Haemoglobulinopathy Flashcards

1
Q

What is the problem in thalassaemia?

A

There is an imbalance of alpha and beta globin chain production, resulting in ineffective erythropoesis and haemolysis

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2
Q

What are the two broad subtypes of thalassaemia?

A

alpha thalassaemia and beta thalassaemia

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3
Q

What is usually the genetic cause of alpha thalassaemia?

A

Mostly gene deletions causing overproduction of beta chains

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4
Q

What is usually the genetic cause of beta thalassaemia?

A

Mostly point mutations causing overproduction of alpha chains

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5
Q

What is the difference between the main two types of beta thalassaemia?

A

Major: homozygous - this is present in the first year of life and requires lifelong transfusions
Minor: heterozygous - this is usually asymptomatic or causes a mild clinical picture

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6
Q

What are the features of beta thalassaemia major?

A
Presents between 3-6 months
Hepatosplenomegaly
Bony expansion/bony deformities
Anaemia
Iron accumulation (repeated blood transfusions)
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7
Q

What can iron overload due to recurrent transfusions do to a baby with beta thalassaemia major?

A

Failure of sexual development
Diabetes
Hepatic and cardiac dysfunction

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8
Q

What does the severity of alpha thalassaemia depend on?

A

The number of alpha chains missing

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9
Q

How do varying numbers of alpha chains affect patients?

A

4 chains missing - incompatible with life
3 missing - moderate anaemia and splenomegaly
1/2 missing - mild anaemia/asymptomatic

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10
Q

Where are beta genes located?

A

Chromosome 11

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11
Q

How many beta genes are there per chromosome?

A

1

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12
Q

Where are alpha genes located?

A

Chromosome 16

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13
Q

How many alpha genes are there per chromosome?

A

2

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14
Q

What does HbA consist of?

A

2 alpha chains and 2 beta chains

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15
Q

What does HbA2 consist of?

A

2 alpha chains and 2 delta chains

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16
Q

In what condition is there increases levels of HbA2?

A

Beta thalassaemia

17
Q

What mutation is it that usually causes alpha thalassaemia?

A

Deletion of one or both of the genes on chromosome 16

18
Q

How is alpha thalassaemia trait treated?

A

Usually asymptomatic - no treatment required

19
Q

How does haemoglobin H disease present?

A

Wide spectrum: anaemia to transfusion dependant
Splenomegaly
Jaundice due to haemolysis

20
Q

What is the pathogenesis of HbH disease?

A

Only one alpha gene working

21
Q

How is HbH disease managed?

A

Folic acid supplementation
Transfusions if unwell - alpha is usually mild
Splenectomy if severe

22
Q

What is the severest form of alpha thalassaemia??

A

Hb Bart’s Hydrops Fetalis Syndrome

23
Q

What mutation is it that usually causes beta thalassaemia?

A

Point mutation

24
Q

What mode of inheritance is beta thalassaemia?

A

Autosomal recessive

25
Q

What are the features of Hb Bart’s hydrops fetalis syndrome?

A

Pallor, oedema
Cardiac failure
Growth retardation
Severe hepatosplenomegaly
Skeletal and cardiovascular abnormalities
Most die in utero
A few survive to term but die shortly after birth

26
Q

What can be seen on blood film in alpha thalassaemia?

A

Target cells

Anisopoikilocytosis

27
Q

What does Anisopoikilocytosis mean?

A

Red blood cells of different shapes and sizes

28
Q

What tests are used to diagnose alpha thalassaemia?

A

High performance liquid chromatography (HPLC) or haemoglobin electrophoresis

29
Q

What are the features of beta thalassaemia trait?

A

Asymptomatic
Low MCV/MCH
Treatment usually not required

30
Q

What are the features of beta thalassaemia intermedia?

A

Moderate severity requiring occasional transfusion

31
Q

What are the features of beta thalassaemia major?

A

Severe, lifelong transfusion dependant

32
Q

What are the clinical features of beta thalassaemia major?

A

Presents aged 6-24 months
Failure to thrive
Pallor
Extramedullary haematopoiesis causing; hepatosplenomegaly, skeletal changes, organ damage

33
Q

What are the consequences of iron overload on the endocrine system?

A

Impaired growth and pubertal development
Diabetes
Osteoporosis

34
Q

What are the consequences of iron overload on the heart?

A

Cardiomyopathy

Arrhythmias

35
Q

What are the consequences of iron overload on the liver?

A

Cirrhosis

Hepatocellular cancer

36
Q

How is iron overload managed?

A

Iron chelating drugs e.g. desferroxamine

Chelators bind to iron, complexes formed are excreted in urine or stool