Thalassemia

Key points

Thalassemia encompasses a group of hematologic disorders in which alpha- or beta-globin production is reduced or absent. The resulting quantitative red cell disorder is referred to as alpha or beta thalassemia, respectively. This genetic disorder can be caused by one or several gene mutations. Its phenotypes range from silent to fatal.
All patients with thalassemia should be cared for by a multidisciplinary team who can access red cell transfusion, monitor for cardiac, liver, endocrine and bone complications, and manage such complications as they arise. Access to a hematopoietic stem-cell transplant centre and transition services to adult care should also be considered.

Epidemiology

The maps below show the prevalence of alpha and beta thalassemias.

Figure 1. Global distribution of α- and β- thalassemia

Source: Weatherall, DJ. Phenotype-genotype relationships in monogenic disease: Lessons from the thalassaemias. Nature Reviews Genetics 2001;2(4):245-55.

Alpha thalassemias

Silent carriers of alpha thalassemia — people who have the alpha-thalassemia trait — usually do not require treatment. Their genetic and clinical characteristics are summarized in this table.

**Table 1: Genetic and clinical characteristics of alpha thalassemias**
Variant	Chromosome 16, gene deletions	Signs and symptoms
Alpha thalassemia silent carrier	One of four	Asymptomatic
Alpha thalassemia trait	Two of four	Asymptomatic
Hemoglobin Constant Spring	Reduced output of alpha globin	Silent or mildly symptomatic
Alpha thalassemia intermedia with significant hemoglobin H (hemoglobin H disease)	Three of four	Moderate-to-severe hemolytic anemia, a modest degree of ineffective erythropoiesis, splenomegaly, variable bone changes
Alpha thalassemia major with significant hemoglobin (Hb Bart’s)	Four of four	Causes nonimmune hydrops fetalis, usually fatal
Reprinted with permission from Alpha and beta thalassemia, August 15, 2009, Vol. 80, No. 4, American Family Physician Copyright ©2009 American Academy of Family Physicians. All Rights Reserved.

Beta thalassemias

Individuals with the beta-thalassemia trait (one gene affected) usually do not require treatment. Patients who have beta thalassemia major (two beta-globin genes affected) are usually transfusion-dependent from an early age and later require chelation therapy due to subsequent iron overload. Iron supplements should be avoided by people who have thalassemia mutations except when a child has proven iron deficiency. Iron loading is a serious complication of thalassemia major and intermedia.

Preconception genetic counselling should be offered to those at risk of having a child with thalassemia.¹

**Table 2**: Genetic and clinical characteristics of beta thalassemias
Variant	Chromosome 11, gene defects	Signs and symptoms
Beta thalassemia trait	One	Asymptomatic
Beta thalassemia intermedia	Two; mild-to-moderate decrease in beta-globin synthesis	Variable degrees of severity of symptoms of thalassemia major
Beta thalassemia major	Two; severe decrease in beta-globin synthesis	Abdominal swelling, growth retardation, irritability, jaundice, pallor, skeletal abnormalities, splenomegaly; requires lifelong blood transfusions
Reprinted with permission from Alpha and beta thalassemia, August 15, 2009, Vol. 80, No. 4, American Family Physician Copyright ©2009 American Academy of Family Physicians. All Rights Reserved.

Management of thalassemia

Canadian guidelines for the care of patients with thalassemia are available.¹

All patients with thalassemia should be cared for by a multidisciplinary team who can access red cell transfusion, monitor for cardiac, liver, endocrine and bone complications, and manage such complications as they arise. Access to a hematopoietic stem-cell transplant centre and transition services to adult care should also be considered.

Selected resources

The Hospital for Sick Children. About Kids’ Health [Handouts]. See What is Thalassemia?
Richardson M. Microcytic anemia. Pediatr Rev 2007;28(1):5-14.
Sayani F, Warner M, Wu J, et al, 2009. Guidelines for the clinical care of patients with thalassemia in Canada.

References

Sayani F, Warner M, Wu J, et al, 2009. Guidelines for the clinical care of patients with thalassemia in Canada.

Editor(s)

Andrea Hunter, MD
Anna Banerji, MD

Last updated: April, 2018