ß Thalassemia:an Overview

by Abdullatif Husseini

What is thalassemia?

Thalassemia is a group of inherited disorders of hemoglobin synthesis characterized by a reduced or absent output of one or more of the globin chains of adult hemoglobin . The name is derived from the Greek words Thalasso = Sea" and "Hemia = Blood" in reference to anemia of the sea.

Alpha ( ) thalassemia

It appears when a person does not produce enough alpha chains for hemoglobin.

It is mainly prevalent in the Africa, the Middle East , India, and occasionally in Mediterranean region countries.

Beta (ß) thalassemia

It appears when a person does not produce enough beta chains for hemoglobin.

It is mainly prevalent in the Mediterranean region countries , such as Greece, Cyprus, Italy, Palestine and Lebanon.

Types of Thalassemia

thalassemia: There are four types categorized according to the severity of their effects on persons with thalassemia.

ß thalassemia: There are 3 types categorized according to severity:

Thalassemia minorThalassemia intermediaThalassemia major

Genetics of ß thalassemia

Monogenic disorder: a single gene disorder

ß thalassemia result from over 150 mutations of the ß globin genes that result in the absence or a reduction of the ß globin chains

Chromosomes

Source: Thalassemia.com

Transmission of ß thalassemia

If a carrier (thalassemia minor) marries a non-carrier, on average half of their children will be carriers, but none will develop thalassemia major.

Transmission ß of thalassemia- Cont

However if two carriers marry, in each pregnancy there is a 25% chance of a non-carrier child, a 50% chance of a carrier child (thalassemia minor), and a 25% chance of a child with thalassemia major.

An example of inheritance:a carrier married to a normal person

Source: Emirates Thalassemia Society

An example of inheritance- Cont:marriage between two carriers

Source: Emirates Thalassemia Society

Types of ß thalassemia

Thalassemia Minor (Trait).

This can also be called (carrier state), meaning that the person carries the genetic trait for thalassemia.

Such people usually practice normal life, but may suffer from a mild form of anemia.

Types of ß thalassemia- Cont

Thalassemia Intermedia.

Caused by the reduced availability of beta chains in hemoglobin and can lead to moderate to severe anemia and an array of complications including bone deformities and splenomegaly.

Types of ß thalassemia- Cont

Thalassemia Major (Cooley's Anemia). Caused by the unavailability of beta

chains in hemoglobin leading to a very severe and fatal if left untreated anemia.

It requires regular blood transfusions leading to iron-overload which is treated with chelation therapy to prevent death from organ failure.

ß thalassemia and malaria

Thalassemic RBCs offers protection against severe malaria caused by Plasmodium falciparum.The effect is associated with reduced parasite multiplication within RBCs.Among the contributing factors may be the variable persistence of hemoglobin F, which is relatively resistant to digestion by malarial hemoglobinases.

Signs and symptoms

Thalassemia carriers (trait): Usually no signs or symptoms are

apparent, except for a mild anemia. Carriers are usually initially detected

through screening, or when performing routine CBC (complete blood count). Later it can be confirmed using hemoglobin electrophoresis.

Signs and symptoms- Cont

Thalassemia major:

Signs such as paleness and growth retardation, are readily detectable since the first year of life. Those are mainly due to severe anemia. Later bone deformities and hepato-splenomegaly develops.

Laboratory diagnosis

Thalassemia minor: -Blood smear shows hypochromia and

microcytosis (similar to Iron Deficiency Anemia).

-Blood indices: MCV< 75 fl, Hb usually> 10, Hematocrit> 30%, RDW < 14%.

-Hemoglobin A2 often elevated > 3%, sometimes reaching 7-8%.

Laboratory diagnosis- Cont

Thalassemia major: -Blood smear shows profound

microcytic anemia, with extreme hypochromia, tear drop, target cells and nucleated RBCs.

-Hemoglobin may be very low at 3-4 g/dl.

Blood picture of a ß thalassemia major patient

                                             

Source: Cooley’s Anemia Foundation

Prenatal diagnosis

Early prenatal diagnosis can be done using first fetal blood sampling, and later chorion villus biopsy and direct analysis of the globin genes.

The error rate in experienced centers is now well under 1%.

Management and treatmentThalassemia minor (trait) :

No need for any treatment, since the carriers are usually symptomless.

Thalassemia major:

The severe life-threatening anemia, requires regular life long blood transfusion, to compensate for damaged red blood cells.

Management and treatment- Cont

Thalassemia Major:

The continuous blood transfusion will eventually lead to iron overload, which must be treated with chelation therapy to avoid organ failure.

Source: Cooley’s Anemia Foundation

Management and treatment- Cont Thalassemia Major -Continued:

Other novel treatments like bone-marrow transplantation are very costly.

New treatments includes the use of oral chelators, to replace the chelation treatment using Desferal delivered by infusion under the skin through a battery-operated pump.

Gene therapy is also an option still researched

Prevention effortsPre marital screening to make sure that the couple are not both carriers.Provision of counseling and health education for the thalassemics, their families and the public .Provision of prenatal testing for thalassemia.Reduction of marriages between relatives.

Thalassemia and migrantsCountries with migrants coming from areas with high prevalence of thalassemia such as the Mediterranean region, should be aware of this problem.Families with thalassemia carriers may have increased number of cases including thalassemia major due to intermarriages between relatives, especially in closed communities

Thalassemia and migrants -ContThe following recommendations are advised:

1- Training physicians and medical staff on thalassemia diagnosis and treatment.

2- Provision of screening and counseling services for those exposed.

3- Provision of appropriate health care and management for thalassemia patients.

Thalassemia and migrants -Cont

4- Overcoming the communication problems, including language barrier through utilizing translators and nurse practitioners.

5- Community educational programs, involving community leaders and providing social support.

Problems commonly faced by thalassemia major patients in developing countries

Reduced availability of blood for transfusion.

Reduced availability of Desferal pumps, less than third of the patients have access to pumps.

High cost of treatment.

Problems commonly faced by thalassemia

major patients in developing countries -Cont

Limited services that blood banks are able to give.

Unavailability of counseling services.

Lack of experience and appropriate training among the health providers to handle thalassemia cases.

AcknowledgementAcknowledgement

I would Like to thank Dr. Hisham Darwish & Dr. Bashar al-Karmi from

Thalassemia Patients’ Friends Society (TPFS)- Palestine

For the valuable information they provided. I would also like to express my sincere thanks for the Palestinian American Research Center (PARC) for providing me with a grant which allowed me to conduct research at the University of Pittsburgh, where I started preparing this lecture.