Other Hb Variants

• Clinical Hematology II, HML2143.
• The presentation introduces hemoglobinopathies, also known as "Other Hb Variants and Thalassemia-like conditions."
• Learning Objective: Describe hemoglobinopathies, addressing their prevalence and importance in the UAE.
• Topic: Describe effects of the interactions between thalassemia and hemoglobin variants.

Other Types of Hb Variants

• These variants result from a single amino acid substitution.
• Hb S (β 6 Glu → Val).
• Hb C (β 6 Glu → Lys).
• Hb E (β 26 Glu → Lys).
• Hb D Punjab (ẞ 121 Glu → Gln).
• Hb O Arab (ẞ 121 Glu→ Lys).
• Hb G Philadelphia (a 68 Asn→ Lys).

Hemoglobin C: Hb C (B 6 Glu → Lys)

• Pathophysiology: Genetic defect causes decreased Hb solubility, leading to crystal formation.
• This, in turn, causes RBCs to become rigid and destroyed in the spleen.
• Blood film shows target cells, folded, and irregularly contracted cells
• Homozygous: More than 90% Hb C and a slight increase in Hb F, not exceeding 7%.
• Hb C trait: *Asymptomatic→ No hematological abnormalities except for target cells in blood smear.
• 60–70% is Hb A, and 30–40% is Hb C

Hemoglobin D: Hb-D Punjab (B 121 Glu → Gln)

• Hb D molecules do not sickle.
• These molecules have normal solubility properties.
• Both homozygous and heterozygous conditions remain asymptomatic.
• No hematological abnormalities are present, but occasionally there is an increase in target cells.

Hemoglobin E: Hb E (β 26 Glu → Lys)

• Hb E is common in Southeast Asia.
• Homozygous individuals experience mild hemolytic anemia with target cells; the trait is asymptomatic.
• Note: The most common β-chain hemoglobin variants are Hb S and Hb C
• In trait, the abnormal Hb usually accounts for less than 50% of the total Hb (60% Hb A & 35–40% Hb S or Hb C).
• In the homozygous state, abnormal Hb constitutes 90–95% of the total Hb.

Hemoglobinopathies (Double Heterozygosity)

• Inheritance of one abnormal gene from each parent.
• Hb SC combines Hb S from one parent and Hb C from the other parent.
• Hb SD combines Hb S and Hb D.
• The Hb S/β-Thalassemia clinical picture resembles homozygous sickle cell disease.
• Hb E/ Thalassemia
• Compound heterozygosity of Hb E and thalassemia (a or β) results in moderate to severe anemia similar to thalassemia major.
• Management: As thalassemia.

Hb M (Met Hemoglobin)

• Pathophysiology: Amino acid substitution leads to stabilization of heme iron in the ferric state (Fe+3), which forms met-hemoglobin.
• Met-hemoglobin cannot bind oxygen.
• Blood turns brownish in color.
• The Hb M level is rarely more than 30%.
• Patients appear cyanotic.

Other Thalassemia-like Conditions, Hb Constant Spring

• Pathogenicity: The a-chain is elongated by 31 amino acids which reduces production, leading to unstable Hb and alpha-thalassemia-like effects.
• Homozygous: associated with Hb Constant Spring.
• Heterozygous: Asymptomatic, with normal Hb F & A₂, and Hb CS & Hb A

Hereditary Persistence of Fetal Hb (HPFH)

• Also known as δ β-thalassemia.
• Pathogenicity: Both ẞ & are defective, impairing the production of Hb A & Hb A2.
• Homozygous: Only Hb F is produced (100%).
• Heterozygous: Hb F increases to 10–30%, while Hb A2 decreases to 1–1.5%, and Hb A accounts for the rest.

Hb Lepore

• Pathogenicity: Unequal crossing over of globin genes results in a hybrid globin chain of δ globin fused with β globin.
• Homozygous individuals exhibit symptoms like β-thala intermedia. Hb Lepore make up 8-30%, with Hb F accounting for the remainder.
• Heterozygous individuals are silent carriers, containing Hb Lepore 10%, with Hb A accounting for 80–90%.

Presentation on "Other Hb Variants and Thalassemia-like conditions." Focus is on the effects of interactions between thalassemia and hemoglobin variants. Describes different types of Hb variants and their genetic defects.