Anaemias are heterogeneous group of disorders, connected with red blood cell (RBC) count and/or haemoglobin concentration decrease. A large group are haemolytic anemias – congenital or acquired diseases caused by various intra- and extracellular factors. Each one of this disorders is connected with shorten lifespan of RBCs and accelerated removal of this cells. They may be the result of haemoglobin synthesis disturbances, caused by mutations in one or more genes coding globing chains. Congenital haemolytic anaemias connected with this variations are divided into two groups. The first one contains disorders in which mutation causes disturbance in aminoacid sequence of globin polypeptide chain and that gives abnormal type of haemoglobin with impaired functions; this group of diseases is called haemoglobinopathies (1). The second group are thalassemias, in which mutation in one or more globin genes leads to absence or decrease in globin protein synthesis. Excessive globin chains damage red blood cells, and that in consequence shortens RBCs lifespan (2, 3).

It was long believed, that haemoglobinopathies and thalassemias are found only in tropical and subtropical regions. High degree of carrier-state in this areas was connected with mechanisms protecting against Plasmodium and malaria (4). In recent years it was noticed that frequency of this disorders is increasing in different regions, like North America, Great Britain, Australia (5) and Germany (1). Cases of thalassemia α and β are also more often described in Poland (6-10). It is related to accelerated migration and increased percentage of mixed marriages, but also to improved diagnostic methods detecting this disorders. It is important to diagnose thalassemia and describe the number and the type of mutations not only to begin the appropriate therapeutic action, but also to determine the carrier state in patients in reproductive age. This strategy is particularly important in regions, where thalassemias are very common and the risk of having a partner with globin disorder is high (11, 12).

Haemoglobin (Hb) is red blood cell protein, and its basic function is oxygen transport. Haemoglobin particle is built of four subunits covalently bound. Each subunit is composed of polipeptyde chain, globin molecule, bound with haeme. The haeme group is the same in all Hb types and is built of porphyrin ring with iron atom in the centre (13). Different kinds of haemoglobin contain various protein chains. Particular globin types are named with Greek alphabet letters α, β, γ, δ, ε and ζ. The correct haemoglobin kinds in adults are HbA (2α2β, 97%), HbA₂ (2α2δ, 2%) and remains of foetal Hb, HbF (2α2γ, 1%) (3). The regular set of haemoglobin types during human life and pathology in thalassemias and haemoglobinopathies is shown in table 1.

All genes coding globin chains are gathered in two clusters: cluster α on chromosome 16, containing genes coding α and ζ globin; cluster β on chromosome 11, containing genes coding β, γ, δ and ε globin (14). Expression of all genes in each cluster is controlled by one regulatory element, α-MRE (major regulatory element) controlling α and ζ genes, and β-LCR (locus control region) controlling β, γ, δ and ε genes. The regulatory element affects the promoter of one of the genes in the cluster and enhances its expression. Expression of other genes in this cluster remains very low or is entirely inhibited (14-17). During foetal life occurs double haemoglobin synthesis switching (17). Around 10 week of foetal life stops the expression of ε and ζ globin, and synthesis of embryonic haemoglobins (Gower I, Gower II and Portland), and the main Hb becomes foetal haemoglobin (HbF). The second haemoglobin switching occurs shortly before birth. Then the γ globin gene expression is silenced and β globin gene expression is enhanced. As a result, synthesis of γ globin and HbF decreases, and synthesis of β globin and HbA increases (18). This process lasts until around six month after birth.

Haemoglobinopathies are diverse group of disorders, with different clinical symptoms and genetic background. Mutations occur usually in β globin gene, less frequently in α globin and other genes. In every case mutation leads to synthesis of a new protein, in varying degrees different from the correct globin chain. A large group of haemoglobinopathies are anaemias connected with point mutations in β globin gene. The examples are haemoglobinopathies C, D and E, in which irregular forms of haemoglobin are produced, respectively, HbC, HbD and HbE (19). In heterozygotes there is about 30-50% of this abnormal haemoglobin, while in homozygotes they can present as much as 90% of total Hb. HbE is most frequent in South-East Asia, where percentage of carriers reaches 60% in some countries (20), HbC in West Africa (1), HbD in South Asia (21). Heterozygotes are carriers of one damaged gene and have no clinical symptoms. Homozygotes suffer from haemolysis, but it is usually mild and does not require therapy (22). Interesting case of haemoglobinopathy is congenital methaemoglobinaemia or haemoglobinopathy M. Mutation occurs in α or β globin gene, and protein is altered in the region next to the iron atom. Iron is stabilized in Fe³⁺ form and that gives abnormal form of Hb- methaemoglobin, incapable of carrying oxygen (23).