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

Keywords: Thalassaemia intermedia, Siriraj I Gγ(Aγδβ)0-thalassaemia, IVS 1-1 (G-T) INTRODUCTION β-thalassaemia is an autosomal haematological disorder resulting in genetic lesions which include all or part of the β-globin gene complex.1 This inherited disorder was originally characteristic of the tropics and subtropics region but is now worldwide due to migratory fuxes from different countries and eventually present as a global public health problem.2 It is estimated that approximately 1% to 5% of the global population carries thalassaemia mutations.3 In Malaysia, thalassaemia is the commonest single gene disorder with a carrier rate of 4.5% to 6%.4 The human β-globin gene cluster resides within 80 kilobases (kb) on the short arm of chromosome 11.5 This complex is structurally arranged and developmentally expressed in the order of 5' e-Gγ-Aγ-δ-β. Both conventional method (gel electrophoresis, capillary electrophoresis or high-performance liquid chromatography) and advanced method (DNA analysis) are required. Peripheral blood flm showed hypochromic microcytic red blood cells and marked anisopoikilocytosis with the presence of target cells, schistocytes, polychromatic cells, nucleated red blood cell and Howell-Jolly bodies. Whereas, heterozygotes for δβ-thalassaemia have a modest increase of HbF (5-20%) with hypochromic microcytic red cell and heterocellular distribution of F-cells in Kleihauer test.11 The molecular characterisation is crucial for differential diagnosis as compound heterozygosity of HPFH and β thalassaemia behaves clinically as thalassaemia minor in opposition to co-inheritance of δβ thalassaemia and β thalassaemia which may give rise to β thalassaemia major.12 In our case, the heterozygous father and sister have raised HbF level (29.4% and 30.7% respectively) with a heterocellular distribution of F-cells and hypochromic microcytic red blood cells.