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Biology Assignment 代写 血红蛋白病的诊断和治疗

Biology Assignment 代写 血红蛋白病的诊断和治疗

Haemoglobinopathy is a genetic inherited disorder. Haemoglobinopaty is associated to geographical distribution disease; it is most common in population of Africa, Middle East, Mediterranean, Asia and Southeast Asia. Haemogloninopathies are subdivided into two main significant genetic diseases thalassaemia and sickle cell disease. Transfusion treatment and bone morrow oar stem cell transplantation therapy use for treatment and management both diseases. But in sickle cell disease (SCD) there are some more treatment used as control the complication of disease such hydroxyurea, and vaccination against some pathogenic disease which are causes infection, and analgesic to relief the pain, and using prophylactic treatment against pneumococcal chest syndrome. Also the patient during the blood transfusion increased the amount of iron which is harmful for many organs in human body particularly the heart muscle tissue. In this case the patient need another therapy is iron chelation such as deferiprone with deferoxamine. The resent study declare that the most curative treatment and is bone marrow transplantation or stem cell transplantation.

The most accurate test for haemoglobinopathy is including high pressure liquid chromatography (HPLC), haemoglobin electrophoresis (EP) and neonatal screening test and DNA parental test.



Haemoglobinopathy is a genetic disease, associated with lack of normal haemoglobin in the red blood cells also the most common monogenic disease in the worldwide. Is inherited defect produce abnormal haemoglobin (Hb) in their structure, Hb playing an important role in red blood cells. This disorder is an autosomal recessive disorder. This disorder related to chronic haemolytic anaemia. (Marie and Fernando 2008) Haemoglobinopaty is geographical distribution disease; is most common in Africa, Middle East, Mediterranean, Asia and Southeast Asia. Also interaction between two genes among this people can causes to number types of thalassaemia disease, three aims for control are homozygous alpha-0 thallassaemia leading to Hb-Bart, homozygous beta-thalassaemia and beta-thalassaemia Hb-E. Hence that is important to detect very quick, immediate and accurate screening for prevention especially those parental are carrying the alpha-0 thalassaemia, beta-thalassaemia and Hb-E. (Fucharoen S et al 2000)

Haemoglobinopathy can spread in the many region of the world because of the mix ethnic and immigration from the countries which are prevalence the disease to non prevalence disease countries.

Haemoglobinopathies occurs due to of the haemoglobins reduced their ability to carry the oxygen. This disorder associated to haemoglobin molecule disorder also that is important to understanding the structure and function of haemoglobin. There are two main types of haemoglobinopathy, SCD and thalassaemia can be passed from parental to offspring trough abnormal haemoglobin genes. Individual can be effect with these disorder while they are be inherited with two abnormal haemoglobin one from paternal and the other from maternal. But individual with only one abnormal haemoglobin gene called as carrier or trait, does not shows any clinical symptom and healthier as well.

Individuals with haemoglobinopthies are either having clinical symptom of this disease, or if the individuals are carrier, unknown of their trait until screened, but If parent both carrier an abnormal hemoglobin gene there is a chance 25% of their pregnancy that offspring will affected with the clinical symptom of haemoglobinopathy

If the maternal affected with haemoglobinopathy, and the paternal only carrier therefore the child 50% can be affected and 50% will carrier.

The haemoglobin Hb molecule is a polymer consisting of four identical monomers. Hb molecule consist of two pairs of globins chains, each containing a haem group, every haem have an iron atom which is attached to oxygen in the lung and the haem which is responsible for transporting the oxygen from the lungs to the tissues and carrying the carbon dioxide (CO2) from the tissue to lung (Figure 1). For the period of foetus development, the foetal Hb predominate (two alpha chains and two gamma chains). Haemoglobin Hb molecule in adult composed of four globins chains two alpha subunit and two beta subunit. The structure Hb changes within embryonic, fetus and adult. Usually the main haemoglobin in normal adult is HbA, and little quantity of HbA2 and HbF. (Morven W et al 2009)

Diagram showing the location of haeme in haemoglobin.

Figure 1: shows the structure of haemoglobin ( accessed 29/01/2011.

Classification of heamoglobinopaties: haemoglobinopathy can divided into two main parts (figure -2)


Sickle cell disease

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Fig 2: (Ronald J 2006)


Biology Assignment 代写 血红蛋白病的诊断和治疗

Thalassemia is hereditary haemoglobin defect which failure the formation more than one polypeptide chain of haemoglobin protein causes mild or severe anaemia. thalassaemia classified into a few categories and each of them can causes different problems. Thalassamia is quantitative abnormality, frequently associated to chronic haemolytic anaemia, the clinical expression of disease including serious of haemolysis and some type of the disease not shows clinical symptom of the disease. Thalassaemia involved in the class of globins chain and number of defective of globins gene. The offspring with thalassamia at the birth frequently are healthy, the sign and symptom of anaemia appear in between age six month to two years old. Without detection and treatment the most of children in age one year old are death because of severe anaemia and infection. (Weatherall. D and Clegg. J 2001)

Some types of thalassaemia initiate with mild condition, but some of them cases serious and life threatening and it cause death. Nearly 5% of the population in the nationwide have been affected with this disease. Foetal Haemoglobin (Hb) is predominantly alpha2 and gama2. In the normal individual the dominating haemoglobin composition is HbA i.e. alpha 2 and beta 2. This implies that the frequent forms of thalassaemia are alpha and beta, each type causes different clinical manifestation. Foetal Haemoglobin (Hb) is predominantly alpha 2 and gamma 2. In the normal individual the dominating haemoglobin composition is HbA i.e. a2b2. This implies that the frequent forms of thalassaemia are alpha and beta. (Fucharoen et al 2007)

Alpha thalassemia:

Individual with alpha-thalassemia characterised by lack of alpha globin chains. It is prevalence in Africa, Middle East, Asia, south east of Asia, and also Mediterranean area.

