Southeast Asian ovalocytosis It is hereditary hemolytic anaemia in which the red blood cell is oval-shaped. The primary defect in SAO differs significantly from other forms of elliptocytosis in that it is a defect in the gene coding for a protein that is not directly involved in the cytoskeleton scaffolding of the cell. Rather, the defect lies in a protein known as the
band 3 protein, which lies in the cell membrane itself. The band 3 protein normally binds to another membrane-bound protein called
ankyrin, but in SAO this bond is stronger than normal. Other abnormalities include tighter tethering of the band 3 protein to the cell membrane, increased
tyrosine phosphorylation of the band 3 protein, reduced
sulfate anion transport through the cell membrane, and more rapid
ATP consumption. These (and probably other) consequences of the SAO mutations lead to the following erythrocyte abnormalities: • A greater robustness of cells to a variety of external forces, including: • Reduction in cellular sensitivity to
osmotic pressures • Reduction in fragility related to temperature change • greater general rigidity of the cell membrane • Loss of sensitivity to substances that cause
spiculation of cells • Reduced anion exchange • Partial
intracellular depletion of ATP • A reduction in expression of multiple
antigens These changes are thought to give rise to the scientifically and clinically interesting phenomenon that those with SAO exhibit: a marked
in vivo resistance to infection by the causative pathogen of
malaria,
Plasmodium falciparum. Unlike those with the Leach phenotype of common hereditary elliptocytosis (see above), there is a clinically significant reduction in both disease severity and prevalence of malaria in those with SAO. Because of this, the 35% incidence rate of SAO along the north coast of
Madang Province in
Papua New Guinea, where malaria in endemic, is a good example of
natural selection. The reasons behind the resistance to malaria become clear when given an explanation the way in which
Plasmodium falciparum invades its host. This parasite is an
obligate intracellular parasite, which must enter the cells of the host it is invading. The band 3 proteins aggregate on the cell membrane at the site of entry, forming a circular
orifice that the parasite squeezes through. These band 3 proteins act as
receptors for the parasite. Normally a process much like
endocytosis occurs, and the parasite is able to isolate itself from the intracellular proteins that are toxic to it while still being inside an erythrocyte (see figure 2). The increased rigidity of the erythrocyte membrane in SAO is thought to reduce the capacity of the band 3 proteins to cluster together, thereby making it more difficult for the malaria parasite to properly attach to and enter the cell. The reduced free ATP within the cell has been postulated as a further mechanism behind which SAO creates a hostile environment for
Plasmodium falciparum. ==Diagnosis==