection. The survival rates were significantly higher in MSD HSCT (53/55, 96.4% vs 27/37, 78.3%, p < 0.01). The outcomes in haploidentical outcomes have significantly improved (2014-2018 vs 2019 to 2023). The cumulative incidence of acute graft-versus-host-disease (GVHD) was 26% (95% CI - 17.9% to 36.8%) and of chronic GVHD was 8.4% (95% CI - 3.7% to 17.1%) at 2-year post-transplant. Viral reactivations were seen in 18 patients. In haploidentical transplants, we gradually drifted toward reduced toxicity conditioning, including Thio-Flu-Cy-TBI-ATG and found better outcomes through the years. The use of post-transplantation (PTCy) has led to a significantly reduced risk of GVHD.