Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Alpha Thalassemia [D56.0]

OMIM numbers: 604131, 141800 (HBA1), 141850 (HBA2)

Dipl.-Biol. Birgit Busse, Dipl.-Biol. Wolfgang Rupprecht

Scientific Background

Alpha-thalassemia is a quantitative disorder of α-globin chain synthesis. Due to a lack of α-globin chains, there is a relative excess of gamma or beta chains which significantly contributes to the clinical picture of alpha-thalassemia. Like other hemoglobinopathies, it is most prevalent in countries with high malaria endemicity suggesting a protective role against the more severe manifestations of malaria. Alpha-thalassemia is particularly found in sub-Saharan Africa, the Middle East, South Asia, Southeast Asia and Mediterranean countries.

The most common molecular genetic cause of alpha-thalassemia is the deletion of one or more α-globin genes. Since the α-globin gene complex in a normal human cell consists of 4 α-globin genes (one HBA1 gene and one HBA2 gene on each chromosome 16), the severity of the symptoms depends on the number of deleted α-globin genes. In rare cases, point mutations or small insertions and deletions in the α-globin genes may be causal for alpha-thalassemia as well. Clinically, the severity of symptoms can be classified into 4 categories:

  • Silent carrier (alpha thalassemia minima): only one α-globin gene is deleted. This condition is usually only discovered by accident, as all hematological parameters are normal.
  • Thalassemia trait (alpha thalassemia minor): deletion of two α-globin genes, minor haematological changes (hypochromia, microcytosis).
  • HbH disease: Only one functional α-globin gene remains. A key feature is the considerable variability of microcytic and hypochromic hemolytic anemia and the detection of hemoglobin H (HbH), a tetramer of four β-globin chains (β4).
  • Hb Bart's hydrops fetalis syndrome: complete loss of all α-globin genes. This condition is usually not compatible with life and affected fetuses are either stillborn or die soon after birth.


MCH = mittlere korpuskuläre Hämoglobin
RDW-SD = Erythrozytenverteilungsbreite (EVB) Standardabweichung
RBC = Erythrozyten (ERY)


MCV = mittleres korpuskuläres Volumen
RBC = Erythrozyten (ERY)

Crystal structure of hemoglobin (Tame and Vallone 2000, PDB entry 1A3N,