32
Ν. G. PON
Finally, some Chinese in Singapore (238), Indians (219), and Papuans
(239, 240) show a deficiency in the dehydrogenase level. Quantitative
differences have also been shown to exist between the dehydrogenase
levels in whole erythrocyte population, young red blood cells, and
leukocytes of affected Caucasians and Negroes (241).
The lack of G-6-P DH thus appears to be an inheritable trait, as
judged from the descriptions in the preceding paragraphs. In fact the
mode of inheritance is sex linked and is controlled by a gene of intermediate dominance (220, 241a) giving a full expression in the hemizygous males and homozygous females and partial expression heterozygous
females. Comparison of families having color-blind sons with G-6-P DH
deficiency shows a fairly close linkage between the sex-linked colorblind locus and the enzyme-deficiency locus (242, 243).
The distribution of G-6-P DH deficiency in certain geographical localities among East Africans and among Sardinians raises several interesting
questions: Is there any relationship between enzyme deficiency and
malaria? In view of the high incidence of thalassemia (a hypochromic
microcytic anemia commonly found in the Mediterranean area) in
Sardinia, is there a connection of this disease with enzyme deficiency?
Siniscalco et al. (232) made such an analysis in Sardinia and found
positive correlations between thalassemia and frequency of the gene for
enzyme deficiency as well as between past malarial incidence and
G-6-P DH deficiency. Moreover, there was an inverse relationship between enzyme deficiency and altitude. Allison (234), while studying the
geographical distribution of enzyme deficiency in East Africa, found that
the incidence of this affliction is high in tribes near the coast and around
Lake Victoria, whereas the incidence is low in the intermediate highlands. All other populations with a high frequency of this trait reside
in the malarial region or where malaria was until recently holoendemic.
The possibility is considered then, that there is less multiplication of
malarial parasites in cells deficient in the enzyme than in normal cells,
because GSH is required for the propagation of the parasite. Indeed,
young malaria-susceptible East African children, in a region where
Plasmodium falciparum malaria is holoendemic, showed lower parasite
counts in the G-6-P DH deficient erythrocytes than in normal red blood
cells.
Both these concepts have been challenged on the grounds that only
3 out of 6 patients with thalassemia had a lack of the enzyme whereas
others with abnormal hemoglobin were not deficient at all (244). Furthermore, a close examination of the distribution pattern of the enzymedeficiency trait among various linguistic groups in New Guinea and New
Britain showed that there are extreme differences in the enzyme-
Ν. G. PON
Finally, some Chinese in Singapore (238), Indians (219), and Papuans
(239, 240) show a deficiency in the dehydrogenase level. Quantitative
differences have also been shown to exist between the dehydrogenase
levels in whole erythrocyte population, young red blood cells, and
leukocytes of affected Caucasians and Negroes (241).
The lack of G-6-P DH thus appears to be an inheritable trait, as
judged from the descriptions in the preceding paragraphs. In fact the
mode of inheritance is sex linked and is controlled by a gene of intermediate dominance (220, 241a) giving a full expression in the hemizygous males and homozygous females and partial expression heterozygous
females. Comparison of families having color-blind sons with G-6-P DH
deficiency shows a fairly close linkage between the sex-linked colorblind locus and the enzyme-deficiency locus (242, 243).
The distribution of G-6-P DH deficiency in certain geographical localities among East Africans and among Sardinians raises several interesting
questions: Is there any relationship between enzyme deficiency and
malaria? In view of the high incidence of thalassemia (a hypochromic
microcytic anemia commonly found in the Mediterranean area) in
Sardinia, is there a connection of this disease with enzyme deficiency?
Siniscalco et al. (232) made such an analysis in Sardinia and found
positive correlations between thalassemia and frequency of the gene for
enzyme deficiency as well as between past malarial incidence and
G-6-P DH deficiency. Moreover, there was an inverse relationship between enzyme deficiency and altitude. Allison (234), while studying the
geographical distribution of enzyme deficiency in East Africa, found that
the incidence of this affliction is high in tribes near the coast and around
Lake Victoria, whereas the incidence is low in the intermediate highlands. All other populations with a high frequency of this trait reside
in the malarial region or where malaria was until recently holoendemic.
The possibility is considered then, that there is less multiplication of
malarial parasites in cells deficient in the enzyme than in normal cells,
because GSH is required for the propagation of the parasite. Indeed,
young malaria-susceptible East African children, in a region where
Plasmodium falciparum malaria is holoendemic, showed lower parasite
counts in the G-6-P DH deficient erythrocytes than in normal red blood
cells.
Both these concepts have been challenged on the grounds that only
3 out of 6 patients with thalassemia had a lack of the enzyme whereas
others with abnormal hemoglobin were not deficient at all (244). Furthermore, a close examination of the distribution pattern of the enzymedeficiency trait among various linguistic groups in New Guinea and New
Britain showed that there are extreme differences in the enzyme-