Sickle Cell Disease in Bahrain: Coexistence and

Interaction with Glucose-6-phosphate Dehydrogenase

(G6PD) Deficiency
by Akbar M. Mohammad, MD, FAAP, Kasim O. Ardatl, MD, FAAP, and Koharik M. Bajakian
Department of Pediatrics, College of Medicine and Medical Sciences, Arabian Gulf University, Bahrain

Downloaded from https://academic.oup.com/tropej/article/44/2/70/1632631 by guest on 22 March 2021

Summary
The object was to determine the frequency of glucose-6-phosphate dehydrogenase in Bahrain!
individuals with HbS as compared to those without HbS. Haemolysates of erythrocytes from 310
Bahrain! individuals attending Health Centres were obtained, electrophoresed on cellulose acetate at
PH 8.2-8.6, and stained for G6PD. HbS was present in 125 individuals (study group) and in 185 only
HbA was present (control group). G6PD deficiency (very low to undetectable) was identified in 59
samples (47 per cent) of the study group and 35 (19 per cent) of the control group. A positive
correlation between G6PD deficiency and HbS is present in Bahrain] individuals tested. This is
similar to the situation in the Eastern Province of Saudi Arabia. We speculate that the observation
could be explained on the basis of historic endemicity of Falciparum malaria in both regions on the
East coast of the Saudi Peninsula.

Introduction consent was obtained from the patients or parents, if

Glucose-6-phosphate dehydrogenase deficiency is the
most common red cell enzyme disorder. There is marked
population difference in its incidence and it affects
millions of people throughout the world.1'2 Likewise
sickle cell hemoglobin (Hbs) is a very common genetic
abnormality reported from various parts of the world
including Bahrain.2"5
In a screening study in over 10000 Bahraini neonates
we have detected G6PD deficiency in 21 per cent. In 11
per cent of these neonates sickle cell trait (ASF) was
present and 2 per cent had sickle cell disease (SF)."
Co-existence of G6PD-deficiency with sickle Hb
(HbS) has been a subject of controversy in the literature.
The interaction of these two red cell genetic abnormal-
ities and their relation to malaria has also generated
scientific debate.
In view of the high incidence of sickle cell gene and
G6PD-deficiency in Bahrain, we would like to report the
results of our study on the co-existence of these two
defects in this population. A review of the controversy on
the subject will also be presented.
the patient was a minor.
RBC enzyme activity
The blood samples were centrifuged and the packed red
blood cells were washed with saline: a haemolysate was
prepared and the G6PD enzyme activity was measured
according to Ardati el al.6
Electrophoresis
Haemoglobin and G6PD electrophoresis was done on
cellulose acetate plates in alkaline buffer: Tris-EDTA-
Boric acid pH 8.2-8.6. The hemoglobin plate was
stained with Ponceau S, whereas the G6PD plate with
G6PD reagent was incubated at 37°C for 20 min (Helena
Laboratory, Texas, USA).
The results were conveyed to the participating health
centres to be discussed with the patients.
Statistical analysis
Statistical level of significance was determined by using
chi-square (x2) for data analysis.

Materials and Methods
Blood from 310 Bahraini individuals (152 males and 158
females) attending four major Health Centres was
collected in acid-citrate-dextrose (ACD) solution. The
age range was 5-74 years. One-hundred-and-twenty-five
of these individuals had either sickle cell disease or
sickle cell trait. They were matched with a control group
with normal haemoglobin pattern. Informed written
Results
Three-hundred-and-ten blood samples, were collected
from 152 males and 158 females. Table 1 shows G6PD
status details and gender distribution within the study
and the control groups.
Severe G6PD-deficiency (Gd~) defined as very low
enzyme activity level (< 12 U/1012 RBC) to undetectable,
was diagnosed in 59 individuals with HbS (47 per cent)
and in 35 individuals with normal hemoglobin pattern

