Successful Steps Towards Complete Management

Published Date: 02 Nov 2017

Introduction

The word (Thalassemia) comes from two parts (thalassa) which means sea and (haima)

which means blood and it is Greek word. Beta thalassemia is a genetic disease that occurs due to

the decreased synthesis of beta globin chain or complete loss of beta globin chain.The resultant

outcome would be anemia and a decline in the synthesis of red blood cells(RBCs). In addition ,

to the amount of Hb inside red blood cells(RBCs) is also diminished. During the early two years

of age, patients with beta thalassemia develop symptoms including the need for blood transfusion

and acute anemia..Beta thalassemia can be subdivided into three classes: major. Intermedia and

minor. (1) Acute anemia that resulted in Beta thalassemia patients occurs due to decreased or

total absence of hemoglobin A synthesis(HbA) that consists of two alpha chains and two beta

chains(α2 β2 ). Total lack of beta globin synthesis causes β0 Thalassemia while decrease in the

synthesis of hemoglobin causes β+ Thalassemia .Symptoms of β-thalassemia are determined to

which grade the divergences between α and β globin chain occur.These divergences affect

erythropoiesis by blocking maturity of erythroid precursors(2)Fatality in beta thalassemia

essentially originates from heart disorders that resulted from excess levels of iron despite the

improvements during the latter two decades in therapy including blood transfusion,bone marrow

transplanrtation and chelation therapy. These improvements led to give better prediction for β-

thalassemia health(1).This paper will review the principal classes of beta thalassemia ,severity of

symptoms and the various methods of treatment with focusing on the gene therapy treatment of

beta thalassemia.

Genetics of Beta-thalassemia

The genetics of β-thalassemia is in autosomal recessive way.This means for a child to be

affected, his parents should be heterozygous for this disease which means that each parent has

only one copy of the defective gene(beta globin chain gene).After pregnancy,there is a

possibility of 25% of having normal child without symptoms,25% of having child with the

disease and 50% of having children with a copy of the defective gene and without

symptoms(carriers). With each gestation,there ia a hazard of 25% of developing a child carried

beta thalassemia in heterozygous parents(1).

Types of Beta-Thalassemia

Beta-Thalassemia Major

Beta –thalassemia major or Cooley anemia indicates combined heterozygous or

homozygous form of the disease.It is also known as Miditerranean anemia and Von Jaksch

anemia. It is represented by presence of severe symptoms such as hemolysis,unable to grow

normally,jaundice in addition to acute anemia.This disease results in ineffective

erythropoiesis.The above symptoms start in early age of the patient(3).Patients with β-

thalassemia major develop symptoms such as fever,pallor,irritability in addition to problems

during feeding and diarrhea.Splenomegaly may also appear. Starting blood transfusion with Hb

level of (95-105)g/L can manage these problems and help the patient to grow normally till the

age of 10 or 11 years old in case the disease is diagnosed at this stage.Insufficient blood

transfusion can lead to the iron accumulation that can be dangerous for the patients.Before the

third decade,non proper transfusion of blood could lead to death in patients with β-thalassemia

major.About 71% of mortality rates in β-thalassemia major are found due to heart problems.

Heart problems are the essential threatening problems resulted from excess iron level.Siderosis

resulted from blood transfusion can be responsible for heart problems.Expectation for patients

health become unlimited in patients receive essential chelation and transfusion of

blood.(4). Iron overload can result from transfusion of blood and can lead to development of

many problems in children such as retardment in sexual maturation and delay of

growth.Hardness of problems caused by excess iron levels and the prevelance of such problems

are highly determined by the modified use of Iron chelation treatments(1).

