Haemoglobin Disorders

Alpha thalassaemia

Alpha thalassaemia (or α-thalassaemia) is a general term for a group of inherited blood disorders, characterised by a reduced production of the α-globin chains of the haemoglobin molecule, while the β-globin chains are normally produced. This means that there will be an accumulation of the β-(unpaired) globin chains, within the developing red cell.

The production of the α-globin chains is regulated by four α-genes, two on each chromosome. This means that there can be more than one type of carrier:

  • Alpha plus (α+) thalassaemia carrier, also known as silent carrier: Such an individual has only one (out of four) non-functional gene. The other three α-globin genes produce nearly normal amounts of haemoglobin. The defective gene may, or may not, result in slightly smaller red cells. For this reason, diagnosis by simple microscopic examination of the blood in the laboratory may be very difficult to be established, hence the name “silent”, given to describe these carriers. Only very specific laboratory tests, based on DNA analysis, can accurately diagnose this type of carriers.
  • Alpha zero (α0) thalassaemia carrier: Such an individual has two (out of four) α-genes missing (deleted) or non-functional and is said to be a carrier of alpha zero thalassaemia. The two missing or defective genes, may be on the same chromosome (cis position) or on different chromosomes (trans position).
  • If three α-globin genes are missing or non-functional, then the individual has a clinically significant anaemia, which is known as HbH disease. In this situation the excess β-chains which continue to be produced by the fully functional β-globin genes, cannot pair up with the α-globin chains to produce common haemoglobin (HbA). Instead, the free β-globin chains join together to form a new haemoglobin (β4) in the patient’s blood known as HbH.  Although this is not the haemoglobin found commonly in human adult red cells, HbH has the capacity, like common adult haemoglobin (HbA) to deliver oxygen efficiently to the tissues. It is, however, a relatively unstable molecule, and its continuous breakdown results in early death, or breakdown, of red cells (haemolysis), which can lead to a moderate to severe anaemia in the affected individual and to other related health problems, such as bone deformation, fatigue, formation of gall stones and enlargement of the spleen which may vary from mild to severe.
  • Haemoglobin Bart’s – Hydrops Fetalis: In this situation the body cannot produce any α-chains. Free γ-globin chains, which normally make up the haemoglobin of the fetus (HbF) along with α-globin chains, join together to form another type of haemoglobin called Hb Barts (γ4). This type of haemoglobin does not have any oxygen carrying capacity and thus cannot sustain life.

Such condition results in severe anaemia that affects the baby while in the womb and causes the heart to fail. It, subsequently, leads to the swelling of the fetus and the placenta and to a marked increase in the volume of the amniotic fluid (hydramnios), which can often lead to premature birth with the baby being usually dead (stillborn) at the time of delivery. The mother may also develop high blood pressure and may have difficulty in delivery. She is also in danger of bleeding after birth, if the contents of the womb are retained. As the life and wellbeing of the mother are at risk, early detection and prevention by premature delivery, sacrificing the fetus, is the most common practice. In some centres in-utero blood transfusion is offered which treats the anaemia and allows the birth of the child who however, will require lifelong blood transfusion and special medical care.

Arrangements of the genes in the forms of alpha thalassaemia:

  1. When both parents are carriers of alpha plus (α+) thalassaemia:

 

 

2. When both parents are carriers of alpha zero (α0) thalassaemia, but the chromosomes are in trans:

 

 

  • The carrier states need no special treatment, however careful explanation must be provided to carriers concerning the risk to their offspring(s), keeping in mind the various combinations of genes that can occur in the parents.
  • HbH disease is a non-transfusion-dependent thalassaemia (NTDT) and can have a spectrum of severity. In the types of mutations that lead to these changes in the genetic makeup of patients, some forms, mostly found in South East Asia, can be severe and require regular blood transfusion. The majority of cases require regular follow-up and transfusion on special occasions, such as pregnancy, surgical operations or passing infections. In the more severe cases splenectomy may be beneficial.
  • Hydrops fetalis can only be treated by intra-uterine blood transfusions and regular transfusions, after the baby is born.

Click to read: Beta Thalassaemia, Alpha Thalassaemia and Sickle Cell Disease Educational Community booklet. TIF Publication. (2014)

الوسوم
زر الذهاب إلى الأعلى
إغلاق
إغلاق