Hemoglobinopathies

Question 1

• Alpha like gene composition?
• Beta like gene composition?
• Embryonic yolk sac Hb’s? Production?
• Early embryogenesis Hb’s? Production?
• Birth/adulthood Hb’s? Production?
• LCR?
• NBS options:
• Normal, Sickle Cell, SC, SB0, SB+, B major, alpha 1 or 2 deletion, alpha major?

Answer 1

• Zeta, a1, a2 (2 copies on 16)
• E, Y, d, B (1 copy on 11)
• Gower 1 = Z2E2 Gower 2 = a2E2 Portland = Z2Y2
• HBF = a2y2; liver/spleen
• HBA = a2B2 HBA2 = a2d2 Bone marrow
• Locus control region = affects expression of different hb genes
• FA; FS; FSC; FS; FSA/FS; F; FABarts; HbH+Barts

Question 2

• Structural/Qualitative Mutations:
• 3 types; inheritance pattern
• What is HbBArts? What is HbH?
• HbS diagnosis?
• Altered HbO2 binding examples? Effect? Can’t distinguish between?

Answer 2

1. ) Sickle Cell (HbSS); B globin Glu-Val; AR
2. ) HbC disease; B globin Glu-Lys; AR
3. ) HbSC = milder anemia
   - Y4; B4
   - MST2 enzyme; HbS = B 1.35; HbA = B 1.15 and 0.20; B of HbA and B of HbC
   - Hb Kempsey = Increased O2 Affinity = Polycythmia
   - Hb Kansas = Decreased O2 affinity = Cyanosis

Question 3

• Thalessemia RBC’s appearance? (3)
• a thallesemmia def?
• Common genotypes and phenotypes? (6)

Answer 3

• hemolysis, microcyatosis, hypochromia
• Diminished a subunit
  1. ) aa/aa = normal
  2. ) aa/a- = silent carrier
  3. ) aa/– = type 1 mild anemia (SE Asia)
  4. ) a-/a- = type 2 mild anemia (Africa)
  5. ) a-/– = Severe anemia (HbH)
  6. ) –/– = Hydrop fetalis (y4)

Question 4

B thallesemia:

• Phenotype?
• 2 types? Def? Treatment?
• Simple?
• Complex?

Answer 4

• Dense frontal bones
• 1.) Major: Either B0 (Cooleys) or B+; needs blood transfusions
  2.) Minor: Either B0 heterozygote or B+ heterozygote; clinically normal but a carrier
  B+ = Decreased expression
  B0 = no B produced
• Mutation impairs production but other globin genes are unaffected
• Large deletions affecting other genes in cluster or LCR

Question 5

Hereditary persistant Fetal Hb: Def?

• Occurs why? (3)
• Treatment:
• B major?
• B trait?
• a 3 gene?

Answer 5

• No d or B production leading to increased y
• Enhancers near Y, large deletions, mutated promoter region
• Frequent transfusions, treat iron overload (chelators), bone marrow transplant
• no treatment needed
• ## HbH = occasional transfusions, splenectomy