ABNORMAL HAEMOGLOBIN IN MALARIA ENDEMIC AREAS AND RELATED DISORDERS
Frequencies of abnormal haemoglobins in different populations very greatly, but some are undoubtedly polymorphic, having frequencies higher than expected by recurrent mutation. Four of these abnormal hemoglobins are as follows:-
- Alpha (a) thalassemia
- Beta (β) thalassemia
- Haemoglobin C
- Haemoglobin E and so on.
Alpha thalassemia attains frequencies of 30% in parts of West Africa (May, et al, 2007). Beta-thalassemia attains frequencies of up to 10% in parts of Italy; Haemoglobin E (β 26 Glu – Lys) attains frequencies of up to 55% in Thailand and other Southeast Asian countries, and Haemoglobin, C (β 6 GLu – Lys) attains frequencies approaching 20% in northern Ghana and Burkina-faso.
All of these are in malarious areas and there is evidence that the persons with alpha-thalassemia, Hbc and HbE have some degree of protection against the practice.
There is no longer doubt that malarial selection played a major role in the distribution of all these polymorphisms. Double heterozygotes for Hbs and β-thalassemia and for Hbs and Hbc, suffer from variant forms of sickle cell disease milder than SS but likely to reduce fitness before modern treatment was available.
There is a negative correlation between frequencies of Hbs and β-thalassemia in different parts of Greece and of Hbs and HbC in West Africa, where there is no adverse interaction of mutations as in the case of abnormal hemoglobins and G6PD deficiency, a positive correlation of these variant alleles in populations would be expected and is found.
Thalassemia is a condition in which there is a suppression of either alpha or beta globin chains. In beta-thalassemia, there is a reduced numbers of beta chains produced. Hence the patient’s blood may contain HbA2 (2 Alpha + 2 delta chains in globin molecules) and HbF (2 alpha + 2 gamma chains).
In alpha-thalassemia, however, levels of HbA, HbA2 and HbF are equally suppressed because all contain alpha chains which are suppressed. In such cases HbH is formed with all beta chains in the globin molecules. (Ochei and Kolhatkar, 2007).
The name is derived from the Greek Words for sea (thalassa) meaning the mediterranean Sea and blood (haima).
- GLUCOSE-6- PHOSPHATE DEHYDROGENASE DEFICIENCY
Glucose-6- phosphate dehydrogenase deficiency (G6PD) is an important enzyme in red cells, metabolizing glucose through the pentose phosphate pathway and maintaining a reducing environment. G6PD is present in all human cells but is particularly important to red blood cells. Since mature red blood cells lacks nuclei and cytoplasmic RNA they cannot synthesize new enzyme molecules to replace genetically abnormal or ageing ones. All proteins including enzymes have to last for the entire lifetime of the red blood cell, which is normally 120 days. In 1956 Alving and his colleagues showed that in some African Americans the antimalarial drug primaquine induces hemolytic anaemia and that those individuals have an inherited deficiency of G6PD in erythrocytes.
G6PD deficiency is sex linked and common in mediterranean, Africa and other populations. In Mediterranean countries such individuals can develop a hemolytic diathesis (favism) after consuming feva beans. G6PD deficient persons are also sensitive to several drugs in addition to primaquine, is the most enzyme deficiency in humans, estimated to affect about 400 million people.
There are many mutations at this locus of which two attain frequencies of 20% or greater in African and Mediterranean populations, these are termed the A-and med mutations. Mutant varieties of G6PD can be more unstable than the naturally occurring enzyme, so that their activity declines more rapidly as red cells age.
- MALARIA IN G6PD-DEFICIENT SUBJECTS
Parasite counts were significantly lower in G6PD deficient persons than in those with normal red cell enzymes.
The association has been studied in individuals which is possible because the enzyme deficiency is sex linked and female heterozygotes are mosaics due to lionization, where random inactivation of an x-chromosome in certain cells creates a population of G6PD deficient red blood cells co-existing with normal red blood cell. Malaria paradsites are significantly more often observed in normal red cells than in enzyme deficient cells.