Alpha vs. Beta Thalassemia: Key Differences Explained

Simple comparison chart for alpha vs. beta thalassemia:

Feature	Alpha Thalassemia	Beta Thalassemia
Cause	Missing alpha genes	Faulty beta genes
Types	Mild to severe (worst = fatal at birth)	Mild to severe (worst needs lifelong transfusions)
Hemoglobin F	❌ Not much change	✅ Increases a lot in severe cases
Main Problem	Less hemoglobin, but some still works	Body makes no normal hemoglobin
Common Where?	Asia, Africa, Mediterranean	Mediterranean, Middle East, South Asia
Treatment	Usually mild, but severe cases need transfusions	Severe cases need regular transfusions + iron removal

Thalassemia is a blood disorder where the body doesn’t make enough hemoglobin, leading to anemia.

There are two main types:

1. Alpha Thalassemia – Problem with alpha hemoglobin.
   • Mild (no or few symptoms).
   • Moderate (some anemia).
   • Severe (can be life-threatening).
2. Beta Thalassemia – Problem with beta hemoglobin.
   • Mild (mild anemia).
   • Moderate (needs occasional treatment).
   • Severe (needs regular blood transfusions).

It’s a genetic condition, meaning it’s inherited from parents.

Thalassemia is a genetic blood disorder where the body makes less hemoglobin than normal. Hemoglobin carries oxygen in red blood cells, so a deficiency leads to anemia. There are two main types:

1. Alpha Thalassemia – Caused by missing or defective alpha-globin genes.
   • Silent Carrier: No symptoms, just one gene missing.
   • Alpha Thalassemia Trait (Minor): Mild anemia, two genes missing.
   • Hemoglobin H Disease: Moderate to severe anemia, three genes missing.
   • Hydrops Fetalis: Severe, often fatal before birth, all four genes missing.
2. Beta Thalassemia – Caused by mutations in the beta-globin gene.
   • Beta Thalassemia Minor (Trait): Mild anemia, one faulty gene.
   • Beta Thalassemia Intermedia: Moderate anemia, two faulty genes but still some hemoglobin production.
   • Beta Thalassemia Major (Cooley’s Anemia): Severe anemia requiring lifelong blood transfusions, both genes missing or severely mutated.

Beta thalassemia major (Cooley’s anemia) has increased hemoglobin F (HbF).

Why?

• Beta thalassemia is caused by mutations in the beta-globin genes, leading to little or no production of beta chains of hemoglobin.
• Normal adult hemoglobin (HbA, made of α2β2) cannot form properly due to the lack of beta chains.
• To compensate, the body increases production of fetal hemoglobin (HbF), which is made of α2γ2 (alpha and gamma chains).
• HbF is usually replaced by adult hemoglobin after birth, but in beta thalassemia, it remains high because the body has no functioning beta chains for normal hemoglobin production.

Here’s a simple comparison chart for alpha and beta thalassemia:

Feature	Alpha Thalassemia	Beta Thalassemia
Cause	Deletion of alpha-globin genes	Mutation in beta-globin genes
Types	– Silent Carrier (1 gene missing) – Alpha Thalassemia Trait (2 genes missing) – Hemoglobin H Disease (3 genes missing) – Hydrops Fetalis (4 genes missing, fatal)	– Beta Thalassemia Minor (1 gene affected, mild anemia) – Beta Thalassemia Intermedia (moderate anemia) – Beta Thalassemia Major (Cooley’s anemia, severe anemia)
Hemoglobin F (HbF) Increase?	❌ No significant increase (except in severe cases)	✅ Yes, especially in Beta Thalassemia Major
Hemoglobin Electrophoresis Findings	Normal or ↓ HbA, HbH present in Hemoglobin H disease	↑ HbF, ↓ or absent HbA, possible ↑ HbA2
Microcytic Anemia?	✅ Yes	✅ Yes
Clinical Symptoms	Mild to severe anemia, hepatosplenomegaly in severe cases	Severe anemia, hepatosplenomegaly, skeletal deformities (due to bone marrow expansion)
Treatment	Depends on severity; transfusions may be needed for severe cases	Blood transfusions, iron chelation, bone marrow transplant (for severe cases)
Geographic Prevalence	Common in Southeast Asia, Africa, and Mediterranean populations	Common in Mediterranean, Middle East, and South Asian populations

Question:
A 2-year-old boy of Mediterranean descent is brought to the clinic for evaluation of pallor and fatigue. His parents report that he has been lethargic and not eating well. Physical examination reveals hepatosplenomegaly. Laboratory studies show microcytic anemia, low hemoglobin, and increased hemoglobin F on electrophoresis. Which of the following is the most likely diagnosis?

A) Iron deficiency anemia
B) Alpha thalassemia minor
C) Beta thalassemia major
D) Lead poisoning
E) Sickle cell disease

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Answer: C) Beta thalassemia major

Explanation:

• The child has microcytic anemia (small red blood cells) and increased hemoglobin F, which is a key finding in beta thalassemia major.
• Mediterranean descent is a risk factor.
• Hepatosplenomegaly happens due to excessive red blood cell destruction.
• Iron deficiency anemia (A) would not show increased hemoglobin F.
• Alpha thalassemia minor (B) usually has mild anemia without major symptoms.
• Lead poisoning (D) can cause anemia but would also show neurological symptoms.
• Sickle cell disease (E) presents with pain crises and sickle-shaped cells, not microcytosis.