70 O Oxford University Press 1998 Journal of Tropical Pediatrics Vol.44 April 1998
A. M. MOHAMMAD ET AL
TABLE I
Type of haemoglobin, gender and G6PD status of
individuals tested
Gender and G6PD status**
MaJes Females
Type of
haemoglobin Gd Gd" Gd Gd~ Total
AA 66 26 84 9 185
SS/SF/AS/ASF 25 35 41 24 125
Total 91 61 125 33 310
2
*X = 18.37; P< 0.001.
*• Gd (normal G6PD activity); Gd~ (reduced G6PD activity).
(19 per cent). Using chi-square (x 2 ), a significant
statistical difference was detected in G6PD-deficiency
between the two groups (P < 0.001).
Discussion
In the last four decades haemoglobin structural abnorm-
alities, such as sickle cell disease and common enzyme
defects such as G6PD-deficiency have attracted great
attention. Interaction between these genetic disorders has
been an issue of controversy. Both disorders, sickle cell
Hb and G6PD-deficiency are very prevalent in Middle
East and particularly in the Arabian Gulf Region.2*37'8
In 1963, a report from Ghana by Lewis and Hathron
revealed an increased frequency of G6PD-deficiency in
patients with sickle cell disease. They suggested a
protective effect of the enzyme deficiency and that it
rendered the disease milder.9
Several reports published between 1960 and 1990 have
emphasized increased frequency of G6PD-deficiency in
patients with sickle cell disease. In these reports there are
contradictory views on the issue of the protective effect
of the enzyme deficiency on the clinical manifestation of
sickle cell anemia. I(M2
Gelpi (1967) emphasized that a notable finding among
the Saudi Oasis subjects has been the association
between G6PD-deficiency and the sickling trait, with a
frequency of the enzyme defect three times greater
among male subjects with the sickling trait than among
male subjects with normal haemoglobin.10 Earlier, Marti
et al. (1965), in a study from Southern Tanzania on a
large group had failed to disclose an association between
the two genetic defects.13
El-Hazmi et al. (1993) in a report on G6PD-deficiency
and sickle cell genes in two Western regions of Saudi
Arabia report lack of interaction between the two
defective genes.14 In another report El-Hazmi and
Wasi (1993) show significant differences in the frequen-
cies of G6PD deficiency and HbS gene in various other
Western Saudi regions endemic for malaria.15
In our study severe G6PD-deficiency (Gd-) was
present in 47 per cent of individuals with HbS while only
19 per cent of those with only HbA had such a
deficiency, indicating a significant statistical difference
Journal of Tropical Pediatrics Vol.44 April 1998
between the two groups (P < 0.001). El-Hazmi and
Warsy (1994), in their report from the Eastern province
of Saudi Arabia, emphasize that Al-Qatif had the highest
gene frequencies for HbS and G6PD deficiency genes.16
It is historically well established that Bahrain and the
Eastern coast of Saudi Arabia were endemic for
Falciparum malaria, to which, partly, we attribute the
similarity in the correlation between the gene defects and
their interactions in the two populations. The close social
interaction culminating in inter-marriages may be
another contributing factor to the defective gene pool
of the two abnormalities.
Downloaded from https://academic.oup.com/tropej/article/44/2/70/1632631 by guest on 22 March 2021
Although malaria has been brought under control in
Bahrain, we believe it is too soon to observe effect of this
change on reduction of the abnormal genes for G6PD
deficiency and HbS. The persistent high rate of con-
sanguinous marriage in Bahrain17 will further delay the
effect of malaria control.
We conclude that in spite of the positive correlation
between G6PD-deficiency in a manner similar to the
situation in Eastern province of Saudi Arabia, there is
still need for a collaborative study between scientists
from both countries involving larger sectors of the
population to be able to shed some more light on the
unresolved aspects of these two red cell genetic
abnormalities and their interaction.
References
1. Warsy AS, El-Hazmi MAF. Glucose-6-phosphate dehydro-
genase in Saudi Arabia—a review. Saudi Med J 1987; 8:
12-20.
2. Al-Awami BH, Niazi GA, El-Mouzan MI, et al. Newborn
screening for sickle cell hemoglobinopathy and other
inherited erythrocyte disorders in Eastern Province of
Saudi Arabia, Saudi Med J 1986; 7: 502-9.
3. Mohammad AM, Al-Hilli F, Nadkami KV, Bhagwat GP,
Bapat JP, Hemoglobinopathies and glucose-6-phosphate
dehydrogenase deficiency in hospital births in Bahrain.
Annl Saudi Med 1992; 12: 536-9.
4. Pearson HA. Neonatal testing for sickle cell disease, a
historical and personal review. Pediatrics 1989; 83 (supp):
825-6.
5. Niazi GA, Rowland AK. Haemozlobinopathies: a review.
Saudi Med J 1989; 10: 340-51.
6. Ardati KO, Bajakian KM, Mohammad AM, Coe EL.
Glucose-6-phosphate dehydrogenase phenotypes in Bahrain.
Quantitative analysis and electrophoretic characterization.
Saudi Med J 1995; 16: 102-4.
7. Abu-Osba YK, Mallouh A, Salamah M, et al. Comprehen-
sive newborn screening program: Aramco experience, the
national needs and recommendations. Annl Saudi Med
1992; 12: 235-40.
8. Livingstone FB. Aspects of the population dynamics of the
abnormal hemoglobin and glucose-6-phosphate dehydro-
genase deficiency genes. Am J Hum Genet 1964; 16: 435.
9. Lewis RA, Hathorn M. Glucose-6-phosphate dehydrogen-
ase deficiency correlated with S hemoglobin. Ghana Med J
1963; 193: 131.
10. Gelpi AP. Glucose-6-phosphate dehydrogenase deficiency,
the sickling trait and malaria in Saudi Arabian children.
JPediat 1967; 71: 138-46.
71

11. El-Hazmi MAF, Warsy AS. Interaction between glucose-6-
phosphate dehydrogenase deficiency and sickle cell gene in
Saudi Arabia. Trap Geogr Med 1987; 39: 32-5.
12 El-Hazmi MAF, Warsy AS. Aspects of sickle cell gene in
Saudi Arabia—interaction with glucose-6-phosphate
dehydrogenase deficiency. Hum Genet 1984; 68: 320-5.
13. Marti HR, Schoepf K, Gsell OR. Frequency of hemoglobin
S and glucose-6-phosphate dehydrogenase deficiency in
Southern Tanzania. Br Med J 1965; I: 1476.
14. El-Hazmi MAF, Warsy AS, Bahakim HM, Al-Swailem
AR. Glucose-6-phosphate dehydrogenase deficiency and
sickle cell genes in two regions of Western Saudi Arabia,
Saudi Med 1993; 13: 251-4.
72
A M MOHAMMAD ET AL.
15. El-Hazmi MAF, Warsy AS. The frequency of HbS and
glucose-6-phosphate dehydrogenase phenotypes in relation
to malaria in Western Saudi Arabia. Saudi Med J 1993; 14:
121-5.
16. El-Hazmi MAF. The frequency of glucose-6-phosphate
dehydrogenase phenotypes and sickle cell genes in Al-Qatif
Oasis. Annl Saudi Med 1994; 14: 491-4.
17. Al-Arrayed S. Consanguinity in the State of Bahrain.
Proceedings of the Symposium on the Medical Genetics in
the Setting of Middle Eastern Populations, KACST,
Riyadh, 1994.
Downloaded from https://academic.oup.com/tropej/article/44/2/70/1632631 by guest on 22 March 2021
Journal of Tropical Pediatrics Vol.44 April 1998