Autism and mental retardation: the genetic relationship and contribution

Autism, a neurodevelopmental disorder first described in 1943, is reviewed. The signs and symptoms of the disorder are described together with the etiological factors. The evidence for a genetic etiology of autism and its association with other genetic disorders are discussed. Possible candidate genes for autism are described

Spectrum of genetic disorders and the impact on health care delivery: an introduction

Until recently, infectious diseases and malnutrition-related disorders constituted the major cause of ill health and mortality in the world population. However, advances in treatment of such disorders and increased understanding of the molecular basis of heredity have led to genetically transmitted conditions becoming a major cause of morbidity and mortality. Several disorders, including chromosomal [Down syndrome, Turner syndrome], single-gene [sickle-cell disease, thalassaemia, glucose-6-phosphate dehydrogenase deficiency, haemophilia, inborn errors of metabolism] and multifactorial disorders [coronary artery disease, arteriosclerosis, diabetes mellitus, hypertension, obesity] are common and becoming increasingly important. As there is no agreed-upon definitive cure with acceptable risk, these disorders are a significant burden on the health care delivery system. This is because the chronic nature of genetic diseases requires lifelong medical attention, expensive supportive and symptomatic therapy and specialist care. This review outlines the genetic disorders, their impact on health care delivery systems and the general framework required to prevent and control these disorders

Potential usefulness of preimplantation genetic diagnosis in the control and prevention of genetic diseases

Prenatal diagnosis of molecular mutations can be of immense value, since diagnosis followed by genetic counselling provides the most appropriate approach to genetic diseases control and prevention. However, ethical, psychosocial and religious considerations hamper adoption of prenatal diagnosis in communities where termination of a pregnancy may not be acceptable. Recently, preimplantation genetic diagnosis has attracted considerable interest. This involves in vitro fertilization, followed by genetic disorder diagnosis using polar bodies or cells extracted from a blastomere stage. The normal blastomere is implanted in the womb and pregnancy proceeds naturally. If an abnormality is diagnosed, the blastomere is not implanted, thus preventing pregnancy with the affected fetus. This paper outlines the potential usefulness of preimplantation genetic diagnosis in the control and prevention of genetic disease in our part of the world

Appraisal of sickle-cell and thalassaemia genes in Saudi Arabia

A comprehensive national survey of the distribution of the sickle-cell [Hb S] gene and thalassaemia genes was initiated in 1982, with more than 30,055 blood samples collected. The Hb S, alpha- and beta-thalassaemia gene frequency range was 0.005-0.145, 0.01-0.40 and 0.01-0.15 respectively in various areas of Saudi Arabia. We present here an appraisal of sickle-cell and thalassaemia gene occurrence in the Saudi population, based on our studies conducted over 10 years in different regions of Saudi Arabia

Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease

We collaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the origin of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula

Pattern for alpha-thalassaemia in Yemeni sickle-cell-disease patients

A group of Yemeni patients with sickle-cell disease [SCD] and normal Hb AA individuals living in Riyadh were studied to determine the incidence of the alpha-gene molecular defect. Blood samples were obtained from 26 SCD patients and 19 controls [the Hb AA group]. In the SCD patients the frequency of single alpha-gene deletion [-alpha/alpha alpha] was 0.346, compared to 0.263 in the Hb AA group. The frequency of two gene deletion [-alpha/-alpha] was 0.231 [0.0 for the Hb AA group]. In one Hb AA case, a triple alpha-gene arrangement [alpha alpha alpha/alpha alpha] was found [frequency 0.053]. The results suggest that alpha-thalassaemia occurs frequently in Yemeni SCD patients. Further studies to determine the overall frequency of alpha-thalassaemia in the Republic of Yemen would be of value for patient management

Molecular studies on Yemeni sickle-cell-disease patients: Xmn I polymorphism

Our studies of the Saudi population have shown that in patients with mild presentation of sickle-cell disease [SCD] from Saudi Arabia's eastern region, the prevalence of polymorphic sites is high. However, the prevalence is very low in patients with severe SCD from the south-west of the country. We expanded these studies to a group of Yemeni patients with severe SCD, resident in Riyadh. We investigated a total of 60 chromosomes carrying the sickle-cell [Hb S] gene and 14 chromosomes carrying the Hb A gene. Amongst the Hb AA group, the prevalence was 42.9% and 57.1% for the presence [+] and absence [-] of Xmn I polymorphic sites. In the Hb SS individuals, the prevalence of Xmn I polymorphic sites was similar to the prevalence reported in the south-western region of Saudi Arabia

