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Background: The retinopathy is an uncommon complication in individuals with sickle cell trait except for the cases of sickle cell trait associated with systemic arterial hypertension, diabetes mellitus, syphilis, tuberculosis and sarcoidosis., Case Presentation: A retinopathy in a 16 year-old child with no history of consanguinity in the parents revealed a sickle S trait associated to heterozygous alpha thalassemia. His mother has Sickle cell anaemia (Hb SS) and his father is a carrier of heterozygous alpha-thalassemia status that it was unknown before., Conclusion: This case report describes a proliferative retinopathy in a 16 year-old patient with co-inheritance of heterozygous alpha + -thalassemia and sickle trait.

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6-35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, -3.7 kb alpha-globin chain deletion, glucose-6-phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for α(+) -thalassaemia. The Hp 2-2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P = 0.005). After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L(-1) ), iron deficiency (ferritin < 12 μg L(-1) ) or vitamin A deficiency (RBP < 0.7 μg L(-1) ), the prevalence of anaemia among those without α(+) -thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common among pre-school children in western Kenya and are important contributors to anaemia., (© 2012 JohnWiley & Sons Ltd.)

Background: The sickle cell trait is a benign asymptomatic condition that should not ordinarily be associated with clinical manifestations of a haemoglobinopathy., Method: This is a case control study of sickle cell trait patients who presented with symptomatology of a haemoglobinopathy. HbA2, HbF and HbS levels as well as the haematocrit and the peripheral film pictures of 10 symptomatic individuals (patients) with the sickle cell trait were compared with those of 20 asymptomatic individuals (controls) with the sickle cell trait., Results: The mean HbA, of the cases was 4.9% compared to the mean of 2.2% for the controls (p < 0.0001). Nine of the patients and none of the controls had a raised HbA, (> 3.5%). The mean HbF of the patients was 5.6% with a range of 1.2-14.0% while the mean of the control was 2.0% and a range of 0. 7-8.4% (p = 0.006). Six (30%) of the controls had normal HbF level (<1%) while none of the patients had a normal HbF level. The mean haematocrit of the patients and controls were 0.33 and 0.37 respectively (p = 0.009). HbS level was below 40% in both groups. Pregnancy did not significantly affect the mean HbF, the mean HbF for pregnant and non-pregnant cases were 2.1% and 3.8% respectively., Conclusion: These findings suggest that the prevalence of the thalassaemia trait may be higher among Nigerians than previously thought with the clinical severity masked by the co-inheritance of other genes like thalassaemia that occur frequently in the same population.

Unlabelled: Concepts allied to ethnicity are increasingly coming under question as legitimate variables for use in health research. A randomised controlled trial of two ethnicity screening questions for ascertaining risk of carrying genes associated with sickle cell and thalassaemia illustrates the challenges and limitations of assessing an association of social constructs and genetic statuses., Objectives: To evaluate two candidate ethnicity screening questions in antenatal screening programmes in low, mixed and high sickle cell prevalence areas, and to identify time taken in administration of the questions by use of the following measures: (1) Proportions of respondents with missing ethnicity data and/or significant changes in ethnic/family origins upon re-interview. (2) Numbers of carriers of clinically significant haemoglobin disorders missed by ethnicity screening questions. (3) Time taken to explain screening question for sickle cell disease (SCD)/thalassaemia and obtain ethnic/family origins. (4) Proportion of clients providing usable ethnic/family origins data. (5) Reported ethnic/family origins in pregnant women at first booking with midwife., Design: Ten-month (September 2002-June 2003) questionnaire study with random allocation to two self-administered ethnicity questions, comparison with laboratory results and results from re-interview. The settings were antenatal booking clinics in four geographical areas of England of varying expected foetal prevalence of SCD: very high (29.75 per 10,000 pregnancies); high (8.2); mixed high and low (1.29); and low (0.18). The subjects were 4,559 pregnant women at first booking with midwife., Results: Proportions of respondents with missing ethnicity data and/or significant changes in ethnic/family origins upon re-interview were 4.33% (CI 2.63-6.68%) for a category-based question and 9.45% (CI 6.86-12.61%) for a binary plus open-ended question. Proportions of carriers missed were 5.74% (CI 2.34-11.46%) and 9.71% (CI 4.75-17.13%) by category-based and binary plus open-ended questions, respectively. Average time taken to ascertain ethnic/family origins for screening was between 2.17 and 5.12 minutes in different areas, and up to 15 minutes at the 95th centile. Usable ethnicity screening data was missing in 2.94% of instances. Errors in interpretation or missing data were 3.2% for a category-based question and 4.71% for a binary plus open-ended ethnicity question. Ethnicity Question A produces fewer cases of missing or misinterpreted data (p < 0.001)., Conclusions: A category-based ethnicity screening question was more effective than a binary plus open-ended question. Using the more effective question, 5.74% (CI 2.34-11.46%) of significant haemoglobinopathies will be missed in a selective screening programme, and 4.33% (CI 2.63-6.68%) of replies to an ethnicity screening question will be unreliable when compared to information given upon re-interview. In specific carefully circumscribed situations, namely, in antenatal screening for sickle cell and thalassaemia, it is possible to measure the degree of association between social constructs of ethnicity and health status in a manner that may help in effecting policy decisions.

