haemoglobinopathies

Question 1

thalassemia caused by

Answer 1

• inherited mutations/deletions in alpha or beta globin genes = reduced synthesis in a or B globin chains
  => anaemia

Question 2

pathophysiology of alpha thalassemia

Answer 2

• one/+ alpha globin genes non-functional (in chrome 16)
  = imbalance in alpha & non-alpha (B, y, d) synthesis
  => Red. Hb synthesis
  => microcytic, hypochromic
  => shortened half-life bc not stable

Question 3

the effects of alpha thalassemia
• 1 gene (-a/aa) =
• 2 genes (-a/-a OR --/aa) =
• 3 genes (--/-a) =
• 4 genes (--/--) =

Answer 3

• 1 = a thalassemia minima
• 2 = a thalassemia minor / trait
• 3 = HbH disease (precip. Hb bc Hb unstable = homotetramer)
• 4 = hydrops fetalis

Question 4

Describe the bloood film for these type of a thalassemia:
• 1 gene (-a/aa) =
• 2 genes (-a/-a OR --/aa) =
• 3 genes (--/-a) =
• 4 genes (--/--) =

Answer 4

• 1 = normocytic & -chromic
• 2 = microcytic &hypochromic, Target cells/poikilocytes, some HbH inclusions
• 3 = “ &”, “ &” , HbH inclusions (w/ supravital stain)
• 4 = excess a chains (a4) = haemoglobin bart’s = homotetramer

Question 5

pathophysiology of beta thalassemia

Answer 5

• point mutations in B gene (in chrom 11)
- B+ => patrial block in B-chain synthesis
- B- => absence of B-chain synthesis
=> decrease HbA = promotes inc in y & d globins = inc HbA2 (a2d2) & HbF (a2y2)

Question 6

difference b/w minor thalassemia vs IDA

Answer 6

• Fe studies = abnormal in IDA
• Hb electrophorhesis = abnormal in thalassemia
• Genetic studies

Question 7

pathophysiology of HbS (sickle cell disease)

Answer 7

• Glu sub to Val on 6th AA on B chain

- Deoxegenation => HbS polymerisation = sickling = microvascular occlusion

Question 8

LAb tests to be done to HbS

Answer 8

• solubility test bc HbS insoluble in deox. state

- electrophorphesis/HPLC

Question 9

pathophysiology of HbC

-

Answer 9

• predominantly in west africans

- Lys sub to GLu in B globin => CRYSTAL form

Question 10

what’s HbE population to find

Answer 10

• south east asian pop

Question 11

Adult Hb composed of HbA, HbA2 & HbF:

• %
• what globins the types Hb contain

Answer 11

• HbA = 97% = a2B2
• HbA2 = 2-3% = a2d2
• HbF = <1% = a2y2

Question 12

the % of the types of Hb in B Thalassemia minor, intermedia, major

Answer 12

• minor: HbA = 90%+ ; HbA2 inc to 2.8-7% ; HbF = <1%
• intermedia: HbA = remaining ; HbA2 = 5-10% HbF = 30-75%
• major: majority HbF