Alpha-thalassemia

Alpha-thalassemia

Alpha-thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. Alpha-thalassemia is caused by mutations in the HBA1 and HBA2 genes, which are responsible for the production of alpha-globin, a component of hemoglobin.

Pathophysiology

In alpha-thalassemia, the production of alpha-globin chains is reduced or absent. This leads to an imbalance in the ratio of alpha to beta-globin chains, resulting in the formation of abnormal hemoglobin molecules. The severity of the disease depends on the number of affected alpha-globin genes.

Genetic Basis

The HBA1 and HBA2 genes are located on chromosome 16. Each person has four alpha-globin genes, two from each parent. The severity of alpha-thalassemia is determined by the number of gene deletions:

• Silent Carrier: One gene deletion, usually asymptomatic.
• Alpha-thalassemia Trait: Two gene deletions, mild anemia.
• Hemoglobin H Disease: Three gene deletions, moderate to severe anemia.
• Hydrops Fetalis: Four gene deletions, usually fatal before or shortly after birth.

Clinical Features

The clinical presentation of alpha-thalassemia varies depending on the number of affected genes.

Silent Carrier

Individuals with one deleted alpha-globin gene are typically asymptomatic and have normal hematological parameters.

Alpha-thalassemia Trait

Individuals with two deleted alpha-globin genes may have mild anemia and microcytosis. They are often asymptomatic and may be identified during routine blood tests.

Hemoglobin H Disease

This condition results from the deletion of three alpha-globin genes. It is characterized by:

• Moderate to severe anemia
• Splenomegaly
• Jaundice
• Bone deformities

Hydrops Fetalis

This is the most severe form of alpha-thalassemia, resulting from the deletion of all four alpha-globin genes. It leads to:

• Severe anemia
• Heart failure
• Edema
• Usually results in stillbirth or death shortly after birth

Diagnosis

Diagnosis of alpha-thalassemia involves:

• Complete blood count (CBC) showing microcytic anemia
• Hemoglobin electrophoresis
• Genetic testing to identify deletions in the HBA1 and HBA2 genes

Management

Management of alpha-thalassemia depends on the severity of the disease:

• Silent Carrier and Alpha-thalassemia Trait: Usually require no treatment.
• Hemoglobin H Disease: May require regular blood transfusions, folic acid supplementation, and splenectomy in severe cases.
• Hydrops Fetalis: Prenatal diagnosis and counseling are important. Intrauterine transfusions may be considered.

Prognosis

The prognosis of alpha-thalassemia varies:

• Silent carriers and individuals with alpha-thalassemia trait generally have a normal life expectancy.
• Hemoglobin H disease can lead to complications but is manageable with treatment.
• Hydrops fetalis is usually fatal without intervention.

Prevention

Genetic counseling is recommended for at-risk couples. Prenatal testing can identify affected fetuses, allowing for informed decision-making.

See Also

• Thalassemia
• Hemoglobinopathy
• Anemia