Thalassemia, Alpha

INTRODUCTION @

Background: Alpha thalassemia, the most prevalent of all thalassemias, is the deficient or absent production of alpha-globin synthesis. Normally, alpha-globin chains bind with beta-globin chains to form the tetramer aa/bb in hemoglobin A. The imbalance of alpha- and beta-globin chains creates the pathology in thalassemia. The alpha thalassemic genetic abnormality primarily affects Southeast Asian and Mediterranean populations. However, the genetic trait is found in 30% of asymptomatic African Americans. The condition results in a variety of clinical syndromes depending on the degree of alpha chain deletion.

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Pathophysiology: Normal adult hemoglobin contains a tetramer of globin chains a2/b2. Two conditions exist in the red blood cell when the alpha-globin synthesis decreases or is absent altogether. Intracellular precipitation of unmatched beta chains form inclusion bodies, causing damage to red blood cell precursors in the marrow and ineffective erythropoiesis.
Diminished hemoglobinization of individual red cells results in hypochromia and microcytosis.

The alpha-globin genes are duplicated on the short arm of chromosome 16. Each individual carries 4 separate loci, 2 from the paternal chromosome and 2 from the maternal chromosome. This results in 4 possible genotypes, each resulting in a different clinical syndrome.

Table 1. Alpha-Globin Genotypes and Clinical Syndromes

Genotype Clinical Syndrome
a-/aa Silent carrier or mild alpha thalassemia minor; alpha+ thalassemia trait
a-/a- Homozygous alpha+ thalassemia or --/aa alpha0 thalassemia trait
a-/-- Hemoglobin H disease
--/-- Hydrops fetalis or homozygous alpha thalassemia; Barts hemoglobin

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Frequency:
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Mortality/Morbidity: Each of the 4 genotypes has an individual clinical course. The most severe alpha thalassemia genotype, --/-- (or hydrops fetalis), is not compatible with life and results in premature, pale, bloated infants that usually are stillborn or in severe respiratory and cardiogenic distress. Death usually occurs within hours after birth. Other morbidities are discussed in Clinical.

Race: The alpha thalassemic genetic abnormalities are common in people of Asian, African, and Mediterranean heritage.
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CLINICAL @

History: Clinical courses and physical findings are different for each of the 4 genotypes. Concomitant beta chain hemoglobinopathies and beta thalassemia alter the clinical course.

DIFFERENTIALS @

Hemoglobin C Disease
Hemolytic Anemia
Iron Deficiency Anemia
Thalassemia, Beta


Other Problems to be Considered:

Beta thalassemia major
Hemoglobin E thalassemia
Hemoglobin S thalassemia syndrome
Hemoglobinopathies
Hereditary persistence of fetal hemoglobin
High hemoglobin F syndromes
Sideroblastic anemia
Thalassemia intermedia
Thalassemia minima
Thalassemia minor

WORKUP @

Lab Studies:
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Imaging Studies:

Other Tests:
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Procedures:
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Histologic Findings: Review of the peripheral blood smear may reveal target cells, microcytosis, hypochromia, and anisopoikilocytosis as a clue to the presence of a thalassemic syndrome. Most individuals with alpha2 thalassemia (trait) have only mild microcytosis, which can be differentiated from other common causes of microcytosis because these people have a serum iron and ferritin concentration within the reference range.

TREATMENT @

Medical Care:

Surgical Care:

FOLLOW-UP @

Prognosis:
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Patient Education:
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MISCELLANEOUS @

Medical/Legal Pitfalls:
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Caption: Picture 1. Peripheral smear from a patient with hemoglobin H disease showing target cells, microcytosis, hypochromia, and anisopoikilocytosis. Morphological abnormalities are similar to those observed in beta thalassemia. In alpha2 thalassemia (silent trait) only mild microcytosis is observed.
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Picture Type: Photo
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