Because changes in the b globin gene are common in the Mediterranean area, people whose ancestors came from such areas as Greece or Italy may wish to be screened for thalassemia. Simple inexpensive screening is done by looking at the MCV (cell volume) on a standard blood count. If the cells are small, suggesting b thalassemia minor, further testing can be done to confirm the diagnosis. Also, prenatal diagnosis is available for pregnancies at risk for severe thalassemia.
Disorders of a globin synthesis are little more complicated because there are four genes involved, two on each copy of chromosome 16. Screening for these disorders is also readily available. If a baby is missing all four a globin genes, there will be no fetal hemoglobin to transport oxygen before birth. The fetal heart fails and the baby is usually stillborn, showing a swelling of the entire body called hydrops fetalis. This problem is especially common in Asia. It happens only if both parents have a condition called athal1, in which one chromosome 16 is lacking both copies of the a globin gene. Despite mild anemia, people with athal1 are usually healthy. And because this anemia is not due to iron deficiency, iron therapy is not helpful.
It is also possible to have a change in just one a globin gene. This condition is called athal2 and it causes no recognizable abnormalities, either clinically or on standard blood tests. If a person with athal2 and a partner with athal1 have children, some of the children may inherit changes in three of their a globin genes.
This causes a condition called hemoglobin H disease, which is common in both Asia and the Mediterranean. People with hemoglobin H disease have only moderate anemia, but they produce an abnormal hemoglobin called hemoglobin H containing of four b chains. Due to the breakdown of this abnormal hemoglobin, the spleen enlarges and may have to be removed. Nevertheless, people with hemoglobin H disease enjoy a prolonged survival.
A very rare form of a thalassemia is due to a deletion of a larger area of chromosome 16 including the a globin genes. This causes only mild thalassemia, but because other genes are deleted as well, there are additional problems--such as birth defects and mental retardation--that do not occur in most thalassemias. Another rare congenital anomaly-mental retardation syndrome called ATR-X results from a mutation of a gene on the X chromosome. For unknown reasons, the ATR-X mutation causes mild a thalassemia even though the a globin gene is normal. Unlike other thalassemias, these very rare a thalassemia-mental retardation syndromes do not preferentially affect any specific ethnic groups. If a severe thalassemia or one of the thalassemia-mental retardation syndromes is diagnosed in a family, prenatal diagnosis during pregnancies at risk is advised.