Alpha-thalassemia
Alpha-thalassemia is an inherited microcytic anemia caused by deletions of one or more of the four alpha-globin genes, ranging from a silent carrier state to fatal hemoglobin Barts hydrops fetalis, and it is distinguished from iron deficiency by a normal or elevated RBC count, a normal RDW, and normal iron studies. Diagnosis of the trait requires excluding iron deficiency and often direct globin gene testing because hemoglobin electrophoresis is typically normal, while hemoglobin H disease shows a detectable beta-globin tetramer and HbH inclusions on supravital stain.
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What this article covers
- Overview
Definition: alpha-thalassemia is an inherited hemoglobin disorder caused by deletion of one or more of the four alpha-globin genes (two on each copy of chromosome 16), producing a relative excess of…
- Epidemiology
Geographic distribution: most common in people of Southeast Asian, African, Mediterranean, and Middle Eastern ancestry; worldwide incidence exceeds that of beta-thalassemia.
- Risk factors
Southeast Asian ancestry: the cis deletion pattern raises the risk that a carrier couple will conceive a fetus with hemoglobin Barts hydrops fetalis or hemoglobin H disease.
- Pathophysiology
Gene dosage defect: the normal genome carries four alpha-globin gene copies (two per chromosome 16); each deletion reduces alpha chain output, and disease severity increases stepwise with the number of genes lost.
- Clinical features
Silent carrier (1 gene deleted): entirely asymptomatic with normal hemoglobin, normal or borderline low-normal MCV, and a normal examination; typically found only through family studies or gene testing.
- Differential diagnosis
Iron deficiency anemia: also microcytic, but distinguished by a low RBC count, an elevated RDW (versus normal in alpha-thalassemia), low ferritin, low serum iron, and high TIBC (anemia-iron-deficiency-anemia).
- Diagnosis
Establish the diagnosis by excluding iron deficiency, then confirming with globin gene testing, because electrophoresis is often normal in trait: a microcytic anemia with a normal or elevated RBC…
- Management
Silent carrier and alpha-thalassemia trait require no specific treatment: no transfusion, no iron chelation, no routine hematology follow-up; the key action is avoiding unnecessary iron…
- Complications
Hemoglobin Barts hydrops fetalis: fatal in utero or in the immediate neonatal period in the vast majority of cases.
- Prognosis
Silent carrier and trait have a normal life expectancy and no disease-related morbidity.
- Prevention
Carrier screening before conception: offer CBC with red cell indices, and gene testing if indicated, to individuals of Southeast Asian, African, Mediterranean, or Middle Eastern ancestry with microcytic anemia and normal iron studies.
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Related articles
- Beta-thalassemia
Beta-thalassemia is an inherited hemoglobinopathy caused by point mutations that reduce or abolish beta-globin chain synthesis, producing a spectrum from asymptomatic trait to transfusion-dependent thalassemia major (Cooley anemia) with ineffective erythropoiesis, marrow expansion, and hepatosplenomegaly. Diagnosis rests on hemoglobin electrophoresis showing elevated HbA2 and HbF, and management of major disease centers on chronic transfusion paired with iron chelation, since transfusional iron overload is the leading cause of death.
- Iron deficiency anemia
Iron deficiency anemia is the most common anemia worldwide, a microcytic hypochromic anemia driven by chronic blood loss, poor intake or malabsorption, or increased iron demand. A ferritin below 15 ng/mL confirms depleted iron stores, and confirmed disease in men or postmenopausal women mandates bidirectional endoscopy to find an occult gastrointestinal source before treating with oral or intravenous iron.
- Sickle cell disease
Sickle cell disease is an autosomal recessive hemoglobinopathy caused by a beta-globin point mutation that produces hemoglobin S, which polymerizes under deoxygenation to sickle erythrocytes and drive chronic hemolysis and vaso-occlusion. Diagnosis is confirmed by hemoglobin electrophoresis or HPLC showing predominant HbS, and lifelong management centers on hydroxyurea, folic acid, penicillin prophylaxis and vaccination for functional asplenia, transcranial Doppler stroke screening, and, in severe disease, transfusion, hematopoietic stem cell transplant, or gene therapy.
- Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that leaves red cells unable to buffer oxidative stress, producing episodic intravascular hemolysis with bite cells and Heinz bodies after infection, fava beans, or oxidant drugs. Diagnosis rests on a G6PD enzyme activity assay that can be falsely normal during the acute episode and must be repeated 2 to 3 months later, while management centers on trigger avoidance, supportive care, and transfusion for severe hemolysis.