Alpha Thalassaemia

Most of our physical characteristics are inherited through the genes we take from our parents; for example, the shape of our nose, the colour of our skin and eyes. We also inherit our haemoglobin (Hb) type from our parents, through the genes.

Haemoglobin (Hb) is the substance in the blood which gives it its red colour. It carries the oxygen we breathe in through our nose to all our body parts; oxygen is vital for maintaining life. Without red blood cells, the body cannot carry oxygen and without oxygen the body cannot live, see Haemoglobin .

The usual and most common adult haemoglobin type is called Haemoglobin A and contains two chains called BETA (β) and ALPHA (α).Alpha (α) chains are essential for making a number of haemoglobins including Fetal (F), Adult (A) and minor adult Haemoglobin (A2), see Haemoglobin , all these need two alpha chains.

The amount and quality of beta and alpha chains a person makes is controlled by the haemoglobin gene they inherit from their parents.

Where a person has inherited haemoglobin A from both parent they will have TWO usual beta genes (βAβA), one from each parent, and Two PAIRS of alpha genes one pair from each parent (αα/αα), (see Diagram 1)

 Inheritance of alpha chains
Diagram 1: Normal

Some people inherit one usual haemoglobin A gene and one unusual Beta Thalassaemia gene, in which case they have a condition known as Beta Thalassaemia trait, (Hb AβThal), often referred to as Beta Thalassaemia ‘minor’ or a ‘carrier’, this is a defect of the beta globin gene and affects the beta chain, see Haemoglobin .

Some people do not inherit the usual number of Alpha genes in which case they will have a Alpha Thalassaemia trait, this is a defect of the alpha globin gene and affects the alpha chain, see Haemoglobin .

The information here is about ALPHA THALASSAEMIA only; for information about Beta Thalassaemia, see Beta Thalassaemia.

Alpha Thalassaemia Trait (Carrier)

Alpha Thalassaemia trait is an inherited genetic defect of red blood cell haemoglobin and is passed on from parents to their offspring in the same way that other physical characteristics are passed on through the genes. There are no outward signs to show if a person has alpha Thalassaemia trait they are perfectly healthy.

If a person is born with alpha Thalassaemia trait they will have it all their life, it is not a disease it will not give rise to any symptoms, they will not feel weak or have any signs of being ill. Because there are no outward signs the alpha Thalassaemia gene may be passed unrecognized through a family for many generations.

Millions of people world wide have alpha Thalassaemia trait, especially in areas where malaria is, or was, common.

The blood of people who have alpha Thalassaemia trait has a slightly lower level of iron. However they do not need to take iron medicines, unless special blood tests have shown that they are lacking in iron and a doctor advises this treatment.

Types of Alpha Thalassaemia Trait

There are three types of alpha Thalassaemia carriers, the most common worldwide is SILENT CARRIER ( - α / α α) and ALPHA PLUS ( - α / - α) THALASSAEMIA TRAIT. The less common is ALPHA ZERO ( - - / α α) THALASSAEMIA TRAIT.

Silent Carrier and Alpha Plus Thalassaemia Trait

These are very common in people whose family come from:

Africa, the Caribbean, the Mediterranean Islands, India, Pakistan, Bangladesh, the Middle East, and Far East & South East Asia.

They would have inherited the Silent Carrier or Alpha Plus Thalassaemia Trait (see diagrams 2 & 3), from their parents but it does NOT affect their own health.

 Inheritance of alpha chains
Diagram 2: Silent Carrier
One reason that it is important for a person to know that they have alpha plus Thalassaemia trait is that it may be mistaken for iron deficiency anaemia, and they may be treated with iron medicines unnecessarily. The second reason is that they may pass this genetic difference to their children and depending on the alpha genes that their partner passes on to their children they could inherit a disease.
 Inheritance of alpha chains
Diagram 3: Alpha Plus Thalassaemia Trait

Alpha Zero Thalassaemia Trait

Alpha zero Thalassaemia trait (diagram 4) is less common but can be inherited by people whose family come from any of the following parts of the world:

the Middle East, South East Asia, China, and the Mediterranean Islands

In this instance, no alpha genes are inherited from one parent, but two normal alpha genes are inherited from the other.

