Alpha Thalassemia

Alpha thalassaemia is reduced alpha globin chain production due to deletions or mutations of HBA1 and HBA2 (four alpha genes).

• Common in Southeast Asia, China, Mediterranean, Africa, Middle East.
• Genotypes:
  • Silent carrier (one gene deleted): normal haematology.
  • Alpha thalassaemia trait (two genes deleted): mild microcytosis.
  • HbH disease (three genes deleted): moderate haemolytic anaemia, HbH inclusions.
  • Hb Bart's hydrops fetalis (four genes deleted): fatal in utero.
• Excess beta chains form HbH (beta4) which is unstable; Hb Bart's (gamma4) in fetal life.
• Hb Constant Spring non deletional HbH disease is more severe.

• Trait: asymptomatic, mild microcytic anaemia.
• HbH disease: chronic haemolysis, jaundice, splenomegaly, gallstones, haemolytic crises with infection or oxidant drugs, skeletal changes, iron overload.
• Hydrops fetalis: severe fetal anaemia, hepatosplenomegaly, ascites; maternal pre-eclampsia, polyhydramnios, haemorrhage.

• Microcytic hypochromic cells (MCV 60 to 75 fL in trait), normal ferritin, normal HbA2; neonatal Hb Bart's (2 to 10% in trait).
• HbH disease: HbH 1 to 40% on electrophoresis, brilliant cresyl blue inclusion bodies.
• Alpha gene deletion/duplication analysis (MLPA, gap PCR) and sequencing.
• Prenatal diagnosis for couples with two gene deletions in cis (--/ in Southeast Asians); fetal ultrasound (cardiothoracic ratio, middle cerebral artery Doppler).
• Ferritin, liver iron MRI.

• Trait and silent carrier: no treatment; avoid unnecessary iron; genetic counselling.
• HbH disease: folic acid 5 mg daily, avoid oxidant drugs (sulfonamides, primaquine), treat infections, transfusion for crises or severe anaemia; chelation guided by iron load (deferasirox 10 to 20 mg/kg daily); splenectomy for hypersplenism or transfusion need (HbH Constant Spring); monitoring for gallstones.
• Hydrops fetalis: intrauterine transfusions and postnatal transplantation in specialised centres; termination offered when diagnosed.
• Stem cell transplantation for severe transfusion dependent disease.
• Preconception counselling and prenatal diagnosis by chorionic villus sampling; preimplantation diagnosis.
• Pregnancy: monitor haemoglobin, transfuse for severe anaemia.