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- 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.
- 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
- 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).
- 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.
- 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
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.
Commonly Associated Conditions