Hemoglobinopathies

Question 1

On what chromosome is the alpha globin gene cluster located?

Answer 1

Chromosome 16

Question 2

On what chromosome is the beta globin gene cluster located

Answer 2

Chromosome 11

Question 3

What is the amino acid substitution that causes sickle cell disease?

Answer 3

Glutamic acid (hydrophilic) changed to valine (hydrophobic)

Question 4

What is the amino acid substitution that causes HbC (mild sickle cell disease)?

Answer 4

Glutamic acid changed to lysine

Question 5

How is sickle cell disease diagnosed?

Answer 5

(1) Hb electrophoresis

(2) Molecular detection of HbS and HbC mutant alleles

Question 6

What are four forms of therapy for sickle cell disease?

Answer 6

(1) Preventative - penicillin prophylaxis, vaccination, avoidance of hypoxia
(2) Hydroxyurea - induce HbF production
(3) Chronic RBC transfusion
(4) Analgesics for pain

Question 7

What does α thalassemia result from?

Answer 7

Gene deletion on chromosome 16

Question 8

What does β thalassemia result from?

Answer 8

Point mutation on chromosome 11

Question 9

What are the consequences of varying numbers of α gene deletions?

Answer 9

(1) αα/α- - silent carrier
(2) αα/– or α-/α- - α-thalassemia trait (mild anemia, microcytosis)
(3) α-/– - HbH disease (β4, moderate to severe hemolytic anemia)
(4) –/– - Hydrops fetalis, homozygous α thalassemia (Hb Bart’s: γ4)

Question 10

What is the clinical presentation of β thalassemia?

Answer 10

(1) Microcytic anemia
(2) Target cells on histology from central blebbing due to low Hb and RBC deflation
(3) Crewcut appearance on x-ray and chipmunk facies from extramedullary hematopoiesis

Question 11

How are mutant alleles classified in β thalassemia?

Answer 11

β+ - partially functional β globin

β0 - no functional β globin made