Description

• A group of inherited hematologic disorders that affect the synthesis of adult hemoglobin tetramer (HbA) (1,2)[C]
• β-thalassemia is due to a deficient synthesis of β-globin chain, whereas α-thalassemia is due to a deficient synthesis of α-globin chain:
  • The synthesis of the unaffected globin chain proceeds normally.
  • This leads to inadequate hemoglobin production and unbalanced accumulation of globin chains, which then results in hypochromic, microcytic RBCs, and hemolytic anemia.
• Thalassemia is prevalent in the Mediterranean region, the Middle East, Southeast Asia, and among ethnic groups originating from these areas.
• β-thalassemia is more common in patients of African and Southeast Asian descent, whereas α-thalassemia is more common in persons of Mediterranean, African, and Southeast Asian descent.
• Types:
  • Thalassemia (minor) trait (α or β): Absent or mild anemia with microcytosis and hypochromia. No transfusion therapy is needed.
  • α-Thalassemia major with hemoglobin Barts usually results in fatal hydrops fetalis (fluid in ≥2 fetal components secondary to anemia and fetal heart failure).
  • α-Thalassemia intermedia with hemoglobin H (hemoglobin H disease): Hemolytic anemia and splenomegaly
  • β-Thalassemia major: Severe anemia, growth retardation, hepatosplenomegaly, bone marrow expansion, and bone deformities. Transfusion therapy is necessary to sustain life.
  • β-Thalassemia intermedia: Milder form; transfusion therapy may not be needed or may be needed later in life.
• Varieties common in Southeast Asians include hemoglobin H disease (a more severe form of α-thalassemia) and hemoglobin E/β-thalassemia, which often mimics α-thalassemia major in its severity.
• System(s) affected: Hematologic/Lymphatic/Immunologic; Cardiac; Hepatic
• Synonym(s): Mediterranean anemia; Hereditary leptocytosis; Thalassemia major and minor; Cooley anemia

• β-Thalassemia major causes symptoms during early childhood, usually starting at 6 months of age, and requires periodic transfusions to sustain life.
• Newborn’s cord blood or heel stick should be screened for hemoglobinopathies with hemoglobin electrophoresis or comparably accurate test, although this primarily detects sickle cell disease.

• Genetic counseling is advised for couples at risk for having a child with thalassemia and for parents or other relatives of a child with thalassemia (3)[A].
• During the 1st trimester, a chorionic villus sample at 10–11 weeks' gestation or an amniocentesis at 15 weeks' gestation to detect point mutations or deletions with polymerase chain reaction (PCR) technology

Epidemiology

• Occurs in ∼4.4/10,000 live births
• Predominant age: Symptoms start to appear 6 months after birth with β-thalassemia major.
• Predominant sex: Male = Female

• Worldwide ∼200,000 people are alive with β-thalassemia major and <1,000 patients are affected in the US.
• Worldwide, an estimated 1.5% are β-thalassemia carriers and 5% α-thalassemia carriers (4).

Risk Factors

Family history

• Inherited in an autosomal recessive pattern
• α-Thalassemia results from the deletion of ≥1 of the 4 genes, 2 on each chromosome 16, responsible for α-globin synthesis. Nondeletional forms do occur rarely. 4-gene deletion results in hemoglobin Barts causing fatal hydrops fetalis. 3-gene deletion results in hemoglobin H, 2-gene deletion is the trait, and 1-gene deletion is a silent carrier state.
• β-thalassemia is caused by any of >200 point mutations and, very rarely, deletions on chromosome 11, although probably 20 alleles account for >80% of the mutations.
• Significantly disparate phenotype with the same genotype occurs because β-globin chain production can range from near normal to absent.

General Prevention

• Prenatal information: Genetic counseling regarding partner selection and information on the availability of diagnostic tests in the event of pregnancy
• Complication prevention:
  • For offspring of adult thalassemia patients, an evaluation for thalassemia by 1 year of age
  • Severe forms:
    • Avoid exposure to sick contacts.
    • Keep immunizations up to date, including pneumococcal vaccine and annual influenza vaccine.
  • Promptly treat bacterial infections (after splenectomy, patients should maintain a supply of an appropriate antibiotic to take at the onset of symptoms of a bacterial infection).
  • Dental checkups every 6 months
  • Avoid activities that could increase the risk of bone fractures.
• Genetic counseling

Pathophysiology

Unknown; it is unclear how the imbalance of α-globin in β-thalassemia and β-globulin in α-thalassemia results in ineffective red cell genesis and hemolysis.

Etiology

Genetic

Commonly Associated Conditions

See “Complications.”