Thalassaemias

Question 1

Define Thalassaemias

Answer 1

Autosomal recessive inherited disorders of haemoglobin, causing reduced globin chain synthesis, resulting in impaired haemoglobin production

Question 2

What is the cause of autosomal recessive inherited disorders of hemoglobin, leading to reduced globin chain synthesis?

Answer 2

Genetic defects in the alpha-globin or beta-globin chains result in impaired hemoglobin production

Question 3

What are the causes of alpha thalassemia?

Answer 3

Defects in the alpha-globin chains, which can result from the deletion of one or both alpha-globin genes on chromosome 16

Question 4

What are the clinical features of the alpha thalassemia trait?

Answer 4

Asymptomatic carrier state with microcytic hypochromic red cells and mild anaemia.

Ferritin levels are normal, and no treatment is needed

Question 5

What is HbH disease in alpha thalassemia?

Answer 5

It occurs when only one alpha gene is left.

It leads to moderate to severe anaemia with very low MCV and MCH.

Excess beta chains form tetramers called HbH

Question 6

What is Hb Barts hydrops fetalis and what is its consequences?

Answer 6

A severe form of alpha thalassemia where no functional alpha genes are present, leading to fetal death.

It causes severe hypoxia, growth retardation, and cardiac failure

Question 7

What causes beta thalassemia?

Answer 7

Mutations affecting the beta-globin chain synthesis, often caused by point mutations on chromosome 11, leading to reduced or absent beta chain production

Question 8

What is the difference between beta thalassemia trait and beta-thalassemia major?

Answer 8

Beta thalassemia trait
= Asymptomatic with mild anaemia, low MCV/MCH, and raised HbA2 levels.

Beta thalassemia major
= Severe anaemia requiring lifelong transfusions presents with pallor, failure to thrive, hepatosplenomegaly, and skeletal changes. Elevated ferritin levels

Question 9

What is the clinical presentation of beta thalassemia major?

Answer 9

(1) Presents early (6-24 months) with severe anaemia
(2) pallor
(3) hepatosplenomegaly
(4) skeletal abnormalities
(5) extramedullary hematopoiesis.
= production of blood cells outside the bone marrow, often in the spleen or liver

Hb analysis shows mainly HbF with no HbA

Question 10

What investigations are used to diagnose thalassemia?

Answer 10

(1) FBC →
Shows microcytic anaemia with decreased Hb, MCV, and MCH.

(2) HPLC or electrophoresis →
Elevated HbA2 is diagnostic of beta thalassemia trait.

(3) DNA testing →
Identifies the genetic abnormality

Question 11

How is thalassemia major managed?

Answer 11

(1) Lifelong blood transfusions to maintain haemoglobin levels (95-105 g/L)

(2) Suppress ineffective erythropoiesis and prevent iron overload.

(3) Bone marrow transplant may be considered before complications

Question 12

What are the complications of thalassemia, especially related to iron overload?

Answer 12

(1) Endocrine dysfunction
(2) Cardiac disease (e.g., cardiomyopathy)
(3) Liver disease (e.g., cirrhosis)
(4) Growth retardation.

Question 13

What is used to manage excess iron?

Answer 13

Iron chelation therapy

= desferrioxamine

Question 14

A 72-year-old gentleman attends his GP for blood as part of a ‘well man’ check-up. The blood demonstrates an Hb of 8.4, MCV of 66, WCC of 8.7, Platelets of 320 and an otherwise unremarkable full blood count. Iron studies are entirely normal.

The patient denies any overt blood loss, tiredness, weight loss or change to his bowel habits. He drinks 4 units of alcohol per week and is a non-smoker. Pending further investigation, what is the most likely cause?

Answer 14

Thalassaemia trait

Question 15

what does elevated HbA2 mean

Answer 15

key diagnostic marker for beta thalassemia trait

Question 16

How does elevated HbA2 come around?

Answer 16

(1) Beta thalassemia trait leads to a reduced production of beta chains.

(2) As a compensatory mechanism, the body increases the production of delta chains

(3) Which is combined with alpha chains to form HbA2.

(4) This results in an elevated level of HbA2, typically greater than 3.5% (normal is 2-3%)

Question 17

When does the transition from HbF (fetal haemoglobin) to HbA (adult haemoglobin) occur?

Answer 17

The transition occurs within the first few months of infancy

Question 18

What causes haemoglobinopathies?

Answer 18

mutations affecting globin chain production

Question 19

What is the inheritance pattern of haemoglobinopathies?

Answer 19

Autosomal recessive manner, with carriers being unaffected

Question 20

What are thalassaemias, and how do they affect globin chain synthesis?

