Case report

Impaired structure of hemoglobin


Hemoglobin consists of four protein chains – 2x  alpha and 2x beta globin. Sickle cell anemia is an autosomal recessive disease characterized by atypical shape of red blood cells, which do not have ability to deform when passing through the capillaries and have a diminished ability to bind oxygen. This is a serious disease caused by mutation of a single amino acid in the beta-globin chain, when substitution of glutamate for valine occurs in position 6.

  1. M. Jackson was a 10-year-old African-American boy who was admitted to the hospital because of severe chest pain. It was not his first hospitalization. He had mild jaundice, he got easily tired and he was feverish. Chest X-ray was abnormal. Pressure of oxygen in arterial blood had a value of pO2 6 kPA (normal values ​​are 10-13 kPa). You assume that M. has sickle cell anemia. What molecular biological / biochemical test would you recommend to confirm your diagnosis, if you have a sample of lysed blood?
  2. How does the presence of valine in the globin cause a sickle cell formation? Would be a mutation of glutamate to aspartate equally fatal?
  3. Current treatment of sickle cell anemia is based on the use of hydroxyurea. This treatment was introduced in 1998. Hydroxyurea leads to the restoration of the expression of fetal globin. Fetal globin is usually substituted by beta globin within two months after birth (gene activity is inhibited by methylation), but fetal globin has similar features as adult globin. Try to explain how the expression of fetal globin can treat patients with sickle cell anemia.
  4. What other treatment would you suggest?
  5. How is it possible that a mutation leading to a potentially fatal disease is represented in up to 40 % of the population in certain African regions? What potential advantage have mutation carriers?
  6. Top American football player with African origin (heterozygous in mutant form of beta globin), attended the match in Mexico, at an altitude of 2200 meters above sea level. During the match he suddenly collapsed. Why could be high altitude one of the triggers of his collapse? What immediate treatment would you indicated?