Sickle cell anemia

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Sickle cell is an inherited disease and it is caused by a mutation that occurs in the beta sub units of the haemoglobin. Haemoglobin is a tetrameric protein made up of 2 alpha subunits and 2 beta subunits and it is the essential part of the blood responsible for oxygen transportation. Sickle cell is a disease that results from a substitution of a polar amino acid known as glutamate with a non polar one valine at position six of the beta polypeptide unit of haemoglobin. The substitution happens as a result of a change in one of the bases in the beta-globin gene from adenine to thymine[1].

As a result of this mutation, the beta polypeptide chains become sticky in low oxygen conditions because the valine sticks out of the chain and interacts with neighbouring non-polar amino acids. The molecules stick together and finally develop into a massive fibrous polymer that causes the distortion of the red blood cells into a “c” or sickle. When the sickle-cell Hb (HbS) loses an oxygen molecule, another hydrophobic patch becomes exposed in both normal Hb and HbS which the hydrophobic Valine interacts with. This causes the formation of fibrous aggregates of Hb which causes the red blood cells to distort into a sickle shape. Oxygen cannot bind to the HbS fibres efficiently therefore, the sickle cell carries less oxygen than a normal Hb. The fibres of the cell cause it to become less flexible and increases the tendency to clump[2]. As opposed to the normal cell, the sickle cell carries less oxygen and it is stiff so it cannot squeeze through blood vessels easily and therefore has a high tendency of blocking arteries that supply oxygen to the cells. This could lead to organ failure and damage for example stroke, heart attack or kidney failure[3][4][5].

Other symptoms of sickle cell anaemia include painful episodes or also known as sickle cell crises. Sickle cell crises occur when blood vessels are blocked and thus pain can be experienced for a long time. Anaemia is another symptom, where levels of haemoglobin are low in the blood causing fatigue and shortness of breath, especially while exercising[6]. The spleen can also be affected where repeated blockages cause it to damage and not function properly. This is also known as splenic sequestration. This can lead to higher vulnerability to infections, especially in younger children[7].

Newborns have a different haemoglobin structure known as haemoglobin F which consists of two alpha and two gamma subunits. This changes to 2 alpha and 2 beta subunits after around 6 months of age, however, this means sickle cell anaemia isn't usually diagnosed until infancy. Some symptoms that may be seen in infants indicating this disease are pain and swelling in hands and feet and throughout childhood, this pain can spread to the back, stomach and chest[8][9][10].

References

  1. Blood. 2011 Jul 7; 118(1): 19–27
  2. Lubert Stryer (1995). The University of Wisconsin-Madison, Biochemistry (4th edition). W.H. Freeman and Company, New York. https://www.chem.wisc.edu/deptfiles/genchem/netorial/modules/biomolecules/modules/protein1/sickle.htm
  3. Understanding Sickle Cell Disease by Mariam Bloom, Ph.D 1995
  4. http://sickle.bwh.harvard.edu/msh.html
  5. http://www.nejm.org/doi/full/10.1056/NEJM199008093230602
  6. Symptoms [Internet]. nhs.uk. 2016 [cited 10 December 2018]. Available from: https://www.nhs.uk/conditions/sickle-cell-disease/symptoms/
  7. Sickle Cell Disease: Splenic Sequestration | UW Health | Madison, WI [Internet]. UW Health. 2017 [cited 10 December 2018]. Available from: https://www.uwhealth.org/health/topic/special/sickle-cell-disease-splenic-sequestration/hw253997.html
  8. Jones,P. (2008)Genes and Disease Sickle Cell Disease. New York: Infobased Publishing p86
  9. Lubert Stryer (1995). The University of Wisconsin-Madison, Biochemistry (4th edition). W.H. Freeman and Company, New York.
  10. https://www.chem.wisc.edu/deptfiles/genchem/netorial/modules/biomolecules/modules/protein1/sickle.htm
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