Alpha-thalassemia

There are at least 4 different and distinct alpha-thalassemias: silent carrier (1 affected alpha-globin gene), alpha-thalassemia trait (2 affected alpha-globin genes), Hb H disease (typically 3 affected alpha-globin genes), and Hb Bart hydrops fetalis syndrome (typically deletion of all 4 alpha-globin genes).

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

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

The vast majority of alpha-thalassemia patients are clinically well and most are asymptomatic. Many patients with Hb H are also clinically well, but are at risk for: acute hemolytic 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 both the risks of acute events and, in genetic counseling, the risks of conceiving a child with Hb H disease or the potentially devastating Hb Bart hydrops fetalis.

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

Alpha-thalassemia is a group of disorders of hemoglobin synthesis, caused by mutations or deletions in at least 1 of the 4 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 anemia and hemolysis of variable severity. [1] Weatherall D. The molecular basis for phenotypic variability of the common thalassaemias. Mol Med Today. 1995;1:15-20. http://www.ncbi.nlm.nih.gov/pubmed/9415132?tool=bestpractice.com Normal human hemoglobin consists of a tetramer of 2 pairs of globin polypeptide chains, 1 pair of alpha-like chains and 1 pair of nonalpha chains, each of which contains a heme 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;7:1045-1053. 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 4 different and distinct alpha-thalassemias: silent carrier (1 affected alpha-globin gene), alpha-thalassemia trait (2 affected alpha-globin genes), Hb H disease (typically 3 affected alpha-globin genes), and Hb Bart hydrops fetalis syndrome (typically deletion of all 4 alpha-globin genes).