6: Haemoglobinopathies Flashcards
Which globin chains are found in
a) adult Hb
b) foetal Hb?
a) 2 alpha, 2 beta
b) 2 alpha, 2 gamma
Which type of haemoglobin is most common in adults?
HbA
Which chromosomes code for
a) alpha chains
b) beta chains?
a) Alpha chains - chromosome 16
b) Beta chains - chromosome 11
Which genetic process causes HbF production to switch to HbA production?
Gene silencing
On chromosomes 16 and 11
What is a haemoglobinopathy?
Inherited conditions affecting globin chain synthesis
What is the common mode of inheritance of haemoglobinopathies?
Autosomal recessive
What is thalassaemia?
Decreased rate of globin chain synthesis
What types of thalassaemia affect the rate of production of
a) alpha chains
b) beta chains?
a) Alpha thalassaemia
b) Beta thalassaemia
___ ___ are toxic in high concentrations.
Globin chains
Accumulation of globin chains leads to ineffective erythropoiesis - what does this mean?
RBC precursors die before they can develop properly due to toxicity
How many alpha chain genes exist on chromosome 16?
4
How many beta chain genes exist on chromosome 11?
2
The more alpha genes which are deleted, the (faster / slower) the rate of alpha globin production.
slower
How many alpha genes are lost from chromosome 16 to cause HbH disease?
3
What is meant by HbH in HbH disease?
Dysfunctional type of haemoglobin made up of 4 beta chains
because alpha chains aren’t produced fast enough
What is the most severe form of alpha thalassaemia?
What is the cause?
Barts hydrops foetalis
Deletion of all 4 alpha genes from chromosome 16
Is Barts hydrops foetalis compatible with life?
No
What disease is caused by point mutations in the beta globulin genes of chromosome 9?
Beta thalassaemia
Which types of haemoglobin are affected by
a) alpha thalassaemia
b) beta thalassaemia?
a) All of them (HbA, HbF etc.) because they all contain alpha chains
b) HbA only
What are the three classifications of beta thalassaemia?
Beta thalassaemia trait
Beta thalassaemia intermedia
Beta thalassaemia major
Increasing in severity as you go
When does beta thalassaemia major present?
Around 6 months, when HbF should be changing to HbA
How is beta thalassaemia major treated?
Blood transfusions to maintain haemoglobin concentration
What is a side effect of regular blood transfusions in beta thalassaemia major?
Iron overload
How is iron overload secondary to blood transfusions treated?
Iron chelating drugs
chelate: to form a solution and excrete via urine
What genetic mutation causes sickle cell anaemia?
Substitution in codon 6 of beta gene in chromosome 9
Glutamine to valine
What type of haemoglobin is produced in sickle cell disease?
HbS
crap structure, crap shape, ‘polymerised’, damages the cell membrane
What happens if you have a heterozygous sickle cell mutation?
Sickle cell trait
Most likely asymptomatic but you can pass the gene on
What is the mode of inheritance of sickle cell anaemia?
Autosomal recessive
Sickle cells have a shortened ___ ___.
What process does this cause?
shortened life span
haemolysis
What is an acute problem seen in sickle cell anaemia?
Infarctions caused by sickle cells occluding circulation - sickle cell crisis
Can affect spleen causing hyposplenism
What are some triggers of sickle cell crisis?
Hypoxia
Dehydration
Cold
Infection
How is a sickle crisis managed?
Analgesia
Hydration
Oxygen
Blood transfusion if severe
What is a complication of hyposplenism secondary to sickle cell anaemia?
Infection
What are the two main causes of microcytic anaemia?
Iron deficiency
Thalassaemia
less common: congenital sideroblastic anaemia, lead poisoning
What would be seen on a FBC of a patient with thalassaemia?
Microcytic hypochromic anaemia
Sickle cell anaemia and thalassaemia are ___ for in pregnant women and their partners.
screened
What is the mode of inheritance of most types of haemoglobinopathy?
Autosomal recessive
Which types of haemoglobin are affected in
a) alpha thalassaemia
b) beta thalassaemia?
a) HbA, HbA2 and HbF (i.e all of them)
b) HbA only
The loss of up to ___ alpha globin genes results in asymptomatic alpha thalassaemia.
up to two
What type of anaemia does thalassaemia cause?
Microcytic, hypochromic anaemia
Both iron deficiency and thalassaemia cause microcytic anaemia.
How would you differentiate them?
Check ferritin levels
Low - probably iron deficiency
What are the clinical features of HbH disease?
Anaemia
Splenomegaly
Jaundice
What occurs in the fingers of sickle crisis patients?
Dactylitis
painful inflamed digits
