49 Thalassemia Flashcards
(96 cards)
Thalassemia was initially called
Cooley anemia
The thalassemia results from mutations in the globin genes and are part of the spectrum of diseases known collectively as the hemoglobinopathies.
What are the 2 types
- Qualitative disorders: structural hemoglobin (Hb) variants are produced, such as sickle cell anemia, unstable Hbs, and methemoglobins
- Quantitative disorders : normal globin production is diminished or absent
TRUE OR FALSE
The majority of qualitative mutations (structural hemoglobin (Hb) variants, sickle cell anemia, unstable Hbs, and methemoglobins), cause no significant change in Hb properties or clinical problems
TRUE
The majority of qualitative mutations (structural hemoglobin (Hb) variants, sickle cell anemia, unstable Hbs, and methemoglobins), cause no significant change in Hb properties or clinical problems
However, some mutations lead to a Hb variant that is also produced in reduced amounts, for example, HbE (β26 Glu→Lys), the most common β-thalassemia mutation in Southeast Asia
The most common β-thalassemia mutation in Southeast Asia
HbE (β26 Glu→Lys)
2 major forms of thalassemia
α-thalassemia and β-thalassemia
Rare: γ-thalassemia, δ-thalassemia, and εγδβ-thalassemia
The clinical severity of thalassemia depends largely on the inherited __________.
Genotype
Result from a large deletion in chromosome 11
Involve the β-LCR
εγδβ-thalassemia
Difference between HPHF heterozygotes vs heterozygotes for δβ-thalassemia
HPFH heterozygotes: normal red cell indices, normal HbA2 levels, and HbF levels of 10% to 35%
δβ-thalassemia heterozygotes: hypochromic microcytic erythrocytes, HbA2 levels are also normal, but the HbF increases are less (5–15%)
The level of compensatory HbF increase is higher in HPFH compared to δβ-thalassemia
TRUE OR FALSE
A deficiency of α-globin chain production affects Hb synthesis in both fetal and adult life
TRUE
As α-globin is an essential part of normal fetal (α2γ2) and normal adult (α2β2) Hb, a deficiency of α-globin chain production affects Hb synthesis in both fetal and adult life.
α-globin genes are found in chromosome
Chromosome 16
α-globin and the rest of fetal hemoglbin
β-globin gene cluster on the short arm of chromosome _____.
Chromosome 11
α- thalassemia is most commonly caused by __________
Deletions
α2β2
HbA
α2δ2
HbA2
less than 3.5%
less than 2% of fetal Hb or HbF (heterodimer of α-globin and γ-globin, α2γ2
Red cells are initially made in the _______ of the developing embryo and prior to week _____ of intrauterine life
yolk sac
8 weeks
3 embryonic Hbs
Gower 1 (ξ2ε2)
Gower 2 (α2ε2)
Portland (ξ2 γ2)
Adult counterparts:
ξ-globin
ε-globin
ξ-globin : α-globin and β-globin
ε-globin : γ-globin, and δ-globin chains
α2γ2
HbF
As the embryo develops into the fetus, erythropoiesis moves to the liver and spleen; there is an orderly switch from ξ-globin to α-globin chain and from ε-globin to γ-globin chain production
HbF
At birth, the ratio of molecules containing Gγ-globin chains to those containing Aγ-globin chains is approximately______
3:1
The ratio of Gγ-globin chains to Aγ-globin chains in the trace amounts of HbF in normal adults’ switches from a ratio of 3:1 to approximately 1:3.
Toward the ____________, the marrow becomes active in erythropoiesis
End of the second trimester
Hb switching, occurs between ________of age
6 and 12 months
Postnatally, γ-globin chain production (HbF) is replaced by β-globin chain production (HbA), commonly referred to as Hb switching
The physiologic nadir of infancy—at a Hb level of 90–100 g/L—usually occurs by _______
8 weeks
β-Globin synthesis commences early during fetal life, at approximately_______ of gestation
8–10 weeks
The production of γ-globin chain persists at very low levels in adults, and the small amount of HbF is confined to an erythrocyte population called _______
F cells