Alpha-Thalassemia:

Cause(s):

α globin chain genes are located on chromosome 16 and there are normally four genes in total (αα/αα), two inherited from each parent. α-thalassemia results when there is a deletion in any number of the α globin gene. The severity of anemia and amount of α globin chain production is dependent the number of genes that are deleted.³

α-Thalassemia Silent Carrier (αα/α-):^1,2

Occurs when one α gene is deleted. There is still adequate production of α to ensure normal hemoglobin synthesis. Patient is asymptomatic and the mutation is benign.

In newborns, there is an excess production of γ globin chains. These γ globin chains tend to also form tetramers and result in Hemoglobin Barts (Hb Barts). Hb Barts has a high oxygen affinity and is inefficient for oxygen delivery to the tissues of the developing fetus. In the silent carrier state, there is only a small amount of Hb Barts produced.

α-Thalassemia Minor (αα/–) or (α-/α-):^1,2

Occurs when two α genes are deleted. There is now a 50% reduction in normal α globin chain production.

In adults, increased production of red blood cells is able to compensate for the decrease in α chain production, and α and β globin chain production is balanced. Patients are asymptomatic and any anemia present is mild.

There is between 5-15% hemoglobin Barts present at birth, but this decreases once β globin chain production takes over and γ globin chain production decreases. In adults, globin chain production is balances, so no Hemoglobin H is formed.

Hemoglobin H Disease (α-/–):^1,2