Hemoglobin最新文献

Background: Sickle cell disease (SCD) is prevalent in Saudi Arabia. This study evaluates the long-term survival rates of a cohort of SCD patients.

Methods: This observational cohort study was conducted at King Saud University Medical City from January 2009 to September 2023. We enrolled 223 SCD patients between 2009 and 2014, collecting comprehensive data at baseline and during follow-up. The primary endpoint was overall survival.

Results: The cohort had a median follow-up of 11.5 years, totaling 2,118 patient-years. The recent median age was 28.9 years (12.2-63.8). The survival rates at ages 20, 30, 40, and 50 years were 100%, 98.4%, 95.1%, and 89.0%, respectively, with no mortality observed before the age of 20 years. The incidence of mortality was 0.28 deaths per 100 patient-years. Among the six deaths (2.7%), causes included non-Hodgkin lymphoma, acute chest syndrome, and a sepsis-like condition, with three unknown causes. The median age of death was 36.3 years. The increased use of hydroxyurea, from 47% to 80%, was associated with reduced pain crises and acute chest syndrome, and improved hemoglobin and HbF levels. Of the patients, 43 (19.2%) were lost to follow-up, 16 (7.2%) were referred for stem cell transplant, and 16 (7.2%) were followed at other institutions.

Conclusions: This study highlights excellent survival rates for SCD patients in our cohort. Nonetheless, the considerable loss to follow-up highlights the need for strategies to address this issue and larger multicenter studies to confirm our results.

Alpha thalassemia major (ATM) is the most severe form of α-thalassemia, with thousands of cases annually throughout the world. It was historically incompatible with life, with almost all affected individuals dying at or before birth. Recent advances utilizing early, serial intrauterine transfusions have resulted in improved outcomes, including improved neurocognitive functioning and less congenital anomalies. At-risk families should be identified pre-conceptually for counseling and options such as preimplantation genetic testing. ATM, when diagnosed prenatally, requires counseling about termination options and transfusion therapy. Postnatally, aggressive transfusion, in contrast to standard thalassemia transfusion protocols, suppresses ineffective erythropoiesis and hemoglobin Barts formation. These advances have changed the course of ATM in utero and postnatally. Preliminary results suggest iron chelation may be safely administered after one year of age with monitoring, including quantitative liver iron measurements. Patients with ATM can now survive on chronic transfusion therapy and potentially be cured by hematopoietic cell transplantation (HCT). New therapies continue to emerge, including in-utero stem cell transplantation using maternal stem cells and Phase 1 gene therapy trials evaluating reactivation of the embryonic α-globin (zeta) gene and encoding the α-globin gene. Globally, an international working group has been formed to address ATM, which should lead to advances worldwide.

Genotype-phenotype correlation and potential genetic risk in the compound heterozygosity for unstable hemoglobins (UHbs) and α⁰-thalassemia were discussed. Capillary electrophoresis and gene sequencing helped to establish the diagnosis. Hematological analysis showed the following findings: MCV 80.6 fL, MCH 27 pg, HGB 133 g/L, RBC 4.93 × 10¹²/L, Hb A: 94%, Hb X: 3.6% (zone 12) and Hb A₂: 2.4%. DNA analysis revealed the patient was a Hb Pontoise carrier (HBA1: c.191C > A). Hb Pontoise resulted from an GCC > GAC substitution at codon 63 of the HBA1 genes, but carriers were usually asymptomatic or with only borderline hematological abnormalities. Due to mild instability of Hb Pontoise, its diagnosis relied on genetic diagnosis. Considering the high frequency of thalassemia in South China, accurate genotyping and appropriate genetic counseling should be performed for unstable hemoglobin carriers.

Sickle cell disease (SCD) primarily affects people of African American descent in the United States. Many individuals do not know their sickle cell trait (SCT) status or might not be aware of SCD. The purpose of this study was to assess SCD knowledge, awareness of SCT status, and its impact on relationships. A cross-sectional study was conducted from August 2018 to June 2019 among students at a Historically Black College and University. Logistic regression was utilized to determine if the student's SCD knowledge and SCT status had a significant impact on the student's choice of relationships. A total of 203 students participated in the study. Most were female (60.1%) and African American (84.7%). The proportion of correct responses on individual questions within a SCD knowledge assessment ranged from 55.2% to 90.6%. Health professional students (Adjusted OR = 4.47; 95% CI = 1.18, 16.96; p = 0.028) and those with SCT (Adjusted OR = 13.00; 95% CI = 1.72, 98.39; p = 0.013) reported that their potential partner's SCT status would have an impact on their current and future relationships. A large number of students are not knowledgeable about SCD and few are aware of their SCT status.

