Characterisation of clinical, hematological and molecular variability in individuals with sickle β-thalassemia

Sickle β-thalassemia (Sβ-thal) is a compound hemoglobinopathy resulting in marked clinical and hematologic heterogeneity. Despite a substantial disease burden in India, large-cohort data integrating molecular, hematologic, and clinical characteristics remain limited, particularly from regions with evolving screening programs.

The study aimed to characterise the clinical, hematological, and molecular features of a large cohort of individuals diagnosed with sickle β-thal.

A retrospective analysis of 206 molecularly confirmed Sβ-thal patients enrolled (2016 and 2024) at ICMR-CRMCH, Chandrapur. The demographic, clinical, and hematological parameters were analysed, including HPLC, along with molecular characterisation of β-globin mutations, α-globin gene deletions, and XmnI polymorphism using polymerase chain reaction-based methods.

The mean age was 16.5 ± 13.2 years; 52.9% were female, and 77.7% were non-tribal. On molecular analysis, IVS I-5 (G > C) was the most common variant (98.0%), followed by Codon 15 (G > A) (1.5%) and Codon 8/9 (+G) (0.5%). The genotype αα/αα was predominant in the cohort (90.9%), and 86% were heterozygous for the Xmn1 polymorphism (+/-). HPLC longitudinal follow-up of children (newborn screening to 36 months) revealed that HbA2 (3.0-4.0%) stabilized after 18-24 months. In the clinical history of hospitalisation (58.5%), blood transfusions (51.8%), acute chest syndrome (27.4%), and splenomegaly (8.6%) were observed.

These findings delineate the genotypic and phenotypic spectrum of Sβ-thal and underscore the need for cautious interpretation of HbA₂ in early childhood diagnosis and follow-up.