α-Thalassemia

Key Features

• Predominately African, Mediterranean, Middle Eastern, Chinese, or Southeast Asian ancestry

• Microcytic, hypochromic anemia of variable severity

• Generally Bart's hemoglobin detected by neonatal screening

Clinical Findings

• Depend on the number of α-globin genes deleted

• Persons with three α-globin genes (one-gene deletion) are asymptomatic

• Persons with two α-globin genes (two-gene deletion) are typically asymptomatic

• Persons with one α-globin gene (three-gene deletion)

  • Have a mild to moderately severe microcytic hemolytic anemia (hemoglobin level of 7–10 g/dL)

  • May be accompanied by hepatosplenomegaly and some bony abnormalities caused by the expanded medullary space

• Deletion of all four α-globin genes

  • Causes severe intrauterine anemia

  • Results in hydrops fetalis and fetal demise or neonatal death shortly after delivery

  • Extreme pallor and massive hepatosplenomegaly are present

Diagnosis

• Persons with three α-globin genes (one-gene deletion): no hematologic abnormalities

• Hemoglobin electrophoresis

  • In the neonatal period shows 0–3% Bart's hemoglobin, which is a variant hemoglobin composed of four γ-globin chains

  • Normal after the first few months of life

• Persons with two α-globin genes (two-gene deletion)

  • Mean corpuscular volume (MCV) is usually less than 100 fL at birth

  • Hematologic studies in older infants and children show a normal or slightly decreased hemoglobin level with a low MCV and a slightly hypochromic blood smear with some target cells

• Persons with one α-globin gene (three-gene deletion)

  • Reticulocyte count is elevated

  • Red cells show marked hypochromia and microcytosis with significant poikilocytosis and some basophilic stippling

  • Incubation of red cells with brilliant cresyl blue (hemoglobin H preparation) shows inclusion bodies formed by denatured hemoglobin H

• Deletion of all four α-globin genes

  • Hemoglobin electrophoresis reveals a predominance of Bart's hemoglobin with a complete absence of normal fetal or adult hemoglobin

Treatment

• Persons with α-thalassemia trait require no treatment

• Those with hemoglobin H disease should receive supplemental folic acid and avoid the same oxidant drugs that cause hemolysis in persons with G6PD deficiency because exposure to these drugs may exacerbate their anemia

• Anemia may also be exacerbated during periods of infection, and transfusions may be required

• Hypersplenism may develop later in childhood and require surgical splenectomy