Thalassemia: Alpha & Beta-Thalassemias, Genetics, Pathophysiology, Diagnosis & Treatment, Animation

Summary

Thalassemia is a group of inherited blood disorders affecting hemoglobin production, leading to anemia. There are two main types: alpha-thalassemia and beta-thalassemia, depending on gene mutations. Alpha-thalassemia varies in severity from silent carriers to life-threatening conditions, while beta-thalassemia can cause severe anemia, bone deformities, and iron overload. Diagnosis involves blood tests, and treatment includes blood transfusions, iron chelation, and sometimes splenectomy. A bone marrow transplant is the only definitive cure. Understanding the severity and treatment of thalassemia is crucial for patient care.

Takeaways

• 🩸 Thalassemia is a group of inherited disorders where the body doesn’t produce enough hemoglobin, leading to anemia.
• ⚠️ Common symptoms include weakness, paleness, shortness of breath, dizziness, and fainting.
• 🧬 Hemoglobin A, composed of 2 alpha and 2 beta subunits, is the main oxygen transporter in adults, while fetal hemoglobin has 2 alpha and 2 gamma chains.
• 🧬 Alpha subunits are encoded by 2 HBA genes on chromosome 16, and beta subunits are encoded by the HBB gene on chromosome 11.
• 🔍 Thalassemia comes in two major forms: alpha-thalassemia and beta-thalassemia, based on which gene is mutated.
• 🧪 In alpha-thalassemia, symptoms vary from mild to severe depending on how many of the 4 gene copies are mutated, with 4 mutated copies leading to fatality in utero.
• 🧬 Beta-thalassemia has two mutation classes: beta-plus (reduced production) and beta-zero (no production), with severity classified into minor, intermedia, and major.
• 🦴 Beta-thalassemia major leads to severe anemia, causing bone marrow hyperactivity, skeletal deformities, and iron overload due to repeated transfusions.
• 💉 Diagnosis includes blood tests showing low hemoglobin, abnormal red blood cells, and high iron levels, confirmed by hemoglobin electrophoresis.
• 🩺 Treatment involves blood transfusions, iron chelation therapy, and in severe cases, bone marrow transplantation as a definitive cure.

Q & A

What is thalassemia?

Thalassemia is a group of inherited disorders in which the body does not produce enough hemoglobin, leading to anemia.

What are the typical symptoms of thalassemia?

Typical symptoms of thalassemia include weakness, paleness, shortness of breath, headaches, dizziness, and fainting.

What is hemoglobin and what is its role in the body?

Hemoglobin is a major component of red blood cells and is responsible for transporting oxygen throughout the body.

What is the difference between adult hemoglobin and fetal hemoglobin?

Adult hemoglobin (hemoglobin A) consists of two alpha and two beta protein subunits, while fetal hemoglobin consists of two alpha and two gamma chains and is predominant during the fetal stage and the first few months of life.

How is the alpha subunit of hemoglobin encoded?

The alpha subunit is encoded by two HBA genes on chromosome 16. Each individual has four copies of alpha-hemoglobin genes, two from each parent.

What are the two major types of thalassemia?

The two major types of thalassemia are alpha-thalassemia and beta-thalassemia, depending on whether the mutation affects the alpha or beta hemoglobin genes.

What are the effects of having one, two, or three mutated copies of the alpha-globin gene?

Patients with one mutated copy are silent carriers, with no symptoms. Patients with two mutated copies have alpha-thalassemia trait, which may result in mild symptoms. Those with three mutated copies may develop hemoglobin H disease, leading to moderate to severe anemia.

What happens when all four alpha-globin genes are mutated?

When all four alpha-globin genes are mutated, the condition is lethal in utero, and babies usually die before or shortly after birth.

What are the two classes of mutations in beta-thalassemia?

In beta-thalassemia, there are beta-plus mutations, which reduce beta-globin production, and beta-zero mutations, which produce no beta-globin at all.

What are the clinical classifications of beta-thalassemia based on severity?

Beta-thalassemia is classified into three groups based on severity: minor (or trait), intermedia, and major. Beta-thalassemia major causes severe anemia.

What are the compensatory responses in beta-thalassemia major?

In beta-thalassemia major, the bone marrow becomes enlarged and hyperactive, leading to changes in bone structure. The gastrointestinal tract absorbs more iron, leading to iron overload, which can affect the heart, liver, and endocrine system.

How is thalassemia diagnosed?

Thalassemia is diagnosed through blood tests, which show low hemoglobin, abnormal red blood cell forms, and high red cell count. Hemoglobin electrophoresis can measure different types of hemoglobin to detect abnormalities.

What are the treatment options for thalassemia?

Thalassemia may be treated with blood transfusions, iron chelation therapy, and in some cases, splenectomy or medications. The only definitive cure is blood or bone marrow transplantation.