Thalassaemia Flashcards
What are the different forms of haemoglobin?
HbA (two alpha chains, two beta)
HbA2 (two alpha and two delta0
HbF (two alpha and two gama)
In adults what type is the majority of haemoglobin
HbA (97 percent)
HbA2 (2.5 percent)
HbF (0.5 percent)
What chromosome are the genes for alpha like globins
16
two alpha chain genes per chromosome - 4 per cell
What chromosome is the beta like genes on
11
one beta gene per chromosome - 2 per cell
how does the expression of globin chains change during embryotic life and child hood
In the fetus and early life the globin types are usually alpha and gamma
gamma decreases and is taken over by beta so that adult haemoglobin is made up mostly of alpha and beta globin
What are haemoglobinopathies and what are the two main groups
Hereditaty conditions affecting globin chain synthesis
Two main types - thalassaemias and structural haemoglobin varients
What are thalassaemias
A hereditary disorder of globin chain synthesis resulting in decreases rate of globin chain production and subsequently impaired haemoglobin production.
What are structural haemoglobinopathies
Normal production of structurally abnormal haemoglobin eg HbS
What type of anaemia occurs in thalassaemias and why
Microcytic hypochromic anaemia due to inadequate Hb production
What are the two variants of thalassaemias
Alpha or beta - depending on whether the alpha or beta globin chain is affected
Why is thalassaemia more common ins certain parts of the world
selective pressure in malaria endemic areas has allowed these mutation to thrive as they provide some protection from malaria
Therefore more common in Africa and south asia
How are reduced and absent alpha globin chain synthesis denoted in alpha thalassaemia
reduced= alpha+
absent=alpha0
What is the pathophysiological mechanism behind alpha thalassemia
A deletion of one (alpha+) or both (alpha0) genes from chromosome 16
What is non-deletional alpha thalassaemia
A point mutations causes more profound alpha chain reduction - rare
What are the classification of alpha thalassaemia
Unaffected have 4 normal genes (aa/aa)
Silent alpha thal trait = one gene affected (-a/aa)
Alpha thal train= two affected genes (–/aa) or (-a,-a)
HbH disease= usually 3 genes affected (–/-a)
Hb Barts hydrops fetalis= no functional genes (–/–)
What is the clinical features of alpha thalassaemia trait
This is due to (–/aa) or (-a/-a)
Asymptomatic, no treatment required
Microcytic, hypochromic red cells with mild anaemia
Different from iron deficiency because the ferritin is normal and there is a raised red cell count)
What is HbH disease?
Severe form of alpha thalassaemia
Only one working alpha gene per cell
Alpha chain production is less than 30 percent of normal
Anaemia with low MCV and MCH
Why is it called HbH disease
due to globin chain imbalance, excess beta chains form tetramers called HbH which cannot carry oxygen
HbH is present in variable amounts
What are the clinical features of HbH disease?
Wide variation from almost asymptomatic to transfusion dependent
Slenomegaly due to extramedullary haematopoiesis
Jaundice due to haemolyisis, ineffective erythropoiesis
Growth retardation, gallstones and iron overload
what is the inheritance of HbH disease
autosomal recessive -like inheritance
where is HbH disease most common
SE Asia, middle east, mediterranean
how is HbH disease managed
transfusion at times of intercurrent illness
if sever may be transfusion dependent
Splenectomy may reduce transfusion need in severe cases
folic acid supplementation
Why is there a need to supplement folate in hbh disease
there is increases RBC turnover so increased demand
What is the most severe form of alpha thalassaemia
Hb Barts Hydrops Fetalis Syndrome
no alpha genes inherited from parents –>minimal or no alpha chain production so HbA cannot be produced
