Haemoglobinopathies in southeast Asia

Area of Science:

• Genetics
• Hematology
• Public Health

Background:

• Southeast Asia exhibits a high prevalence of alpha-thalassaemia, beta-thalassaemia, Haemoglobin E, and Haemoglobin Constant Spring.
• These genetic factors combine to create over 60 distinct thalassaemia syndromes, representing the most complex genotypic landscape globally.
• Major thalassaemic conditions include Hb Bart's hydrops fetalis, homozygous beta-thalassaemia, beta-thalassaemia/Hb E, and Hb H diseases.

Purpose of the Study:

• To outline the complex genetic landscape of thalassaemia in Southeast Asia.
• To describe the molecular basis and clinical spectrum of common thalassaemia syndromes.
• To propose a framework for thalassaemia prevention and control.

Main Methods:

• Review of existing literature on thalassaemia genetics and clinical manifestations in Southeast Asia.
• Analysis of molecular defects, including gene deletions and mutations in the beta-globin gene.
• Correlation of genotypes with clinical phenotypes and disease severity.

Main Results:

• Alpha-thalassaemia commonly results from gene deletions, while beta-thalassaemias stem from point mutations or small insertions/deletions.
• Clinical severity ranges from asymptomatic to lethal, with Hb Bart's hydrops fetalis and homozygous beta-thalassaemia being severe forms.
• Beta-thalassaemia/Hb E presents variable anaemia severity, and alpha-thalassaemia with increased Hb F can lead to milder phenotypes, indicating modulating factors.

Conclusions:

• Effective prevention and control of thalassaemia in Southeast Asia require population screening for heterozygotes.
• Genetic counselling and prenatal diagnosis with selective abortion are essential components of a comprehensive strategy.
• Further research into unknown factors modulating disease severity is warranted to refine management and prevention.