264b Thalassemias

Question 1

thalassemias

Answer 1

decreased synthesis of Hb due to gene defects in a or b globin

Question 2

B-thalessemia - mutation type? who gets it?

Answer 2

variety of point mutations in splice sites and promoter sequences –> decreased B-globin synthesis.

Prevalent in Mediterranean populations.

Question 3

B-thalessemia minor (heterozygote) - what happens? symptoms? dx?

Answer 3

B-chain is underproduced.
Usually asymptomatic.
Diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis.

Question 4

B-thalassemia major (homozygote) - what happens? treatment? xray? Hb type?

Answer 4

B-chain is absent –> severe anemia requiring blood transfusion (2° hemochromatosis).

Marrow expansion (“crew cut” on skull x-ray)

skeletal deformities. “Chipmunk” facies.

Extramedullary hematopoiesis (leads to
hepatosplenomegaly). increased risk of parvovirus B19-induced aplastic crisis.

Major –> increased HbF (a2g2). HbF is protective in the infant and disease only becomes symptomatic after 6 months.

Question 5

HbS/B-thalassemia heterozygote:

Answer 5

mild to moderate sickle cell disease depending on amount of #-globin production.

Question 6

a-thalassemia - defect?

Answer 6

Defect: a-globin gene deletions decreased A-globin synthesis.

cis deletion prevalent in Asian populations; trans
deletion prevalent in African populations.

Question 7

a-thalassemia - all 4 alleles deleted?

Answer 7

4 allele deletion: No a-globin. Excess B-globin forms B4 (Hb Barts).

Incompatible with life (causes hydrops fetalis).

Question 8

a-thalassemia - 3 allele deletion?

Answer 8

HbH disease (4xB). Very little a-globin.

Excess B-globin forms B4 (HbH).

Question 9

a-thalassemia - 1-2 allele deletion?

Answer 9

1–2 allele deletion: no clinically significant anemia.