Thalassemia Reports

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Open AccessArticle

Cascade Screening of β-Thalassemia in an Indian Family Using Flow Injection Analysis–Triple Quadrupole Mass Spectrometry: Comparison of Micro Sampling Approaches with Conventional Electrophoresis

by Ankitha K. Puthiyaveettil, Harshini K. Musuvathi and Deepalakshmi D. Putchen

Thalass. Rep. 2026, 16(1), 3; https://doi.org/10.3390/thalassrep16010003 - 24 Feb 2026

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Abstract

Background: β-thalassemia is a rare genetic disorder affecting 1–5% of the global population and poses a health burden due to migration of individuals from endemic regions. Identifying asymptomatic β-thalassemia carriers is essential to prevent the birth of thalassemic babies. A simple, sensitive method compatible with self-sampling could enhance the detection of β-thalassemia in the population. Methods: Capillary blood was collected via dried blood spot (DBS) and dried blood matrix (DBM) from 18 members (52.9%, 18/34) of a three-generation family. Hemoglobin was extracted, and globin chains were analyzed on a triple quadrupole mass spectrometer (TQMS). δ/β (%) was utilized as a biomarker to identify β-thalassemia. Venous blood collected from positive and negative individuals (n = 11) was further tested to confirm the findings and validated with complete blood count (CBC) and Capillary Electrophoresis (CE). Results: β-thalassemia was detected in seven individuals: three from generation I, three from generation II, and one from generation III. CBC showed thalassemia indices, while CE demonstrated elevated HbA2 consistent with β-thalassemia. Molecular sequencing of two samples confirmed the heterozygous c.92 + 5 G > C mutation in the β-globin gene. The overall prevalence of β-thalassemia in the family was 20.6% (7/34). High clinical performance was achieved across sample types, with 100% sensitivity for DBS, 100% specificity for DBM, and an overall accuracy of 91% when compared with CE. Conclusions: TQMS in combination with CBC parameters successfully identified asymptomatic heterozygous β-thalassemia carriers using self-sampling techniques. Cascade screening within affected families emerges as a possible strategy for early detection of β-thalassemia pending comprehensive validation. Full article

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7 pages, 980 KB

Open AccessCase Report

A Heterozygous ABCC6 Variant as a Potential Contributor to Choroidal Neovascularization in a β-Thalassemia Patient

by Debashis Pal, Dipankar Saha, Prosanto Kumar Chowdhury, Arup Das and Anupam Basu

Thalass. Rep. 2026, 16(1), 2; https://doi.org/10.3390/thalassrep16010002 - 29 Jan 2026

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Abstract

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. Full article

(This article belongs to the Section Quality of Life)

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5 pages, 301 KB

Open AccessCase Report

The First Gene Therapy for Treating an Indonesian Child with Thalassemia Major: A New Hope for Indonesia

by Edi Setiawan Tehuteru, Teck Onn Lim, Anky Tri Rini Kusumaning Edhy, Ludi Dhyani Rahmartani, Stephen Diah Iskandar, Cresentia Irene, Rendi Prawira Gunawan, Reganedgary Jonlean and Grace Erdiana

Thalass. Rep. 2026, 16(1), 1; https://doi.org/10.3390/thalassrep16010001 - 19 Dec 2025

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Abstract

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. Full article

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Thalass. Rep., Volume 16, Issue 1 (March 2026) – 3 articles

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