What is thalassaemia?

The thalassaemia is a hereditary blood alteration that involves proteins contained in the red blood cell, called globins (α, β , δ, γ) being part of haemoglobin.

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What is “microcitemia”?

The 'microcitemia' (or thalassaemia trait) is a thalassaemic alteration whose carrier is considered a clinically healthy subject and whose more remarkable risk is that not to be identified and/or informed about the risk of having children affected by a severe anaemia condition called Mediterranean anaemia, if he will procreate with another thalassaemia carrier.

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How find out “microcitemia”?

The "microcitemia" can be evidenced through haematochimic investigations among which:

• haemochromocytometric exam (alone it is not sufficient);
• study of the different haemoglobin fractions (alone it is not sufficient);
• sideremia, iron chelation ability, ferritin;
• osmotic globular resistance;
• erythrocytic morphological exam.

All these analyses, the family study, the possible DNA testing and/or the globin chain synthesis in vitro, allow a specific medical counselling.

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What is mediterranean anaemia?

The subjects affected by Mediterranean anaemia (or thalassaemia major or Cooley's anaemia) are born from a couple both having β thalassaemia trait. The bone marrow of sick subjects does not succeed in producing the normal red blood cells and therefore the survival of the patients dependent on blood transfusions. The first anaemia manifestations are only after 3^rd or 4^th month of life of the newborn.

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What is mediterranean anaemia treatment?

Regular transfusions, iron chelation therapy, frequent necessities of cardiological treatments, endocrinological ones, etc. The iron chelation therapy helps the organism to release the iron molecules resulting from the destruction of RBCs and causing an iron accomulation in all the organs with a progressive damage of then (above all as it regards liver, heart and endocrine glands). Today, for patients with an HLA-matched donor, the bone marrow transplantation (or stem cells' one) can be considered already in childish age. In many successful cases, the thalassaemic disease is solved.

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What is thalassaemia intermedia?

A clinical condition with an extremely ample variability because of the great variety of genetic alterations that originates it.

It frequently simulates the picture of a thalassaemia trait with light splenomegaly and/or hyperbilirubinemia; in other cases it can be as severe as the Mediterranean anaemia requiring transfusions for some periods of life.

It can be caused both from α globin genes mutations and from those β ones and also from more complex compound alterations of β and α globin genes present in the same subject.

The most common and mild forms of thalassaemia intermedia are those given by the presence in a same individual both of severe β gene defects (β⁰) and of mild ones (β⁺) (i. e,. β⁰39, β⁺⁺ -101).

A form slightly marked but rarely dependent on transfusions is the Hb H thalassaemia resulting from a α thalassaemic parent with 2 not-working genes upon 4 and from a α thalassaemic one with 1 altered gene upon 4 (α thalassaemia intermedia).

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What are thalassaemia intermedia symptoms?

Generally, it shows a haemoglobin reduction (ranging between 8 and 10 g /100ml) and notable alterations of the red blood cells' morphology, a more elevated bilirubin than the normal one and an increased volume of the spleen and sometime of the liver.

Other times, the anaemia degree requires blood transfusions for longer cycles of treatment.

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What is the difference between β thalassaemia and α thalassaemia?

They are genetically very different. These alterations occur in very distant points on DNA, situated even on different chromosomes. Both of them have the implicated proteins (globins) contributing to constitute the haemoglobin delivering the oxygen around the blood.

The blood testes evidence characteristics that are similar to each other because both show: increased number of the circulating RBCs, reduction of their measures and lower haemoglobin amount. However, while the β thalassaemia is characterized by an increased HbA₂, the α one has normal percentages of various types of haemoglobin fractions (HbA, HbA₂, Hb F). Also the anemias due to iron deficiency show an haemoglobin reduction and notable alterations of the red blood cells. Because an alpha thalassaemia trait may be mistaken for a simple iron deficiency anaemia, when a sideropenic anaemia affection is verified, it is particularly important to check the patient during time.

Obviously, these indications do not take in consideration all those forms showing very mild characteristics and that, to be individualized, need genetic studies.

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How is beta thalassaemia transmitted?

The thalassaemia is transmitted from parents to their children through the genes, without jumps of generation and is not a sex-linked alteration.

