A REVIEW OF THALASSAEMIA SYNDROMES IN WEST MALAYSIA AND AN EVALUATION OF SERUM FERRITIN LEVELS IN THIS CONDITION

Abstract

Iron deficiency and iron overload may be seen in patients with thalassaemia. In this study, the iron status with the use of serum ferritin and the molecular defects that cause thalassaemia in West Malaysia are reviewed. The heterogeneity of clinical expression of the thalassaemias in West Malaysia are now explainable with the identification in the last 6 years of the spectrum of mutations that cause ?- and ?-thalassaemia. The interaction of hereditary ovalocytosis with thalassaemia aggravates the clinical severity of thalassaemia. The measurement of serum ferritin has proved a useful method of estimating iron stores. However, with marked increases in the iron load, ferritin turns to haemosiderin or may be released from damaged parenchymal cells. Patients with Hb E B-thalassaemia, Hb H disease and carriers of ?-thalassaemia trait remained asymptomatic in the absence of blood transfusions. Blood transfusions may be required during pregnancy and fulminant infection in patients with Hb H disease and Hb E ?-thalassaemia. Regular blood transfusions in patients with homozygous ?-thalassaemia and Hb E ?-thalassaemia in the absence of adequate iron chelation therapy with desferrioxamine resulted in patients requiring splenectomy at some stage of the disease and a possibility of death in the second decade of life as a consequence of organ failure secondary to iron overload or to overwhelming infection. Carriers of ?-thalassaemia had normal growth and development. Patients with Hb E ?-thalassaemia in the absence of blood transfusions were short, with moderate to marked thalassaemia facies and sexual maturation that was normal or delayed. Patients with Hb H disease had mild to moderate thalassaemia facies, normal growth sexual maturity. Seventy-five percent (75%) of the patients with homozygous ?-thalassaemia who were above 10 years of age were below the 3rd centile of the growth chart and spontaneous puberty is not anticipated in this group. Only few patients were on iron chelation therapy. Poor compliance, inadequate dosage, and late initiation of iron chelation therapy were considered in the patients with failure of response to iron chelation therapy. In the four year follow-up there were no deaths in the group with homozygous ?-thalassaemia where the oldest patient was 14 years of age. In contrast there were three deaths among the patients with Hb E ?-thalassaemia where all three had been splenectomised and death was due to fulminant infection. The oldest patient who was aged 81 years old was discovered to have Hb H disease while being investigated for renal failure carriers of ?-thalassaemia had serum ferritin levels in the range of the normal control groups. Patients with Hb H disease and Hb E ?-thalassaemia had serum ferritin levels that were less than 500 ug/L. In contrast, patients with transfusion dependent homozygous ?-thalassaemia had serum ferritin levels >500 ug/L, with levels >4000 ug/L by the age of 9 years. Anaemia was present in 31.3 % of male and 73.6% of female carriers of ?-thalassaemia where none of the males had serum ferritin levels <10 ug/L. In contrast 10.5% of female ?-thalassaemia carriers had iron deficiency anaemia. In the absence of blood transfusions there is a need to monitor serum ferritin levels in patients with thalassaemia intermedia as they have a risk of iron overload from increased gastrointestinal absorption of iron. On the basis of these findings, I conclude that assays of serum ferritin will indicate if there is a need for supplemental iron therapy in subjects heterozygous for ?-thalassaemia and Hb H disease in countries where iron deficiency and thalassaemia are highly prevalent. A simple relationship between serum ferritin and iron stores cannot be assumed when iron overload is excessive in patients with thalassaemia.