We report a rare case of capitate osteonecrosis in a 51-year-old woman with thalassemia presenting with persistent wrist pain. Imaging findings were consistent with osteonecrosis of the capitate, and the patient underwent surgical treatment with a vascularized bone graft from the second metacarpal and cancellous bone graft from the iliac crest. Histopathological examination confirmed ischemic osteonecrosis. At 15 months after surgery, clinical improvement was limited; however, magnetic resonance imaging demonstrated preservation of capitate morphology and reduced signal abnormalities. Capitate osteonecrosis in patients with thalassemia is extremely rare but should be considered in the differential diagnosis of wrist pain. Early recognition may facilitate timely intervention and help prevent disease progression.

Thalassemia, hemoglobinopathies, and glucose-6-phosphate dehydrogenase (G6PD) deficiency represent highly prevalent and genetically heterogeneous inherited hematologic disorders or diseases in Thailand. Conventional molecular approaches require multiple targeted assays to detect deletional and non-deletional variants across globin gene clusters and the G6PD gene, resulting in increased complexity, turnaround time, and cost. We developed and analytically validated a comprehensive long-read sequencing workflow using Oxford Nanopore Technologies for simultaneous detection of pathogenic variants in HBA 1, HBA 2, HBB, and G6PD. A total of 63 genomic DNA samples with previously characterized genotypes were analyzed using multiplex long-amplicon PCR followed by nanopore sequencing and bioinformatic variant calling with Clair 3. Variant annotation was performed using Ensembl VEP, and classification followed ACMG guidelines. All samples were successfully genotyped, demonstrating 100% concordance with conventional PCR, and Sanger sequencing. The platform accurately identified large α-globin deletions, β-thalassemia mutations, structural hemoglobin variants, and major Southeast Asian G6PD variants. A total of 39 distinct variants were detected and classified. Long-read sequencing effectively resolved homologous regions between HBA 1 and HBA 2 and enabled accurate characterization of multilocus co-inheritance patterns. This integrated nanopore-based workflow provides a robust, high-resolution, and scalable single-platform solution for comprehensive molecular diagnosis of thalassemia, hemoglobinopathies, and G6PD deficiency in genetically heterogeneous populations.

Congenital dyserythropoietic anemia type IV (CDA IV) is a rare inherited erythroid disorder within the broad phenotypic spectrum associated with pathogenic variants in Krüppel-like factor 1 (KLF1), a master transcriptional regulator of erythropoiesis. This study aimed to describe the clinical picture, genetic causes, global distribution, and treatment of CDA IV. We retrospectively reviewed three pediatric patients diagnosed and treated at the Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, since December 2014. Demographic, clinical, genetic, laboratory, treatment, transplantation, and follow-up data were collected, including conditioning regimens, graft-versus-host disease (GVHD) prophylaxis, engraftment, complications, and donor chimerism. We also conducted a literature review of CDA IV cases reported worldwide between January 1991 and December 2024. All three children developed symptoms within the first month of life. They had neonatal jaundice and anemia. One of them needed intrauterine transfusion. Gene testing found four KLF1 variants: c.525_526insCGGCGCC, c.1012C > T, c.1012C > A, and c.973G > A. Before hematopoietic stem cell transplantation (HSCT), all three patients needed regular red blood cell transfusions and had iron overload. All three then received HSCT from a parent or sibling. Neutrophils and platelets engrafted in every case. Donor chimerism stayed above 95% during follow-up, and no graft failure happened. No patient had acute or chronic GVHD. Viral reactivation after HSCT was mainly cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, and no severe infection was seen. At the last follow-up, all three patients were free of transfusion. Serum ferritin levels went down after HSCT, but liver or heart iron overload did not fully go away in some patients. For carefully chosen children with severe transfusion-dependent KLF1-related red cell disease, allogeneic HSCT may be a feasible curative option. Stable donor chimerism and lasting freedom from transfusion can be achieved. CDA IV has many clinical forms and can be mistaken for thalassemia or Evans syndrome, so early gene testing is very important for correct diagnosis. In areas where thalassemia is common, KLF1 mutation screening should be considered when the cause of microcytic anemia is unclear. Bigger studies with longer follow-up are still needed to better judge the long-term results of HSCT.

