ICD-11

A disease caused by genetically inherited autosomal recessive mutations leading to abnormal production of haemoglobin. This disease is characterised by destruction of red blood cells leading to anaemia and abnormal production of haemoglobin. This disease may present with pallor, jaundice, iron overload, fatigue, or shortness of breath. Confirmation is by identification of mutations through genetic testing.

Beta-thalassemia (BT) is a haemoglobinopathy characterised by deficiency (Beta+) or absence (Beta0) of synthesis of the beta globin chains of haemoglobin (Hb). Three main types of BT have been described: minor, intermedia and major with clinical presentation ranging from asymptomatic forms to microcytic anaemia and splenomegaly due to defective erythropoiesis and haemolysis.

Beta-thalassaemia (BT) is marked by deficiency (B+) or absence (B0) of synthesis of the beta globulin chain of the haemoglobin (Hb) protein. Prevalence is unknown but incidence at birth of the severe form is estimated at 100,000/year. The disease was initially described in the Mediterranean basin but severe forms of BT occur throughout the Middle East, South East Asia, India and China. Population migration has lead to global distribution of the disease. Three types of BT have been described. 1) Thalassaemia minor (BT-minor) is the heterozygous form and is usually asymptomatic. 2) Thalassaemia major (Cooley anaemia; BT-major) is the homozygous form and is associated with microcytic and hypochromic anaemia resulting from dyserythropoiesis and haemolysis. Splenomegaly is also present. Onset occurs from 6-24 months of age. The severe anaemia requires systematic transfusions to maintain Hb levels within the range of 90-100 g/L and allow normal activity. Transfusion of red cell concentrates results in iron overload which hampers the vital prognosis (due to cardiac involvement) and causes significant morbidity (due to endocrinal and hepatic manifestations). 3) Thalassaemia intermedia (BTI) groups together around 10% of homozygous disease forms with numerous compound heterozygous forms. The degree of anaemia in BTI is variable, but is less severe and is diagnosed later than that in BT-major. Patients with BTI may or may not require occasional transfusions. Hypersplenism, biliary lithiasis, extramedullary haematopoiesis, thrombotic complications and progressive iron overload may occur. Diagnosis of BT relies on analysis of Hb by electrophoresis or HPLC. In BT-major, HbA is absent or greatly reduced and HbF predominates. In BT-minor, the levels of Hb A2 are increased and the levels Hb are usually normal with microcytic and hypochromic pseudopolycythaemia. Transmission is autosomal recessive and around 200 mutations (B0 or B+) have been identified. Genetic counselling is recommended for characterising the mutation, preparing management for the affected child and, in some cases, for prenatal diagnosis. There are two lines of treatment for BT. 1) A combination of transfusions and chelators (early and regular parenteral deferoxamine has led to increased survival during the last 30 years). Oral administration of active iron chelators and surveillance of tissue iron overload by MRI will probably result in further improvements but long-term follow-up is needed to evaluate impact on morbidity and mortality. In 2006, deferasirox obtained EU marketing authorisation as an Orphan drug for treatment of BT. Despite its cardioprotective properties, the marketing authorisation for deferasirox is restricted to cases in which treatment with deferoxamine fails or is contraindicated. 2) Haematopoietic stem cell transplant is the only curative treatment for BT: results are very favourable for children with HLA-identical familial donors.