Southeast Asian ovalocytosis is a blood disorder that is similar to, but distinct from

hereditary elliptocytosis Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive ...

. It is common in some communities in

Malaysia Malaysia ( ; ) is a country in Southeast Asia. The federal constitutional monarchy consists of thirteen states and three federal territories, separated by the South China Sea into two regions: Peninsular Malaysia and Borneo's East Mal ...

and

Papua New Guinea Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...

, as it confers some resistance to cerebral Falciparum

Malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...

Pathophysiology

Southeast Asian ovalocytosis

It is hereditary haemolytic 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 Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans. Band 3 anion transport protein is a phylogenetically-preserved ...

, which lies in the cell membrane itself. The band 3 protein normally binds to another membrane-bound protein called

ankyrin Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral mem ...

, 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 -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

of the band 3 protein, reduced

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

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 Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region ...

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 This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

depletion of ATP * A reduction in expression of multiple

antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

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 Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...

, ''

Plasmodium falciparum ''Plasmodium falciparum'' is a unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female '' Anopheles'' mosquito and causes the ...

''. 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 Madang is a province of Papua New Guinea. The province is on the northern coast of mainland Papua New Guinea and has many of the country's highest peaks, active volcanoes and its biggest mix of languages. The capital is the town of Madang. ...

, where malaria in endemic, is a good example of

natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...

. 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 Intracellular parasites are microparasites that are capable of growing and reproducing inside the cells of a host. Types of parasites There are two main types of intracellular parasites: Facultative and Obligate. Facultative intracellular pa ...

, 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 An orifice is any opening, mouth, hole or vent, as in a pipe, a plate, or a body * Body orifice, any opening in the body of a human or animal *Orifice plate, a restriction used to measure flow or to control pressure or flow, sometimes given specia ...

that the parasite squeezes through. These band 3 proteins act as

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

for the parasite. Normally a process much like

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. ...

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

Diagnosis is based on presence of ovalocytes on a peripheral blood smear in absence of haemolysis, and should be differentiated from other forms of hereditory elliptocytosis and hereditary spherocytosis. Genetic assays such as PCR amplification may be used to confirm mutation of the SLC4A1 gene.

Treatment

Homozygous SAO appears to be largely incompatible with life, although there have been reports of individuals surviving till adolescence with prompt intervention. Patients with heterozygous SAO are largely asymptomatic or may present with only compensated haemolytic anemia, hence treatment is generally not necessary. Patients with severe haemolytic anemia may require splenectomy.

References

External links