Haemaglobinopathies Flashcards
Name the three types of haemoglobin
HbA - two alpha two beta
HbA2 - two alpha two delta
HbF - two alpha two gamma
Where are the alpha globin genes found and how many are there?
Chromosome 16 - two per chromosome and four per cell
Where are the beta globulin genes found and how many are there?
Chromosome 11 - one per chromosome and two per cell
When does globulin expression reach adult levels?
6-12 months
Define haemoglobinopathy
Hereditary conditions that affect globulin chain synthesis
What mode of inheritance do haemoglobulinopathies follow?
Autosomal recessive
What disease is linked to haemoglobinopathies?
Malaria
Name the two groups of haemoglobinopathies
Thalassaemias
Structural Hb variants
What is thalassaemia?
Reduced globulin chain synthesis and Hb production
What do thalassaemias cause?
Microcytic hypochromic anaemia
Name the three variations of alpha thalassaemia
Trait
HbH disease
Hb Barts hydrops fetalis
Describe alpha thalassaemia trait
One or two missing genes, asymptomatic carrier with microcytic hypochromic red cells but normal ferritin
How does HbH disease arise?
Loss of three alpha genes
Moderate to severe anaemia
Excess beta chains form HbH
Where is HbH disease most common?
SE asia due to alpha nought endemic
How will HbH present?
Jaundice, severe anaemia, splenomegaly
When may patients with HbH require a transfusion?
During acute illness
What genetic issues leads to Hb Barts hydrops fetalis?
No functional genes - incompatible with life
Excess beta chains form HbH
Excess gamma chains form Hb Barts
How will Hb Barts hydros fetalis present?
Profound anaemia, cardiac failure, hepatosplenomegaly, growth retardation, skeletal abnormalities
What types of Hb are beta chains present?
HbA
Name three beta thalamassamias
Trait
Intermedia
Major
Describe beta thalassaemia trait
Asymptomatic, no/mild anaemia due to one abnormal copy of the gene
What is the genetic cause of beta thalassaemia intermedia?
Two defective genes
One defective gene and one deletion
How will beta thalassaemia intermedia present?
Moderate severity - microcytic hypochromic anaemia need regular monitoring and may need transfusion
What is the genetic cause of beta thalassaemia major?
Two deletion genes
How does beta thalassaemia major present?
Severe microcytic hypochromic anaemia Hepatosplenomegaly Skeletal deformity Failure to thrive Palor
At what age does beta thalassaemia major commonly present?
6-24 months
What happens to the Hb in beta thalassaemia major?
No HbA, mainly HbF
Why do you see skeletal deformity in beta thalassaemia major?
Extramedullary haematopoiesis
What skeletal changes are classical of beta thalassaemia major?
Frontal bossing
Hair on end skull x-ray
How is beta thalassaemia major managed?
Regular transfusion
What is the major risk of regular transfusion?
Iron overload
What are the consequences of iron overload?
Endocrine dysfunction - diabetes, osteoporosis
Cardiac Disease - arrhythmias, cardiomyopathy
Liver Disease - cirrhosis, cancer
Sepsis
What drug can be given with transfusion to prevent overload?
Iron chelating drugs
How do sickling disorders arise?
Point mutations in beta globulin gene cause glutamine to change to valine and produce HbS
What happens to HbS?
It can polymerise if exposed to low oxygen levels for a prolonged time with distorts the red cell and damages the membrane
What is sickle cell trait?
Asymptomatic carrier state, generally HbS levels are too low to have an effect
What does sickle cell anaemia cause?
Episodes of tissue infarction due to microvascular occlusion
How does sickle cell crisis present?
Severe pain due to ischaemia and inflammation
What is the effect of sickle cell on the spleen?
Chronic haemolysis due to distorted red cells, shorter life span - sequestered in the spleen causing splenic infarcts and hyposplenism
What can precipitate a sickle cell crisis?
Hypoxia, dehydration, infection, stress, fatigue
How is sickle cell crisis treated?
Opiate, hydrate, oxygen, red cell exchange transfusion if severe crisis
How is sickle cell anaemia managed long term?
Hyposplenism - prophylactic penicillin and vaccination
Folic Acid Supplement
Hydroxycarbamide - induces HbF production
Regular transfusion therapy
What is the most common technique for diagnosing thalassaemia?
High power liquid chromatography
