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1.
Acta Med Indones ; 56(1): 13-19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38561881

RESUMO

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.


Assuntos
Hipogonadismo , Talassemia , Talassemia beta , Adulto , Humanos , Masculino , Talassemia beta/complicações , Talassemia beta/terapia , Estudos Transversais , Qualidade de Vida , Talassemia/complicações , Talassemia/terapia , Hipogonadismo/complicações , Testosterona , Hormônio Foliculoestimulante
2.
Acta Med Indones ; 56(1): 20-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38561882

RESUMO

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.


Assuntos
Osteoporose , Talassemia , Masculino , Humanos , Feminino , Osteoprotegerina , Densidade Óssea , Osteoporose/etiologia , Osteoporose/patologia , Talassemia/terapia , Talassemia/complicações , Transferrinas , Ligante RANK
3.
Ann Med ; 56(1): 2338246, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38604224

RESUMO

BACKGROUND: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. OBJECTIVES: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. PATIENTS AND METHODS: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. RESULTS: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. CONCLUSIONS: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.


Assuntos
Cardiopatias , Sobrecarga de Ferro , Talassemia , Talassemia beta , Humanos , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/terapia , Tailândia/epidemiologia , Causas de Morte , Talassemia/complicações , Fatores de Risco , Sobrecarga de Ferro/etiologia
5.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474150

RESUMO

Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the ß-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Talassemia , Talassemia beta , Humanos , Densidade Óssea , Hemoglobinopatias/genética , Anemia Falciforme/genética , Hemoglobina Falciforme , Talassemia beta/genética
6.
Pediatr Hematol Oncol ; 41(3): 179-197, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38424668

RESUMO

Objective: Increased survival rate of patients with Transfusion-dependent Thalassemia (TDT) should be in line with their good quality of life (QoL). The study aimed to analyze the relationship between sociodemographic factors and clinical characteristics with the QoL of children with TDT. Methods: A cross-sectional study was conducted at Hasan Sadikin General Hospital from December 2022 to February 2023. A total of 158 eligible subjects aged 5-18 years with TDT were included in the analysis. QoL assessment was performed using child self-report and parent-proxy report questionnaires, along with physical examination findings. Bivariate and multivariate analyses were conducted to analyze the data. Results: A total of 158 subjects who met the research criteria were included in the analysis. Of 58.9% of children with TDT had a low adherence rate to iron chelating therapy (ICT). School function had the lowest score in QoL based on child-self report and parent proxy. Gender (p<0,05) and adherence to ICT (p<0,05) were significantly associated with lower quality of life. Conclusion: Female and adherence to ICT were predictors of children with TDT's QoL.


Assuntos
Qualidade de Vida , Talassemia , Humanos , Feminino , Estudos Transversais , Talassemia/terapia , Inquéritos e Questionários , Transfusão de Sangue
7.
Pediatr Blood Cancer ; 71(5): e30923, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38385860

RESUMO

BACKGROUND: In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. PROCEDURE: We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). RESULTS: Sixty-three (73%) patients had pancreatic IO (R2* > 38 Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18 ± 3 months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. CONCLUSIONS: In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.


Assuntos
Sobrecarga de Ferro , Siderose , Talassemia , Talassemia beta , Humanos , Criança , Ferro , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem , Talassemia beta/terapia , Siderose/complicações , Siderose/metabolismo , Siderose/patologia , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Pâncreas/patologia , Talassemia/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Ferritinas , Glucose/metabolismo
8.
Health Qual Life Outcomes ; 22(1): 14, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302961

RESUMO

Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.


Assuntos
Quelantes de Ferro , Talassemia , Humanos , Quelantes de Ferro/uso terapêutico , Deferasirox , Deferiprona , Desferroxamina/uso terapêutico , Qualidade de Vida , Piridonas/efeitos adversos , Benzoatos/efeitos adversos , Triazóis/efeitos adversos , Talassemia/tratamento farmacológico , Terapia por Quelação , Ferritinas , Avaliação de Resultados em Cuidados de Saúde
10.
Niger J Clin Pract ; 27(2): 188-193, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38409146

