Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (β0) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.

UNASSIGNED: Thalassemia is an inherited blood disorder with a defect in the sufficient production of a protein called hemoglobin. We aimed to investigate the simple blood indices of patients with Beta Thalassemia Trait (BTT) and Iron Deficiency Anemia (IDA) to propose a new formula using logistic regression for differentiate two characteristics from each other.
UNASSIGNED: Among the 702 records of the BTT Counseling Center (Khoy, Iran-2022), 292 cases (219 iron deficiency anemia (IDA) and 73 BTT) were eligible for the study. Blood indices such as RBC, HGB, HbA2 described and used to diagnose two types of participants. Blood indices had high multicollinearity that was modified. Logistic regression for blood indices fitted and goodness of fit indices with Area Under ROC curve (AUC) estimated.
UNASSIGNED: The average age of the participants was 24.56 yr. The status of Multicollinearity between independent variables was modified. The HGB, MCV, HbA2, and HbA variables were used in the model and only HbA2 status was significant (P<0.001). According to the output of the model, for each unit increase in HbA2, the chance of having BTT was about 8.5 times higher than IDA. The sensitivity, specificity, AUC curve, and accuracy of the final model were estimated to be 97, 72, 84, and 93%, respectively. A regression formula to differentiate BTT from IDA proposed.
UNASSIGNED: In studies related to the differentiation of the BTT from IDA, the presence of the HbA2 index in the model and prediction is very necessary.

Beta-thalassemia (β-thalassemia) is a hematologic genetic condition that causes microcytic anemia due to defective synthesis of the hemoglobin beta chain. As a hypochromic microcytic anemia that is commonly associated with symptoms such as fatigue and pallor when identified in adulthood, β-thalassemia may be commonly underdiagnosed or misdiagnosed as iron deficiency anemia. This study presents a case of a patient with β-thalassemia who was initially misdiagnosed with treatment-resistant iron deficiency anemia. Here, we present the case of a 66-year-old male of Mediterranean descent with a history of military service who presented with persistent fatigue. He had a past medical history of hypertension, diabetes mellitus type 2, sleep apnea, and iron deficiency anemia. Despite undergoing unnecessarily prolonged iron supplementation for suspected iron deficiency anemia, the patient\'s complete blood count and peripheral blood smear continued to identify hypochromic microcytic anemia. Ultimately, hemoglobin electrophoresis was performed, and mutations were identified in the hemoglobin beta chain consistent with β-thalassemia minor. Due to its rarity and wide variation in presentation, β-thalassemia may be frequently misdiagnosed. β-thalassemia is a spectrum of disorders ranging from β-thalassemia minor, which may be asymptomatic and incidentally discovered in adulthood, to β-thalassemia major, which may include bone marrow deformities from extramedullary hematopoiesis and require frequent blood transfusions to sustain life. Therefore, patients who present with symptoms of β-thalassemia minor may not be identified until later in life after undergoing decades of ineffective treatment. β-thalassemia is a multifactorial disease with a variety of clinical presentations that can easily be misdiagnosed as other types of anemia. This case highlights the importance of performing thorough laboratory testing and casting a wide net of differential diagnoses when evaluating patients with treatment-resistant anemia. This case calls for further research on the genetic contributions to β-thalassemia as well as improved ways to identify this disorder, particularly in patients who may not have a severe form that is easily diagnosed in early childhood.