Hemoglobinopathies are the most common single gene disorders in man. There are several hundred of these disorders though the thalassemias -- alpha and beta and the sickling disorders make up the vast majority. Recent advances in the understanding of the hemoglobin structure and the genetics of its synthesis has contributed significantly to the understanding of these diseases. Disorders include those with reduced globin synthesis, abnormal globin chains and failure to switch globin chain synthesis at the appropriate age. This review focuses on the clinical features, diagnosis and management strategies of the alpha and beta thalassemias, the sickling disorders and touches on a few rarer hemoglobinopathies. It also emphasizes prevention strategies and chronic transfusion safety in countries like India where there are limited resources.

In Bahrain and neighbouring countries inherited disorders of haemoglobin, i.e. sickle-cell disease, thalassaemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency, are common. As part of the National Student Screening Project to determine the prevalence of genetic blood disorders and raise awareness among young Bahrainis, we screened 11th-grade students from 38 schools (5685 students), organized lectures and distributed information about these disorders. Haemoglobin electrophoresis, high performance liquid chromatography, blood grouping and G6PD deficiency testing were performed. Prevalences were: 1.2% sickle-cell disease; 13.8% sickle-cell trait; 0.09% beta-thalassaemia; 2.9% beta-thalassaemia trait; 23.2% G6PD deficiency; 1.9% G6PD deficiency carrier. Health education, carrier screening and premarital counselling remain the best ways to reduce disease incidence with potentially significant financial savings and social and health benefits.

We have determined the beta S haplotypes in 709 patients with sickle cell anemia, 30 with SC disease, 91 with S-beta-thalassemia, and in 322 Hb S heterozygotes from different countries. The methodology concerned the detection of mutations in the promoter sequences of the G gamma- and A gamma-globin genes through dot blot analysis of amplified DNA with 32P-labeled probes, and an analysis of isolated Hb F by reversed phase high performance liquid chromatography to detect the presence of the A gamma T chain [A gamma 75(E19)Ile----Thr] that is characteristic for haplotype 17 (Cameroon). The results support previously published data obtained with conventional methodology that indicates that the beta S gene arose separately in different locations. The present methodology has the advantage of being relatively inexpensive and fast, allowing the collection of a vast body of data in a short period of time. It also offers the opportunity of identifying unusual beta S haplotypes that may be associated with a milder expression of the disease. The numerous blood samples obtained from many SS patients living in different countries made it possible to compare their hematological data. Such information is included (as average values) for 395 SS patients with haplotype 19/19, for 2 with haplotype 17/17, for 50 with haplotype 20/20, for 2 with haplotype 3/3, and for 37 with haplotype 31/31. Some information on haplotype characteristics of normal beta A chromosomes is also presented.