Beta-Thalassemia Intermedia

Compound heterozygous β+ , homozygous β0or homozygous δ β mutations can result in

β-thalassemia intermedia.(3).Patients with β thalassemia intermedia do not need regular

transfusion of blood or they infrequently need transfusion of blood besides the development of

moderate anemia.Delay of development and growth occur in these patients despite the fact that

they are able to live without the need for frequent transfusion of blood.The clinical symptoms

usually appear between the age of 2 and 6 years old. The raised absorption of iron from the

intestine in β-thalassemia intermedia leads to increase the possibility of developing excess iron

level. There is infrequent occurrence of diabetes,hypogonadism and hypothyroidism(1). The

problems resulting from excess iron level can be dangerous and similar to these problems found

in patients with β-thalassemia major that arise due to their dependence on blood transfusion

although these problems can appear at late age(4). Comparing with β-thalassemia major, growth

and development are improved for patients with β-thalassemia intermedia and sexual maturation

is enhanced. Although these pateints may develop problems like heart problems, liver failure and

chronic anemia, they have more extended life compared with β-thalassemia major(3).

Beta-Thalassemia Minor

Individuals with β-thalassemia minor appear without developing symptoms of the disease

although there is an evidence of developing moderate anemia(1).These patients develop normal

life despite the presence of moderate symptoms.Patients with β-thalassemia minor do not need

treatment although they have moderate anemia.Iron deficiency demonstrates that the presence of

β-thalassemia minor and it is indicative for the diagnosis of the disease(3).

Management of Beta-Thalassemia

Blood Transfusion

Blood transfusion is important to repair the anemia,inhibition of erythropiesis and

suppression for absorption of iron in the gastrointestine.These results occur due to the

ineffective and increased erythropoiesis in patients do not depend on the blood

transfusion(1).Transfusion of blood should be done every 2 or 3 weeks.The goal of transfusion of

blood is to achieve Hb concentaration of (95-100)g/L(4).The laboratory results for diagnosis of

this disease are the essential determinants for stating blood transfusionin children.Testing the

blood that is transfused against Hepatitis C started in1991 and against human immunodeficiency

viral infections started in 1985.Testing the blood before transfusion is highly important to

reduce the occurrence of infections due to blood transfusion.The appropriate amount of blood

each year depends on supply of blood in each visit,levels of Hb and the weight of the

patient(3).With blood transfusion,there is a chain of dangerous problems that make the patients

more liable for developing hazardous outcomes despite their vital role in patient recovery.The

most crucial problem accompanied blood transfusion is excess iron level(1).

Bone Marrow and Cord Blood Transplantation

The single applicable method that provides complete treatment for beta thalassemia

patients is bone marrow transplantation(BMT)(1).Transplantation in bone marrow employs

hematopoietic stem cells(HSCs) that are found in umbilical cord blood,peripheral blood or bone

marrow.The presence of matched sibling donor,the state of the organ in the children received

chelation therapy in addition to the efficient performance of transplantation are crucial factors for

the powerful outcomes of transplantation(2). Immunological problems arise in making

unsuccessful transplantation and this makes the choice of the donor is highly essential.HLA-

matched siblings can give high results of transplantation.Cord blood transplantation is essentially

used in pediatric patients. This method includes several profits such as its convenience,low

presence of GVHD and contamination with viruses is also limited.Unsuccessful umbilical cord

blood transplantation is due to the limited size or the insufficient number of stem cells in

umbilical cord blood(3).The opportunity of developing graft versus host disease(GVHD) or

rejection for the graft in addition to the possibility of matched donor make the principal

limitation for (HSCs)transplantation(2).

Gene Therapy

Gene therapy proves its ability to be the absolute therapeutic method that can repair the genetic defect in β-thalassemia and Sickle cell disease(5).4/25/2013

(1) Galanello R, Origa R. Review: Beta-thalassemia. Orphanet J Rare Dis 2010;5(11).

(2) Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011 Sep 29;118(13):3479-3488.

 

(1) Galanello R, Origa R. Review: Beta-thalassemia. Orphanet J Rare Dis 2010;5(11).

 

(1) Galanello R, Origa R. Review: Beta-thalassemia. Orphanet J Rare Dis 2010;5(11).