Alpha-thalassaemia

There are at least four distinct alpha-thalassaemias: silent carrier (1 affected alpha-globin gene), alpha-thalassaemia trait (2 affected alpha-globin genes), haemoglobin H (Hb H) disease (typically 3 affected alpha-globin genes), and alpha-thalassaemia major (also known as Hb Bart hydrops fetalis syndrome; typically deletion of all 4 alpha-globin genes).

The severity of the clinical manifestations of anaemia and haemolysis correspond with the genetic defect and the degree of impairment in alpha-globin synthesis.

Alpha-thalassaemia is found in malarial regions of the world (sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia) and should be suspected in patients with these ethnic backgrounds and with microcytosis and/or anaemia.

The vast majority of alpha-thalassaemia patients are clinically well and most are asymptomatic. Many patients with Hb H are also clinically well, but are at risk for acute haemolytic episodes, aplastic crises, iron overload (even in the absence of chronic transfusions), hypersplenism, and endocrine disease.

Education is an important part of management and should cover the risks of acute events and, in genetic counselling, the risks of conceiving a child with Hb H disease or the potentially devastating alpha-thalassaemia major.

Acquired Hb H disease is rare and occurs in association with haematological disorders, most commonly in male patients with myelodysplastic syndrome.

Alpha-thalassaemia is a group of disorders of haemoglobin synthesis, caused by mutations or deletions in at least one of the four alpha-globin genes, leading to variably impaired alpha-globin chain production, with accumulation of the now excess and unpaired beta-globin chains. These defects lead to the corresponding clinical manifestations of anaemia and haemolysis of variable severity.[1]Weatherall D. The molecular basis for phenotypic variability of the common thalassaemias. Mol Med Today. 1995 Apr;1(1):15-20. http://www.ncbi.nlm.nih.gov/pubmed/9415132?tool=bestpractice.com

Normal human haemoglobin consists of a tetramer of two pairs of globin polypeptide chains, one pair of alpha-like chains and one pair of non-alpha chains, each of which contains a haem group. Two copies of the alpha-globin gene (designated alpha-2 and alpha-1) are located on each chromosome 16. The upstream regulatory element HS-40 controls alpha-globin expression.[2]Ribeiro DM, Sonati MF. Regulation of human alpha-globin gene expression and alpha-thalassemia. Genet Mol Res. 2008 Oct 14;7(4):1045-53. http://www.funpecrp.com.br/gmr/year2008/vol7-4/pdf/gmr472.pdf http://www.ncbi.nlm.nih.gov/pubmed/19048483?tool=bestpractice.com

There are at least four distinct alpha-thalassaemias: silent carrier (1 affected alpha-globin gene), alpha-thalassaemia trait (2 affected alpha-globin genes), haemoglobin H (Hb H) disease (typically 3 affected alpha-globin genes), and alpha-thalassaemia major (typically deletion of all 4 alpha-globin genes).