α-Thalassemia is an autosomal recessive disorder characterized by reduced synthesis of α-globin chains, most commonly due to deletions within the α-globin gene cluster. Non-deletional variants are less common and contribute to the molecular heterogeneity of the disease. Advances in long-read sequencing have improved the analysis of complex genomic regions, including highly homologous genes such as HBA1 and HBA2. Targeted long-range PCR amplification of the HBA1 and HBA2 genes was followed by long-read sequencing on the PromethION 24 platform (Oxford Nanopore Technologies). Subsequently, the sequencing data were analyzed and visualized using the Integrative Genomics Viewer (IGV). Long-read sequencing achieved an average depth of >390x across all target regions, enabling reliable variant detection. This analysis identified five variants in the HBA1 and HBA2 genes, namely HBA1:c.326C > A (p.Thr108Asn; Hb Rogliano), HBA1:c.-41C > G, HBA2:c0.300 + 55T > G, HBA2:c0.301-24delinsCTCGGCCC, and HBA2:c.-41C > G. Based on ClinVar classification, HBA1:c.326C > A (p.Thr108Asn) was categorized as likely pathogenic, while the remaining variants were classified as benign or likely benign. To our knowledge, this is the first report of Hb Rogliano in Indonesia and highlights the utility of long-read sequencing for the molecular characterization of rare α-globin variants.

Although thyroid dysfunction (TD) is a known complication in patients with thalassemia major, data on patients with β thalassemia intermedia (βTI) are limited. Therefore, this study was conducted to investigate the prevalence and gender pattern of TD in βTI in Yasuj city. In this cross-sectional analytical study, 200 eligible patients with βTI were selected by the census method. Serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS version 27 at a significance level of 0.05. Of the 200 patients, 90 (45%) were male, and 110 (55%) were female, with a mean age of 34.6 ± 11 years. The mean serum levels of T3, T4, and TSH were 1.74 ± 0.53 ng/ml, 7.99 ± 1.6 µg/dl, and 3.23 ± 1.83 µIU/ml, respectively. The overall prevalence of hypothyroidism was 6.0% (n = 12), comprising 5.5% (n = 11) subclinical and 0.5% (n = 1) primary hypothyroidism. A significant gender-based difference was observed in hormone levels: women exhibited higher mean T3 (1.81 vs. 1.66 ng/ml, p = 0.04) and T4 (8.25 vs. 7.7 µg/dl, p = 0.01) compared to men. However, no significant gender disparity was found in TSH levels. T3 and T4 hormone levels are higher in female patients with βTI compared to males. The presence of hypothyroid cases underscores the necessity for regular monitoring of thyroid function in these patients, particularly within the framework of iron overload management. Timely diagnosis and treatment can improve clinical outcomes.

Extramedullary haematopoiesis (EMH) is a rare cause of posterior mediastinal masses, often linked to chronic anaemia. A man in his late 60s with recurrent biliary disease was referred for evaluation of posterior mediastinal masses incidentally found during hospitalisation for choledocholithiasis. Imaging and biopsy revealed paravertebral EMH. Laboratory testing showed compensated haemolytic anaemia with stomatocytes, elevated eosin-5-maleimide binding, decreased erythrocyte osmotic fragility, and a PIEZO1 mutation (p.K2323T), leading to diagnosis of hereditary xerocytosis (HX). Family screening revealed the same condition in his son. HX, a rare congenital haemolytic anaemia, often remains undiagnosed due to mild symptoms and subtle findings. This case highlights HX as a unifying cause of recurrent biliary disease and posterior mediastinal EMH, emphasising the importance of recognising this rare condition to avoid inappropriate interventions such as splenectomy.

Splenosis is the autotransplantation of splenic tissue that can occur after splenic rupture or splenectomy. It is usually asymptomatic and discovered incidentally. Nephrolithiasis is a common cause of acute flank pain, often diagnosed by non-contrast computed tomography imaging. Splenectomy has been reported as a risk factor for nephrolithiasis in selected hematologic conditions, although its relevance in patients without hematologic disease remains uncertain. A 65-year-old man presented with acute left flank pain. Results of computed tomography imaging of the abdomen confirmed left-sided nephrolithiasis and also revealed multiple well-circumscribed soft tissue nodules in the lower abdomen and pelvis, raising concern for metastatic disease. A detailed history revealed previous splenectomy following an automobile accident at the age of 6 and confirmed splenosis years earlier by technetium scan prior to this admission. The patient's past medical history of splenectomy and proper history supported the diagnosis of splenosis. This case report highlights the importance of recognizing splenosis as a benign mimic of malignancy on imaging. Thorough history-taking and awareness can prevent unnecessary diagnostic testing and interventions. A history of splenectomy can be a risk factor for nephrolithiasis in individuals with certain hematological diseases.

