Genetic mutations of Transfusion Dependent Thalassaemia (TDT) in paediatric patients

Thalassaemia comprises inherited disorders characterised by impaired synthesis of globin chains, leading to varying phenotypes from mild to severe anaemia, transfusion-dependent. The Malaysian Thalassaemia Registry reports that 57.69% of patients are classified as Transfusion-Dependant Thalassaemia (TDT). Despite diagnostic advancements, local data linking genetic mutations with clinical and laboratory features of TDT remain limited. This study aims to address this gap by evaluating paediatric TDT patients at Hospital Tuanku Azizah (HTA), Kuala Lumpur, Malaysia.

A single-centre, cross-sectional study involving TDT patients at HTA from January to December 2022.

The cohort included 95 patients (52.6% male, 47.4% female), predominantly Malay (88.4%). Twenty-seven distinct genetic mutations were identified across alpha and beta globin genes, the most common being βE. All patients had at least two mutations, with the most prevalent combination being HbE beta thalassaemia (45.3%), followed by beta thalassaemia major (32.6%), HbH disease (15.8%), and co-inheritance of alpha and beta thalassaemia (6.3%). Beta thalassaemia major shows the most severe phenotype: mean age at diagnosis is 12 months, mean haemoglobin at diagnosis of 5.2 g/dL, and mean age of regular transfusion is 16 months. Mean serum ferritin is highest in co-inheritance of alpha and beta thalassaemia (2616µg/L). The One-Way ANOVA test confirms the statistically significant differences in the median age of diagnosis (p=0.006), median age of starting regular transfusion (p=0.001), and median haemoglobin level at diagnosis (p=0.002) among different DNA combinations.

This study demonstrates that genetic mutations significantly influence the phenotypes of TDT patients and are essential in guiding management and prognosis.