RESUMO

BACKGROUND: Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal diagnostic measures are undertaken to prevent births with thalassemia major, a locally widespread genetic disease. AIM: This study aims to evaluate the results of prenatal invasive diagnostic tests performed in a private obstetrics clinic in Northern Cyprus and show the diagnosis process of thalassemia and chromosomal anomalies. MATERIALS AND METHODS: This study is a retrospective, descriptive study. Chorionic villus sampling (CVS) results and the amniocentesis tests performed between 1990 and 2022 are evaluated. Thalassemia and chromosome analysis of samples obtained by CVS and amniocentesis tests were performed. To diagnose alpha or beta thalassemia and sickle cell, 239 CVS was performed. And to diagnose chromosomal anomalies, 396 CVS and amniocentesis were performed. RESULTS: The mean age of the 480 pregnant women included in the study was 31.12 years (18-46) and 30% of them were older than 34 years. The most common indications for invasive prenatal diagnostic test (IPDT) were; mother/father thalassemia minor/major, advanced maternal age, high risk of ultrasonography erase findings, and the noninvasive screening test. The result of IPDT detected 7.3% chromosomal anomaly and 69.5% thalassemia and sickle cell anemia. Of the 239 CVS performed to diagnose alpha or beta thalasemia and sickle cell, 23.4% beta major, 42.3% beta minor, and 2.1% alpha minor were diagnosed. Of the 396 CVS and amniocentesis performed to diagnose chromosomal anormalies; 2.8% of Down syndrome and 4.54% of other chromosomal anomalies were diagnosed. CONCLUSION: IPDT is important in correctly diagnosing fetal anomalies at the prenatal stage to help families decide at the right time.


Assuntos
Anemia Falciforme , Transtornos Cromossômicos , Talassemia , Gravidez , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Chipre , Diagnóstico Pré-Natal/métodos , Amostra da Vilosidade Coriônica , Aberrações Cromossômicas , Testes Diagnósticos de Rotina
11.
Pediatr Transplant ; 28(1): e14688, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38317344

RESUMO

OBJECTIVES: Graft-versus-host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia. MATERIALS AND METHODS: This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020. RESULTS: Despite the GvHD prophylaxis, grade II-IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI-related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p = .013). There was no significant difference between the groups in terms of engraftment syndrome, veno-occlusive disease, CMV reactivation, PRES, or graft rejection. CONCLUSION: Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia , Humanos , Criança , Ciclosporina/uso terapêutico , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Receptores de Antígenos de Linfócitos T
12.
Hemoglobin ; 48(1): 47-55, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38369714

RESUMO

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/ß-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.


Assuntos
Sobrecarga de Ferro , Talassemia , Humanos , Criança , Deferasirox/efeitos adversos , Quelantes de Ferro/efeitos adversos , Benzoatos/efeitos adversos , Triazóis/efeitos adversos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Talassemia/tratamento farmacológico , Ferro , Ferritinas
13.
Eur J Clin Pharmacol ; 80(5): 685-696, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38329479

RESUMO

PURPOSE: To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA. METHODS: Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model. RESULTS: A one-compartment model with first-order absorption was employed to fit the base model. A total of 74 pediatric patients and 600 observations of whole blood concentration were included. The final model included weight (WT) in clearance (CL), alongside post-operative day (POD), fluconazole (FLUC), voriconazole (VORI), posaconazole (POSA), and red blood cell count (RBC) significantly. All the model evaluations were passed. CONCLUSION: In the PPK model based on the pediatric cohort on CsA with thalassemia undergoing allogeneic HSCT, WT, POD, FLUC, VORI, POSA, and RBC were found to be the significant factors influencing CL of CsA. The reliability and robustness of the final model were excellent. It is expected that the PPK model can assist in individualizing dosing strategy clinically.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Talassemia , Humanos , Criança , Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Estudos Retrospectivos , Reprodutibilidade dos Testes , Modelos Biológicos , Voriconazol , Fluconazol , Talassemia/cirurgia
14.
Int J Paleopathol ; 44: 90-104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38181478

