Hemoglobin最新文献

Unstable hemoglobin (Hb) variants are a rare cause of congenital hemolytic anemia. We describe a Chinese girl who presented with transfusion-dependent anemia in early infancy. Her diagnosis of Hb Calgary [β64(E8)Gly > Val; HBB:c.194G > T] was not made until molecular testing was performed at the age of 5 years. Our case highlights the importance of early genetic testing in order to make the diagnosis, which may not only be useful for patient management and family counseling, but also for avoiding further unnecessary investigative attempts.

We report a new δ-chain hemoglobin (Hb) variant observed in a 5-year-old female living in Yulin, Guangxi, China. Capillary electrophoresis revealed splitting of the Hb A₂ peak into two fractions (Hb A₂ and Hb A₂ variant), and the Hb A₂ variant was also detected by high-performance liquid chromatography. However, it could not be detected using matrix-assisted laser desorption lonization-time of flight mass spectrometry. CD41-42 (-TCTT) heterozygosity was observed on the HBB gene by PCR and reverse dot-blot hybridization. Sanger sequencing showed a new transition (G > A) at codon 46 of the HBD gene, resulting in glycine changing to arginine. Based on the patient's place of residence, the new variant was named Hb A₂-Yulin [δ46(CD5)Gly→Arg,HBD:c.139G > A].

In this report, we describe a 6-year-old girl with a medical history of pallor, mild icterus, anemia, blood transfusion and abnormal hemoglobin variant analysis on capillary electrophoresis. She was referred for further analysis. DNA sequencing of the proband revealed a de novo mutation in Codon 88 (CTG > CCG) of the β-globin gene (HBB: c.266T > C) in a heterozygous state compatible with hemoglobin Santa Ana, an unstable hemoglobin. This is the first case of Hb Santa Ana from Iran associated with moderate to severe anemia who underwent splenectomy with clinical improvement.

Long noncoding RNAs (lncRNAs) are important because they are involved in a variety of life activities and have many downstream targets. Moreover, there is also increasing evidence that some lncRNAs play important roles in the expression and regulation of γ-globin genes. In our previous study, we analyzed genetic material from nucleated red blood cells (NRBCs) extracted from premature and full-term umbilical cord blood samples. Through RNA sequencing (RNA-Seq) analysis, lncRNA H19 emerged as a differentially expressed transcript between the two blood types. While this discovery provided insight into H19, previous studies had not investigated its effect on the γ-globin gene. Therefore, the focus of our study was to explore the impact of H19 on the γ-globin gene. In this study, we discovered that overexpressing H19 led to a decrease in HBG mRNA levels during erythroid differentiation in K562 cells. Conversely, in CD34+ hematopoietic stem cells and human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, HBG expression increased. Additionally, we observed that H19 was primarily located in the nucleus of K562 cells, while in HUDEP-2 cells, H19 was present predominantly in the cytoplasm. These findings suggest a significant upregulation of HBG due to H19 overexpression. Notably, cytoplasmic localization in HUDEP-2 cells hints at its potential role as a competing endogenous RNA (ceRNA), regulating γ-globin expression by targeting microRNA/mRNA interactions.

Malaria is considered an important cause of morbidity and mortality among people living with sickle cell disease (SCD). This has partly been attributed to the loss of splenic function that occurs early in the disease process. We conducted a cross-sectional study and determined the frequency of malaria infection among SCD patients and explored the association with spleen's presence on ultrasonography and spleen function assessed using the frequency of Howell-Jolly bodies (HJBs). A total of 395 participants consisting of 119 acutely-ill SCD patients, 168 steady-state SCD controls, and 108 healthy non-SCD controls were studied. The prevalence of Plasmodium falciparum parasitemia was 51.3% in acutely-ill SCD patients, 31.7% in steady-state SCD controls, and 11.0% in the healthy non-SCD controls; however, the mean parasite density was significantly higher in the non-SCD controls compared to both SCD groups (p = 0.0001). Among the acutely-ill SCD patients, the prevalence of clinical malaria and severe malaria anemia were highest in children <5 years of age. The prevalence of parasitemia (p = 0.540) and parasite density (p = 0.975) showed no association with spleen presence or absence on ultrasonography. Similarly, the frequency of HJB red cells was not associated with the presence of parasitemia (p = 0.183). Our study highlights the frequency and role of malaria infection in acutely-ill SCD patients, especially in those younger than five years. Although we have found no evidence of an increased risk of malaria parasitemia or parasite density with markers of hyposplenism, the role played by an underlying immunity to malaria among SCD patients in malaria-endemic region is not clear and needs further studies.

Unstable variant hemoglobinopathies are an uncommon cause of hemolysis in the pediatric patient and may cause a delay in diagnosis if there is not a high index of suspicion. Hemoglobin (Hb) Mizuho is a rare unstable hemoglobinopathy caused by a pathogenic variant of the HBB gene with a severe phenotype. Here we report on the first known case of Hb Mizuho in Australia, presenting with features of acute and chronic hemolysis. The morphological features on blood film review, in conjunction with biochemical findings and other clinical features, did not immediately suggest an alternative diagnosis and a Next Generation Sequencing gene analysis approach was taken to investigate genes associated with red blood cell disorders and atypical uremic syndrome. The HBB Mizuho variant was detected and established the diagnosis. This report highlights the challenge of diagnosing Hb Mizuho on conventional testing and the need for early genomic testing to clarify a diagnosis.

The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/β-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia.

A pregnant woman living in Fujian Province, southeastern China, presented due to a risk of having a baby with β-thalassemia major, during her second pregnancy, since she and her husband were suspected as β-thalassemia carriers and their affected daughter was a transfusion-dependent patient. Using the common α-thalassemia and β-thalassemia genotypes test, the pregnant woman was diagnosed as a β-thalassemia carrier with β^{IVS-2 - 654 (C→T)}/β^N genotype and her daughter had a homozygosity for IVS - 2 - 654 (C→T) mutation, however, no abnormalities were detected in her husband. SMRT identified a Filipino β⁰-deletion in her husband, and MLPA also revealed an unknown deletion in the HBB gene. Electrophoresis showed approximately 350 bp of the PCR product, and the β-Filipino genotype presented novel fracture fragments ranging from 5,112,884 to 5,231,358 bp, and lacked a 118,475 bp fragment relative to the wild-type sequence. The daughter was therefore diagnosed with the β^{IVS-2 - 654 (C→T)}/β^Filipino genotype. Prenatal diagnosis with umbilical cord blood at 27th week of gestation showed heteroztgosity for IVS - 2 - 654 (C→T) mutation in the fetus and continued pregnancy was recommended. In conclusion, we identified the Filipino β⁰-deletion in a Chinese family, from Fujian area, for the first time, during prenatal screening.

Patients with the genotype of β⁰/β⁰ for β-thalassemia (β-thal) usually behave as β-thal major (β-TM) phenotype which is transfusion-dependent. The pathophysiology of β-thal is the imbalance between α/β-globin chains. The degree of α/β-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of β-TM. We report a Chinese child who had homozygous β⁰-thal and a heterozygous KLF1 mutation. The patient had a moderate anemia since 6 months old, keeping a baseline Hb value of 8.0-9.0 g/dL. She had normal development except for a short stature (3rd percentile) until 6 years old, when splenomegaly and facial bone deformities occurred. Although genetic alteration of KLF1 expression in β⁰/β⁰ patients can result in some degree of disease alleviation, our case shows that it is insufficient to ameliorate satisfactorily the presentation. This point should be borne in mind for physicians who provide the genetic counseling and prenatal diagnosis to at-risk families.