Haemoglobinopathies Flashcards
Describe the structure of haemoglobin
Tetramer made of 2 alpha globin like chains and 2 beta globin like chains - one haem group attached to each globin chain
HbA
2 alpha chains and 2 beta chains
HbA2
2 alpha chains and 2 delta chains
HbF
2 alpha chains and 2 gamma chains
Which is the major form of haemoglobin present in adults?
HbA (97%)
also HbA2
Alpha like genes are on which chromosome?
Chromosome 16
Beta like genes are on which chromosome?
Chromosome 11
Which type of globin makes up fetal hemaglobin?
HbF (2 alpa, 2 delta)
-fetal haemoglobin tails off in early life, within first few months
What are haemoglobinopathies?
Hereditary conditions affecting globin chain synthesis
Thalassaemias
Decreased rate of globin chain production
Structural haemoglobin variants of haemoglobinopathies
Normal production rate but abnormal globin chain produced (variant haemoglobin e.g. HbS)
Alpha thalassemia
Alpha chains affected
Beta thalassaemia
Beta chains affected
Inadequate Hb production leads to which type of anaemia
Microcytic hypochromic anaemia
Unbalanced accumulation of globin chains leads to _____
Ineffective erythropoiesis and haemolysis
Endocrine dysfunction that can result from iron overload
- Impaired growth and pubertal development
- Diabetes
- Osteoporosis
Cardiac disease that can result from iron overload
- Cardiomyopathy
- Arrythmias
Liver disease that can result from iron overload
- Cirrhosis
- Hepatocellular cancer
Inadequate Hb production leads to which type of anaemia?
Microcytic hypochromic anaemia
Genetic mutations that cause thalassaemias -discuss deletions and point mutations
Deletions are common (deletion of 1 gene = reduced synthesis, deletion of both genes = absent synthesis)
Point mutations are rare and cause a more profound alpha chain reduction, so these are called non-deletional alpha thalassaemia
Management of HbH disease
Mild: transfusion only needed at times of intercurrent illness
Severe cases: transfusion dependent
Splenectomy may reduce transfusion need in severe cases
Folic acid supplementation
HbA chains in Hydrops Fetalis?
There are no chains in hydrops fetalis!!! (no alpha genes inherited from either parent, HbA can’t be produced!)
Prevention of Barts Hydrops Fetalis?
Antenatal screening to identify parents at high risk (i.e. both possible alpha0 carriers)
- family origin questionnaire and FBC
- further testing if from high-risk area or abnormal RBC indices
Name a procedure that could do the following:
- quantify HbA, HbA2 and HbF
- Identify abnormal haemoglonins e.g. HbH
- ecludes beta thal trait etc
High performance liquid chromatography (HPLC) or haemoglobin electrophoresis
