Thalassemias

The next hemoglobin condition we will go through is thalassemia which is defined as a blood disorder involving less than normal hemoglobin due to decreased globin chain synthesis. So a hemoglobinopathy is an abnormality in hemoglobin structure, and thalassemia is less than the normal amount of hemoglobin. This is an important distinction.

Types of thalassemia:

Alpha thalassemia:
There are two genetic loci for alpha globin chains, which means every person has 4 copies, 2 from mom and 2 from dad. There are five different phenotypes which are listed below:

Normal α chain production	αα/αα
One deleted α gene	-α/αα
Two deleted α genes	--/αα, -α/-α
Three deleted α genes	--/-α
Four deleted α genes	--/--

One deleted gene will give you a silent carrier and normal lab results
Two deleted genes yields a mild microcytic, hypochromic anemia
Three deleted genes yields hemoglobin H disease.
Four deleted genes yields Bart’s hydrops fetalis syndrome

Study Tip
Decreased production of a particular globin chain will usually lead to a rise of excess globin chain of another type that it usually pairs with. For example, decreased alpha chain leads to an excess of beta chain (alpha thalassemia). Likewise, decreased beta chain, leads to an excess of alpha chain (beta thalassemia). Along with the decreased hemoglobin formed due to the missing globin chain, the excess unmatched chain floating around causes physiological problems. Think your way through these problems by remembering the type of thalassemia is the globin chain that is decreased.

Hemoglobin H disease:
Hemoglobin H disease is characterized by microcytic, hypochromic anemia and chronic hemolytic disease due to the decreased alpha chain production. In hemoglobin H disease only one α chain gene is functioning resulting in a lot of free beta chains which form beta tetramers (β4). These beta tetramers are referred to as hemoglobin H, and they have abnormal function.

Bart’s hydrops fetalis syndrome:
This syndrome is incompatible with life. Babies born with this condition die in utero or shortly after birth. They do not produce any α chains and the result is hemoglobin Bart’s (γ4, gamma tetramers) and hemoglobin Portland (ζ2γ2). Hemoglobin Bart’s carries no oxygen. Their survival is completely dependent on hemoglobin Portland which is unsustainable.

Beta thalassemia minor:
If a patient has decreased production of beta chains (heterozygous) they will present with microcytic, hypochromic anemia and hemoglobin in the 10-13 g/dL range. On the peripheral smear there may be mild anisocytosis and poikilocytosis as well as target cells, and basophilic stipplings. Patients tend to be asymptomatic except when under stress such as illness, pregnancy, or folic acid deficiency.

Beta thalassemia major:
Very little or no production of beta chain which leads to low hemoglobin A production. Hemoglobin F is the primary hemoglobin seen. Beta thalassemia major will present within the first year of life. Remember, there is little beta chain production until it ramps up at birth so this condition will not be detected until this increase occurs (around 6 months of age). Beta thalassemia major will result in a severe microcytic, hypochromic anemia that will have a hemoglobin value around 8 g/dL. This condition requires blood transfusions throughout life.