Sickle Cell Disease

Sickle cell disease is caused by a single point mutation in the gene that encodes the /3-globin chain of hemoglobin A. The result

0Oc '0Ó o.

of this mutation is an abnormal 0-globin chain in which the amino acid valine is substituted for glutamic acid in position 6. Hemoglobin containing this abnormal /3-globin chain is designated sickle hemoglobin (HbS). The substitution of the hydrophobic valine for the hydrophilic glutamic acid causes HbS to aggregate under conditions of reduced oxygen tension. Instead of the normal biconcave disk shape, many of the erythrocytes become sickle-shaped at low oxygen tension, hence the name of this disease (Fig. 9.6). Sickled erythrocytes are more rigid than normal cells and adhere more readily to the endothelial surface. Thus, sickled erythrocytes may pile up in the smallest capillaries, depriving portions of tissues and organs of oxygen and nutrients. Large-vessel obstruction may also occur, which in children frequently leads to stroke. Sickled erythrocytes are also more fragile and break down or are destroyed more quickly than normal erythrocytes.

Sickle cell disease is a homozygous recessive genetic disorder. However, heterozygous individuals may occasionally have clinical consequences at high altitude or under extreme physical stress.

0 0

Post a comment