Beta Thalassemia (Mediterranean Anemia), HBB Gene

Definition

An inherited blood disorder in which not enough hemoglobin can be produced because of a defect in the HBB gene, which encodes the beta chain of hemoglobin.

CRITICAL FOR CYPRUS, carrier frequency:

PopulationCarrier frequency
Cyprus14%
Sardinia12%

Beta thalassemia is more common in populations of Mediterranean origin; the highest known carrier rate belongs to Cyprus. In other words, approximately one in every 7 Cypriots is a carrier.

This explains why thalassemia carrier screening is so important in the region AdaGen serves. Premarital screening programs are implemented in many Mediterranean countries for exactly this reason.

Three clinical forms:

FormPresentation
Thalassemia major (Cooley anemia)Severe form, requires regular blood transfusions from early childhood. Presents between 6 and 24 months of age with pallor, growth retardation and enlargement of the liver and spleen
Thalassemia intermediaMilder anemia, regular transfusions are not required from childhood. Variable course; complications such as leg ulcers and pulmonary hypertension may occur
Thalassemia minor (carrier state)Heterozygous carrier, typically symptom-free, but microcytosis and mild anemia are seen

A commonly confused point: Thalassemia minor (carrier state) is not a disease. Because of the mild anemia and small red blood cells (low MCV), it is frequently confused with iron deficiency anemia, and unnecessary iron treatment may be given. The distinction is made by hemoglobin electrophoresis.

Diagnosis:

  • In patients under 12 months: Detection of biallelic pathogenic variants in HBB by molecular genetic testing + supportive laboratory findings
  • In older patients: Hemoglobin electrophoresis, absence/reduction of HbA, increase in HbA2 and HbF

Inheritance

Autosomal recessive

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