Identification and key management of non-transfusion-dependent thalassaemia patients: not a rare but potentially under-recognised condition

Patients with non-transfusion-dependent thalassaemia (NTDT) have a genetic defect or combination of defects that affect haemoglobin synthesis, but which is not severe enough to require regular blood transfusions. The carrier frequency of NTDT is high (up to 80% in some parts of the world) but the prevalence of symptomatic patients varies with geography and is estimated to be from 1 in 100,000 to 1 in 100. NTDT has a variable presentation that may include mild to severe anaemia, enlarged spleen and/or liver, skeletal deformities, growth retardation, elevated serum ferritin and iron overload. The contributing factors to disease progression are ineffective erythropoiesis and increased haemolysis, which lead to chronic anaemia. The body’s attempts to correct the anaemia result in constantly activated erythropoiesis, leading to marrow expansion and extramedullary haematopoiesis. Diagnosis of NTDT is largely clinical but can be confirmed by genetic sequencing. NTDT must be differentiated from other anaemias including sideroblastic anaemia, paroxysmal nocturnal haemoglobinuria, congenital dyserythropoietic anaemia, myelodysplastic syndromes and iron-deficiency anaemia. Management of NTDT is based on managing symptoms, and includes blood transfusions, hydroxyurea treatment, iron chelation and sometimes splenectomy. Prognosis for well managed patients is good, with most patients living a normal life. Since NTDT is mainly prevalent in sub-tropical regions, patients who present in other parts of the world, in particular the Northern hemisphere, might not been correctly recognised and it can be considered a ‘rare’ condition. It is particularly important to identify and diagnose patients early, thereby preventing complications.