SCIENTIFIC BACKGROUND
Alpha thalassemia is a result of a quantitative disorder of α-globin chain synthesis. The deficit of α-globin chains leads to the formation of excess hemoglobins which are significantly responsible for the clinical picture of alpha thalassemia. Like other hemoglobinopathies, the disease occurs more frequently in countries where malaria is endemic and is therefore associated with a certain resistance to plasmodia. Alpha thalassemia is particularly common in populations of Asia, Arabia, and Africa, as well as Mediterranean countries.
The most common molecular genetic cause of alpha thalassemia is the deletion of one or more α-globin genes. In normal human cells, the α-globin gene complex consists of 4 α-globin genes (one HBA1 and one HBA2 gene on each chromosome 16), therefore the severity of the clinical picture depends on the number of deleted α-globin genes. In rare cases, point mutations or minor deletions and insertions in the α-globin genes can also be causative for alpha thalassemia.
Most carriers of alpha thalassemia are diagnosed by chance during a routine examination. The blood count or sometimes also a lowered Hb value reveals a microcytosis and/or hypochromia. In the course of diagnosis, iron deficiency should first be ruled out by determining serum ferritin, which is the most common cause of microcytic hypochromic anemia. In advance, the Huber-Herklotz formula can already be used to estimate whether the diagnosis is more likely an iron deficiency anemia or an alpha thalassemia.
If iron deficiency has been ruled out, the presence of hemoglobinopathy can be investigated by Hb differentiation. In many cases, the question of a predisposing carrier of a hemoglobinopathy arises only in the context of conceiving a child, either because of a positive family history or because of ethnic origin. In the case of an already existing pregnancy, a rapid diagnosis is important in order to be able to assess the risk of a severe form of hemoglobinopathy in the offspring as early as possible.
Since hemoglobinopathies can occur in a wide variety of combinations, hematologic findings should always be compared with molecular genetics results and checked for validity.
References
Origa R, Moi P. Alpha thalassemia. 2005 Nov 1 [Updated 2016 Dec 29]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019 / Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. S1-Leitlinie: Thalassämie. 30.06.2016 / Kohne et Kleihauer 2010, Dtsch Arztebl Int 107:65 / Weatherall et Clegg 2001, The Thalassaemia Syndromes, 4th ed. Oxford: Blackwell Science / Kleihauer et al. 1996, Anomale Hämoglobine und Thalassämiesyndrome, ecomed Verlag