Hemoglobinopathies are the most common monogenic disorders in the world. Traditional diagnostic algorithms generated by conventional methods for thalassemia can be labor-intensive and time-consuming due to the complexities of the genes involved and the variability in disease-causing mutations. With the advantages of next-generation sequencing (NGS) technology, molecular analysis of highly complex diseases such as hemoglobinopathies has become easier. Next-generation sequencing is a highly sensitive and effective method due to its capacity to sequence many gene regions simultaneously while allowing good read depths. In this study, single nucleotide changes, small deletions and copy number variations in HBA1, HBA2 and HBB in 914 patients with suspected hemoglobinopathy were analysed with NGS. At least one HBA1, HBA2, HBB or HBD variant was detected in 483 (52.8%) patients. Ten novel variants were detected in HBA1 and HBA2, three in HBB, and one in HBD. From these variants, c.*76T > A, c.301-24 G > A, c.301-24G > C c.-41C > G, c.-37-40C > G, c.-9G > C, c. 95 + 9C > T, c.95 + 26C > A, c.95 + 38C > T and c.*18C > G variants were located in α-globin genes, c.-25T > C, c.*103T > C and c92 + 39A > G variants were located in β-globin genes, and c.-43C > A was located in HBD. This is the first comprehensive study using NGS for the molecular diagnosis of hemoglobinopathies in Turkey. Accurate molecular diagnosis is of critical importance in hemoglobinopathies which are a public health problem due to their increased prevalence, high burden to society, and lack of curative treatment. Currently, NGS appears to be an advanced option over conventional methods to detect all variants occurring by molecular mechanisms and simultaneously analyse many genomic sequences.

Hypomethylating therapies using decitabine or azacitidine are actively investigated to treat acute myeloid leukemia, myelodysplastic syndromes, as maintenance therapy after allogenic stem cell transplant and hemoglobinopathies. The therapeutic mechanism is to de-repress genes that have been turned off through oncogenesis or development via methylation. The therapy can be non-cytotoxic at low dosage, sparing healthy stem cells and operating on committed precursors. Because the methods of determining maximum tolerated dose are not well suited to this paradigm, and because the mechanism of action, which is depletion of DNA methylase 1 (DNMT1), is complex and dependent on passing through a cell cycle, a pharmacodynamic assay that measures DNMT1 can inform clinical trials aimed at establishing and improving therapy. Herein, we provide an assay that measures DNMT1 relative levels in circulating T cells of peripheral blood.

暂无摘要。

Urethral meatus edema is a rare finding and may infer a more severe form of volume overload. Management of patients with thalassemia vary in terms of the severity of the kidney injury due to transfusion, chronicity, and severity of volume overload.

UNASSIGNED: Sickle cell disease and beta thalassemia are some of the first targets for potentially curative cell-based therapies. Currently, bone marrow transplants, stem cell transplants, and gene therapy are being researched and utilized for people living with these hemoglobinopathies. Although these therapies are often described as curative, there is not a clear definition of what cure means for these hemoglobinopathies.
UNASSIGNED: Five databases were searched for this scoping review. Two reviewers screened each article at the title/abstract and full text levels using Covidence. Articles were included if they were (1) about bone marrow transplants, stem cell transplants, or gene therapy; (2) conditions of focus were sickle cell disease or beta thalassemia; and (3) reported original data on clinical outcomes, psychosocial outcomes, or key stakeholder perspectives and opinions. Data were collected by 2 reviewers also using Covidence, and analyses were conducted in Excel and R.
UNASSIGNED: We found that, although cure is widely and indiscriminately used, it is not often defined, and when cure is defined, there is no clear convergence or consensus on the definition. Furthermore, cure is often qualified and undefined euphemisms for cure are often used. We also report the major ways in which the success and complications of these treatment modalities are described.
UNASSIGNED: We frame the significance of our findings by discussing their scientific, ethical, and social implications and focus on the need for precise and clear terminology that centers lived experience and acknowledges the interplay between scientific and lay expertise and perceptions.

