Gene therapy: recent advances, future directions and concerns

There is now convincing experimental evidence which suggests that gene therapy, a procedure to correct inherited disorders by molecular techniques, may become a clinical reality in the near future. The modes of gene delivery to appropriate target cells and tissues are now more specific. Of the viral and nonviral methods of gene transfer, adenovirus based vectors have produced the best clinical results. Successful gene therapy trials which have recently taken place on some selected genetic disorders, indicate that the somatic gene manipulation as shown by the long-term stable expression of the transferred genes, will be more practical and a safer approach for the time being. This is compared to germ-line therapy which involves insertion of gene into gamete forming cells in such a way that the disorders in the offspring would also be corrected. Despite all this optimism there are still many difficulties to overcome, particularly the isolation of genes and their regulatory function. Ethical and religious considerations of gene therapy are also very important as both irrational and rational fears are associated with deliberate genetic manipulation. These will dissipate eventually, once reasonable success in gene manipulation is achieved

Low mean corpuscular volume: a useful diagnostic hematological parameter for detection of alpha-thalassemia at birth

Regional variations in the incidence of alpha -thalassaemia have been reported from Saudi Arabia. In a recent study, we observed that approximately 6-7% of the Saudi Arabia National Guard [SANG] newborn population had very low mean corpuscular volume [MCV] [100 fI]. The restriction analyses data showed that 28 of 31 [90%] with low MCV [

Erythrocytic glucose-6-phosphate dehydrogenase deficiency and anaemia

This study demonstrates that glucose-6-phosphate dehydrogenase [G6PD] activity in anaemic patients is significantly increased compared with that in normal blood donors. There are inverse correlations between G6PD levels and several haematological indices. These correlations are difficult to explain as the reticulocyte counts in our anaemic patients were not greatly increased. A likely reason for these results is an effect of red cell age that is not properly reflected in the reticulocyte counts, and some unidentified factors affecting erythropoeisis may be responsible for the increased production of G6PD in these anaemic patients

Erythrocytic genetic disorders in the newborn population of the Saudi Arabian national guard

A cord blood screening programme initiated at King Fahad National Guard Hospital, Riyadh, revealed that the incidence of the commonly prevalent red cell genetic disorders was low in our newborn population. Approximately 5% had a-thalassaemia, 1% sickle cell disease and there was an overall incidence of 2.2% for severe G6PD deficiency. One-quarter of the G6PD deficient newborns were females, a significant finding in a condition known to have an X-linked mode of inheritance. This finding suggests that screening for this enzymopathy should include both sexes. In addition marked anisopoikilocytosis was detected on routine examination of cord blood films of four newborns. The clinical findings and the morphologic features of the parents' erythrocytes in two of them were highly suggestive of the genetic erythrocytic membrane defect, pyropoikilocytosis

effect of transfusing g6pd-deficient blood and prevalence of this enzymopathy in a Riyadh hospital blood donor population

A study was designed in a Riyadh hospital to determine the effects of transfusing glucose-6-phosphate dehydrogenase [G6PD]-deficient blood and to evaluate the prevalence of this enzymopathy in a hospital blood donor population. Approximately 2% of Saudi blood donors [almost all male] were found to be severely G6PD-deficient and a statistically significant difference in the normal levels of G6PD was found between various ethnic donor groups. Analysis of the preliminary data on patients transfused with G6PD-deficient blood failed to reveal any changes in morphology or biochemical parameters consistent with haemolysis compared with those receiving normal units of blood. It was therefore concluded that it is unjustified to proscribe G6PD-deficient blood

Haemoglobinopathies: a review

The inherited disorders of the haemoglobin molecule are commonly known as haemoglobinopathies. Since the discovery of sickle cell haemoglobin in 1959, almost 500 human haemoglobin variants mostly rare, have been reported; about one-third manifest their presence by clinical syndromes due to alteration in the function, solubility or stability of the haemoglobin module. The range of abnormal haemoglobins and their prevalence in the Middle East remains to be determined and this concise review presents current information on haemoglobinopathies

Genes and molecular probes in haemoglobinopathies

Red cell genetic disorders constitute a major public health problem in many parts of the world. The analysis of human DNA using recombinant technology is fast becoming an integral part of the diagnosis and prevention of several types of major haemoglobinopathies. This review presents advances made in this important field and describes current methods used for antenatal diagnosis of haemoglobinopathies as a prelude to genetic counselling

Sickle cell trait in the Eastern Province of Saudi Arabia: effect of concurrent alpha-thalassemia

The proportions of sickle haemoglobin in the peripheral blood were determined in 126 asymptomatic sickle cell trait parents of SS cohort babies. The sickle cell haemoglobin [Hb S] levels ranged between 18 and 48% and the values below 38% are presumably due to the interaction of various types of alpha thalassaemia genes with sickle cell genes. The haematological paramers correlated well with the amounts of Hb S in the red blood cells and the comparison of these erythrocytic indices with sickle cell traits from north western province revealed inter-province variations in haematological values, especially the mean cell volume [MCV] and mean cell haemoglobin [MCH]. These two parameters were significantly reduced in the sickle cell heterozygotes from the Eastern province as compared with those from the north western province, in particular the Khaiber area, for which the explanation remains obscure

Measurement of glycated haemoglobins in Saudi patients with sickle cell anaemia and other haemoglobinopathies

The levels of glycated haemoglobins were determined in 284 Saudis [both diabetics and non-diabetics] from the Eastern region with normal and abnormal haemoglobin electrophoretic patterns by the boronate affinity chromatography method. A marked decrease in the level of glycated haemoglobin was observed in patients with sickle cell anaemia. A less significant decrease in glycation was noticed in patients with sickle beta 0 and beta + thalassaemia. These changes presumably reflected an altered circulatory half-life of red cells in these disorders. In diabetic patients having an abnormal haemoglobin not associated with haemolysis, the increased amount of glycation was similar to that observed in patients with normal haemoglobin