Alpha globin is made by four genes, two on each strand of chromosome 16. Alpha thalassaemia usually occurs by deletion of some of these four genes. Depending on the total number of alpha genes that a patient has, there are different outcomes:
Alpha globin genes:
4 alpha globin genes: most common scenario, person is not a carrier.
3 alpha globin genes: silent alpha thalassaemia carrier. There is overlap between the red blood cell indices of these individuals and those with 4 gene copies, although the MCV may be slightly lower.
2 alpha globin genes: alpha thalassaemia carrier (also called alpha thalassaemia trait). Individuals who have alpha thalassaemia trait are identified by microcytosis, erythrocytosis, hypochromia and mild anaemia. Individuals with a thalassaemia trait will experience no significant health problems except a possible slight anaemia which cannot be treated with iron, with consequent mild fatigue symptoms.
1 alpha globin gene: the person will be affected with haemoglobin H disease. Haemoglobin H disease is characterized by mild to moderate anaemia, hypochromia and microcytosis. Individuals who have haemoglobin H disease generally have a persistent stable state of anemia, which may be accentuated by increased haemolysis during viral infections and by exposure to oxidant medications, chemicals and foods such as sulfa drugs, benzene, and fava beans (similar to individuals who have G6PD deficiency).
As the red cells mature they lose their ability to withstand oxidant stress and haemoglobin H precipitates, leading to haemolysis. Therapy for individuals who have haemoglobin H disease includes folate, avoidance of oxidant drugs and foods and frequent medical check ups.
No alpha globin genes: the absence of alfa chains causes severe anaemia and leads to hydrops foetalis. This diagnosis is frequently made in the last months of pregnancy when fetal ultrasound indicates a hydropic fetus. The mother frequently exhibits toxemia and can develop severe postpartum hemorrhage. These infants are usually stillborn. There can be other congenital anomalies, though none are pathognomonic for alpha thalassaemia major. If the diagnosis is made early, intrauterine transfusions can be performed.
More uncommonly, alpha thalassaemia can also be caused by point mutations in any of the four alfa globin genes. Some examples of these haemoglobin variants are: Constant-Spring, Icaria, Seal Rock, Pakse, Quong Sze, Sun-Praire and Adana.