Epidemiology and etiology

Sickle cell trait (SCT) is the heterozygous form (HbAS) of SCD in which a person inherits one normal adult hemoglobin (HbA) gene and one sickle hemoglobin (HbS) gene. These individuals are carriers of the SCT and are usually asymptomatic.2 Symptomatic disease is seen in homozygous and compound heterozygous genotypes of

SCD. Sickle cell anemia (SCA) is the homozygous (HbSS) state of SCD2 It is the most common and severe form of SCD. Compound heterozygosity is seen when individuals inherit one copy of the mutation that causes HbS and one copy of another abnormal hemoglobin gene. Compound heterozygosity may also include the coin-

heritance of HbS and one of the many different mutations of ft-thalasssemia (HbSft

0-thalassemia and HbS ft -thalassemia). " SCA affects both males and females equally because it is not a sex-linked disease.

Nine percent of African Americans possess the SCT and 1 in 600 has HbSS.4 Two thousand infants are identified with SCD annually in the United States.5 For every infant diagnosed with SCD, 50 are identified as carriers.5 HbSS (approximately 45%) is the most common genotypic expression, followed by HbSC (approximately 25%), HbSft + -thalassemia (approximately 8%), and HbSft 0-thalassemia (approximately

2%). Other variants account for less than 1% of patients. '

Having the sickle hemoglobin gene protects heterozygous carriers from succumbing to Plasmodium falciparum (malaria) infection.1 The microorganism cannot parasitize abnormal red blood cells (RBCs) as easily as normal RBCs. Consequently, persons with heterozygous sickle gene (SCT) have a selective advantage in tropical regions where malaria is endemic.

The highest incidence of SCD is seen in those with African heritage, but SCD also affects persons of Indian, Saudi Arabian, Mediterranean, South and Central American, and Caribbean ancestry5,6

Normal adult hemoglobin (HbA) is composed of two a-chains and two ft-chains (a2ft2). A single substitution of the amino acid valine for glutamic acid at position 6 of the ft-polypeptide chain is responsible for the production of a defective form of hemoglobin called sickle hemoglobin (HbS).1 Different genetic mutations encode for other hemoglobin variants such as hemoglobin C (HbC). HbC is produced by the substitution of lysine for glutamic acid at the sixth amino acid position in the ft-globulin chain. The a-chains of HbS, HbA, and HbC are structurally identical. The chemical differences in the ft-chain are responsible for RBC sickling and its associated sequelae.

SCA is the homozygous (HbSS) state of SCD in which individuals inherit the mutant hemoglobin gene (HbS) from both parents. The progeny of two carriers will have a 25% probability of having SCD and a 50% risk of being a carrier (Fig. 68-1). ft-Thalassemia can be found in conjunction with HbS. Patients with HbSS and HbSft

O-thalassemia do not have normal /^-globulin production and usually have a more severe course than those with HbSC and HbS/? -thalassemia. SCD involves multiple organ systems, and its clinical manifestations vary greatly between and among genotypes.


Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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