thalassemia syndromes

Question 1

Describe 3 mechanisms for hemoglobinopathies.

Answer 1

1. abnormal hemoglobin
2. reduced rate of production of Hb chains
3. persistence of fetal hemoglobin
   Most are Genetic

Question 2

Describe normal hemoglobin structure.

Answer 2

HbA: a2b2
HbA2: a2d2
HbF: a2y2be

Question 3

What are the genotypes of beta-thalassaemia major, intermedia, and minor?

Answer 3

minor: B+/B or B0/B, one normal allele
intermedia: Very rarely can have one but usually have two mutant alleles, often with other modifying factors
Major: Two mutant alleles, e.g., B+/B+, B+/B0, B0/B0

Question 4

What are the features of beta thalassemia minor?

Answer 4

microcytic, increased number of cells, target cells, Hb a little low, no clinical problems

Question 5

What are the features of beta thalassemia major?

Answer 5

Homozygous, more severe form of disease.

• lack of beta glob in chain production
• anemia from 3 months onward, born normally (have Hb F)
• bloated abdomen
• crew cut appearance of skull

Question 6

What are the genotypes of alpha thalassemia?

Answer 6

• 1 gene deletion: mild microcytosis, occasional Hb H bodies inside cells. Little clinically
• 2 gene deletion: cis or trans-mild anemia, lightly increase RBC, cis worst because can pass on
• 3 genes deletion: HbH disease. Severe anemia
• 4 gene deletion: still born, Hydrops Fetalis

Question 7

What is the pathogenesis of thalassemia?

Answer 7

unbalanced chain synthesis
Precipitate on nuclear membrane –>apoptosis (ineffective erythropoiesis)
precipitate on cell membrane → destruction by macrophage in spleen/liver (hemolysis)
-Dyserythropoiesis and reduced red cell survival < 10 minutes–>hypersplenism
-overactive marrow–>bone changes, facial changes, increased fractures, increased plasma volume, effective protein malnutrition/stunting, increased GIT iron absorption

Question 8

What is the treatment for thalassemia major?

Answer 8

transfusion and chelation therapy.

• vaccinations
• splenectomy when needed
• vaccination against encapsulated baceria: meningococcal and pneumococcal

Question 9

Describe Hb E.

Answer 9

• common in South East Asia
• beta globin mutation glu–>lys
• ->chain imbalance, more alpha chains
• heterozygotes: like thalassemia minor
• homozygotes: severe microcytosis, little anemia