Global Study of Thalassaemia

The inherited disorders of haemoglobin are by far the commonest genetic diseases and will cause an increasing global health problem in the future. This programme is directed at trying to develop better ways of estimating the true global burden of these diseases, and, in particular, better to understand the reasons for why some of them are so remarkably diverse despite being due to the same genetic defect. A better understanding of these mechanisms are absolutely critical to improving the future management of many of these diseases in the developing countries.

The inherited disorders of haemoglobin are by far the commonest monogenic diseases. Over 300,000 babies are born each year with either sickle cell anaemia or a form of thalassaemia; 80% of these births occur in low or middle-income countries. The commonest forms of severe thalassaemia are the ? thalassaemias, which are divided into ? thalassaemia major and the co-inheritance of ? thalassaemia and haemoglobin (Hb) E, HbE ? thalassaemia. Globally, HbE ? thalassaemia comprises about 50% of severe cases of ? thalassaemia and occurs at its highest incidence in parts of India, Bangladesh and throughout Southeast Asia. The management of HbE ? thalassaemia is in many ways more difficult than that of other severe forms of ? thalassaemia because it has such an extraordinarily diverse clinical phenotype, ranging from a transfusion-dependent disorder similar to ? thalassaemia major to a condition which is compatible with survival into adult life with little or no transfusion. As well as this phenotypic diversity the management of HbE ? thalassaemia is further complicated by the instability of its clinical manifestations over the first few years of life. Another difficult aspect of the phenotype associated with its clinical management is the fact that the steady-state haemoglobin levels in the mild and severe phenotypes often only vary between 1-2 g/dl. Surprisingly however, there are very few data on the natural history of this disease and its overall mortality, either in the developed or developing countries. Over the last 15 years we have developed partnerships with a variety of countries in Asia, notably Sri Lanka, to study HbE ? thalassaemia. This work has two major objectives. First, to try to understand some of the reasons for the remarkable phenotypic variability of the disease. Second, to describe its natural history and, in particular, to follow the course of older patients with this condition who have not received regular transfusion to determine whether a lifelong course of a low haemoglobin level is associated with complications as these patients age. By raising money from several different sources it has been possible to build a new treatment centre for these patients in Kurunegala, Sri Lanka, which now cares for over 600 patients with ? thalassaemia, 200 of which have HbE ? thalassaemia. We have also raised money for the building of a major diagnostic centre at the University of Kelaniya in Colombo, to which is attached an adult thalassaemia centre and full facilities for diagnosis at the protein and DNA level. The third aspect of this programme is directed at micromapping the frequency of the thalassaemias in Asian countries. Little work has been done on the population frequency of these diseases since the 1980s and there are very limited data, a major deficiency in trying to determine their true public health problems. Most of the published data is based on one or two centres and it is already clear that the distribution of the thalassaemias is extremely heterogeneous within different countries. Therefore extensive mapping of their frequency is required from numerous different regions in high-frequency populations. Towards this end we have carried out several micromapping studies and are also trying to develop an Asian Network between countries which have already developed this type of technology and those where facilities for the diagnosis and management of the thalassaemias are non-existent.