This study presents the hematological and genetic analysis of a child with severe β-thalassemia harboring triple heterozygous mutations. The child, diagnosed with anemia at the age of 1 year, became transfusion-dependent and maintained a hemoglobin level of 72.00-84.00 g/L following regular blood transfusions. At the age of 9 years, genetic analysis was conducted using PCR-reverse dot blot (PCR-RDB), Sanger sequencing, and third-generation nanopore sequencing. Sanger sequencing identified a triple heterozygous mutation in the β-globin gene: -28(A > G) (HBB:c.-78A > G), IVS-I-5(G > A) (HBB:c0.92 + 5G > A), and CD 71/72(+A) (HBB:c.216_217insA). Nanopore sequencing further confirmed the genotype as β^{-28(A>G), IVS-I-5(G>A)}/β^{CD 71/72(+A)}. The combination of these mutations represents a rare β-thalassemia genotype in China, contributing to the β-globin gene mutation database for the Chinese population. This study highlights the importance of employing family analysis or third-generation sequencing technologies to clarify complex mutation linkages when Sanger sequencing alone cannot determine the relationship between multiple mutations.

The 3.7 kb deletion is the most common known mutation in the α-globin gene cluster worldwide. The aim of this study is to investigate the most common types of 3.7 kb deletions in the Iranian population and, on the other hand, to compare the extent of deletion of the different reported types.

In this study, 50 Iranian α-thalassemia carriers in whom the 3.7 kb deletion had been previously identified by multiplex gap PCR, were further investigated by MLPA. A map of the region where the 3.7 kb deletion occurs was also created and the extents of the reported types were compared.

Approximately 90% of chromosomes with 3.7 kb deletion in this study had MLPA type D and 10% had MLPA type F. This study showed that subtype I of the 3.7 kb deletion reported by Higgs and his coworkers can be classified into at least 5 MLPA types.

The results of this study can be used to complete the information on the distribution of the 3.7 kb deletion subtypes in different populations. Investigation of further populations using higher resolution methods may lead to more information being obtained in this field.

Children with sickle cell anemia (SCA) experience recurrent vaso-occlusive crises and complications, significantly impacting their health-related quality of life (HRQoL). This study determined HRQoL in 130 children aged 5 -15 years with SCA in The Gambia, compared to 130 age- and sex-matched hemoglobin AA (HbAA) children. HRQoL was measured using the Pediatric Quality of Life Inventory (PedsQL), with scores below 69.7 defined as poor HRQoL. Predictors of poor HRQoL were analyzed using binary logistic regression. The mean ages of children with SCA and HbAA were similar (9.83 ± 2.79 years vs. 9.65 ± 2.84 years, p = 0.598), with a male-to-female ratio of 1.1:1. SCA children showed significantly higher rates of underweight (p = 0.019) and stunting (p = 0.045) compared to HbAA children. HRQoL scores were significantly lower in the SCA group across physical, emotional, social, school, and overall domains (p < 0.001). A majority (57.7%) of SCA children had poor HRQoL. Key predictors of poor HRQoL among SCA children included frequent pain episodes (>3 episodes in the past 12 months; odds ratio [OR] = 1.9, p = 0.028), late diagnosis of SCA (OR = 1.8, p = 0.012), and clinical stroke (OR = 69.3, p = 0.037). This study demonstrates that SCA significantly reduces HRQoL in all domains. Early diagnosis, effective pain management, and prevention of complications like stroke are critical to improving outcomes. Tailored interventions are needed to mitigate the physical and psychosocial burdens of SCA among children in The Gambia.

