Sickle cell thalassemia occurs when you inherit both a sickle cell gene mutation and a thalassemia gene mutation. Symptoms are similar to other types of sickle cell disease but can vary depending on the specific mutation.
Hemoglobin is the main component of your red blood cells. It’s responsible for carrying oxygen from your lungs to all your organs and tissues. Mutations in the genes that build hemoglobin can cause various blood diseases.
The most well-known of these is sickle cell anemia (SCA). SCA is the most common genetic disease in the United States. About
Hemoglobin gene mutations can also cause thalassemias, which are quite common in people of Southeast Asian, African, or Mediterranean ancestry.
The gene mutations that cause SCA and thalassemias are commonplace in certain populations because they protect against contracting severe malaria.
Because of the high prevalence of SCA and thalassemia mutations, some children inherit both. This causes sickle cell thalassemia disease. The most significant form of sickle cell thalassemia is called sickle beta-thalassemia.
Typical adult hemoglobin comprises four proteins: two alpha-globin and two beta-globin chains. Usually, you inherit four copies of the alpha-globin gene and two copies of the beta-globin gene — half from each biological parent.
Mutations in any of these genes can cause you to have varying degrees of SCA or thalassemia, or to be a “silent” carrier for one of the conditions. That means you can pass on the disease but don’t have any symptoms yourself.
As both conditions are autosomal recessive traits, you need to inherit gene mutations from both your parents. If one parent has the SCA mutation and the other a thalassemia mutation, you could inherit both. In this case, you’ll have sickle cell thalassemia.
Sickle cell and beta-thalassemia
Sickle cell thalassemia usually refers more specifically to sickle beta-thalassemia. Both SCA and beta-thalassemia result from mutations in the gene that makes beta-globin, located on chromosome 11.
There are two types of sickle beta-thalassemia:
- Sickle beta0-thalassemia: One beta-globin gene makes sickle hemoglobin, and the other is essentially non-functional. Symptoms are severe.
- Sickle beta+-thalassemia: One beta-globin gene makes sickle hemoglobin, and the other makes a reduced amount of healthy hemoglobin. Symptoms are often milder.
Sickle cell and alpha-thalassemia
It’s also possible to inherit the SCA mutation together with alpha-thalassemia mutations, which are located on a different chromosome. But having both alpha-thalassemia trait and sickle cell trait usually doesn’t cause serious illness. Research has even shown that co-inheriting both traits may lessen any symptoms.
It’s rarer to see sickle cell trait in combination with alpha thalassemia disease (aka hemoglobin H disease) since these two genetic conditions tend to occur in different populations. But
The symptoms of sickle beta-thalassemia can vary, depending on the type of beta-thalassemia mutation you inherited.
In sickle beta0-thalassemia, your body makes almost entirely sickle hemoglobin. Serious symptoms appear early. The illness is nearly identical to someone with SCA.
People with sickle beta+-thalassemia still produce some typical hemoglobin. Symptoms are typically much less severe.
There are also other forms of sickle cell disease that don’t involve thalassemias. In these conditions, symptoms are often milder than in SCA.
Healthy red blood cells are shaped like squishy discs. But sickle hemoglobin tends to devolve into a rigid crescent shape, deforming and damaging your red blood cells.
These dysfunctional red blood cells then block small blood vessels, reducing the flow of oxygen to your tissues. This causes symptoms and complications such as:
- anemia
- severe pain (due to vaso-occlusive crisis)
- poor growth and delayed puberty
- fatigue or weakness
- swelling of hands and feet
- increased infection risk
- vision problems
- enlarged spleen
- stroke
- priapism
- heart and lung disease
- bone and kidney damage
People with sickle beta+-thalassemia may experience these symptoms, but less severely.
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If a doctor suspects sickle cell thalassemia, they can confirm a diagnosis with blood tests like a complete blood count and hemoglobin electrophoresis. Sometimes, they may recommend genetic testing.
Treatments are available to help reduce the risk of complications and manage symptoms. These include:
- vaccines and prophylactic antibiotics to prevent infection
- hydroxyurea
- blood transfusions, IV fluids, or both
- pain medication during vaso-occlusive crises
- routine screenings for stroke risks and eye, heart, lung or kidney problems
Potential cures that alter the genetic basis of sickle cell disease include:
- stem cell transplants
- gene therapies newly
approved for SCA and sickle beta0-thalassemia
Sickle beta-thalassemia typically requires lifelong follow-ups with a hematologist. Some people experience complication rates similar to those seen in people with SCA.
People with sickle beta+-thalassemia usually have a milder disease course, with survival rates similar to people without the disease.
Life expectancy for people with sickle beta0-thalassemia is similar to life expectancy with SCA. Median survival has improved over recent decades to reach
Scientists expect that ongoing advances in treatment, including gene therapy and stem cell transplants, will continue to improve outcomes.
What is the difference between sickle cell anemia and thalassemia?
SCA and thalassemia both result from gene mutations in the genes that build your hemoglobin. SCA is due to a beta-globin mutation that affects the shape of your red blood cells. These sickled cells clog your blood vessels and stop oxygen from reaching your organs, causing severe anemia and other symptoms.
Thalassemia can result from either alpha- or beta-globin mutations. It causes severe anemia, unusually small and fragile red blood cells, and other complications, including iron overload.
How does sickle cell thalassemia compare to sickle cell anemia?
Sickle cell-thalassemia disease generally refers to the two types of sickle-beta thalassemia.
People with sickle beta0-thalassemia have symptoms and outcomes nearly identical to those with SCA.
Sickle beta+-thalassemia is often milder than SCA, although symptoms can vary.
What is the most severe type of sickle cell disease?
The
But people with sickle beta0-thalassemia (Hb SB0) can experience equally severe disease.
Other common forms of sickle cell disease, such as sickle beta+-thalassemia (Hb SB+) or Hb SC disease, tend to be milder.
Inheriting both the sickle cell and beta thalassemia mutation can result in a clinically significant disease called sickle beta-thalassemia, of which there are two forms.
Sickle beta0-thalassemia closely resembles SCA, with early and potentially severe symptoms. Sickle beta+-thalassemia is usually milder.
Regardless of form, people with sickle beta-thalassemia will need lifelong close monitoring with a hematologist and will likely require extra vaccines, medications, screenings, and treatments.
Advances in treatments such as gene therapy and stem cell transplantation are ongoing, offering hope for a cure for these genetic conditions.