In the present study, the levels of fetal hemoglobin (HbF) in sickle cell anemia patients were compared with sickle cell trait, beta thalassemia major and control. The mean HbF levels in beta thalassemia major and sickle cell anemia were 51.62 and 19.63% respectively. However, when the amount of HbF was expressed in terms of gram hemoglobin per deciliter whole blood, the mean values were 2.88 and 1.81 respectively between the two groups, suggesting that the genetic mechanism controlling the different threshold levels of increased HbF in these disorders could probably be similar. The elevated. HbF level in sickle cell anemia along with moderate hematologic profile observed in the present study is suggested to provide amelioration of the clinical severity unlike in beta thalassemia major where despite raised HbF levels, the severe clinical implications are attributed to marked imbalance in the globin chain synthesis.

During a 10-month period, 10 couples originating from Africa (3), the tropics (1) and the thalassemia-belt region (6), living in Switzerland, requested prenatal diagnosis of hemoglobinopathies. Hb SS (twice), Hb Bart's (Hydrops fetalis) and beta-thalassemia major were diagnosed either by gene mapping or by direct detection of the mutations in DNA amplified by the PCR procedure. Whenever it was possible to obtain fetal blood or tissue, diagnosis was confirmed. In one Vietnamese man, concomitant existence of alpha-thal 1 with beta-thalassemia resulted in an unusually high Hb level because of balanced alpha and beta globin synthesis. The 10 couples examined originated from 7 different countries and presented at least 7 different Hb pathologies. This variety of pathologies represents the main difficulty for prenatal diagnosis of hemoglobinopathies in a non-endemic country. A diagnostic approach to overcome this problem is developed.

We analyzed the mutations present in 19 patients with beta-thalassemia major, in 11 patients with Hb S-beta-thalassemia, and the beta S haplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different known beta-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The common beta-thalassemia mutations at codon 39 (C----T) and at IVS-I-110 (G----A) were also most prevalent among the Tunisian patients, while the milder T----C mutation at IVS-I-6 was not found. All mutations cause a beta 0-thalassemia or a severe beta + -thalassemia [T----A at -30; IVS-I-5 (G----A); IVS-I-110 (G----A)] which explains the need for regular blood transfusions in the thalassemia major and S-beta-thalassemia patients. Nearly all sickle cell anemia patients carried the beta S mutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of the beta S haplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in the G gamma and A gamma promoter sequences, specific for this haplotype.

A trimodal distribution of the amounts of Hb S in 56 sickle cell heterozygotes was observed. The variable amounts of Hb S were directly related to the mean cell volume and the mean cell Hb and were a result of the difference in net synthesis of Hb S due to the presence of the alpha-thalassaemia. Double heterozygotes for the Hb S and alpha-thalassaemia-1 genes, besides having a lower amount of Hb S in the red blood cells, were found to have lower Hb and slightly elevated Hb A2 levels.

Hematologic and globin synthesis studies were performed in a black American family in which the genes for alpha-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait + alpha-thalassemia; mother, HbC trait + alpha-thalassemia, propositus, HbSC + alpha-thalassemia; older sibling, alpha-thalassemia trait; and younger sibling, hemoglobin H disease. The child with HbSC-alpha-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2, 3-diphosphoglycerate (2, 3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin H disease exhibited 26% Bart's (gamma4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin H disease appeared, with HbH making up 6.5% of the total hemoglobin.

A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

In a family of Low-Zaïre, a child with sickle cell beta+-thalassaemia disease, aged 7, presented 33.6% haemoglobin A. The clinical evolution was benign, except for the occurrence of an extensive bilateral ischemic necrosis of the ribs. This is the third case of sickle cell thalassaemia with the haemoglobin phenotype SFA reported in Zaïrians, whereas the SF phenotype has repeatedly been found: beta+-thalassaemia seems therefore much rarer in Zaïrians than betadegrees-thalassaemia. Besides the thalassaemia trait and the sickle cell trait, hereditary elliptocytosis was also segregating in this family; double heterozygotes for Hb S and elliptocytosis or for beta-thalassaemia and elliptocytosis did not show any definite sign of genetic or clinical interaction between both traits.

