Hemoglobinopathies Flashcards
What chromosome is alpha globin gene on?
Chromosome 16
What chromosome is the beta globin & Epsilon gene on?
Chromosome 11
Key points: What is alpha globin?
ɑ globin is the primary ɑ-like chain at all stages.
Key points: What is ϒ globin?
ϒ globin is the primary β-like globin in fetal development in HbF
Key points: What is β globin prdominant and what type of hemoglobin?
Not until ~6 months postpartum in HbA
Key points: What is δ globin? What hemoglobin?
δ globin is a minor adult β -like globin chain (HbA2)
Pathophysiology of the thalassemias (4 steps and lead to 3 things)
- Decreased synthesis of either alpha or beta globin
- Imbalance of alpha and beta subunits
- Damage to erythrocyte precursors (red blood cells unhealthy)
- Ineffective erythropoiesis and hemolysis cells are more fragile and break down)
Leads to anemia, extramedullary hematopoiesis, and increased intestinal iron absorption.
How does absence of Beta globin genes impact development?
Absence of functional β globin genes in survivable in fetal life because of ϒ chain production.
Nomenclature: Silent carrier ɑ thalassemia
ɑ - / ɑ ɑ
Nomenclature: ɑ thal trait
ɑɑ/- - or ɑ - / ɑ -
Nomenclature: ɑ Thalassemia Intermedia
ɑ - / - - (HbH Disease)
Nomenclature: ɑ Thalassemia Major
ɑ - / - -
Nomenclature: β Thalassemia Trait
β / β+ or β / β0
Nomenclature: β Thalassemia Intermedia
β+/β+ or β+/β0
Nomenclature: β Thalassemia Major
β+/β0 or β0 / β0 or βE/β0
Primary genetic cause for Alpha Thal
Deletional Mutation
What disease is - - / - - ?
Hemoglobin Bart’s hydrops fetalis
Beta-thalassemia most common genetic mutation. What is the rarer type of mutation?
Common: Point mutations affecting gene expression.
Rare: Deletions affecting the beta globin locus or the entire LCR
What do blood cells look like on thalassemia blood smears? What is this feature a sign of?
Nucleated blood cells, and a sign of bone marrow stress.
What are complications from thalassemia?
- Growth failure
- Hepatosplenomegaly due to extra medullary erythropoiesis
How does iron overload occur?
Results from transfusions and from increased GI absorption of iron
Target organs from iron overload, and what happens to them?
- Liver: Cirrhosis
- Heart: Cardiomyopathy, conduction abnormalities
- Pancreas: Diabetes
- Pituitary: Growth failure, other hormonal disturbances.
Thalassemia treatments
- Transfusion as needed
- Iron chelation to eliminate excess iron
- Bone marrow transplantation
- Luscpartercept (TGFbeta signaling inhibitor)
- Gene therapy
What is sickle cell disease caused by?
Caused by homozygosity for βs or compound heterozygosity of βs with other variants
