Syndrome | Genotype | Typical findings on CBC | Hemoglobin analysis (HPLC or other protein chemistry method) |
Alpha thalassemias (reduction in alpha globin chains) | |||
Alpha thalassemia major (ATM) | (– – / – –) | Severe microcytic anemia with hydrops fetalis; usually fatal in utero | Hb Barts (γ globin tetramers); Hb Portland (embryonic hemoglobin); no Hb F, Hb A, or Hb A2 |
Hb H disease | (α – / – –) or (α αt / – –)* | Moderate microcytic anemia | Hb H (up to 30%); Hb A2 (up to 4%) |
Alpha thalassemia minor (also called alpha thalassemia trait) | (α – / α –) or (α α / – –) | Mild microcytic anemia | Hb Barts (3 to 8%, only in the newborn period) |
Alpha thalassemia minima (also called silent carrier) | (α α / α –) | Normal or mildly decreased hemoglobin, normal or mildly decreased MCV | Normal |
Beta thalassemias (reduction in beta globin chains) | |||
Transfusion-dependent (TDT, previously called beta thalassemia major) | β0 / β0¶ or β0 / β+ | Severe microcytic anemia with target cells (typical Hb 3 to 4 g/dL) | Hb A2 (5% or more); Hb F (up to 95%); no Hb A |
Non-transfusion-dependent (NTDT, previously called beta thalassemia intermedia) | β+ / β+¶ or β0 / β+ or Coinheritance of other variantsΔ | Moderate microcytic anemia | Hb A2 (4% or more); Hb F (up to 50%) |
Beta thalassemia minor (also called trait or carrier) | β / β0 or β / β+ | Mild microcytic anemia | Hb A2 (4% or more); Hb F (up to 5%) |
CBC: complete blood count; HPLC: high-performance liquid chromatography; Hb: hemoglobin; Hb F: fetal hemoglobin; Hb A: adult hemoglobin; MCV: mean corpuscular volume; TDT: transfusion-dependent beta thalassemia; NTDT: non-transfusion-dependent beta thalassemia.
* The "t" stands for an alpha globin with a structural mutation that can result in very low hemoglobin output (usually 1 to 10%), such as Hb constant spring (α αcs / – –) causing a more severe phenotype than (α – / – –). Other Hb H disease genotypes are possible such as (αt – / α –) or (αt – / αt –).
¶ β0 refers to no beta globin production; β+ refers to decreased beta globin production; Hb E is a β+ mutation.
Δ Other variants that can be seen in NTDT include Hb E (in combination with heterozygosity for a beta thalassemia variant), hereditary persistence of fetal hemoglobin (HPFH; in combination with homozygous beta thalassemia), alpha thalassemia (in combination with homozygous β+ thalassemia), or triplicated or quadruplicated alpha genes (αα / ααα or αα / αααα; in combination with heterozygous beta thalassemia). Dominantly acting beta thalassemia variants can also occur.Do you want to add Medilib to your home screen?