JigSaw #1: Hemoglobinopathies

Question 1

HbA subunit make-up:

Answer 1

α₂β₂

Question 2

HbA₂ subunit make-up:

Answer 2

α₂δ₂

Question 3

HbF subunit make-up:

Answer 3

α₂γ₂

Question 4

HbH subunit make-up:

Answer 4

β₄

Question 5

HbSS subunit make-up:

Answer 5

α₂β^s₂

Question 6

Hb Barts subunit make-up:

Answer 6

γ₄

Question 7

α-thalassemia trait mutations:

Answer 7

• two functional α genes
• one or two α genes mutated (αα/– or α-/α-)
• α-chain production is only at 50%

Question 8

β-thalassemia trait mutations:

Answer 8

• reduced beta chain synthesis leads to reduced HbA synthesis
• three types:
  
  • thallessemia major (no β produced)
  • thallessemia intermedia
  • thallessemia minor

Question 9

Thalassemia major Hb make-up and symptoms:

Answer 9

• nearly all HbF, some HbA₂
• Severe anemia
• Onset few months after birth

Question 10

Thalassemia intermedia Hb make-up and symptoms:

Answer 10

• decreased HbA
• increased HbA₂ and HbF to compensate

Question 11

Thalassemia minor Hb make-up and symptoms:

Answer 11

• slightly reduced HbA
• slightly increased HbA₂
• mostly unaffected (no symptoms)

Question 12

HbH make-up and symptoms:

Answer 12

• one functional α gene
• α-chain production is only at 25%
• increased β₄ tetramers
• moderate to severe anemia

Question 13

Hb Barts make-up and symptoms:

Answer 13

• zero functional α genes
• Hb is γ₄ tetramer
• severe intrauterine hypoxia
• hydrops fetalis
  
  • massive generalized fluid accumulation at birth
• fetal death

Question 14

How does HbS protect against malaria?

Answer 14

• parasite enters RBC and creates metabolic waste
• cell becomes more acidic, favors T-state of Hb, HbS begins to sickle.
• cell becomes weaker and inhospitable to parasite

Question 15

Treatments for HbSS:

Answer 15

• hydroxyurea
• penicillin prophylactic
• blood transfusion
• bone marrow transplant
• routine immunizations
• hydration
• narcotics

Question 16

Why is hydroxyurea usually used for the treatment of sickle cell and beta-thalassemias?

Answer 16

• increases HbF which prevents HbS polymerization and vaso-occlusion.
• decreases leukocytes which decreases neutrophilic adhesion to veins/arteries
• EXACT MECHANISM UNKNOWN

Question 17

Should hydroxyurea be utilized in neonates/infants?

Answer 17

• no
• neonates and infants have high levels of HbF already, and hydroxyurea most likely would not do much benefit.

Question 18

HbC subunit make-up:

Answer 18

• mutation βGlu6 → Lys
  
  • similar to HbS (βGlu6 → Val)
• has allostery similar to HbA

Question 19

HbS mutation:

Answer 19

βGlu6 → Val

• adds an extra hydrophobic residue
• sickle in DEOXY (t-state)
  
  • T-state opens up hydrophobic pockets

Question 20

Compared to a healthy individual, the percent of HbA1c is _____ in a person with sickle cell anemia.

Answer 20

decreased

due to reduced lifetime of the red blood cells in SCA