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Hassan I. Yahya, Khalid J. Khalel, Nasir A.S. Al-Allawi and Ferial Helmi

Abstract: To estimate the prevalence of thalassaemia genes in Baghdad, a study was made of 502 randomly selected pregnant women attending a major maternity care clinic in the city. A reduced mean corpuscular volume (MCV) of 80 fl was used as a screening test for thalassaemia in this population followed by battery of tests including haemoglobin analysis and iron studies to confirm the diagnosis using approach 22 cases were diagnosed b-thalassaemia trait five a-thalassaemia one case db-thalassaemia based on these figures estimated prevalence rates b- a- traits baghdad would be 4 1 0 2 respectively study also includes discussion above findings context those reported other neighbouring countries.

Introduction

Thalassaemia syndromes are inherited defects in the rate of synthesis of one or more of the globin chains of haemoglobin. These disorders are widely distributed throughout the world, but occur in considerable frequencies in Mediterranean, Indian, south-east Asian and Middle Eastern populations [1]. Some studies have focused on the prevalence of thalassaemia genes in some Middle Eastern countries [1-4], but none were from Iraq, in spite of evidence suggesting that thalassaemias are not uncommon among Iraqis [5].

The aim in this study was to address this issue, by utilizing electronically measured mean corpuscular volume (MCV), coupled with a battery of confirmatory haemoglobin (Hb) and iron studies [6], to screen and confirm the diagnosis of thalassaemia in an obstetric population attending a major maternity care clinic in central Baghdad.

Baghdad, virtually at the heart of Iraq, has a population of about 4 million people (around 25% of the population of Iraq). It is the major business and cultural centre in Iraq and has always attracted people from all over the country. The bulk of these people have become permanently integrated over the decades, many through intermarriage, with the population of the city. Thus, unlike most other cities in Iraq, Baghdad's population is rather heterogeneous with most ethnic groups being represented to one extent or another.

Materials and methods

The study included 502 pregnant women (aged 15-45 years) in their second (306 women) and third trimesters of pregnancy (196 women). The subjects were randomly selected over a three-month period (1 May to 31 July 1990) from pregnant women attending a large maternity care clinic (Sheikh Omar Maternity Care Centre) in central Baghdad.

Full blood counts were performed on all subjects using an electronic Coulter S-plus counter. The Coulter counter was calibrated each day using a calibrant material provided by the manufacturers. Based on these blood counts, all subjects with microcytosis (as defined by an MCV <80 fl were investigated further these investigations included may-gr nwald and giemsa-stained blood smears reticulocyte counts hb h preparations haemoglobin electrophoresis on cellulose acetate strips ph="8.6)," a sub>2 quantification (Marengo-Rowe method), Hb F quantification (Betke et al. method), serum ferritin by radio-immunoassay (ferritin kit—Amersham International UK) and serum iron and total iron binding capacity (atomic absorpion spectrometry) [7]. These investigations were performed by standard laboratory procedures as detailed by Dacie and Lewis [8], except where otherwise specified.

Results

Microcytosis was found in 98 of the 502 (19.5%) pregnant women investigated. bthalassaemia heterozygosity (b-thalassaemia trait) was identified in 22 (22.4%) of these microcytic subjects, based on elevated Hb A2 level (>3.5%; normal range in our laboratory 1.7% to 3.5%). Hb A levels ranged in this category of patients between 3.8% and 6.1%, while Hb F levels ranged between 0.6% and 4.2%, with 35.4% having an increased F level (>1%). Furthermore, when the predictive value of MCV was utilized to categorize patients into those with b° or b+ mutations (MCV >66.96 fl carries a b⁺ mutation as proposed by Rund and colleagues [9]), 45.5% of bthalassaemia cases had the b° mutation, the rest b⁺.

db-thalassaemia heterozygosity (trait) was identified in one subject based on the presence of microcytosis with increased Hb F (17%) and low Hb A (2%). Red-cell indices in this patient were a haemoglobin level of 10.49 g/dl, MCV of 71.9 fl, mean corpuscular haemoglobin (MCH) of 22.7 pg and a red cell count of 4.65 ´ 10¹² per litre.

a-thalassaemia trait, on the other hand, was diagnosed in five subjects, based on the presence of microcytosis, with normal Hb A₂ and F and normal serum ferritin level (i.e. by exclusion of b- and db-thalassaemia, and iron deficiency as causes of microcytosis). No cases with haemoglobin H disease were identified in the studied cases. The remaining 70 cases with microcytosis had iron deficiency, based on reduced serum ferritin levels (<10 mg l it is noteworthy that when a 15 transferrin concentration was used to identify iron-deficient cases managed pick up all such as detected by serum ferritin except one this indicates the high level of reliability latter approach and thus future screening studies in our country could utilize instead more expensive less readily available assays p>

Based on the above results the projected prevalence of b-thalassaemia trait in Baghdad is 4.4%, that of a-thalassaemia trait is 1.0% and that of db-thalassaemia trait is 0.2%. The full haematological profile of a- and b-thalassaemia, compared with cases of microcytosis due to iron deficiency are outlined in Table 1.

Discussion

Malaria was endemic throughout Iraq (including Baghdad) until the late 1950s (data from the records of the Centre for the Control of Communicable Diseases, Baghdad). It would not be unexpected to find thalassaemia genes prevalent in Baghdad, or in other parts of Iraq, in view of the theory of malaria selection [1] which has been offered as an explanation of the high prevalence rates observed in many parts of the world, including the Arabian Peninsula [1-4,10].

The prevalence rate of b-thalassaemia trait observed in this study is intermediate between those reported from Saudi Arabia and that from Turkey (Table 2). The findings of relatively equal numbers of b⁺ and b° mutations in subjects in this study (based on the predictive value of the MCV) [9], although requiring confirmation by proper DNA studies, is quite interesting and appears to be different from preliminary reports from Saudi Arabia implying that the large majority of their mutations are b⁺ [4].

a-thalassaemia is, however, quite common in the Arabian Peninsula [2,4], and although the prevalence rate in Baghdad, as found in this study, is much lower (Table 2), preliminary reports from the Basra area, in the southern part of Iraq, suggest a prevalence rate of about 20% (Dr D. Al-Shawi, personal communication, 1992). This latter figure is nearer to those from the Arabian Peninsula. a-thalassaemia in Iraq according to the experience of the authors is mostly caused by an a⁺ defect, since haemoglobin Bart's hydrops fetalis has not been reported, while haemoglobin H disease is rare. Comprehensive studies from Saudi Arabia have also implicated a⁺ defects to be almost solely responsible for their a-thalassaemia [11]. The latter point is important, and would imply that the low prevalence rate of a-thalassaemia obtained in this study may be an underestimation, since it is well known that a proportion of a⁺ heterozygotes would be missed if the MCV is used as a screening test [12]. However, reliable conclusions on the molecular pathology of thalassaemia in Iraq will eventually require appropriate DNA studies.

While a-thalassaemia has never been a health problem in Iraq, b-thalassaemia in its homozygous state is [5]. It is the authors' opinion that the high prevalence rate of heterozygous b-thalassaemia, and that of consanguineous marriages in the community, in addition to high morbidity and mortality rates, and the heavy burden imposed on the health services in association with homozygous thalassaemia, should prompt the health authorities to establish an effective prenatal diagnostic programme. Such a programme could only be possible by initiating research programmes to determine the molecular pathology of this type of thalassaemia in Iraq. Moreover, further studies to estimate the prevalence of thalassaemia in other regions of the country, utilizing a similar approach as in the current study, is of prime importance in order to establish a comprehensive national programme to combat this important health problem.

References

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