Recent advances in molecular genetics have permitted detailed study of the human alpha-globin genes and the causes of alpha-thalassemia. In this review, we examine the causes of alpha-thalassemia in the black population and the consequences of the interactions between alpha-thalassemia and structural hemoglobin variants.

In a study in northern Liberia of the malaria and beta-thalassaemia hypothesis, the frequencies of beta-thalassaemia and HbS traits were 9.1 and 3.4% in the Mano and 9.5 and 1.7% in the Gio tribal samples. HbC and HbN were present at low frequency. G6PD deficiency was found in 16% of males. An observed increase with age of beta-thalassaemia trait frequencies was consistent with the selection hypothesis. However, we could not entirely exclude that associated iron deficiency influenced the results in the six to 11 month age group. Malaria was holoendemic; Plasmodium falciparum predominated, P. malariae and P. ovale were also identified. Plasmodium falciparum prevalence rates were similar in normal and beta-thalassaemia trait children but parasite densities were consistently lower in the latter. Using the criterion of a falciparum parasite density of 1 x 10(9) 1(-1) or greater to indicate a potentially important infection, the relative risk in beta-thalassaemia traits one to four years old from the cross-sectional study was 0.45 (upper 95% confidence interval 0.79) and 0.41 (0.61) in two to nine year trait carriers from a longitudinal study. Plasmodium falciparum gametocyte rates were lower in beta-thalassaemia trait children (P less than 0.005). The geometric mean titre of P. falciparum antibodies was lower in beta-thalassaemia trait children from the one to four year group (P less than 0.05). Otherwise immunological studies showed little difference between the different Hb types. Parasitological findings were consistent with relative resistance of HbS trait carriers towards P. falciparum infection. We found no evidence for relative resistance of beta-thalassaemia traits towards P. malariae infection nor that G6PD deficient males were more resistant to P. falciparum than those with normal activity. We conclude that the results are consistent with relative resistance of beta-thalassaemia trait carriers to P. falciparum malaria.

The rarity of hemoglobin (Hb) H disease in combination with sickle trait may be due in part to the absence of actual Hb H in individuals who, nonetheless, have inherited the deletion of three alpha-globin genes. We describe here a boy with persistent microcytic, hypochromic anemia despite adequate iron stores, who exhibited splenomegaly with a normal reticulocyte count and only rare inclusions in circulating erythrocytes. Starch gel electrophoresis and isoelectric focusing at age 5 yr showed 21% Hb S, persistent Hb Bart's, but no Hb H. Recticulocyte alpha/non-alpha globin chain synthesis ratio was 0.58 at age 5. The mother (Asian) had laboratory evidence of alpha-thalassemia trait and the father (Black) had sickle trait. The nature of alpha-thalassemia in this patient was investigated both by liquid hybridization and by the Southern method of gene mapping, in which DNA is digested with restriction endonucleases and the DNA fragments that contained the alpha-globin structural gene identified by hybridization with complementary DNA. The patient had only one alpha-globin structural gene, located in a DNA fragment shorter than that found in normal or alpha-thalassemia trait individuals, but similar to that present in other patients with Hb H disease. Morphologic studies of bone marrow by light and electron microscopy revealed erythroid hyperplasia with inclusions in polychromatic and orthochromatic erythroblasts, suggesting early precipitation of an unstable hemoglobin. The lack of demonstrable Hb H may be the result of both diminished amounts of beta(A) available for Hb H formation (since one beta-globin gene is beta(S)) and the greater affinity of alpha-chains for beta(A) than beta(S)-globin chains leading to the formation of relatively more Hb A than Hb S. The presence of a beta(S) gene may thus modify the usual clinical expression of Hb H disease.

We have determined the frequency of deletional alpha-thalassemia in black populations in the USA and Africa that harbor sickle cell anemia. In normals, the frequency of the chromosome bearing a deletion of one of the two normal alpha gene loci, designated (-alpha), ranged from 0.12 to 0.16, and in sickle trait subjects, the frequency ranged from 0.18 to 0.20. By contrast, in sickle cell anemia subjects, the frequency was significantly greater and ranged from 0.22 to 0.33. Analysis demonstrated that the greater frequency in the last group was primarily a result of an increased number of subjects with alpha-thalassemia trait (also called homozygous alpha-thalassemia-2). In addition, the frequency of the (-alpha) chromosome was found to increase progressively with age, supporting the hypothesis that alpha-thalassemia is favorable to the survival of subjects with sickle cell anemia. Thus, individuals who inherit alpha-thalassemia and sickle cell anemia may represent a subgroup of patients with a longer life expectancy.