Glutathione reductase deficiency in Saudi Arabia

Glutathione reductase [GR] is a ubiquitous enzyme required for the conversion of oxidized glutathione [GSSG] to reduced glutathione [GSH] concomitantly oxidizing reduced nicotinamide adenine dinucleotide phosphate [NADPH] in a reaction essential for the stability and integrity of red cells. Mutations in the GR gene and nutritional deficiency of riboflavin, a co-factor required for the normal functioning of GR, can cause GR deficiency. We conducted a study on 1691 Saudi individuals to determine the overall frequency of GR deficiency and to identify whether the deficiency results from genetic or acquired causes or both. The activity of GR was measured in freshly prepared red cell haemolysate in the presence and absence of flavin adenine dinucleotide [FAD] and the activity coefficient [AC] was determined. Samples with low GR activity [> 2.0 IU/g haemoglobin] both in the presence and absence of FAD and an AC between 0.9 and 1.2 were considered GR-deficient. Samples with AC >/= 1.3 were considered riboflavin-deficient. The overall frequency of partial GR deficiency was 24.5% and 20.3% in males and females respectively. In addition, 17.8% of males and 22.4% of females suffered from GR deficiency due to riboflavin deficiency. This could be easily corrected by dietary supplementation with riboflavin. No cases of severe GR deficiency were identified

Diabetes mellitus, hypertension and obesity-common multifactorial disorders in Saudis

Diabetes mellitus, hypertension and obesity are among the multifactorial disorders that occur at a higher prevalence in older age groups. Their prevalence is affected by both genetic and environmental factors. We investigated the distribution of diabetes mellitus, hypertension and obesity in Saudi males and females by conducting a household screening survey during the period 1992-1996 of the adult population [> 14 years] in five different areas of Saudi Arabia. Height, weight, age and other essential details were recorded and diastolic and systolic blood pressures measured. Glucose levels were measured in blood taken after fasting and 2 hours after a glucose load. The data were used to classify the individuals as diabetic, glucose intolerant and normal, using WHO criteria. The individuals were further classified as type 1 diabetes mellitus and type 2 diabetes mellitus. The overall prevalence of diabetes mellitus was 9.7% and 7.0%, obesity 13.05% and 20.26%, overweight 27.23% and 25.20%, and hypertension 5.39% and 3.65% in the adult male and female populations respectively. A significant increase was observed in the prevalence of diabetes, obesity and hypertension with age in both males and females. In addition, the prevalence of obesity and overweight was significantly higher in the individuals with diabetes mellitus

frequency of Hb S and glucose-6-phosphate dehydrogenase phenotypes in relation to malaria in western Saudi Arabia

This study was conducted on 6265 Saudi males and females living in six different areas i.e. Yanbu, Makkah, AI-Qunfuda, Bisha, AI-Baha and Jaizan, in western Saudi Arabia. It was conceived to determine and relate the frequency of Hb S and of glucose-6-phosphate dehydrogenase [G-6-PD] deficiency phenotypes in the different areas and to relate them to malaria endemicity. The sickle cell gene was encountered in each of the areas investigated at frequencies ranging from 0.015 in Yanbu to 0.115 in AI-Qunfuda. The normal G-6-PD in each region was G-6-PD-B+, and variants identified included G-6-PD-A+, G-6-PD-A-, G-6-PD-Mediterranean and G-6-PD-Weak. Severe G-6-PD deficiency was encountered in each region and was caused mainly by G-6-PD-Mediterranean at frequencies ranging from 0.0179 to 0.204 in the male population and 0.0064 to 0.1158 in the female population. This paper shows significant differences in the frequencies of G-6-PD phenotypes and Hb S genes within malaria endemic regions

Human hemoglobinopathies in thalassemia syndromes genetics, molecular and laboratory aspects

Haemoglobin disorders are classified, in general, as intracorpuscular defects that may induce haemolytic anaemia. The genetically determined abnormalities of human haemoglobin can result from structural alteration in the haemoglobin molecule and this in turn can be the manifestation of sickle cell gene homozygosity and unstable haemoglobin or abnormally functioning haemoglobin. The variations will be outlined, and the state of knowledge regarding the haemoglobinopathies and thalassaemias in genetic terms and laboratory diagnosis is presented with particular emphasis on these disorders in Saudi Arabia