Signs and Symptoms of Beta Thalassemia

The symptoms of β-thalassemia vary depending upon the severity of the HBB mutations, and the resulting production of β-globin. The most distinguishing feature of β-thalassemia is anemia. At birth, all affected infants appear entirely normal. The predominant form of hemoglobin in infants is fetal hemoglobin. Like adult hemoglobin, fetal hemoglobin also has two α-globin chains. However, instead of two β-globin chains, fetal hemoglobin has two gamma globin (γ-globin) chains, therefore is fully functional in babies with β-thalassemia. In the first few months, the fetal hemoglobin is replaced with adult hemoglobin, and the symptoms of β-thalassemia become apparent.

Beta Thalassemia Minor (carrier)

An individual that has one normal HBB gene and one defective HBB is referred to as a carrier, β-thalassemia minor or β-thalassemia trait. The defective HBB gene may have either a β⁺ or β⁰ mutation, while the normal HBB gene does not have any mutations and is fully functional. Individuals who have only one defective copy of the HBB gene often do not show any symptoms. However in a blood test, they may display increased HbA2 levels (hemoglobin made of two α-chains and two δ-chains), microcytosis (small red blood cells) and hypochromia (pale red blood cells). People with β-thalassemia minor may also have mild anemia that resembles mild iron-deficiency anemia. Several environmental and genetic factors can stimulate β-thalassemia symptoms in carriers. Inheriting genetic defects that cause alpha thalassemia or inheriting a copy of HBB that makes β-globin extremely unstable are two examples of external factors that can lead to symptoms of β-thalassemia in the presence of only one defective copy of HBB.

Beta Thalassemia Major

β-thalassemia major is also known as Cooley’s anemia and was named after the physician who first described the symptoms of β-thalassemia major. This is the most severe form of β-thalassemia. These individuals have two defective copies of HBB that both contain a β⁰ mutation preventing the production of any β-globin. Babies with β-thalassemia major have no symptoms at birth, but the signs of β-thalassemia major manifest early in life (before the age of 2 years), as the body makes the switch from fetal hemoglobin to adult hemoglobin, HbA. Children develop life-threatening anemia and jaundice, fail to thrive (slow growth) and suffer from fatigue and muscle weakness. They may also have an enlarged spleen, liver and heart as well as misshapen bones. Adolescents with β-thalassemia major will experience delayed puberty. Several other complications can arise from β-thalassemia major that include maxillary hyperplasia, dental malocclusion and cholelithiasis (gallstones), along with an increased susceptibility to infections. Blood analyses of affected individuals reveal severe microcytic and hypochromic anemia, a reduced average volume of red blood cells, low mean corpus hemoglobin (average mass of hemoglobin), anisocytosis (unequal sized red blood cells), poikilocytosis (tear drop shaped or very long cells), and nucleated red blood cells.

Beta Thalassemia Intermedia

Symptoms of an individual with β-thalassemia intermedia, can range in severity from resembling a β-thalassemia carrier to the severe symptoms occurring in a person with β-thalassemia major. They usually have moderate anemia with some hematological symptoms seen in people with β-thalassemia major. The symptoms may worsen under certain conditions like pregnancy and illness.

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Cao A, Galanello R (2010). Beta-thalassemia. Genetics in Medicine 12, 61–76;

Muncie HL, Campbell JS (2009). Alpha and Beta Thalassemia. Am Fam Physician. 80(4): 339-344.