Genetic compounds--Hb S, thalassaemias and enzymopathies: spectrum of interactions

Abstract

In areas with high occurrence of the red cell genetic abnormalities, i.e. sickle cell gene, alpha- and beta-thalassaemias, and glucose-6-phosphate dehydrogenase deficiency, various genes frequently co-exist in the same population. Co-inheritance of two or more abnormal genes in the same individual is frequently encountered, particularly in certain 'closed' tribes in Arabia in which consanguinity is the norm. Such genetic interactions modify the clinical presentations of the disease state. During our studies, we encountered a large number of individuals who were carriers of two or more abnormal genes. The most frequent genetic compounds were double heterozygous HbS-beta zero-thalassaemia and HbS-beta(+)-thalassaemia with associated alpha-thalassaemia or G-6-PD deficiency. Clinical history, and assessment, as well as blood analysis for haematological, biochemical, and molecular pathology determinants were carried out. The patients were classified into subgroups, based on the genetic findings. The clinical, haematological and biochemical data were assessed separately for each group. Sickle cell anaemia (Hb SS) cases, without any other abnormal gene, were used as a reference group. The results showed severe anaemia in patients with HbS/beta zero-thalassaemia and associated alpha-thalassaemia and/or G-6-PD deficiency. Patients with HbS/beta zero-thalassaemia exhibited features similar to that of the sickle cell anaemia. While sickle cell anaemia patients with alpha-thalassaemia and G-6-PD deficiency exhibited a milder presentation. This paper presents various forms of genetic associations, their influence on the clinical presentation and the laboratory parameter data, and discusses the implications of the findings.