What are the chances of having alpha thalassemia or being a carrier of the alpha thalassemia trait in an individual of East Asian descent with low Mean Corpuscular Hemoglobin (MCH) and no anemia?

Alpha Thalassemia Risk Assessment in East Asians with Low MCH but No Anemia

East Asian individuals with low Mean Corpuscular Hemoglobin (MCH) but normal hemoglobin levels have a high probability (approximately 5-10%) of being carriers of alpha thalassemia trait. 1, 2

Prevalence and Risk Assessment

Alpha thalassemia is particularly common in Southeast Asian populations:

• In Hong Kong, screening studies found that approximately 4.5% of individuals were carriers of the Southeast Asian (SEA) deletion type of alpha thalassemia 2
• Overall alpha thalassemia carrier rate in East Asian populations ranges from 5-10% 1, 2
• The SEA deletion (deletion of both alpha-globin genes on the same chromosome) is the most common type in East Asian populations 3

Diagnostic Indicators

Low MCH without anemia is a key indicator of possible alpha thalassemia trait:

• MCH is a more reliable marker of iron deficiency than MCV and is reduced in both absolute and functional iron deficiency 1
• MCH parameter is significantly different between normal individuals and those with alpha thalassemia trait (p<0.001) 3
• MCH is more reliable than MCV for identifying the number of defective genes (p=0.003) 3

Diagnostic Algorithm

For East Asian individuals with low MCH but no anemia:

1. Rule out iron deficiency:

   • Check serum ferritin (should be >30 μg/L)
   • If ferritin is low, treat with iron and reassess

2. If iron studies are normal:

   • Consider hemoglobinopathy evaluation, particularly for alpha thalassemia
   • Hemoglobin electrophoresis is recommended, though it may be normal in alpha thalassemia carriers 1

3. Definitive diagnosis:

   • DNA analysis using multiplex gap-PCR to detect common alpha thalassemia deletions (3.7kb, 4.2kb, and SEA deletions) 3

Clinical Implications

• Alpha thalassemia carriers (trait) are generally asymptomatic and require no treatment 4
• Carriers have a normal life expectancy 4
• The condition becomes clinically significant for reproductive planning:
  • When both parents are carriers, there's risk of having children with more severe forms
  • Alpha thalassemia major with hemoglobin Bart's usually results in fatal hydrops fetalis 1

Important Considerations

• Alpha thalassemia trait is often misdiagnosed as iron deficiency anemia, leading to unnecessary iron supplementation
• In individuals of East Asian descent with persistent microcytosis despite normal iron studies, alpha thalassemia should be strongly suspected
• Genetic counseling is recommended for carriers planning pregnancy, especially if their partner is also of East Asian descent 4

Pitfalls to Avoid

• Relying solely on hemoglobin H preparation tests for screening is unreliable with high false-negative rates in certain populations 5
• Assuming that all microcytosis is due to iron deficiency without considering ethnic background
• Failing to distinguish between alpha and beta thalassemia traits, which have different inheritance patterns and clinical implications

Alpha thalassemia testing is particularly important for reproductive planning in East Asian populations due to the risk of severe fetal complications when both parents are carriers 1, 4.