What condition results when 3 out of 4 genes are deficient in Alpha thalassemia?

In the context of Alpha thalassemia, having three out of four alpha globin genes deficient leads to a condition known as Hb H disease. This genetic disorder is characterized by the production of an abnormal form of hemoglobin (Hb H) due to the reduced synthesis of alpha globin chains. As a result, the excess beta globin chains form tetramers (clusters of four) that can not effectively carry oxygen, leading to a range of clinical symptoms.

Patients with Hb H disease typically experience moderate to severe anemia, splenomegaly, and may have characteristic features on a peripheral blood smear, such as target cells and hypochromic microcytic red blood cells. The condition represents a significant phenotype on the spectrum of alpha thalassemia, distinguishing it from conditions such as beta thalassemia or less severe alpha thalassemia traits where fewer genes are affected. This is fundamental to understanding how the number of affected genes influences clinical presentation and severity in thalassemias.