RESUMO

OBJECTIVE: This paper reviews factors confounding the understanding of the past occurrence of anemia. Using the evidence gathered, a framework is presented of ways forward to enable greater confidence in diagnosing acquired anemia in paleopathology, facilitating insights into longer-term perspectives on this globally relevant condition. RESULTS: To date, porotic lesions have been central to paleopathological investigations of anemia. The fact that porotic bone lesions are omnipresent and have multiple causes but are likely to have a relatively low, age-related frequency in individuals with anemia, a condition that will have been common in past communities, is confounding. METHODS: Establishing frameworks that move away from porotic lesions is proposed to facilitate higher levels of more accurate anemia diagnoses in paleopathology. SIGNIFICANCE: Acceptance of the fundamental principle that anemia may be better considered as a condition requiring metric evaluation of bone structures, supplemented by careful consideration of lesions, will advance understanding of acquired anemia in past communities. Such an approach would provide a clear basis for further consideration of congenital conditions causing anemia, such as sickle-cell disease and thalassemia. LIMITATIONS: This paper simply opens the conversation on the better diagnosis of anemia in paleopathology; it starts the iterative process of achieving some consensus and progress on diagnosing anemia in paleopathology. SUGGESTIONS FOR FURTHER RESEARCH: Engagement with ideas presented, sharing data and development of metric parameters will assist in identifying the effects of marrow hyperplasia on bone, enabling more robust work on the important topic of anemia.


Assuntos
Doenças Ósseas , Talassemia , Humanos , Paleopatologia , Comunicação , Consenso
15.
Hemoglobin ; 48(1): 24-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38240123

RESUMO

δß-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese Gγ(Aγδß)0-thalassemia, Yunnanese Gγ(Aγδß)0-thalassemia, Cantonese Gγ(Aγδß)0-thalassemia in China. Due to the low rate of δß-thalassemia carriers, there are few reports of δß-thalassemia combined with ß-thalassemia causing ß-thalassemia major. Herein, we described the combination of Chinese Gγ(Aγδß)0-thalassemia and ß-thalassemia leading to ß-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with ßCD17M/ßCD17M using routine genetic analysis. However, her father was heterozygous for CD17 in ß-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese Gγ(Aγδß)0-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from ßCD17M/ßCD17M to ßCD17M/ßGγ(Aγδß)0. This is the first report of Chinese Gγ(Aγδß)0-thalassemia combined with ß-thalassemia resulting in ß-thalassemia major in China. Screening for δß-thalassemia by Hb analysis could be an effective method.


Assuntos
Talassemia , Talassemia beta , Feminino , Humanos , Talassemia beta/complicações , Talassemia beta/diagnóstico , Talassemia beta/genética , Hemoglobina Fetal/genética , Talassemia/genética , Hemoglobinas/genética , Erros de Diagnóstico
16.
Mol Genet Genomic Med ; 12(1): e2365, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284449

RESUMO

BACKGROUND: Rare and novel variants of HBA1/2 and HBB genes resulting in thalassemia and hemoglobin (Hb) variants have been increasingly identified. Our goal was to identify two rare Hb variants in Chinese population using third-generation sequencing (TGS) technology. METHODS: Enrolled in this study were two Chinese families from Fujian Province. Hematological screening was conducted using routine blood analysis and Hb capillary electrophoresis analysis. Routine thalassemia gene testing was carried out to detect the common mutations of α- and ß-thalassemia in Chinese population. Rare or novel α- and ß-globin gene variants were further investigated by TGS. RESULTS: The proband of family 1 was a female aged 32, with decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), Hb A2, and abnormal Hb bands in zone 5 and zone 12. No common thalassemia mutations were detected by routine thalassemia analysis, while a rare α-globin gene variant Hb Jilin [α139(HC1)Lys>Gln (AAA>CAA); HBA2:c.418A>C] was identified by TGS. Subsequent pedigree analysis showed that the proband's son also harbored the Hb Jilin variant with slightly low levels of MCH, Hb A2, and abnormal Hb bands. The proband of family 2 was a male at 41 years of age, exhibiting normal MCV and MCH, but a low level of Hb A2 and an abnormal Hb band in zone 12 without any common α- and ß-thalassemia mutations. The subsequent TGS detection demonstrated a rare Hb Beijing [α16(A14)Lys>Asn (AAG>AAT); HBA2:c.51G>T] variant in HBA2 gene. CONCLUSION: In this study, for the first time, we present two rare Hb variants of Hb Jilin and Hb Beijing in Fujian Province, Southeast China, using TGS technology.


