Hemoglobinopathies are genetic disorders of the globin genes leading to a qualitative or quantitative abnormality of globin synthesis.
Hemoglobin
Hemoglobin consists of heme (iron + protoporphyrin) + globin.
- Primitive hemopoiesis: 2 pairs of zetta-epsilon (Hb-Gower1) or alpha-epsilon (Hb-Gower2) or zetta-gamma (Hb-Portland)
- Fetal: 2 pairs of alpha-gamma (Hb-F)
- Adult: 2 pairs of alpha-beta (Hb-A) or the much less common alpha-delta (Hb-A2)
Classification
- Abnormal hemoglobin synthesis (qualitative)
- Sickle-cell anemia
- Hemoglobin C/D/E
- Reduced rate of synthesis of alpha or beta chains (quantitative)
- Thalassemias (alpha, beta, intermedia)
Sickle-cell anemia
Sickle-cell anemia is a group of autosomal recessive disorders characterized by a defective beta-globin chain, leading to the formation of sickle-cells.
- Caused by the substitution of valine for glutamic acid in the beta chain, forming hemoglobin S.
- Hemoglobin S forms crystals in low-oxygen environments, polymerizing into long strands that distort the shape of the RBCs into a sickle shape.
- The homozygous form is the most common severe form and is often symptomatic, while the heterozygous form is most often asymptomstic.
Clinical presentation
Sickle cells can clump up and cause