thalassemia syndromes Flashcards
Describe 3 mechanisms for hemoglobinopathies.
- abnormal hemoglobin
- reduced rate of production of Hb chains
- persistence of fetal hemoglobin
Most are Genetic
Describe normal hemoglobin structure.
HbA: a2b2
HbA2: a2d2
HbF: a2y2be
What are the genotypes of beta-thalassaemia major, intermedia, and minor?
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
What are the features of beta thalassemia minor?
microcytic, increased number of cells, target cells, Hb a little low, no clinical problems
What are the features of beta thalassemia major?
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
What are the genotypes of alpha thalassemia?
- 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
What is the pathogenesis of thalassemia?
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
What is the treatment for thalassemia major?
transfusion and chelation therapy.
- vaccinations
- splenectomy when needed
- vaccination against encapsulated baceria: meningococcal and pneumococcal
Describe Hb E.
- common in South East Asia
- beta globin mutation glu–>lys
- ->chain imbalance, more alpha chains
- heterozygotes: like thalassemia minor
- homozygotes: severe microcytosis, little anemia