Thalassemia is caused by inherited changes in genes that help the body make hemoglobin, the protein in red blood cells that carries oxygen. These changes reduce the production of alpha-globin or beta-globin, two parts of hemoglobin. A child inherits the relevant gene changes from their parents. The type of thalassemia and its effects depend on which genes are affected and how much normal hemoglobin the body can produce.
How do gene changes cause thalassemia?
Hemoglobin allows red blood cells to carry oxygen from the lungs to the body's tissues. It is made from four protein chains: usually two alpha-globin chains and two beta-globin chains. Genes contain the instructions for making these proteins. When a gene change reduces or prevents the production of one type of globin chain, the body cannot make hemoglobin normally.
As a result, red blood cells may develop abnormally or break down sooner than usual. This can reduce the number of healthy red blood cells and lead to anemia, a condition in which the blood cannot carry enough oxygen to meet the body's needs. According to the US Centers for Disease Control and Prevention (CDC), the type of thalassemia depends on the inherited gene changes and can influence how severely anemia affects a person.
What genetic changes cause the main types of thalassemia?
The two main types are alpha thalassemia and beta thalassemia. They differ according to which globin protein is affected and how the relevant genes have changed.
Alpha thalassemia
Alpha thalassemia occurs when changes involving the HBA1 or HBA2 genes reduce the production of alpha-globin. These changes most often involve missing sections of genetic material, called deletions, although other gene variants can also cause the condition.
People normally have four alpha-globin gene copies, with two inherited from each parent. The effects depend partly on how many copies are missing or altered and which copies are affected. Changes involving one copy may have little or no noticeable effect, while changes involving several copies can cause more significant anemia. The MedlinePlus Genetics overview of alpha thalassemia explains how these different gene patterns are associated with different forms of the condition.
Beta thalassemia
Beta thalassemia is caused by variants in the HBB gene, which provides instructions for making beta-globin. Some variants prevent the body from producing beta-globin from the affected gene, while others allow it to produce a reduced amount. Both types of changes can interfere with normal hemoglobin production.
People inherit two copies of the HBB gene, one from each parent. The combination of gene variants influences the amount of beta-globin the body can make and contributes to the form of thalassemia that develops. According to MedlinePlus Genetics, beta thalassemia can range from forms with few symptoms to forms associated with severe anemia and other health problems.
How is thalassemia passed from parents to children?
Thalassemia is an inherited condition, meaning the relevant gene changes are passed through families. It is not caused by something a parent ate, did, or experienced during pregnancy. It is also not contagious and cannot spread through everyday contact.
For many forms of thalassemia, a child develops a more significant condition when they inherit relevant altered genes from both parents. A person who inherits a thalassemia-related gene change may be a carrier, sometimes called having thalassemia trait. Carriers often have no symptoms, although some have mild anemia or smaller-than-usual red blood cells.
The inheritance pattern is not identical for every type. Alpha thalassemia depends on the number and arrangement of affected alpha-globin gene copies, while beta thalassemia usually depends on the combination of variants inherited in the two HBB gene copies. The National Heart, Lung, and Blood Institute (NHLBI) provides further information about these inheritance patterns.
What happens if both parents are carriers?
If both parents carry a variant associated with beta thalassemia, each pregnancy has its own set of possible genetic outcomes. When both parents carry a typical disease-causing variant in one copy of the HBB gene, each pregnancy has a 25% chance of a child inheriting both altered copies, a 50% chance of inheriting one altered copy and being a carrier, and a 25% chance of inheriting neither altered copy.
These percentages apply to that specific inheritance pattern, not to every family affected by thalassemia. Alpha thalassemia can have different outcomes depending on which gene copies are affected. Genetic counseling can help prospective parents understand their particular risks, including whether testing or other reproductive options may be relevant.
Does family background affect the risk of thalassemia?
Thalassemia-related gene variants are more common among people with ancestry from certain regions, including the Mediterranean, South Asia, Southeast Asia, the Middle East, and parts of Africa. This distribution reflects how these variants occur in different populations; it does not mean that everyone from these backgrounds carries them.
Family history can also be relevant. A person may carry a gene variant without knowing it because carriers often have no obvious symptoms. The UK National Health Service (NHS) explains that thalassemia is caused by inherited gene changes and that carrier status can matter when assessing the chance of passing the condition to a child.
Ancestry and family history can help guide decisions about testing, but neither can establish whether a person carries a variant. Blood tests and, when appropriate, genetic testing can help clarify the situation.
Can thalassemia develop because of iron deficiency or lifestyle factors?
No. Thalassemia itself is caused by inherited gene changes, not by iron deficiency, diet, stress, exercise, or an infection. Iron deficiency can also cause anemia, but it is a different condition with a different underlying cause. A person can have both iron deficiency and thalassemia, so one should not automatically be assumed to explain the other.
Because both conditions can be associated with anemia and small red blood cells, healthcare professionals may use blood counts, iron studies, hemoglobin testing, and sometimes genetic testing to distinguish between them. Iron supplements do not correct the inherited gene changes responsible for thalassemia and should not be started solely because anemia is present without appropriate assessment.
When should families consider testing?
Testing may be useful when a family member has thalassemia, when blood tests show unexplained anemia or unusually small red blood cells, or when someone is planning a pregnancy and may carry a thalassemia-related gene variant. A healthcare professional can review the family history and decide which tests are appropriate.
For couples who may both carry relevant variants, genetic counseling can explain the possible inheritance patterns and available testing options. This is particularly important because some carriers feel completely well and may not know about their status until testing is offered or a relative is diagnosed.