Answer 20

Thalassaemias are conditions characterised by a decreased rate of globin chain synthesis

Question 21

When should you suspect thalassaemia?

Answer 21

if a patient has microcytic hypochromic anaemia with normal ferritin levels.

Question 22

What clinical features will be found on examination of a patient with thalassaemia?

Answer 22

(1) Younger than the age of 2
(2) More commonly those of Mediterranean origin
(3) Microcytic anaemia
(4) Failure to thrive
(5) Hepatosplenomegaly

Question 23

What do iron studies show in the case of thalassaemia?

Answer 23

Increased serum iron and increased iron binding capacity

Question 24

What is the mode of inheritance of Thalassemia?

Answer 24

Autosomal Recessive

Question 25

A microcytic anaemia with a low mean cell volume in the absence of other symptoms particularly in individuals of Mediterranean origin may suggest what?

Answer 25

Thalassemia traits

Question 26

Repeated blood transfusions (for example for beta thalassaemia patients) can lead to what happening?

Answer 26

Iron overload which can cause joint pain and hyperpigmentation of the palmar crease

Question 27

Jaundice
Fatigue
Facial bone deformities

What do these symptoms suggest?

Answer 27

Patient has beta or Alpha-thalassaemia. Mainly beta

Question 28

Those with beta-thalassaemia major should have regular ? blood transfusions of packed red blood cells for the rest of their life

Answer 28

2-4 weeks

Question 29

A 2-year-old Turkish boy presents to his GP. His parents say that he has not been himself. In particular, he seems less fit than his peers and appears pale. His height and weight are much lower than expected. On examination, he has signs of an enlarged liver and spleen. His parents state that his cousin has experienced similar symptoms. His birth was at term and there were no complications. His immunisations are up to date.

What investigation will confirm the diagnosis? and what will it show?

Answer 29

Haemoglobin electrophoresis

= an increase in HbF or HbA2

Question 30

A G1P0, 23-year-old woman, who is 10+1 weeks pregnant, attends her obstetrician for the results of her recent blood tests. Her recent blood test confirms a diagnosis of alpha (α) thalassaemia minor. She is concerned about how this diagnosis may affect her baby.

What foetal complication is associated with α-thalassaemia?

Answer 30

Bart’s hydrops fetalis

Question 31

A 20-year-old male presents with microcytic hypochromic anaemia and an elevated haemoglobin A2 level on electrophoresis. What is the likely diagnosis?

Answer 31

Beta-thalassemia trait

Question 32

A 20-year-old male presents with microcytic hypochromic anaemia and a decrease in alpha-globin production which does not cause an elevated haemoglobin A2 level. What is the likely diagnosis?

Answer 32

Alpha-thalassemia trait

Question 33

“All four beta globin genes are damaged or missing”

Answer 33

alpha thalassaemia major

Question 34

“Two damaged or missing genes for beta-globin”

Answer 34

beta thalassaemia major

Question 35

A 35-year-old woman with beta-thalassemia major comes into the emergency department complaining of bruising on her legs. She is otherwise well.

On examination, she has multiple reddish/brown macules over her legs.
What is the most likely diagnosis?

Answer 35

Haemosiderosis

= transfusion-induced

Question 36

HbA2 is a form of haemoglobin made up of what?

Answer 36

2 alpha and 2 delta chains

Question 37

What is the inheritance and presentation of alpha-thalassemia trait?

Answer 37

Inheritance
= One defective alpha-globin gene (heterozygous).

Presentation
= Mild microcytic hypochromic anaemia, usually asymptomatic or mild symptoms.

Labs
= Normal or slightly low MCV/MCH, normal HbA2 levels

Question 38

What is the inheritance and presentation of alpha-thalassemia major?

Answer 38

Inheritance
= Three or four defective alpha-globin genes (homozygous or compound heterozygous)

Presentation
= Severe anaemia from birth, hydrops fetalis, jaundice, splenomegaly, failure to thrive, and cardiac failure.

Labs
= Hb Bart’s and Hb H. Fatal without treatment.

Question 39

What is the inheritance and presentation of beta-thalassemia trait?

Answer 39

Inheritance
= One defective beta-globin gene (heterozygous).
Presentation

= Mild microcytic anaemia, often asymptomatic.
Labs

= Elevated HbA2 levels (>3.5%).

Question 40

What is the inheritance and presentation of beta-thalassemia major?

Answer 40

Inheritance
= Two defective beta-globin genes (homozygous or compound heterozygous)

Presentation
= Severe anaemia, failure to thrive, splenomegaly, hepatomegaly, bone deformities, and jaundice.

Labs
= Very low HbA, elevated HbF and HbA2