The α thalassaemias are disorders in which there is defective synthesis of α chains with resulting depression of production of the haemoglobins that contain of α chains, i.e. Hb-A, Hb-A₂ and Hb-F. The deficiency of α chains leads to an excess of γ chains in the fetus, and of β chains in the adult. The γ chains form the tetramer Hb-Bart’s (γ₄) and the unstable β chains precipitate and form Hb-H (β₄). The presence of Hb-Bart’s and Hb-H in the red cell has serious consequences as both haemoglobins have a high oxygen affinity and thus are unable to deliver adequate oxygen to the tissues. Clinically and haematological studies of α thalassaemia in the 1950 s and 1960 s identified four forms of the disorder. Alpha thalassaemia 2 usually showed no abnormalities on routine haematological examination and α thalassaemia 1 was a benign condition with a variable mild anaemia and red cell hypochromia. The clinical picture of Hb-H disease was intermediate between that of β thalassaemia minor and major and infants with Hb-Bart’s hydrops fetalis died in utero or shortly after birth.

Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome or Hb Bart syndrome. The milder form is called HbH disease.

Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. As a result of these serious health problems, most babies with this condition are stillborn or die soon after birth. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.

HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). Some affected individuals also have bone changes such as overgrowth of the upper jaw and an unusually prominent forehead. The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood.