Thalassaemia Flashcards
Define thalassaemia.
The thalassaemias are a group of recessively autosomal inherited conditions characterised by decreased or absence of synthesis of one of the two polypeptide chains (α or β) that form the normal adult human haemoglobin molecule (HbA, α2/β2), which results in reduced haemoglobin in red cells, and anaemia.
β-globin gene defects may give rise to β thalassaemia, while mutations of the α globin gene may cause α thalassaemia.
What is the aetiology of thalassaemia?
Autosomal recessive condition - genetically inherited
Results in defective synthesis of globin chains (beta/alpha)
What is the epidemiology of thalassaemia?
- Beta thal is common in Mediterranean countries, Middle East and Asia
- Alpha thal is prevalent in Africa, India and Southeast Asia
- 1.5% of world population are carriers of beta thal and 5% are carriers of alpha thal
What are the different types of globin chains?
The types of globin are called alpha (α), beta (β), gamma (γ) and delta (δ).
Most types of haemoglobin have two α chains and two other identical types.
- HbA, the most common form of adult haemoglobin, has two α and two β chains.
- Fetal haemoglobin (HbF) has two α and two γ components (this is the predominant type of Hb before birth).
- HbA2 is present in smaller amounts, with two α and two δ chains.
What are the types of beta thalassaemia?
Beta thalassaemia = beta globin gene mutation. There is only one beta globin gene on chromosome 11 (unlike alpha globin gene)
- beta+ = means beta globin production reduced
- beta0 = means no production of beta globin gene
Genotypes:
-
beta0beta0 or beta+beta+ = beta thal major
- Transfusion dependent
- Feature of Cooley’s anaemia - thalassaemic face, bone marrow expansion and hepatosplenomegaly
-
beta0beta+ = beta thal intermedia
- variable
- reduced alpha chain synthesis or increased gamma chains
- symptomatic usually when Hb <7g/dL, V low MCV and MCH
- splenomegaly, varaible transfusion dependency
-
beta0beta or beta+beta - beta thal trait
- slight anaemia, low MCV and MCH
- clinically asymptomatic
What are the types of alpha thalassaemia?
There are 4 alpha genes altogether (2 on each chromosome 16 allele)
Losing:
- 1 = normal
- 2 = alpha thal trait (microcytosis with mild anaemia)
- 3 = HbH disease (anaemia but not too severe, splenomegaly)
- 4 = hydrops fetalis (only Hb Barts synthesised leading to death in utero or shortly after birth). Hb Bart is 4gamma chains.
What is HbA?
The adult haemoglobin molecule made up of two alpha and two beta globin chains.
What are the levels of severity of thalassaemia?
major
interediate
minor
What is HbH disease?
Results from deletion or inactivation of three alpha globin genes –> alpha thal intermedia
Shows unique inclusions on blood films called “Heinz bodies” which represent beta-chain tetramers (HbH) which precipitate out and look like a golf ball
What are some signs of thalassaemia?
- Hepatosplenomegaly.
- Bony deformities (frontal bossing, prominent facial bones, and dental malocclusion).
- Marked pallor and slight to moderate jaundice.
- Exercise intolerance, cardiac flow murmur or heart failure secondary to severe anaemia.
Growth restriction is common even with well-controlled chelation therapy.
Iron overload can cause endocrinopathy with diabetes, thyroid, adrenal and pituitary disorders.
When do symptoms of beta thalassaemia appear and why?
Symptoms of anaemia start when the γ chain production ceases and the β chains fail to form in adequate numbers. This is usually in the latter part of the first year of life but can be as late as 5 years old because of delay in stopping HbF production.
Symptoms:
- failure to thrive
- vomiting
- sleepiness
- stunted growth
- irritability
What are the general symptoms of anaemia?
beta thal major - anaemia presenting at 3-6 months when gamma chain synthesis switches to beta; failure to thrive, infections
alpha or beta intermedia - may be asymptomatic; detected on routine blood tests or from a FH
Signs:
- Pallor, malaise, dyspnoea, mild jaundice
- Frontal bossing and thalassaemic facies (marroe hyperplasia)
- Hepatosplenomegaly (erythrocyte pooling, extramedullary haematopoiesis)
- Patients with beta-thalassaemia intermedia may also have the aforementioned signs
What investigations would you do for thalassaemia?
FBC - low Hb, MCV, MCH
Blood film - hypochromic, microcytic anaemia with target cells, nucleated RBCs and increased reticulocyte count
Hb electrophoresis - absent or low HbA and high HbF (fetal Hb, 2alpha2gamma)
Bone marrow - hypercellular with erythroid hyperplasia
Genetic testing - rarely necessary
Skull X ray
What would you see on skull x-ray in beta thalassaemia major?
‘Hair-on-end’ appearance (caused by expansion of marrow into cortex) in b-thalassaemia major.
How is thalassemia diagnosed?
Newborn screening
FBC - microcytic anaemia
Peripheral smear - microcytic red cells, tear drops, target cells, fragments, nucleated RBCs
Hb analysis
Genetic testing
Other:
- LFTs
- XR skull and long bones- widening of diploeic space, osteopenia
- Abdominal USS
