Haemoglobinopathies refers to a range of genetically inherited disorders of red blood cell haemoglobin and includes sickle cell disease and the thalassaemias. Sickle cell disease and beta thalassaemia major are two of the commonest forms of these genetically inherited disorders.
They occur most commonly in populations whose ancestors come from Africa, Asia, Mediterranean Islands, Middle and Far East, because of migration and intermarriage they are also seen in the Caribbean, South America and other parts of the world including Britain and North America. Alpha thalassaemia is most common in South East Asia, Hong Kong and China. In the UK an estimated one in 300 babies of African-Caribbean parents and one in 60 of West African parents are born with sickle cell disease each year. An estimated 8,000-10,000 people with sickle cell disease and 600 with thalassaemia major live in the UK.
Approximately 1 in 4 West African, 1 in 10 African-Caribbean, 1 in 50 Asian
and 1 in 100 Northern Greek have sickle cell trait (carrier state). Whilst
1 in 7 Greek, 1 in 10-20 Asian, 1 in 50 African and African-Caribbean and
1 in 1000 English people have beta thalassaemia trait. Worldwide a thalassaemia
carrier states are commoner than ß thalassaemia carrier states.
How the Haemoglobin Type Results in Sickle Cell Disease and Thalassaemia?
The type of haemoglobin that an individual has is determined by the haemoglobin
gene that they have inherited from both their parents. Haemoglobin is the
component of the red blood cell that carries oxygen around the body and
each individual inherits one haemoglobin gene from each parent. The normal
adult
haemoglobin which predominates in individuals over the age of one year
is called haemoglobin 'A' (Hb bA),
commonly written (HbA). It is made up of a pair of alpha and a pair of beta
chains.
Synthesis (production) of the beta
chain is controlled by the beta globin gene located on chromosome 11, whilst
production of alpha chains is controlled by the alpha globin gene located
on chromosome 16. The beta gene is expressed once on each of chromosome
11 but the alpha gene is expressed twice on each of chromosome 16 and therefore
synthesises a double amount of alpha chains.
When expressed it is written thus:
b
|
b
|
bA
|
bA
|
|||
a a
|
/
|
a a
|
=
|
a a
|
/
|
a a
|
Where an individual has inherited two normal adult haemoglobins, one from
each parent they have HbbAbA,
commonly written (HbAA). Sickle cell disease (SCD) is the family of haemoglobin
disorders in which both Hb b chains
are abnormal, with one or both of the Hb b chain
genes having the sickle mutation (bS). The homozygote
state is HbSS, sickle cell anaemia, and a variety of compound heterozygotes
exist.
Thalassaemias are a group of disorders caused by the underproduction of one
or more of the chains that make up the haemoglobin molecule. Hundreds of different
mutations of the a- and b– globin genes cause the clinically important
thalassaemias.
What is trait condition?
Where an individual has inherited one normal beta globin gene and one abnormal
beta globin gene the individual has a carrier state or trait condition, which
is usually benign and does not give rise to clinical symptoms or illness.
For example, sickle cell trait (HbAS) and beta thalassaemia trait (HbAbThal),
however, carrier states have genetic implications for an individual's offspring
because if their partner is also a carrier there is a one in four chance
that their children can inherit a disease state.
How do we get sickle cell or thalassaemia syndrome?
A person can only get sickle cell disease or thalassaemia from their parents,
as they can only be inherited through the genes. Each parent is born with
two haemoglobin genes. Each time a couple is expecting a child, the child
will have one haemoglobin gene from each parent, to be able to make their
own haemoglobin genes. In each pregnancy there are always FOUR POSSIBLE combinations
the child can have, known as chances.
For example, if both parents have the usual most common combination of haemoglobin
genes (HbAA) this couples children have a 100% chance of inheriting the usual
combination of haemoglobins. None of their children will inherit a sickle cell
or thalassaemia syndrome as shown in Figure1.
Figure 1: Parents with normal haemoglobins
Father (HbAA) Mother (HbAA)
When both parents have trait conditions, where they have one normal haemoglobin gene and one abnormal haemoglobin gene such as sickle trait (HbAS) or b thalassaemia trait (Hb AbThal) there is a chance that their children will inherit the abnormal haemoglobin gene from either or both of them as shown in Figure 2. Couples of carriers have a one in four (25%) chance in each pregnancy of having a child with the disease; a one in two (50%) chance of having a child with the trait condition; and a one in four (25%) chance that the child will inherit a normal gene from both parents, and so will be completely normal.
Figure 2: Both parents have trait conditions
Father (HbAS) Mother (HbAS)
Children:
HbSS HbAS HbAS HbAA
If you want to know more about sickle cell disease or the thalassaemias visit
the following websites:
Last updated July 21, 2003 10:39.
Copyright © 2003 Haemoglobinopathy Registry - Haematology Department - Central Middlesex Hospital All rights reserved.
The North West London Hospitals NHS Trust - Associated University - Imperial College Medical School.
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