 Inheritance of alpha chains
Diagram 4: Alpha Zero Thalassaemia Trait

Having alpha zero Thalassaemia trait does not affect the person’s health; these individuals have sufficient alpha chains for making sufficient haemoglobin. However, if that person and their partner both have alpha zero Thalassaemia trait, and are planning to have children, there is chance in EACH pregnancy that the baby could inherit a severe anaemia called ALPHA THALASSAEMIA MAJOR.

This is how the inheritance works - If both parents have alpha zero Thalassaemia trait, each time they are expecting a child there is a 1 in 4 chance that the child could inherit the usual number of alpha genes, a 2 in 4 chance the child could inherit alpha zero Thalassaemia trait and a 1 in 4 chance the child could inherit alpha Thalassaemia major.  Inheritance diagram
Example 1

Alpha Thalassaemia Major

If a child inherits alpha Thalassaemia major, the child will not be able to make alpha chains and therefore will not be able to make normal healthy haemoglobin, including Fetal, Adult and A2 haemoglobin since all these haemoglobins need a pair of alpha chains (LINK TO Hb INTRODUCTION) in order to produce the correct quality and quantity of each of these haemoglobins.

Alpha Thalassaemia major is a serious disease because it affects the baby whilst it is still growing in its mother’s womb, because it is unable to produce Fetal haemoglobin. If a baby inherits this condition, the mother will also be at risk of serious complications during pregnancy.

This condition is life threatening: babies who have alpha Thalassaemia major are unlikely to survive pregnancy.

If a coupe both have Alpha Thalassaemia Trait, they will need to see a genetic counsellor or specialist nurse who will be able to explain what this may mean for them and their children. This can be arranged by the couples GP, family planning clinic, antenatal clinic, or by their contacting one of the specialist National Sickle Cell / Thalassaemia Centres.

A baby can only inherit Alpha Thalassaemia Major if:

  • both parents have Alpha Zero Thalassaemia Trait, or
  • one parent has a condition known as H Disease and the other has Alpha Thalassaemia Trait, or
  • both parents have H Disease

If One Parent has Alpha Plus Thalassaemia Trait and the other has Alpha Zero Thalassaemia Trait

If one parent has Alpha Plus Thalassaemia Trait and other parent has Alpha Zero Thalassaemia Trait (see example 2); EACH time they are expecting a child there is a 1 in 4 chance the child could inherit the usual number of alpha genes, a 1 in 4 chance of inheriting Alpha Zero Thalassaemia Trait (just like one of their parents), a 1 in 4 chance of inheriting Alpha Plus Thalassaemia Trait, (like the other parent) or a 1 in 4 chance of inheriting a condition called HAEMOGLOBIN H DISEASE ( - - / - α).  Inheritance diagram
Example 2

Haemoglobin H Disease

In this condition the baby usually makes sufficient haemoglobin to allow for normal life; however, the red blood cells have less red pigment than usual. On occasions, this condition may need medical treatment; for example, blood transfusion and special medications.

If a couple both have Alpha Thalassaemia Trait or H Disease and they want to have a Baby

Where a couple have Alpha Zero Thalassaemia Trait or H Disease, they have the following options open to them if they want to have children:

  • ignore the information, get pregnant the usual way and let nature take it course,
  • have the baby tested in the womb in early pregnancy,
  • adopt a child,
  • use a donor egg or sperm and have In Vitro Fertilisation (IVF).

Testing the baby in the womb is called Prenatal Diagnosis and can be done as early as ten weeks of pregnancy in most cases. The test is usually done in a special clinic in a hospital and depending on the type of test that the woman / couple are offered the result is usually available within a few days, but can take up to two weeks. The couple can also obtain a copy of the leaflet which explains prenatal diagnosis from the Brent Sickle Cell & Thalassaemia Centre.

It is advisable for an individual or couple to discuss the various options that are available with a GP, Midwife, hospital doctor, genetic counsellor or a specialist nurse at the specialist at one of the specialist National Sickle Cell / Thalassaemia Centres. They will be able to provide more information, advice, and support to help them reach a decision that is best for them.

The Family Connection

Once Alpha Thalassaemia or any other unusual haemoglobin gene has been found in one family member it is important to be aware that other members of the same family may also have the unusual haemoglobin gene. Therefore, it is important to share the information with other family members especially with those who are of child bearing age, planning to get married, start a family or have more children - brother, sisters, aunts, uncles, cousins.

Testing for Alpha Thalassaemia

Anyone who wants to be tested to find out which haemoglobin they have inherited from their parents can visit their GP or contact their local specialist National Sickle Cell / Thalassaemia Centre.