Lecture 11

HbC Variant and Its Effects

• The HbC variant is caused by a substitution of glutamic acid with lysine at position 6 of the beta-globin chain.
• This variant primarily leads to the distortion of red blood cells, causing them to become rigid and take on a sickle-like shape, which can impair circulation.

Geographic Prevalence of HbC

• The HbC variant is most commonly found in West Africa and among individuals of African descent.

Alpha Thalassemia Characteristics

• Alpha thalassemia is characterized by a reduction or absence of alpha-chain synthesis, crucial for hemoglobin function.
• Each cell contains four alpha-globin genes, producing the alpha chains of hemoglobin.

Clinical Presentation of Alpha Thalassemia Minor

• Typically asymptomatic or mild microcytic anemia is present.
• Individuals often have normal life expectancy but may have slight anemia.

Symptoms of HbH Disease

• HbH disease features more pronounced symptoms, including moderate to severe microcytic anemia, splenomegaly, and skeletal deformities due to hyperplasia of the marrow.

Severe Thalassemia in Fetuses

• Beta-thalassemia, specifically the major form, can lead to severe anemia in the fetus and is often incompatible with life.

Beta-Thalassemia Gene Count

• Each cell has two beta-thalassemia genes present, one on each chromosome.

Differences Between Beta+ and Beta0 Mutations

• Beta+ mutations allow reduced production of beta-globin, while beta0 mutations lead to a complete absence of beta-globin synthesis, causing more severe symptoms.

Severity Comparison: Beta vs. Alpha Thalassemia

• Symptoms of beta-thalassemia are generally more severe due to the critical role of beta-globin in forming adult hemoglobin (HbA), leading to more significant oxygen transport issues.

Clinical Symptoms: Beta-Thalassemia Major

• Symptoms include severe anemia, growth delay, jaundice, splenomegaly, and bone abnormalities due to marrow expansion.

Hereditary Persistence of Fetal Hemoglobin (HPFH)

• HPFH is a condition where levels of fetal hemoglobin remain high in adulthood, providing some protective effects against sickle cell disease and beta-thalassemia symptoms.

Treatment for Severe Thalassemia

• Severe thalassemia often requires regular blood transfusions, iron chelation therapy, and possibly stem cell transplantation.

ZYNTELGO

• ZYNTELGO is a novel gene therapy aimed at treating beta-thalassemia by introducing functioning copies of the beta-globin gene to restore healthy hemoglobin production.

Genetics Lecture 11