Haemoglobin Sickle D Punjab: - A Case Report

Haemoglobin S D-Punjab is a rare compound heterozygous haemoglobinopathy characterised by the presence of two β globin gene variants: β6(GAG→GTG) and β121(GAA→CAA). These patients’ clinical and haematological features mimic haemoglobin S disease. We describe the first case of doubly heterozygous HbSD-Punjab from Malaysia managed with regular blood transfusion at the age of one. This case highlights the propensity for occurrence of rare phenotypes within our multi-ethnic population and emphasises the importance of accurate genotyping to avoid erroneous counselling, and to plan an effective patient management strategy before complication evolves.

Detection of β-globin Gene Mutations Among β-thalassaemia Carriers and Patients in Malaysia: Application of Multiplex Amplification Refractory Mutation System– Polymerase Chain Reaction

Background: β-thalassaemia is one of the most common single-gene disorders worldwide. Each ethnic population has its own common mutations, accounting for the majority of cases, with a small number of mutations for the rarer alleles. Due to the heterogeneity of β-thalassaemia and the multi-ethnicity of Malaysians, molecular diagnostics may be expensive and time consuming. Methods: A simple polymerase chain reaction (PCR) approach involving a multiplex amplification refractory mutation system (MARMS) and one amplification refractory mutation system (ARMS), consisting of 20 β-globin gene mutations, were designed and employed to investigate β-thalassaemia patients and carriers. Results: Out of 169 carriers tested with the MARMS, Cd 41/42 (–TTCT), Cd 26 (A–G) HbE, IVS 1–1 (G–T), and IVS 1–5 (G–C) were the most common mutations, accounting for 78.1%. Among the Malays, Cd 26 (A–G) HbE, Cd 41/42 (–TTCT), IVS 1–1 (G–T), and IVS 1–5 (G–C) were the most common mutations, accounting for 81.4%, whereas Cd 41/42 (–TTCT) and IVS 2–654 (C–T) were most common among the Chinese (79.1%). Conclusion: We propose the use of this cheap, easy to interpret, and simple system for the molecular diagnostics of β-thalassaemia among Malaysians at the Institute for Medical Research (IMR)

Distribution of alpha thalassaemia in 16 year old Malaysian Students in Penang, Melaka and Sabah

Objectives: Alpha thalassaemia is wide spread in Malaysia and is a public health problem. This study aimed to describe the carrier frequencies of α‒thalassaemia and its distribution among major ethnic groups in three states of Malaysia. Methods: Educational forums were organised and study was explained to students from three schools. Students were invited to take part in the screening with parent consent. A total of 8420 adolescent students aged 16 years volunteered to participate in the study. Peripheral blood samples were analysed for complete blood counts, haemoglobin quantification and typing, and serum ferritin levels. Genomic DNA was used for screening alpha thalassaemia alleles by PCR based molecular methods. Results: We identified seven α‒globin gene defects in 341 (4.08%) students: amongst them α+‒ and α0‒thalassaemias were detected in 232 (2.77%) and 107 (1.28%) students respectively. Genotype ‒α3.7/αα was the most prevalent among sub-populations of Malay, indigenous communities of Sahab and Indian, while ‒‒SEA/αα deletion is more prevalent in Malaysian Chinese. It is estimated that 63 pregnancies annually are at risk of Hb Bart’s hydrops fetalis. Conclusions: We have demonstrated the prevalence and mutation patterns of α‒thalassaemia in the 16 year olds in three states of Malaysia. High α0‒thalassaemia deletions amongst the study subjects place these carriers at an increased risk of conceiving fetuses with HbH disease and Hb Bart’s hydrops fetalis should they choose another heterozygous partner. It is therefore highly recommended to institute community screening programmes and provide prospective carriers with genetic counselling to help them make informed choices.