Lecture 10 - Hemoglobinopathies Flashcards
The structure of Hb is ___ subunits: two alpha subunits encoded by HBA on chromosome ____ and two beta subunits encoded by HBB on chromosome ___.
4 subunits:
HBA - chromosome16
HBB - chromosome 11
Hemoglobin content varies with _______.
developmental stage
Which type of (general type of) hemoglobinopathy is a structural chain variant?
Qualitative
What happens to babies with sickle cell disease at 6 months of age?
Enough Beta S that it starts to sickle
Which specific type of sickle cell crisis is a transient condition marked by the sudden increased lysis of RBC?
acute anemic crisis
Which specific type of sickle cell crisis is a transient condition marked by the sudden disappearance of erythroblasts from the bone marrow?
acute aplastic crisis
In sickle cell disease, the Beta subunit of HBB has a __________ mutation on chromosome 11.
missense mutation (GAT to GTG)
What are the three classes of structural chain variants in SCD (usually caused by point mutations in one of the globin genes)?
- Variants that cause hemolytic anemia
- Variants with altered oxygen transport
- Variants that cause Thalassemia
What are the three types of hemoglobinopathies?
- Qualitative (structural chain variants)
- Quantitative (disrupt SYNTHESIS of globin chains)
- Regulatory (impair switching of gamma-globin to beta-globin synthesis)
Which of the 3 general types of hemoglobinopathies impairs switching of gamma-globin to beta-globin synthesis?
Regulatory hemoglobinopathy
Which of the 3 general types of hemoglobinopathies disrupts SYNTHESIS of globin chains?
Quantitative hemoglobinopathy
What disorder is caused by reduced synthesis or stability of HBB or HBA?
Thalassemia - sometimes described as the most common human single gene disorder
alpha-Thalassemia is usually caused by _______ mutations.
deletion
beta-Thalassemia is usually caused by _______ mutations.
point
What are the two main types of alpha-Thalassemia?
- Hydrops Fetalis (complete absence of a-chain in utero)
2. HbH disease (excess of Beta chains)
What are the two main types of beta-Thalassemia?
- Thalassemia major (absence of B-chain)
2. Beta+ thalassemia (some B-chain produced)
Carriers of one Beta-thalassemia allele have:
Thalassemia minor
The most physiologically important enzyme is:
methemoglobin reductase
What enzyme maintains the heme iron in a reduced state?
methemoglobin reductase
Cytochrome B5 reductase deficiency is an autosomal recessive disorder that falls into what class of structural chain variants?
Variants with altered oxygen transport
Hemoglobin S is discovered by electrophoresis in a man who was skiing when he complained of severe skeletal pain and fever. Was the solubility of the HbS increased or decreased in the deoxygenated state?
HbS has decreased solubility in deoxygenated state
Most alpha-thalassemias involve deletions of alpha-chain genes because of:
non-homologous cross over
The major abnormal form of hemoglobin that accumulates in a fetus with the severe form of alpha-thalassemia is composed of:
A tetramer of 4 gamma-subunits
Severe B-thalassemia may not become clinically apparent until a child is several months old because:
the gamma- to beta-globin switch is not complete until several months after birth
