Box Phenotype of sickle cell disease

The clinical manifestations of sickle cell disease are severe and potentially life threatening (Ashley-Koch et al. 2000). The disease becomes symptomatic as P globin expression replaces y globin during the first 6 months of life, with anaemia and jaundice as a result of increased haemolysis of the red blood cells. The red blood cells have an irregular sickled appearance in low oxygen states (see Fig. 1.4) and tend to adhere to blood vessel walls with reduced blood flow and risk of complete vascular occlusion. Symptomatically, sickle cell disease is characterized by acute painful crises affecting the musculo-skeletal system; a pneumonia-like illness described as acute chest syndrome; stroke; and increased susceptibility to bacterial infection. A longitudinal prospective cohort study (the Cooperative Study of Sickle Cell Disease) highlighted the high incidence of severe pneumococcal infection in infancy which led to routine neonatal screening for the disorder and use of prophylactic penicillin (Gaston and Rosse 1982; Gaston et al. 1986). Sickle cell disease is associated with premature death, with 11% of patients having a stroke by age 20 and 24% by age 45 years (Platt et al. 1994; Ohene-Frempong et al. 1998). The use of hydroxyurea which is associated with an increase in the level of Hb F has proved a very important therapeutic intervention in sickle cell disease, reducing sickling, the frequency of painful crises, and mortality (Letvin et al. 1984; Charache et al. 1995; Steinberg et al. 2003).

Parent with sickle cell trait

Parent with sickle cell trait

Parent with sickle cell trait

Parent with sickle cell trait

Figure 1.5 Inheritance of alleles for sickle haemoglobin. Illustration of two parents who have one allele bearing the sickle variant of p globin (S) and one with the normal variant (A) which shows the likelihood of their offspring having different combinations of the alleles. Individuals with sickle cell trait are carriers of the disease-associated allele: having two parents who are carriers ('AS') results in a 25% chance that a child will have two disease alleles ('SS') and develop sickle cell disease; 50% chance of a child being a carrier ('AS'); and 25% chance of a child having two alleles without the disease-causing variant ('AA')

Figure 1.5 Inheritance of alleles for sickle haemoglobin. Illustration of two parents who have one allele bearing the sickle variant of p globin (S) and one with the normal variant (A) which shows the likelihood of their offspring having different combinations of the alleles. Individuals with sickle cell trait are carriers of the disease-associated allele: having two parents who are carriers ('AS') results in a 25% chance that a child will have two disease alleles ('SS') and develop sickle cell disease; 50% chance of a child being a carrier ('AS'); and 25% chance of a child having two alleles without the disease-causing variant ('AA')

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