Schema genetico

If one parent has a β thalassaemia trait and the other one is normal, each time they are expecting a child, there is a 1 in 2 chance (50%) the child could inherit the thalassaemia trait.

If a couple both have β thalassaemia trait, each time they are expecting a child, there is a 1 in 4 chance (25%) the child could be affected by Mediterranean anemia, a 1 in 2 chance (50%) the child could inherit the thalassaemia trait and a 1 in 4 chance (25%) the child could be normal.

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Where is the thalassaemia diffused?

The thalassaemia is diffused all over the world with different genetic characteristics in the various zones. In Italy, it reaches particularly elevated frequencies (8-15%) in the whole south, in the islands and in the delta Padano. In all the other zones, the incidence of the healthy carrier is around 1.5-2%.

Diffusione delle microcitemie in Italia

It has a very high frequency in all the Mediterranean countries (Albania, all the nations that lean out on Adriatic sea, Greece, Cyprus, Turkey, Morocco, Algeria, Libya, Egypt, the territory of Palestine, Syria).

Diffusione delle microcitemie nel mondo

In Africa (particularly among the tropics) an alteration regarding the same DNA fragment of the β thalassemia is very diffused, however giving arise to the formation of a type of haemoglobin (HbS) that if associated, in the same subject, with α or β thalassaemias or another HbS defect, is cause of two serious haemoglobinopathies called microdrepanocytosis and drepanocytosis (sickling disease) respectively.

In Italy the Hb S is rather frequent in Sicily. A certain presence is found in USA in the population of color and in Brazil where an elevated incidence of β thalassaemia is also reached, derived by immigration of population phenomenons, both from the Mediterranean and African area.

In the Asian east South another type of abnormal haemoglobin is often found (Hb E). It has the haematological and genetic characteristics typical of thalassaemias. In the same zones all the α thalassaemias are diffused at high frequency and consequently the hydrops ascites foetalis, due to the total absence of α globin genes, that is incompatible with the life.

China has an elevated incidence of β and α thalassaemia.

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To who recommend the specific analyses?

The diagnosis for the thalassaemia (a complete series of hamatological examinations) should be prescribed routinely to the subjects in fertile age. In fact, the scientific information today in our possession that have evidenced a lot of silent forms, have led us to affirm that the only haemochromocytometric exam does not allow excluding different forms of thalassaemia.

Besides a correct diagnosis allows also being able to offer detailed preventive information to families according to the different situations.

Moreover, It would be correct not to select patients to test with the specific analyses according to the origins where the different forms of thalassaemia are more diffused considering it has relegated neither only in the south of Italy neither in the basin of the Mediterranean.

The haemoglobin S, in the carrier state, does not behave any change in the haemochrom and it is only evidenced with a specific examination. Furthermore, in order to identify the healthy carriers of Hb S, it is necessary to perform a series of specific checks.

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Do thalassaemic patients need cares?

The thalassaemic trait subject is a healthy individual thereby it does not need particular cares. Sometimes, he can be pale and asthenic. If these symptoms are manifested in accented way, after a haematological check, a therapy with folic acid is recommended to administer and eventually, if there is a documented necessity, also a therapy with iron.

During the pregnancy the thalassaemic woman can go toward a further reduction of the haemoglobin value. Some checks of the serum iron level and of the ferritin level would be recommended.

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Which analysis to perform during the pregnancy?

The examination that allows knowing if the foetus has inherited the thalassaemia from both, or from one or from none of his parents, is the villocentesis. This investigation consists in a biopsy of chorionic villi sampling (plotted of foetal origin) performed ambulatorily through a needle aspiration gained with transabdominal approach of some cells from which the foetal DNA can be extracted. The villocentesis carries out, as a rule, at 10-12 weeks of pregnancy.

Villocentesi

It is extremely important to know that the villocentesis can only be performed if the genetic alterations that characterizes the thalassaemia of both parents are known. Then it is opportune that the thalassaemic couple submits to the DNA study before the beginning of the pregnancy. A delay in this phase can involve the risk to have to postpone the collecting of the foetal material.

The villocentesis allows coming to knowledge of the foetus genetic state: thalassaemic disease evidence could be followed by the parents' choice of pregnancy termination of affected foetus. The science is studying the possibility to intervene on the foetus to treat it in the utero, but today techniques that assure a successful resolution of the illness is not been set yet.

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