Thalassemia

Thalassemia (by Paul Ko)

Thalassemia

General

Thalassemia is one of the most common genetic diseases in the world and is common in Southern China, Hong Kong and S.E. Asia.
Over the last half century, great progress in the management has been made, with some forms of the Thalassemia change from a lethal condition to a disease with definitive treatment.
The advances from laboratory bench, clinical bedside, regional community healthcare to global understanding of this disease has benefit Chinese Diaspora on the worldwide basis.
The high incidence of Thalassemia carrier status and the diverse heterogeneity of genotype and phenotype amongst Chinese demonstrate the importance of understanding the molecular basis of Thalassemia in Chinese.
A list of reference was cited to show that due to increase in Chinese migration, a diagnostic approach and awareness of disease in Chinese in non-endemic countries is important.
Australia, Canada, Indonesia, Malaysia, Singapore and Thailand are some of the countries outside greater China that have developed guidelines to diagnostic approach to Chinese with Thalassemia.
The life long management of this condition poses a great financial burden on the healthcare budget of any nation endemic for this disease.

Epidemiology

Thalassemia now a global problem
Chinese through migration from their native area are now residing in Europe, Americans, Australia and South E. Asia in large numbers.
Advances in molecular basis of this disease help to illuminate the phenotypic feature and epidemiology of Thalassemia.
Indirect evidence from historical site showed this gene been in existence for over 4,000 years.
Recent advances in molecular basis of this disease and epidemiology also help to trace the migratory pathway of these mutant genes and the diversity of the mutation and its association with malaria and others environmental factors.
There is great heterogeneity of these mutants genes of Chinese in different regions in China and South East Asia.
Carrier status of α - Thalassemia for Chinese range from 2 - 7.6% of general population in areas studied.
Some interesting epidemiology work in Chinese with Thalassemia in different areas within and outside China are presented.
A list of some of the epidemiology work done from Argentina, Burma, Cyprus, Greek, to UAE etc.

Natural History

3.1	Clinical features of transfusion dependent patients during 1950-1960. Description of wide range of clinical spectrum on non-transfusion dependent patients for child of Chinese origin.
3.2	Clinical feature of patients with hypertransfusion scheme. Iron chelation therapy, effect of iron on endocrine system, liver, heart etc. Problem with short term and long term iron chelation therapy.
3.3	Stem cell transplantation (Bone Marrow Transplant), special features in Chinese, management problem after transplant.
3.4	Stem cell transplant (cord blood)
3.5	In utero transplantation.
3.6	Diagnosis and clinical feature of different types of thalassemia. Changing pattern of disease over last 20 years.
3.7	Pregnancy of transfusion dependent thalassemia patients.

Prevention

4.1

Genotype of thalassemia of different countries and different region in China are discussed.
The ease of migration of thalassemia gene carriers to other countries in the last 30 years.
Understanding of the molecular basis of this condition vital in the prevention of this disease in migrant Chinese.
Different region in China has different genetic defect and the phenotypic features and management are different.

4.2

Prenatal diagnosis - PRC, Hong Kong, Taiwan, UK, Thailand, Malaysia etc. are listed.
Prenatal diagnosis - Laboratory test / clinical advance etc.

Reports of cordocentesis to compare results between different countries - e.g. Hong Kong and Thailand.
Accuracy of prenatal diagnosis of 25 years in UK discussed, over all error rate 0.41%.

4.3

Carriers thalassemia carried status in Hong Kong

Economy of carrier screening
Ethical Issue involved
Religious difference e.g. with Muslin religion. Iran use pre-martial counseling. Pakistan allows prenatal diagnosis up to 17/40 gestation and abortion of affected fetus.

Lists of different countries in South East Asia and different the strategy to prevent and to control of thalassemia.

Conclusion: Thalassemia likely to be the 1st genetic disease to be controlled by genetic therapy.

Treatment

	Review of milestones in the treatment of thalassemia. Transfusion dependent and thalassemia independent patients Iron chalating Bone marrow transplant Cord blood transplant
5.1	Transfusion Possibility of adversely influence the outcome of HIV infection by high iron status. Problem with blood transfusion, infection with hepatitis etc. In children with thalassemia, growth retardation is still a problem and the effect of use of growth hormone still has to be determinded.
5.2	Iron chelating agents. S/C + I/V toxic effect with long term used of S/C dexferroxamine is standard treatment in Hong Kong, but not in PRC. Oral in deferiprone, L1, problematic with side effect, recent controversy with L1, especially regarding hepatitis fibrosis. The need for cheap and effective oral iron chelating agent in a developing country cannot be overstated. Combination of S/C and oral iron chelating agent.
5.3	Pharmaclogical agents : Inducers of fetal haemoglobin These drugs are not effective on all thalassemia, but useful in some transfusion independent patients, decrease need for occasional transfusion with illness etc. Hydroxy urea Erythropoietin (not useful in thalassemia major) Buteyrate derivative Hemin The use of combination of all these drugs are on trial. Antioxidant and other supportive therapies. This will protect RBC membranes a protective effect against antioxidant damage.
5.4	Bone marrow transplantation (conventional allergenic) Difference in drug dosage in Chinese Mortality in Taiwan mainly due to hepatitis B Problem with iron absorption after born marrow transplant Ethnical and economy issues 1st 1982 - now over 1000 BMT
5.5	Cord blood transplantation: First 1995
5.6	Interurine bone marrow transplantation only very early stage.

6 Genetic Therapy

3 approaches

Gene transfer
Molecular biological tricks to either correct the DNA, therapy correcting mutation.
Methods of down regulated the of α - globin gene.