Genetic Diagnosis of Globin Gene Disorders

Volume 4, Issue 2, August 2009

Dr Jason C. C. So

Associate Professor, Division of Haematology, Department of Pathology, The University of Hong Kong, Queen Mary Hospital


Globin gene disorders as a whole are the commonest group of monogenic disease in the world. In Southern China and Southeast Asia, alpha and beta thalassaemias, as well as specific types of haemoglobin (Hb) variants such as Hb E, are prevalent. Most people who have inherited these mutated globin genes are asymptomatic carriers. The number of severely affected patients is relatively small in developed regions where comprehensive antenatal screening and prenatal diagnosis programmes are in place. This is not the situation in less developed countries where the clinical, economical and social load of globin gene disorders is still heavily felt.

Phenotypic Diagnosis of Globin Gene Disorders 

The clinical and haematological manifestations of different forms of thalassaemias are well known. The approach to phenotypic diagnosis is largely standardised among haematology laboratories. Complete blood counting reveals the degree of anaemia. A low mean corpuscular volume (MCV) of red cells serves as an important screening parameter for further testing. Quantitation of HbA2 and F is performed for diagnosis of beta thalassaemia, delta-beta thalassaemia and hereditary persistence of foetal haemoglobin (HPFH). Demonstration of excess beta globin chains (Hb H) indicates alpha thalassaemia. When a Hb variant is suspected, its electrophoretic  mobility is assessed and compared with knownvariants. The advent of technological advances, including sophisticated blood cell analysers, automated high performance liquid chromatography (HPLC), capillary electrophoresis and antibody-based assays has made the analysis of Hb quicker, more accurate and precise. In most cases, the diagnosis of thalassaemias and common Hb variants is straight forward.

Download Volume 4, Issue 2, August 2009

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