Assuntos
Talassemia , Talassemia beta , Humanos , Masculino , Feminino , Talassemia beta/genética , Talassemia/genética , Mutação , Índices de Eritrócitos , China/epidemiologia
17.
Ann N Y Acad Sci ; 1532(1): 50-62, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38270933

RESUMO

Health-related quality of life (HRQOL) is a patient-reported outcome that assesses the impact of a disease or illness on different domains of a patient's life. Different general and disease-specific measures can be used to evaluate HRQOL. This article aimed to summarize the evidence for HRQOL among patients with transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). We included HRQOL data related to standard therapy with blood transfusions, iron chelation, and/or luspatercept in TDT and NTDT, as well as curative therapies for TDT, including hematopoietic stem cell transplant (HSCT) and gene therapy. Patients with thalassemia had worse HRQOL scores compared to the general population, and chronic pain was seen to increase in frequency and severity over time with age. NTDT patients reported worse physical health and functioning, mental health, general health, and vitality than TDT patients. However, TDT patients reported worse pain, change in health, and social support than NTDT. Most therapies improved overall HRQOL among thalassemia patients. Deferasirox, an oral iron chelator, was associated with more HRQOL benefits compared to deferoxamine, an intravenous iron chelator. Luspatercept showed clinically meaningful improvement in physical functioning among TDT and NTDT. Furthermore, HSCT and gene therapy were associated with better physical, emotional, and mental domains scores.


Assuntos
Dor Crônica , Sobrecarga de Ferro , Talassemia , Humanos , Qualidade de Vida , Talassemia/terapia , Talassemia/complicações , Quelantes de Ferro/uso terapêutico , Transfusão de Sangue , Sobrecarga de Ferro/complicações
19.
BMC Med Genomics ; 17(1): 9, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167091

RESUMO

BACKGROUND: People with autosomal recessive disorders often were born without awareness of the carrier status of their parents. The American College of Medical Genetics and Genomics (ACMG) recommends screening 113 genes known to cause autosomal recessive and X-linked conditions in couples seeking to learn about their risk of having children with these disorders to have an appropriate reproductive plan. METHODS: We analyzed the exome sequencing data of 1,642 unrelated Thai individuals to identify the pathogenic variant (PV) frequencies in genes recommended by ACMG. RESULTS: In the 113 ACMG-recommended genes, 165 PV and likely PVs in 60 genes of 559 exomes (34%, 559/1642) were identified. The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added. The carrier rate was still as high as 14.7% when thalassemia and hemoglobinopathies were excluded. In addition to thalassemia, hemoglobinopathies, and G6PD deficiency, carrier frequencies of > 1% were found for Gaucher disease, primary hyperoxaluria, Pendred syndrome, and Wilson disease. Nearly 2% of the couples were at risk of having offsprings with the tested autosomal recessive conditions. CONCLUSIONS: Based on the study samples, the expanded carrier screening, which specifically targeted common autosomal recessive conditions in Thai individuals, will benefit clinical outcomes, regarding preconception/prenatal genetic carrier screening.


Assuntos
Hemoglobinopatias , Talassemia , Criança , Gravidez , Feminino , Humanos , Tailândia , Sequenciamento do Exoma , Exoma , Hemoglobinopatias/genética , Talassemia/genética
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(1): 122-127, 2024 Jan 06.
Artigo em Chinês | MEDLINE | ID: mdl-38228559

RESUMO

Thalassemia trait is an autosomal recessive genetic disease, which is a hemolytic anemia caused by disturbance of erythrocyte hemoglobin production caused by gene mutation or deletion. Iron deficiency anemia is caused by a lack of iron in the body due to an imbalance between the demand and supply of iron. The laboratory manifestations of both are microcytic hypochromic anemia, but the treatment schemes are completely different, and it is difficult to distinguish them from the results of blood count. Erythrocyte parameters can be used to establish a formula or model to differentiate them, which can achieve the purpose of early screening, early diagnosis and early treatment,preventing the occurrence of severe anemia and providing a scientific basis for the thalassemia and iron deficiency anemia prevention. This article will review the research progress of using erythrocyte parameters to distinguish thalassemia trait with iron deficiency anemia.


Assuntos
Anemia Ferropriva , Talassemia , Talassemia beta , Humanos , Anemia Ferropriva/diagnóstico , Diagnóstico Diferencial , Talassemia beta/diagnóstico , Eritrócitos , Talassemia/diagnóstico , Talassemia/genética , Ferro
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