Anaemia - α thalassaemia
Haemoglobin is the oxygen carrying molecule in the blood and is packaged in the red blood cells. If the level of haemoglobin is reduced the patient is described as having anaemia. If the level is very low then the patient will look "anaemic", and the skin and especially the lips, eyelids and tongue will be pale. In ATR-X syndrome the reduction in haemoglobin is usually very mild and only apparent on blood testing.
There are many causes of anaemia but in ATR-X it is due to a reduction in the manufacture of one of the proteins, α globin, that makes up haemoglobin. This form of anaemia is called α thalassaemia. The term 'thalassaemia' comes from the Greek for sea and the name derives from the fact that this type of anaemia is common in the Mediterranean. Although the anaemia in ATR-X shares the same name it has little else in common with the Mediterranean variety and this will be discussed further below.
α Thalassaemia can be diagnosed with a simple blood test. A drop of blood is mixed with a blue dye and left to incubate for a few hours. A spot of this blood is then spread on a slide and looked at under the microscope. If α thalassaemia is present then some of the red cells, instead of having a uniform blue colour, will appear to be full of blue dots (haemoglobin H inclusions).
Haemoglobin is normally made up of 2 proteins, α globin and β globin. In α thalassaemia there is a reduction in the amount of α globin and consequently a relative excess of β globin. Some of this excess β globin combines on its own to form an abnormal protein called haemoglobin H which forms the blue dots when the cells are dyed.
It is a quick and useful test, but like all medical tests it is not foolproof. If the inclusions are plentiful then there is little doubt the test is positive and it is likely that the diagnosis of ATR-X is correct. Sometimes rare cells with inclusions may be seen in unaffected individuals and so if only occasional cells are seen in a patient it is not possible to say that this is ATR-X. If inclusions are not present, ATR-X is less likely to be the correct diagnosis. Nevertheless, it does not exclude ATR-X because we know of some cases in whom the genetic tests have established the diagnosis of ATR-X although haemoglobin H inclusions are absent.
Sometimes it is worth retesting individuals to see if they are "positive" and it is always worth looking at other affected members of a family in whom the blood changes may be more obvious.
In our experience the anaemia itself is usually very mild, does not lead to any problems and does not require any treatment. In particular, there is no benefit in taking extra iron.