Thalassemia Reports

β-thalassemia patients often experience ocular abnormalities such as angioid streaks (ASs), retinal pigmented epithelium degradation, visual field defects, and in rare instances choroidal neovascularization (CNV). Although ASs are common in individuals with hemoglobinopathies, the occurrence of choroidal neovascularization without preceding ASs is exceptionally rare. In this report, we describe a β-thalassemia patient who had developed CNV at the age of 27 years and also had experience of renal stones at the age of 19 years. He had undergone splenectomy and was under conservative therapy of iron supplementation. We conducted whole-exome sequencing (WES) in search of CNV-associated variants. Through variant filtering and Phenolyzer analysis, we have identified a rare heterozygous missense variant in the ABCC6 gene, ABCC6:NM_001171:exon25:c.3524T>C (rs376062004). In silico analysis revealed that this variant is present in the highly conserved region and is likely to decrease the stability of the protein. Mutation in the ABCC6 gene leads to pseudoxanthoma elasticum (PXE). Previously, it was believed that ASs and subsequent CNV-like ocular complication may develop due to the pathophysiological condition of thalassemia. However, our study provides compelling evidence that rare mutations in the ABCC6 gene, in combination with oxygen insufficiency, may contribute to the development of CNV in β-thalassemia patients. This finding highlights the potential genetic basis of PXE-mediated CNV development in β-thalassemia.

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to undergo gene therapy. Methods: Medical summaries were gathered across multiple time points. The gene therapy process consisted of several phases: screening, apheresis and cell manufacturing, conditioning, cell infusion, and post-treatment follow-up. The therapy utilized autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), which were genetically modified using a lentiviral vector carrying the beta-globin gene. The primary outcome of this study was transfusion independence, determined through serial assessments of hematological parameters over a six-month period following gene therapy. Results: A 15-year-old female had been diagnosed with thalassemia major at the age of five. DNA analysis revealed compound heterozygous mutations Hb Malay (codon 19, AAC^Asn > AGC^Ser) and IVS1-nt5 (G > C). She had been receiving regular blood transfusions every 3–4 weeks, and hemosiderosis was detected in the liver and pancreas. Given the patient’s age—over 10 years—hematopoietic stem cell transplantation carries increased risks, making gene therapy the most suitable curative option. During the six-month follow-up period after gene therapy, the patient remained transfusion-independent and experienced no complications. Conclusions: In selecting an appropriate curative therapy for thalassemia patients, several factors must be considered. The successful implementation of the first gene therapy in an Indonesian pediatric thalassemia patient should serve as a catalyst for the continued development and expansion of curative treatment options for thalassemia patients across the country.

Background/Objectives: Thalassemia is among the most common hereditary disorders globally, characterized by impaired hemoglobin synthesis and ineffective erythropoiesis. This study analyzed data on hemoglobinopathies, with a particular focus on thalassemia, to support the development of a comprehensive national database and to improve understanding of the disease burden in the Kurdistan Region of Iraq. Methods: In this retrospective cross-sectional study, a total of 910 patients admitted to the region’s sole blood disorder center since its establishment were included. Results: The study analyzed 46.7% male and 53.3% female thalassemia patients in Duhok, with 58.46% reporting parental consanguinity. Hepatitis C virus (HCV) prevalence was 11.87%, while 8.90% underwent bone marrow transplantation (BMT) and 30.11% had splenectomies. Blood group distribution was O⁺ (36.26%), A⁺ (30.99%), and B⁺ (18.46%). Common medications included Deferasirox (34.62%), Hydroxyurea (26.70%), and Deferoxamine (5.82%), with 8.24% and 4.40% discontinuing Deferasirox and Hydroxyurea, respectively. Geographically, 29% of the patients originated from Duhok City, which exhibited a consanguinity rate of 18.65% (p = 0.020). The most prevalent conditions were β-thalassemia major (32.53%) and sickle cell anemia (24.73%). HCV-positive patients were predominantly diagnosed with β-thalassemia major (43.40%) and sickle cell anemia (33.96%). BMT recipients were mostly β-thalassemia major patients (80.25%), while splenectomy was common in β-thalassemia major (43.40%) and sickle cell β-thalassemia (22.64%). Vaccination rates included Pneumococcal (50.78%), Influenza (47.76%), and Hepatitis (39.08%, first dose). Six patients (0.66%) died, with 30.18% diagnosed before age 1 and 43.89% between 1 and 2 years. In conclusion, this study underscores the high prevalence of β-thalassemia major and sickle cell anemia in Duhok, with strong associations to parental consanguinity and low socioeconomic status. Gaps in early diagnosis and vaccination coverage remain significant challenges.