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.

Secondary polycythaemia in a Malay girl with homozygous Hb Tak

Hb Tak is one of more than 200 high affinity haemoglobin variants reported worldwide. It resultsfrom the insertion of two nucleotides (AC) at the termination codon, between codon 146 and codon147 of the beta-globin gene [Beta 147 (+AC)]. Polycythaemia is the main clinical feature althoughaffected carriers are usually asymptomatic and do not require intervention. Several case studies inthis region have reported the co-inheritance of Hb Tak with Hb E, delta beta and beta thalassaemiawith one case of homozygous Hb Tak in a Thai boy. In this case report, a cluster of haemoglobinTak was found in a family of Malay ethnic origin. Cascade family screening was conducted whileinvestigating a 4-year old girl who presented with symptomatic polycythaemia. She had 2 previousHb analysis done, at 7-month and 2-year-old with the diagnosis of possible Hb Q Thailand andHomozygous Hb D, respectively. Both diagnosis did not fit her clinical presentations. She was plethoric,had reduced exercise tolerance as well as cardiomyopathy. Her parents were consanguineouslymarried and later diagnosed as asymptomatic carriers of Hb Tak. Consequently, re-analysis of thegirl’s blood sample revealed a homozygous state of Hb Tak. In conclusion, high oxygen affinityhaemoglobin like Hb Tak should be considered in the investigation of polycythaemic patients withabnormal Hb analyses. In this case, DNA analysis was crucial in determining the correct diagnosis.