In southern China, α-thalassemia is the most prevalent hereditary monogenic disorder, and deletion variants are the predominant form. Conventional thalassemia diagnosis techniques are numerous, however they are all limited in their ability to detect rare deletions. Here, we discuss a family who sought genetic counseling during their fourth pregnancy after experiencing Hb Bart's hydrops fetalis in two of their previous pregnancies. To ascertain the thalassemia genotype, the family members underwent hematological testing, routine genetic analysis and multiplex ligation-dependent probe amplification (MLPA). The precise deletion locations could not be identified, while MLPA detected an unknown copy number variant. Lastly, a rare 11.1 kb deletion located in the HBA gene (Chr16: 170,832-182,004, GRch38/hg38) was directly identified by single-molecule real-time technology (SMRT) sequencing. Furthermore, we confirmed the compound heterozygosity of --^11.1 allele and --^SEA allele, which contributed to the explanation of the Hb Bart's hydrops fetalis syndrome in the fetuses from the second and third pregnancies. We have first verified a compound heterozygosity for --^11.1 allele and --^SEA allele. This study may provide a reference strategy for the discovery of rare and potentially novel thalassemia variants using a comprehensive method combining SMRT sequencing and conventional diagnostic technology, improving the accuracy and efficacy of thalassemia diagnosis.

Hemoglobin disorders are highly prevalent inherited hematological defects in Southern China. The identification of novel variants in globin genes and accurate assessment of hematological parameters play a crucial role in precise genetic counseling and clinical practice. Peripheral blood samples were collected for hematological analysis, including red blood cell and hemoglobin assessment, while serum ferritin levels were measured to detect iron depletion. Thalassemia carrier identification was conducted in four subjects admitted to Jiangxi Maternal and Child Health Hospital using next-generation sequencing and Gap-PCR due to the high prevalence of thalassemia in Jiangxi Province. The identified rare or novel small nucleotide variants were subsequently validated through Sanger sequencing. A total of four novel variants were identified incidentally in four unrelated subjects, including HBA1: c.300G > C (p.Lys100Asn), HBA2: c.212T > A (p.Val71Glu), HBB: c.28T > A (p.Ser10Thr) and c.167T > C (p.Met56Thr). The proband carrying the c.212T > A and c.300G > C variants exhibited normal hematological findings, while capillary electrophoresis revealed the presence of abnormal hemoglobin fractions at 22.4% and 10.9%. The subjects with variant HBB: c.28T > A and c.167T > C all demonstrated normal hematological findings and normal hemoglobin fraction as determined by capillary electrophoresis or ion exchange high-resolution liquid chromatography (HPLC). The two variants exhibiting abnormal fractions of hemoglobin were designated as Hb Jiangxi (HBA2: c.212T > A) and Hb Fulton (HBA1: c.300G > C). Meanwhile, HBB: c.28T > A and HBB: c.167T > C were referred to as Hb Yichun and Hb Jinxian, respectively. We here reported four novel variants in globin genes and their hematological findings in for unrelated Chinese individuals in Southern China. Our research has expanded the existing genetic spectrum of globin genes and enhanced our understanding of the hematological profiles associated with variant hemoglobin.

This study aimed to analyze the clinical phenotype of the HBA2: c.95G>A mutation in the Chinese population and to provide guidance for clinical diagnosis and genetic counseling. Peripheral blood samples were collected from 16 patients, including 6 newborns, 2 children, and 8 adults. Hematological parameters and hemoglobin electrophoresis were analyzed, and genotypes were identified using methods such as PCR combined with reverse dot blot (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), and DNA sequencing. The results showed that 10 patients had mild anemia, 2 had moderate anemia, and 12 exhibited microcytic hypochromic features with MCV values ranging from 53 to 74.7 fl and MCH values from 16.2 to 25.4 pg. Additionally, 3 cases displayed obvious HbH + HbBarts bands (>15%). Among the 16 cases, various combinations of the HBA2: c.95G>A mutation were observed: one case had -α^3.7 combined with HBA2: c.95G>A, another had -α^4.2 combined with HBA2: c.95G>A, and five had -^SEA combined with HBA2: c.95G>A, while the remaining cases were HBA2: c.95G>A heterozygotes. The study concludes that the HBA2: c.95G>A mutation in the α2 globin gene causes α+ thalassemia. When this mutation is combined with the Southeast Asian deletion (-^SEA), it results in HbH disease, characterized by moderate microcytic hypochromic anemia and the presence of HbH + HbBarts bands.