Disease state: mechanism of disease

Beta-thalassemia is caused by mutations in the HBB gene that can impair production of HbA1,2

People without beta-thalassemia:

Produce normal levels of HbA (composed of 2 α-globin and 2 β-globin subunits), enabling transport of oxygen to tissues and organs1,2

  • A healthy beta globin gene
    A healthy β‑globin gene
  • Production of β-globin gene is balanced with a-globin production
    Production of β‑globin gene is balanced with α‑globin production
  • Balanced globin expression leads to sufficient production of HbA
    Balanced globin expression leads to sufficient production of HbA. β‑globin is essential for forming HbA
  • Red blood cells form and function normally
    RBCs form and function normally
  • HbA in RBCs delivers adequate oxygen throughout the body
    HbA in RBCs delivers adequate oxygen throughout the body
Back
to Top
People with beta-thalassemia:

Produce reduced levels of HbA due to deficient1 β-globin synthesis, causing an imbalance of globin subunits that affects the survival of RBCs and may lead to anemia1,2

  • A mutation in the β-globin gene
    A mutation in the β‑globin gene
  • Reduced or absent production of β-globin
    Reduced or absent production of β‑globin
  • The body fails to produce sufficient levels of HbA due to deficient β-globin synthesis
    The body fails to produce sufficient levels of HbA due to deficient β‑globin synthesis
  • Fewer RBCs and abnormal RBC morphology
    Fewer RBCs and abnormal RBC morphology
  • RBCs that have reduced amounts of HbA have shorter lifespans
    RBCs that have reduced amounts of HbA, or none at all, have shorter lifespans and carry less oxygen throughout the body
THE SWITCH FROM HbF TO HbA IS NORMAL FOR A FUNCTIONING BODY AS IT GROWS1

Level of HbF and HbA after birth1,3

HbA becomes the predominant form of hemoglobin at around 6 months of age. For a person with beta-thalassemia, their body will not produce sufficient β-globin after birth, resulting in lower levels of HbA HbA becomes the predominant form of hemoglobin at around 6 months of age. For a person with beta-thalassemia, their body will not produce sufficient β-globin after birth, resulting in lower levels of HbA
Adapted from the Thalassemia International Federation guidelines.1

Healthy individual HbA
HbA becomes the predominant form of hemoglobin at around 6 months of age and is approximately 97%–98% of total hemoglobin in the red blood cells.1

Beta-thalassemia HbA
For a person with beta-thalassemia, their body will not produce sufficient β-globin after birth, resulting in lower levels of HbA.1
*HbA levels vary in patients with beta-thalassemia.

HbF
When a fetus is developing, the body begins making HbF. This starts around 6 weeks after conception, but then decreases after birth until only trace amounts are produced.4

See how a One-Time Gene Therapy Enables Production of a Modified Functional HbA (HbAT87Q)

For patients with beta-thalassemia who require regular RBC transfusions, there is a need for
additional treatment options that address the genetic cause of the disease

In patients with beta-thalassemia who require regular RBC transfusions:

Lifelong transfusions treat the symptoms of beta-thalassemia but do not address the underlying genetic cause1

Chronic supportive care can be a long-term treatment burden for these patients5

Regular transfusions provide patients with RBCs containing normal ranges of HbA, thereby alleviating anemia

Patients with beta-thalassemia who require regular transfusions may be referred to as having transfusion-dependent beta-thalassemia (TDT)

  • Over time, RBC transfusions can lead to unavoidable iron overload
  • Chelation therapy helps to reduce the iron overload caused by lifelong transfusions
Find a Qualified
Treatment Center

Stay Connected

Stay Connected

Sign up to receive emails for additional ZYNTEGLO information and resources