A total of 102 apparently healthy and randomly selected Turks who either immigrated from Western Thrace or were still living there were studied for haemoglobin variants, high Hb A2 beta thalassaemia, G6PD deficiency, and haptoglobin types. The incidence of haemoglobins S and O Arab were 2.9 and 3.9% respectively. The incidence of high A2 beta thalassaemia was 10.8% and that of G6PD deficiency 5%. The gene frequencies of Hp1 and Hp2 were 0.326 and 0.674, respectively.

Sickle cell thalassemia in an Israeli family of Indian extraction is described. The family demonstrates the segregation of the betaS- and beta-thal genes and the interaction phenomenon known to exist in this condition is demonstrated clearly in the propositus.

A Turkish Cypriot family was investigated for suspected heterozygous sickle cell disease, which had been reported in a maternal branch of the family resident in England. Two maternal grandparents were of African Negro origin. Pseudosickling was noted in members of the family who were found to have an abnormal hemoglobin fraction. This abnormal fraction proved to be Hemoglobin Setif (alpha 94 Asp leads to Tyr). Family studies demonstrated the presence of this hemoglobin in varying proportions in the mother and 2 of the 4 children. alpha and beta thalassemia traits are also present in several family members.

The Indian rubber estate workers in Negri Sembilan, Malaysia, who originated from Orissa in India were found to have a high frequency of Hb S (Joishy SK, Hassan K: Clin Res 28:280, 1980). Unlike the usually severe clinical picture of sickle cell anemia seen in African and American blacks, the clinical picture of the disease in this population was mild and many have reached old age. We studied the leukocyte DNA of 12 patients with sickle cell anemia, ranging in age from 4 to 61 years and 30 sickle cell trait carriers, ranging in age from 7 to 63 years, for the presence of alpha-globin gene deletions by gene mapping according to Southern (Southern EM: J Mol Biol 98:503, 1975), using alpha- and zeta-globin gene probes obtained by nick translation of the alpha- and zeta-globin genes cloned into plasmid. All 12 sickle cell anemia patients were found to have alpha-thalassemia2 (alpha-thal2), either in the homozygous or heterozygous condition. Of the Hb S trait carriers, six did not have alpha-thal2 or alpha-thal1 and 24 had alpha-thal2 (15 heterozygous, 9 homozygous). Seven of these Hb S trait carriers with alpha-thal2 had an additional gene abnormality. Five of them had a fast-moving Eco RI fragment 5.6 kb long that hybridized with zeta-specific probe but not with alpha-specific probe. An unusual DNA pattern of a different type was further found in the other two. Bgl II restriction analysis showed that the alpha-thal2 was mostly of the rightward deletion alpha-thal1 genotype. None of the sickle cell anemia patients and Hb S trait carriers had deletion type alpha-thal1. The sickle cell anemia patients had very high levels of Hb F and low levels of Hb A2. The Hb S trait carriers with alpha-thal2 had relatively low levels of Hb S.

Sickle/beta thalassemia is a sickling disorder of varying severity which results from compound heterozygosity for sickle cell trait and beta-thalassemia trait. Clinical and genetic studies have shown an inverse correlation between the level of hemoglobin A and the severity of the disease. It has been suggested that the level of hemoglobin A may be a function of the severity of the beta-thalassemia defect. In this study, we use molecular biological techniques to test this hypothesis. We show that the interaction of the mildest of the beta+-thalassemia genes with the sickle gene results in a high level of hemoglobin A. However, the interaction in this case resulted in a severe sickling disorder in the absence of significant anemia. We hypothesize that a mild beta+-thalassemia gene may have two opposite effects on the clinical course of sickle/beta+ thalassemia: (1) A high level of hemoglobin A which probably confers a favorable antisickling effect and (2) decreased hemolysis leading to increased numbers of total circulating red cells, thereby increasing the blood viscosity and the propensity for sickling. The inheritance of heterozygous alpha thalassemia 2 in conjunction with the mild beta+-thalassemia gene and sickle gene in this patient may have further enhanced the latter effect and resulted in a severe sickling disorder.

