Alpha Thalassemia *

Osmosis

What is alpha-thalassemia?

Alpha-thalassemia is a genetic disorder characterized by deficient production of alpha-globin chains of hemoglobin

What are the four major types of globin chains in hemoglobin?

Alpha (α)

What is the composition of fetal hemoglobin (HbF)?

Two α-globin chains and two γ-globin chains.

What is the composition of adult hemoglobin (HbA)?

Two α-globin chains and two β-globin chains.

What is the composition of hemoglobin A2 (HbA2)?

Two α-globin chains and two δ-globin chains; makes up a small fraction of adult hemoglobin.

How is alpha-globin chain synthesis genetically controlled?

By four alpha-globin genes

What is the most common cause of alpha-thalassemia?

Deletion of one or more alpha-globin genes.

What is the inheritance pattern of alpha-thalassemia?

Autosomal recessive – disease occurs if both parents pass defective genes.

What is a silent carrier in alpha-thalassemia?

A person with one defective alpha-globin gene; asymptomatic but can pass the gene to children.

What is alpha-thalassemia minor?

Condition caused by two defective alpha genes; results in mild anemia.

What is the difference between cis and trans deletions in alpha-thalassemia minor?

Cis-deletion: both mutated genes on the same chromosome (common in Asians). Trans-deletion: mutated genes on different chromosomes (common in Africans).

What is hemoglobin H (HbH) disease?

Moderate alpha-thalassemia caused by three defective alpha genes

How does HbH cause hypoxia?

1) Damages red blood cell membranes causing intramedullary or extravascular hemolysis. 2) Has very high oxygen affinity and does not release oxygen to tissues.

What complications arise due to hypoxia in HbH disease?

Bone marrow

What is Hb Bart’s hydrops fetalis?

Severe alpha-thalassemia caused by deletion of all four alpha genes; γ-globin chains form tetramers (γ4) called Hb Bart’s

Why is Hb Bart’s hydrops fetalis incompatible with life?

Hb Bart’s has extremely high oxygen affinity (~100× normal)

What are common initial symptoms of minor and moderate alpha-thalassemia?

Anemia symptoms: pallor

What laboratory findings are seen in alpha-thalassemia?

Low hemoglobin

How is hemoglobin electrophoresis used in alpha-thalassemia?

Identifies types of hemoglobin present; HbH appears as an extra band ahead of HbA.

How is the diagnosis of alpha-thalassemia confirmed?

Genetic testing for alpha-globin gene deletions or mutations; can also be done prenatally via chorionic villus sampling or amniocentesis.

How are alpha-thalassemia subtypes classified based on transfusion requirements?

1) Transfusion-dependent thalassemias: require regular transfusions (severe HbH

What treatment is used for severe alpha-thalassemia?

Blood transfusions; iron chelation may be needed to prevent transfusion-related iron overload.

What prenatal treatment options exist for Hb Bart’s hydrops fetalis?

Intrauterine transfusions and later bone marrow transplantation.

Recap: What are the clinical consequences of 1

2

What is the key takeaway about alpha-thalassemia?

It is an inherited disorder of alpha-globin deficiency