Siriraj I Gγ(Aγδβ)0 -thalassaemia causing severe thalassaemia intermedia in compound heterozygous state with IVS1-1(G→T) mutation

@#The Siriraj I Gγ(Aγδβ)0 -thalassaemia is a novel mutation involving a 118kb deletion of the β-globin gene cluster. It was first reported in 2012 in two unrelated families from the southern part of Thailand. The carriers in the heterozygous state are clinically asymptomatic. Nonetheless, its complex interaction with other β-thalassaemia could give rise to different clinical phenotypes, ranging from mild thalassaemia intermedia to thalassaemia major. We report here a case of a six-year-old Malay boy, presented with pallor, growth failure and hepatosplenomegaly. His haemoglobin at presentation was 9.2g/dL with a mean cell haemoglobin of 22.6pg and a mean cell volume of 69.9fl. His peripheral blood smear showed features of thalassaemia intermedia. Haemoglobin (Hb) analysis revealed markedly raised Hb F (83%), normal HbA2 levels and absent HbA. Deoxyribonucleic acid (DNA) analysis showed compound heterozygous IVS1-1 (G→T) β-globin gene mutation and Siriraj I Gγ(Aγδβ)0 -deletion (genotype βIVS1-1/ β Siriraj I deletion). Both his father and elder sister are carriers of Siriraj I Gγ(Aγδβ)0 -thalassaemia while his mother carries IVS1-1 (G→T) gene mutation. Clinically, the patient is transfusion dependent on six weekly regime. To the best of our knowledge, this is the first reported case in Malaysia involving unique Siriraj I Gγ(Aγδβ)0 -thalassaemia and IVS1-1 (G→T) in a compound heterozygous state. In summary, detection of Siriraj I Gγ(Aγδβ)0 -thalassaemia is essential as this deletion can lead to severe disease upon interaction with a β-thalassemia point mutation as demonstrated in our case. The establishment of effective carrier screening and genetic counselling is important to prevent its adverse consequences.

Optimal Mean Corpuscular Haemoglobin (MCH) Cut-Off Value for Differentiating Alpha Plus and Alpha Zero Thalassaemia in Thalassaemia Screening

@#Introduction: The aim of thalassaemia screening is to reduce thalassaemia syndromes with significant clinical implication. Therefore, detection of α0 thalassaemia with two genes deletion is clinically more important than α+ thalassaemia with one gene deletion. The aim of this study is to determine the mean corpuscular haemoglobin (MCH) cut-off point for α0 thalassaemia screening. Method: A total of 688 α0 and α+ thalassaemia cases confirmed by DNA analysis were analysed. Red cell indices (MCV, MCH, RBC, Hb) were retrieved from the laboratory information system. Receiver operating characteristic (ROC) curve is generated to determine the MCH cut-off point for α0 thalassaemia. The diagnostic performance of MCH cut-off value was evaluated with a validation group comprising 100 samples of alpha thalassaemia carriers. Results: ROC curve analysis with area under the curve (AUC) of 0.969 showed that MCH at cut-off of 23.5pg has high sensitivity and specificity in detecting α0 thalassaemia with 98% sensitivity and 85% specificity. Conclusion: MCH cut-off value of 23.5pg can be adopted as the cut-off point for α0 thalassaemia screening to detect clinically significant thalassaemia syndrome and reduce cost and burden of screening.