The ratio of total globin alpha to beta chain synthesis was determined in reticulocytes isolated from the blood of the members of a black family, some of whom had sickle cell trait with low blood HbS concentrations (25-30%). The results support the hypothesis that sickle cell trait individuals with low HbS concentrations also carry a gene for alpha-thalassemia.

We describe here the screening of a small group of apparently healthy individuals belonging to the tribal communities of Koya Dora and Konda Reddi. A remarkably high incidence of deletion and nondeletion alpha + thalassemia mutants has been found with allele frequencies and distributions characteristic to each tribe. We have confirmed the strict relationship between Hb S levels and the number of alpha globin genes in double heterozygotes for the S gene and alpha thalassemia. In this population sample we did not find either heterozygous carriers of alpha 0 thalassemia (deletion of both alpha genes in "cis") or individuals showing hemolytic anemia due to inactivation of three alpha-globin genes (Hb H disease). Selection by malaria is most probably responsible for the prevalence of the various alpha + thalassemia haplotypes among the two tribal populations of Andhra Pradesh.

Northern Nigeria is an endemic area for sickle haemoglobin (HbS), and it is common practice in many hospitals to accept blood for transfusion from donors with sickle cell trait (HbAS). In 212 healthy HbAS blood donors, the proportion of HbS was found to range between 24-47%. The HbS levels less than 38% were presumably due to the interaction of sickle-cell gene with the alpha + thalassaemia gene. Low HbS levels and presumed alpha + thalassaemia were associated with significant microcytosis and relatively low Hb A2 and Hb F, but differences were minimal. Carriers of sickle cell trait, with or without alpha + thalassaemia, appear to be acceptable as blood donors. Beta thalassaemia was not detected amongst 710 blood-donors.

Clinical and haematological features in 41 patients with sickle cell-beta0 thalassaemia (Sbeta0 thalassemia) and in 123 age--sex matched controls with homozygous sickle cell (SS) disease were compared. Persistence of splenomegaly was more common and fetal loss less common in Sbeta0 thalassemia but other clinical features were similar in the two genotypes. Total haemoglobin, Hb A2, PCV, CCV, and red cell count were significantly higher and MCV, MCH, MCHC, and ISC counts significantly lower in Sbeta0 thalassaemia. Proportional reticulocyte counts were significantly lower in Sbeta0 thalassaemia but there was no difference in absolute reticulocyte counts. Persistence of splenomegaly and low ISC counts are compatible with decreased intravascular sickling which may result from the lower mean cell haemoglobin S concentration in Sbeta0 thalassaemia. If beneficial effects of a low MCHC can be confirmed then a carefully monitored trial of iron deficiency in SS disease may be a logical experimental procedure.

The frequencies of four major red cell genetic defects, sickle haemoglobin (Hb S), glucose 6 phosphate dehydrogenase deficiency (G6PD), and alpha and beta thalassaemia, have been determined in nearly 5000 subjects from the three major Peninsular Arab States, namely Yemen (North and South), the United Arab Emirates, and Oman. All four defects are common with an overall pattern of alpha thalassaemia greater than G6PD deficiency greater than beta thalassaemia greater than Hb A/S. However, the frequencies of these within each state varies and they are, respectively, Oman: 0.389, 0.328, 0.024, and 0.038; the United Arab Emirates: 0.165, 0.087, 0.017, and 0.019; and Yemen: 0.065, 0.062, 0.0624, and 0.0095. Two, namely alpha thalassaemia and G6PD deficiency, are extremely common, but in spite of this there appears to be a lack of observed clinical disease. For example, Hb H disease and Barts hydrops fetalis were not seen and the oxidative haemolytic syndromes are rare.

