What are the risk factors for thalassemia?

Risk Factors for Thalassemia

The primary risk factor for thalassemia is having parents who are carriers of thalassemia gene mutations, particularly in individuals with ancestry from regions where thalassemia is prevalent, including the Mediterranean, Middle East, Africa, and Southeast Asia. 1, 2

Genetic Risk Factors

• Family history: Having one or both parents who are carriers of thalassemia mutations is the most significant risk factor 3
• Ethnic background: Higher prevalence in specific populations:
  • Mediterranean regions (Italy, Greece, Turkey)
  • Middle Eastern countries
  • Parts of Africa
  • Southeast Asia (particularly Thailand, Malaysia, and Southern China)
  • Indian subcontinent 2, 4

Types of Genetic Inheritance

• Alpha thalassemia: Results from mutations in the alpha-globin gene cluster on chromosome 16

  • Requires mutations in multiple genes due to the presence of four alpha-globin genes
  • Severity depends on the number of affected genes (1-4) 3, 5

• Beta thalassemia: Results from mutations in the beta-globin gene on chromosome 11

  • More than 200 disease-causing mutations have been identified
  • Most mutations are single nucleotide substitutions, deletions, or insertions 3

Factors Affecting Disease Severity

• Type of mutation: Different mutations cause varying degrees of reduced or absent globin chain synthesis 3
• Coinheritance of other hemoglobinopathies: Inheriting other hemoglobin disorders (such as hemoglobin E or sickle cell trait) alongside thalassemia mutations can modify disease severity 4
• Genetic modifiers: Factors outside the globin gene cluster can affect disease phenotype, including those influencing:
  • Bilirubin metabolism
  • Iron metabolism
  • Bone metabolism 3

Complications Risk Factors

For patients with established thalassemia, additional risk factors for complications include:

• Transfusion dependency: Patients requiring regular transfusions are at higher risk for iron overload and related complications 6
• Inadequate iron chelation: Poor compliance with chelation therapy increases risk of iron-related organ damage 1
• Viral hepatitis: Thalassemia patients, especially those transfused before 1992, have higher rates of hepatitis B and C infection
  • HBsAg positivity: 0.3-5.7% of thalassemia patients worldwide
  • Anti-HCV antibody positivity: 4.4-85.4% of thalassemia patients worldwide 7
• Cardiac iron overload: T2* cardiovascular magnetic resonance <10 ms indicates severe cardiac iron and risk for cardiac complications 1, 6

Prevention and Screening

• Genetic counseling: Recommended for families with history of thalassemia 1
• Prenatal diagnosis: Available through amniocentesis or chorionic villus sampling with DNA analysis 1
• Population screening: Effective in high-prevalence regions when combined with genetic counseling 3
• Migration patterns: Changing global demographics have increased prevalence in previously low-incidence regions like Northern Europe and North America 2

Clinical Implications

Understanding these risk factors is crucial for:

• Identifying at-risk individuals for genetic counseling
• Implementing appropriate screening programs in high-risk populations
• Preventing complications through early diagnosis and management
• Developing region-specific prevention programs aligned with local healthcare resources and cultural values 2