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Synonym(s) -
Prevalence 1-5 / 10 000
Inheritance Autosomal recessive
Age of onset All ages
  • D56.0
  • C0002312
  • C1456873
  • D017085
  • 10043390


Disease definition

Alpha-thalassemia is an inherited hemoglobinopathy characterized by impaired synthesis of alpha-globin chains leading to a variable clinical picture depending on the number of affected alleles.


Like other globin gene disorders, alpha-thalassemia is highly prevalent in all tropical and subtropical regions (around 1/10,000), particularly in the African equatorial belt. Intermediate and severe forms of alpha-thalassemia are very rare in North America and Northern Europe (about 1/1,000,000), and are predominantly seen in immigrant populations from South-East Asia or Mediterranean countries.

Clinical description

The disease can be classified into clinical subtypes of increasing severity: silent alpha thalassemia, alpha thalassemia trait (or alpha thalassemia minor), hemoglobin H disease (HbH), and Hb Bart's hydrops fetalis. A rare form called alpha-thalassemia-intellectual deficit syndrome linked to chromosome 16 (16p13.3) has also been identified (see these terms). Alpha thalassemia trait causes microcytosis and hypochromia with absent or mild anemia (often detected on routine blood tests), generally with no other symptoms. HbH patients develop moderate hemolytic anemia with variable amounts of HbH along with occasionally severe splenomegaly, sometimes complicated by hypersplenism. Hb Bart's hydrops fetalis involves a severe deficiency in alpha-globin with serious developmental implications. Alpha-thalassemia-intellectual deficit syndrome is characterized by very mild to severe anemia associated with developmental abnormalities.


Alpha globin synthesis is regulated by four alpha-globin genes, two on each copy of chromosome 16 (16p13.3). Alpha-thalassemia most frequently results from deletion of one or both alleles (HBA1 and HBA2). More rarely, point mutations in critical regions of these genes may cause non-deletional alpha-thalassemia. Deletions of regulatory elements located upstream of the alpha-globin genes have also been found. The severity of the clinical picture is correlated with the degree of alpha-globin chain deficiency. It has been found that interactions involving non-deletional forms lead to more severe manifestations than those involving deletional forms. Deletion of 1 allele results in the silent form, 2 alleles in alpha-thalassemia trait, and 3 alleles in HbH.

Diagnostic methods

Diagnosis is based on hematologic testing of red blood cell (RBC) indices, peripheral blood smear, supravital stain to detect RBC inclusion bodies, and qualitative and quantitative hemoglobin analysis. Confirmation of diagnosis is based on molecular genetic testing.

Differential diagnosis

Differential diagnosis should include iron deficiency anemia and defects in heme synthesis. An acquired form known as alpha-thalassemia-myelodysplastic syndrome (ATMDS; see this term) has been described mainly in adult males and should also be considered. It is characterized by myelodysplasia (MD) associated with HbH.

Antenatal diagnosis

Prenatal diagnosis should be made available for pregnancies at risk for Hb Bart's hydrops fetalis or severe forms of HbH disease.

Genetic counseling

Alpha-thalassemia is transmitted in an autosomal recessive manner. Genetic counseling can be offered but may be complex due to the large number of alleles and mutations involved.

Management and treatment

Patients with silent alpha-thalassemia or thalassemia trait do not require treatment. Specific treatment is however required for other forms of the disease and may include occasional red blood cell transfusions, iron chelation, and other supportive measures.


The prognosis for carriers of silent alpha-thalassemia or alpha-thalassemia trait is very good. Neonates with Hb Bart's hydrops fetalis usually die in the perinatal period. In patients with hemoglobin H disease, the prognosis is usually good, but depends on complications and care.

Expert reviewer(s)

  • Dr Corinne PONDARRE

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