In regions with high thalassemia prevalence, such as southern China and Southeast Asia, chronic shortages of professional genetic counseling resources have driven interest in large language models (LLMs) as auxiliary tools, yet their performance and safety boundaries in this setting remain uncharacterized. This single-center retrospective study evaluated four LLMs (ChatGPT-5.2 Thinking, DeepSeek-V3.2 chat, Gemini 3 Flash, and Grok 4.1 Fast) using 1,080 standardized knowledge questions administered across five independent sessions and 150 real-world clinical cases scored by six senior experts across eight dimensions. All models exceeded 90% accuracy on single-choice and true-false questions. Between-model differences were most pronounced in multiple-choice questions, where ChatGPT-5.2 Thinking achieved the highest accuracy (87.28% ± 1.69%), significantly outperforming Grok 4.1 Fast (72.06% ± 1.69%, P < 0.001). DeepSeek-V3.2 chat showed lower cross-session consistency than the other three models. In clinical case analysis, all models scored below human expert levels overall, with ChatGPT-5.2 Thinking performing closest to experts. Test report interpretation was generally adequate, whereas larger gaps emerged in genetic risk estimation, phenotype prediction, and counseling recommendations (all P < 0.001 vs. human experts, with limited exceptions for ChatGPT-5.2 Thinking in β-thalassemia subtypes). All 145 severe errors were confined to α-thalassemia and α-combined-β-thalassemia subtypes, concentrated in phenotype prediction (76/145, 52.4%) and risk estimation (40/145, 27.6%). LLMs may support knowledge retrieval and structured report interpretation in thalassemia genetic counseling but should not be used independently for risk assessment or final counseling decisions, particularly in complex α-related cases.

Background/Objectives: Omentin-1 (intelectin-1) is an adipocytokine with anti-inflammatory, insulin-sensitizing, and iron-regulatory properties. This study aimed to compare circulating omentin-1 levels in patients with (IDA) and β-thalassemia trait and to evaluate their associations with haematological, iron-related, and metabolic parameters. Methods: A total of 90 adults (n = 90), including 29 patients with IDA, 31 individuals with β-thalassemia trait, and 30 healthy controls. Haematological indices, iron parameters, biochemical markers, and plasma omentin-1 levels were measured. Group comparisons, correlation analyses, multivariable linear regression, and receiver operating characteristic (ROC) curve analyses were performed. Results: Plasma omentin-1 concentrations were significantly lower in patients with hypochromic microcytic anaemia than in healthy controls (36.4 vs. 147.7 ng/mL, p < 0.001). Among subgroups, the lowest levels were observed in IDA patients, followed by β-thalassemia trait and controls (p < 0.001). Omentin-1 showed positive correlations with haemoglobin, MCV, MCH, ferritin, serum iron, total cholesterol, HDL-C, and LDL-C, whereas negative correlations were observed with age, HbA1c, glucose, RDW, and total iron-binding capacity (all p < 0.05). In multivariable analysis, age (β = -0.215, p = 0.046), female sex (β = 0.305, p = 0.028), and MCV (β = 0.334, p = 0.015) were independent predictors of omentin-1 levels. ROC analysis demonstrated excellent discrimination between IDA and controls (AUC = 0.93) and good discrimination between β-thalassemia trait and controls (AUC = 0.79). Conclusions: Omentin-1 levels are reduced in IDA and β-thalassemia trait and are closely associated with iron status, erythroid indices, and metabolic parameters. Omentin-1 may serve as an adjunct biomarker for hypochromic microcytic anaemia, particularly in distinguishing affected individuals from healthy subjects. However, its limited utility in distinguishing iron-deficiency anaemia from β-thalassemia trait indicates that it should be used alongside established haematological and iron-related parameters.