A rare association of three haemoglobin defects, viz: traits for deletion form of alpha-thalassaemia, beta-thalassaemia, and sickle cell gene, in a family of French West Indies origin, was studied both at phenotype and genotype levels. In this sickle cell beta-thalassaemia, interacting alpha-thalassaemia is shown to influence the foetal haemoglobin expression. A reverse relationship between the foetal haemoglobin level and the number of alpha genes was observed.

The sickle cell (beta s) gene occurs at a high frequency in the oasis populations of Eastern Saudi Arabia. However, as compared with the disorder in Africans, sickle cell anemia runs an unusually benign clinical course in this populations; this has been attributed in part to the relatively high levels of fetal hemoglobin (Hb F) which characterize Saudi Arabians with this condition [1, 2]. As yet, there is no satisfactory explanation for this remarkable phenomenon. To learn more about the expression of the beta s gene in Eastern Saudi Arabia, we examined its interaction with beta 0 thalassemia. We found that remarkably high levels of Hb F in this population are not restricted to individuals with sickle cell anemia but also occur in compound heterozygotes for the beta s and beta 0 thalassemia (beta 0 thal) genes. Additionally, this study has characterized sickle cell-beta 0 thalassemia (S-beta 0 thal) in Eastern Saudi Arabia for the first time.

This study was conducted in the Eastern Province of Saudi Arabia where both thalassaemia and Hb S genes occur at a high frequency. In 171 Saudi Hb S heterozygotes, the range for Hb S was found to be 17-45% with a mean of 31.0%. Frequency distribution histograms showed a trimodal distribution. Peak A, B and C had 18-28, 28-35 and 35-45% Hb S values, respectively. Determination of alpha/beta ratio showed that these findings result from interaction of Hb S with the alpha-thalassaemia gene. Peak C with mean for Hb S of 40% consisted of a majority of individuals with no thalassaemia gene, and the alpha/beta ratio was 0.98% +/- 0.06. Peak B individuals were heterozygous for alpha-thalassaemia 2 with an alpha/beta ratio of 0.80% +/- 0.06 and peak A individuals were homozygous to alpha-thalassaemia 2 with an alpha/beta ratio of 0.58 +/- 0.08. The presence of alpha-thalassaemia 2 in homozygotes results in hypochromia and microcytosis, with little effect on haematological parameters.

Abnormal haemoglobins produce a variety of anaemias which range in effect from being very mild to lethal. The most common of these are the sickle cell disorders and thalassaemias. In London, thalassaemia affects 3.5% of the Maltese population, 2.5% of the Italian population and 1.5% of the West Indian population respectively. Seventeen per cent of the Cypriot population carry a thalassaemia gene. Sickle cell disease occurs in 500:100,000 people in Britain's black population but is not exclusive to people of Afro-Caribbean origin. The gene is carried by 1 in 10 people. Sickle cell disease is statistically more prevalent among the host population than is phenylketonuria (10-12:100,000), hypothyroidism (20:100,000) and cystic fibrosis (62-63:100,000) in the general population. Although these diseases are routinely screened for at birth, there is no general strategy among district health authorities for sickle cell screening. It has been shown that of 76 health districts with a 3+% ethnic minority population, 30 of which have an ethnic minority population of 'over 10%', only 6 have a comprehensive health care policy for people with sickle cell disease.

Silent carrier alpha-thalassemia was identified in two individuals, one with sickle-cell trait and the other hemoglobin (Hb) C trait. Both are parents of a child with characteristic hematologic features of the Hb SC-alpha thalassemia syndrome, including microcytosis and an unbalanced pattern of globin synthesis. In contrast to the typical findings that accompany heterozygous Hb S or Hb C with concomitant alpha-thalassemia trait, neither of the parents had microcytosis nor a percent of the abnormal hemoglobin in their erythrocytes that was below the normal range. In both, however, globin synthesis of peripheral blood reticulocytes was unbalanced, consistent with mild alpha-thalassemia. These findings suggest that the alpha-thalassemia silent carrier may be hematologically indistinguishable from the nonthalassemic individual, even when hemoglobin S or C are present.