Strong correlation of F-reticulocyte levels within sib pairs with sickle cell (SS) anemia suggests that the wide-ranging levels found in the SS population are governed by genes linked to the beta S-site. Correlations between F-cell levels in parents and F-reticulocyte levels in their children indicates that these same genes regulate F-cell production in nonanemic persons. Comparison of outcrossed and inbred SS populations suggests that relative well-being arises from homozygosity for alleles dictating high F-reticulocyte response to anemia.

Anemia, Sickle Cell↗

PubMed1980

A new genetic basis for hemoglobin-H disease.

We studied 11 families with alpha-thalassemia from the Qatif population of eastern Saudi Arabia to determine the genetic and molecular basis of hemoglobin-H disease, which is being encountered in this area with increasing frequency. The results show that there are two common alpha-thalassemia haplotypes, a deletion (-alpha/) determinant and a nondeletion (alpha alpha T/) determinant, which interact to produce a series of overlapping phenotypes. The most severe, hemoglobin-H disease, results from the homozygous state for the nondeletion determinant--a pattern of inheritance not previously recognized for this condition. Its molecular and genetic properties are thus different from those that produce the condition in Oriental or Mediterranean populations.

Child↗

PubMed1980

Hb F synthesis in sickle cell anaemia: a comparison of Saudi Arab cases with those of African origin.

Fetal haemoglobin (Hb F) synthesis has been studied in 22 cases of sickle cell anemia (SS) from Saudi Arabia and compared with an equal number of cases of African origin. Among the Saudi Arabs gamma chain synthesis ranged from 4.0% to 19.9% of the total non-alpha chain synthesis (mean 8.1%) while the corresponding range for the Negro cases was < 0.3% to 4.6% (mean 1.7%). In both groups the peripheral blood Hb F level was on average 3--4 times higher than the proportion synthesized, indicating that the selective survival of Hb F containing cells (F cells) was an important factor in determining the final Hb F levels. Among the Saudi Arab cases there was a significant negative correlation between the degree of F cell enrichment and either the Hb F level of the percentage gamma chain synthesis. No such correlation was observed among the Negro cases. A high proportion of the cases in both groups were carriers of alpha thalassaemia in addition to SS, but no effect of alpha thalassaemia on Hb F production was observed.

Adolescent↗

PubMed1980

Sickle beta 0 thalassemia in Eastern Saudi Arabia.

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.

Adolescent↗

PubMed1979

Genetic registers.

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Child↗

PubMed1978

Fetal haemoglobin production and the sickle gene in the oases of Eastern Saudi Arabia.

Fetal haemoglobin (HbF) levels have been measured in 137 normal (AA) subjects, 109 with the sickle-cell trait (AS) and 237 with sickle-cell anaemia (SS) from the oasis population of Eastern Saudi Arabia. In addition the proportion of F-cells has been estimated in 71 AA, 51 AS and 34 SS subjects. The mean HbF% (and the range of F-cells %) were: AA 0.77 (0.3--18), AS 1.38 (2.3--43) and SS 25.56 (33--98). The distribution of Hb F was always heterocellular. The influence of pregnancy accounts for most of the excess female subjects with sickle-cell trait showing raised Hb F and F-cells. Whilst the normal Arabs and those with sickle-cell trait did not differ from comparable groups of American blacks, both the % Hb F and % F-cells in Saudi Arabian patients with sickle-cell anaemia were much higher than in Blacks. The high Hb F levels in individuals with sickle-cell anaemia are not due to coexistent glucose-6-phosphate dehydrogenase deficiency or alpha-thalassaemia trait, and the Hb F level showed an inverse correlation with the degree of haemolysis. These findings indicate that the unusually elevated levels of Hb F are not due to an associated high frequency of a gene for hetero-cellular hereditary persistence of fetal haemoglobin in the oasis population, but rather from a genetically determined absolute increase in Hb F production related in some way to the SS genotype.

Adolescent↗

PubMed1978

Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects.

We studied 270 Saudi Arabs with homozygous sickle cell anemia, using chart review, a register (since 1969), and home visiting in 42 cases. Average follow-up for the total group was 10 years. Seventy-four percent of those diagnosed by age 3 years presented on screening or with merely anemia; 26% presented with illness, abnormal physical findings, or pain. Compared with American or Jamaican blacks, serious complications occurred only 6% to 25% as frequently; leg ulcers did not occur at all; the mortality under age 15 years was 10% as great; mean levels of blood hemoglobin were higher (10 g/dl), reticulocyte count was lower (5% to 6%), and mean fetal hemoglobin (HbF), which was inversely correlated with reticulocytes, was higher (22% to 26.8%). The high HbF is believed to account for the very mild clinical manifestations.

Adolescent↗

PubMed1975

Haemoglobin Bart's in Saudi Arabia.

The haemoglobin (Hb) patterns of 345 Shiite Saudi Arab cord bloods were examined by alkaline starch-gel electrophoresis. A fast-moving component, identified by structural analysis as Hb Bart's, was found in 52% of cases, the highest incidence of this variant yet recorded. The levels of Hb Bart's ranged from 0.5 to 16% of the total haemoglobin. The relative rates of synthesis of the alpha, beta and gamma-chains, measured by [3H]leucine incorporation, were estimated in 12 newborn Arab infants. There was an excellent correlation between the amount of Hb Bart's and the alpha/non-alpha-globin-chain production ratio. Furthermore there was a significant correlation between the level of Hb Bart's and morphological abnormalities of the red cells and the mean cell haemoglobin (MCH). These findings indicate that elevated levels of Hb Bart's in this population are due to the presence of alpha thalassaemia. The absence of hydrops fetalis and the rarity of Hb-H disease despite the intense inbreeding in this population, points to an alpha-thalassaemia genotype that is, in terms of phenotypic expression, intermediate between the heterozygous state for alpha-thalassaemia I and Hb-H disease. A possible molecular basis for this genotype is suggested.

Electrophoresis, Starch Gel↗

PubMed1974

Pharmacogenetics.

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Acetyltransferases↗

PubMed1973

Thalassaemia in the British.

Different forms of thalassaemia or related disorders were found in 116 people of apparently pure British stock. Among them were one family with a child homozygous for beta-thalassaemia and eight heterozygous relatives, 16 families with 83 persons heterozygous for beta-thalassaemia, two families with three persons with Hb H disease and three heterozygous for alpha-thalassaemia 1, one family with a child apparently homozygous for the "silent beta-thalassaemia gene," one family with six members heterozygous for a form of beta-thalassaemia intermedia, and three families with 11 members heterozygous for different types of hereditary persistence of fetal haemoglobin. The clinical, haematological, and haemoglobin biosynthetic findings in these persons were similar to those of patients with thalassaemia from other racial groups. The heterozygous state for beta-thalassaemia is overlooked in British patients, particularly during pregnancy, because it is not considered in the differential diagnosis of refractory anaemia. In many cases this leads to much unnecessary investigation and potentially harmful treatment.There seem to be several varieties of hereditary persistence of fetal haemoglobin production among British people. These conditions, while not causing anaemia, may cause difficulties during examination of maternal blood for fetal cells and may, if inherited with a beta-thalassaemia gene, produce an unusually high level of Hb F in a person heterozygous for beta-thalassaemia.

Adolescent↗

PubMed1973