UNASSIGNED: We aimed to determine the effects of fetal hemoglobin induction therapy in restricting or even reversing the cephalometric changes associated with beta thalassemia.
UNASSIGNED: In this comparative observational study, 90 participants were equally divided into three groups: a control group; patients with thalassemia major receiving blood transfusion (BT group); and patients receiving induction therapy (i.e., hydroxyl urea (5-10 mg/kg/day) or as much as 20 mg/kg/day) and thalidomide (2-10 mg/kg/day) along with blood transfusion (IT group). All patients underwent history taking and examination, photographic assessment, and radiographic evaluation with a lateral cephalogram. One-way ANOVA followed by post-hoc Tukey test was used to determine differences among groups.
UNASSIGNED: The IT group differed significantly from the BT group in all photographic and skull table parameters, and most cephalometric parameters, such as facial angle (p ≤ 0.001), middle and lower facial heights (p ≤ 0.001), and inter-incisal angle (p = 0.036); the mean values in the IT group were similar to those in the control group. In-addition, dental and soft tissue measurements significantly differed among groups. For most parameters, the mean difference indicated higher values in the BT group.
UNASSIGNED: Induction therapy appeared to improve the facial angles, heights, and inter-incisal angles, whereas a class II skeletal pattern was observed in the transfusion only group. These findings suggest that fetal hemoglobin induction therapy might have restricted some of the cephalometric changes in patients with beta thalassemia.
UNASSIGNED: تهدف الدراسة إلى تقييم ما إذا كان العلاج التعريفي للهيموجلوبين الجنيني قادرا على تقييد أو حتى عكس التغيرات العظمية الرأسية المرتبطة لدى مرضى الثلاسيميا بيتا.
UNASSIGNED: لقد كانت دراسة رصدية مقارنة. تم تقسيم ما مجموعه 90 مشاركا بالتساوي إلى 3 مجموعات، مجموعة السيطرة ومجموعتي مرضى الثلاسيميا الكبرى الذين يخضعون لعمليات نقل الدم (مجموعة ثلاسيميا بيتا وأولئك الذين يتلقون العلاج التعريفي مع نقل الدم). بالإضافة إلى التاريخ والفحص، خضع جميع هؤلاء المرضى للتقييم الفوتوغرافي والتقييم الشعاعي باستخدام مخطط الرأس الجانبي. تم استخدام أنوفا أحادي الاتجاه متبوعا باختبار توكي اللاحق لتحديد الاختلافات بين المجموعات الثلاث.
UNASSIGNED: اختلف العلاج التعريفي مع مجموعة نقل الدم بشكل كبير من حيث جميع الصور الفوتوغرافية وجدول الجمجمة وأغلبية المعلمات الرأسية مثل زوايا الوجه وارتفاعات الوجه الوسطى والسفلى والزاوية بين القواطع (ع = 0.036) من مجموعة الثلاسيميا بيتا حيث كانت القيم المتوسطة للعلاج التعريفي إلى جانب مجموعة نقل الدم مماثلة تقريبا لتلك الخاصة بالمجموعة الضابطة. بالإضافة إلى ذلك، كانت بعض قياسات الأسنان والأنسجة الرخوة أيضا فرقا كبيرا بين المجموعات الثلاث. بالنسبة لغالبية هذه المعلمات، أظهر متوسط الفرق قيما أعلى لمجموعة بيتا ثلاسيميا.
UNASSIGNED: يبدو أن العلاج التعريفي قد أدى إلى تحسين زوايا الوجه والارتفاعات والزاوية بين القواطع بينما لوحظ نمط الهيكل العظمي من الدرجة الثانية في مجموعة نقل الدم فقط. تشير هذه النتائج إلى أن العلاج بتعريف الهيموجلوبين الجنيني ربما يكون قد قيد بعض التغيرات في قياسات الرأس لدى مرضى الثلاسيميا بيتا.

Thalassemia management has reached new milestones, with new therapies promising the dawning of a new era. However, conventional and new approaches require accessibility, affordability, acceptability/adherence by patients, and medical expertise from healthcare providers. Current treatments still do not offer the expected duration and quality of life, and inequalities in patient care are almost a universal phenomenon. To understand the requirements to achieve improved care, including the adoption of new therapies, for the maximum number of the global patient population, it is necessary to recognize the weaknesses that are experienced in the present so that future corrective action can be taken. Deficits in service provision are due to poor political and financial support, lack of prioritization during resource rationing, and absence of epidemiological information for policy making. These system weaknesses require improved resource management and would benefit from patient support organizations, improved psychosocial support and patient welfare, and an increase in professional expertise through educational programs. Medical products and technology must also be made affordable and widely available, and the curative treatments and cheaper approaches to technology must be recognized as resource saving. Improvements in the access to innovative and quality care, and even a cure, require concerted actions by all stakeholders, including physicians and the patient community.