The alpha-globin gene made up by four genes, found on chromosome 16p13.3 (Figure 4) and including the embryonic zeta-globins gene and two alpha globins genes, usually there are four alpha globins gene, mutation affected on one or more alpha-globins gene causes lack of formation of alpha- globin chain lead to alpha thalassaemia. (Weatherall. D and Clegg. J 2001) The patient with only one unusual alpha globin gene is called alpha thalassaemia carrier. In this case one globin genes defective or missing, and not show any clinical symptom of anaemia, and difficult to diagnosis also known as silent carrier. Normal carrier has an offspring with haemoglobin H (HbH). It is can be to detect by DNA examination. If the individual has missing two of four globin genes call as alpha thalasaemia trait, both abnormal alpha-globin genes can be found on one chromosome or one on each chromosome.

The parents both have alpha thalasaemia trait therefore their offspring effective with alpha thalassaemia trait. The patient with this disease has mild anaemia and the red cells are smaller the normal size call microcytosis. And the patient does not show the clinical manifestation. (Leung. W et al 2008)

Also if one of the parents has alpha thalassaemia trait and the other one has silent carrier there is 25% chance of their offspring born with HbH. But if the both parent have alpha thalassaemia trait there is 25% chance their offspring inherited with alpha-thalassaemia major. Individual with condition has no chance to live for long term and mostly die in childhood, the reason for that because of lack or defects of the alpha globin chain and causes the severe anaemia and causes health damaging such as spleenomegaly, bone malformation and tiredness.


The beta-thalassaemia is an inherited disease associated with haemoglobin disorder, is congenital anaemia, occur because of lack or reduce formation of beta-globin chain causes reduce the number of red cells or produce unfunctional red cells, most of erythrocyte are failure to mature from the bone marrow that is cause serious anaemia. The beta- globin chain deficit causes the intracellular precipitation and increases of alpha-globin chain, leading to ineffective erythropoiesis and haemolysis anaemia. (Ronald J 2006) Beta-thalassaemia is the most common molecular deficiency as the consequence of point mutation and deletion that effect the transcription and mRNA translation. Infants with homozygous beta-thalassaemia are healthy but after birth as the haemoglobin from fetus replaced to adult haemoglobin the absent of beta-globin causes the serious anaemia. Also the level of anaemia is deference rely on the level of beta-globin deficiency and the formation of fetal haemoglobin. (Lin. Y et al 2009)

The clinical manifestations of beta-thalassaemia including of anaemia shows in the first year of life, also the spleen enlargement resulting from accumulation large amount of destruction os erythrocyte in the spleen, growth of bone marrow because the body compensated the red cells destruction which is leading to abnormal growth the long bones and deformation the skull. Beta-thalassemia is most prevalence in the Asia, and became the main health problem among people. (Weatherall. J 2001)

In developing countries the patients with this disease are suffering and death within childhood. The recent study of the national thalassemia register reveals that the patients survive for longer in the UK, half population of patients with beta-thalassemia die under the age of 35 years old.

Sickle cell disease (SCD)

SCD is genetic defected haemoglobinopathy characterised by stiffen shaped cells which can block blood vessels and caused severe pain, organ damage and infection. Was found at the beginning the twentieth century, is an autosomal dominant genetic disorder, it is related to qualitative globin gene defect, and formation of abnormal globin chain, SCD results in morbidity and mortality. There are 500 unusual Hb found but only four of them are common such as HbS (beta 6 glu-val), HbC (beta 6 Glu-Lys), HbD (beta 87 Thr-Lys), HbE (beta 26 Glu-Lys). The disease is characterized by abnormality in shape of RBCs, the cell become sickle-shape which is rigid and stiffen and can leading to obstruction the blood vessels and tissue ischemia, which causes the organ damage. Also this abnormality can cause painful episodes, severe infection and chronic anaemia. SCD is the mutation in the haemoglobin gene and causes sickling the cells, mutation increased in different part of the Hb molecule, SCD can be detected through infant screening haemoglobin electrophoresis. SCD occur because of mutation on short arm of chromosome 11 (figure-4), this mutation leading to replace the valine to glutamine of the amino acid at the sixth positions of beta-globin chain of HbA, resulting in the production of HbS which is biochemically unstable molecule and it can precipitate at the deoxygenated state. (Hoffbrand. A.V. 2001)


Figure- 4 Globin encoding genes are found on chromosome 11 and 16. Figure 3

SCD was the first disease has been described as a molecular disorder in a gene, and it is detected by infant screening program. Its causes reduce lifespan and associated to chronic disease. SCD occur in that part of the world where Plasmodium Palciparum has endemic and then spread because of migration to other part of the world for example north of Europe and United States. SCD is more common in those people are originally came from the Africa, Mediterranean, middle and south of America, Asia and middle east. (Figure 4) SCD occurs due to the newborn inherited the defect haemoglobin gene from parental mother and father HB SS causes severe anaemia, if only one sickle haemoglobin gene from one parent and one normal haemoglobin gene from other parent transfer to infant, therefore the infant become a carrier also known as sickle cell trait. (Marie. J and Ronald. L 2004)